In order to study the regulating effect of electroacupuncture at specific acupoints on the depression level of drug addicts, we randomly selected 42 drug addicts from Sichuan drug rehabilitation center of women and divided them into treatment group (13), comfort group (10) and control group (19) from April to August 2019. Venous blood was taken before and after treatment, and the serum samples such as Noradrenalin (NA) and brain-derived neurotrophic factor (BDNF) were systematically detected. At the same time, Beck Depression Scale was used to detect the level of depression before and after treatment. Results showed that the level of depression in the real acupuncture group decreased significantly after treatment (p < 0.05). The contents of NA and BDNF in the serum of the real acupuncture group increased after treatment, but did not reach a significant level. In a word, the combination therapy of electroacupuncture can improve the levels of BDNF and NA in drug addicts and adjust their depression level, which is worthy of clinical promotion.

Helicobacter pylori (H. pylori) infection is widely prevalent worldwide. H. pylori infection has been reported to be a risk factor for the development of insulin resistance, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), liver fibrosis, and cirrhosis. Because treatment for NAFLD, other than weight loss is limited, the treatment for H. pylori infection is well established. It is important to determine whether screening and treatment for H. pylori infection should be considered in patients with no gastrointestinal symptoms. The aim of this mini-review is to evaluate the association between H. pylori infection and NAFLD including epidemiology, pathogenesis, and the evidence for H. pylori infection as a modifiable risk factor for preventing or treating NAFLD.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies. It has high mortality and poor clinical outcomes, but the molecular mechanisms in the pathogenesis of HCC are not understood. The tumor immune microenvironment (TIME) is a highly intricate system with distinct populations of innate and adaptive immune cells, as well as other stromal cells. They interact and evolve with tumor cells to influence tumor growth, migration, invasion, immune evasion, and response to therapy. Emerging evidence has shown noncoding RNAs (ncRNAs) are prominent regulators of TIME in HCC. In this review, we elaborate on the functions and molecular mechanisms of ncRNAs in remodeling TIME of HCC and discuss their diagnostic and therapeutic potential for HCC treatment.

To determine whether liver stiffness measurement (LSM) indicates liver inflammation in chronic hepatitis B (CHB) with different upper limits of normal (ULNs) for alanine aminotransferase (ALT).

We grouped 439 CHB patients using different ULNs for ALT: cohort I, ≤40 U/L (439 subjects); cohort II, ≤35/25 U/L (males/females; 330 subjects); and cohort III, ≤30/19 U/L (males/females; 231 subjects). Furthermore, 84 and 96 CHB patients with normal ALT (≤40 U/L) formed the external and prospective validation groups, respectively. We evaluated the correlation between LSM and biopsy-confirmed liver inflammation, and determined diagnostic accuracy using area under the curve (AUC). A noninvasive LSM-based model was developed using multivariate logistic regression.

Fibrosis-adjusted LSM values significantly increased with increasing inflammation. The AUCs of LSM in cohorts I, II, and III were 0.799, 0.796, and 0.814, respectively, for significant inflammation (A≥2) and 0.779, 0.767, and 0.770, respectively, for severe inflammation (A=3). Cutoff LSM values in all cohorts for A≥2 and A=3 were 6.3 and 7.5 kPa, respectively. Internal, external, and prospective validations showed high diagnostic accuracy of LSM for A≥2 and A=3, and no significant differences in AUCs among the four groups. LSM and globulin independently predicted A≥2. The AUC of an LSM-globulin model for A≥2 exceeded those of globulin, ALT, and AST, but was similar to that of LSM.

LSM predicted liver inflammation and guided the indication of antiviral therapy for CHB in patients with normal ALT.

Prostate cancer is a heterogeneous disease with a wide spectrum of pathological, clinical, and molecular features. The diagnosis and classification of prostate cancer have been constantly modified with the incorporation of new data. The 5th edition of the World Health Organization (WHO) Classification of Urinary and Genital Tumors was recently published six years after the 4th edition. In this new edition, the classification of prostate cancer has been refined in the diagnostic criteria, grading, nomenclature, and genomics. This review summarizes significant updates to the new WHO classification of prostate cancer, including high-grade prostatic intraepithelial neoplasia, acinar adenocarcinoma, intraductal carcinoma, ductal carcinoma, and neuroendocrine tumors. Controversial issues in the Gleason grading are discussed, such as intraductal carcinoma and tertiary grade. We also highlight distinct genetic and epigenetic alterations in prostate cancer that may contribute to its diverse clinicopathologic features. Overall, the 5th edition of the WHO classification provides a comprehensive assessment of prostate cancer with morphologic, immunohistochemical, genomic, and clinical data, which may represent an optimal paradigm for diagnosing and treating prostate cancer.

As for resection for colorectal liver metastasis (CRLM), securing an adequate surgical margin is important for achieving a better prognosis. However, it is often difficult to achieve adequate margins for the resection of CRLM. So the current survival impact of sub-centi/millimeter surgical margins in hepatectomy for CRLM should be evaluated. In the current era of multidisciplinary treatment options, this review focused on the prognostic impact of a sub-centi/millimeter surgical margin width in hepatectomy for CRLM. We systematically reviewed retrospective studies that clearly described the surgical margin width for hepatectomy for CRLM. We selected studies conducted since 2000 that involved patients diagnosed as having CRLM. We focused on studies that investigated not only surgical margins, but also microscopic surgical curability such as R0 (microscopically complete resection) or R1 (microscopically incomplete resection), which clearly describe their definitions. Based on our literature review, 1, 2, or 5 mm was considered the minimum surgical margin width for hepatectomy for CRLM. Although a surgical margin width of 1 mm is acceptable for hepatectomy for CRLM, submillimeter margins, which are defined as R1 in many reports, are only acceptable for limited patients such as those who have undergone preoperative chemotherapy. Zero-mm margins are also acceptable in limited patients such as those who show a good response to preoperative chemotherapy. New chemotherapy agents have been reported to reduce the prognostic impact of a narrow surgical margin width. The incidence of margin recurrence, which is a major concern regarding R1 resection of CRLM, is about 20–30% according to the majority of earlier reports. As evaluations of the actual prognostic impact of the surgical margin remain difficult, further study is warranted.

Cervical cancer has caused numerous deaths in women worldwide over the past few decades. It is a serious clinical problem that needs to be solved, though its morbidity and mortality have declined in recent years. The current treatments against cervical cancer are hysterectomy, radiotherapy, and chemotherapy, with certain limitations. Meanwhile, progress has been made in the screening and prevention of cervical cancer, focusing on human papillomavirus (HPV) infection, which is considered a necessary but insufficient cause. This review summarizes our current knowledge of screening and prevention of cervical cancer and its relation to HPV.

Aminoacyl-tRNA synthetases (ARSs) participate in tumor initiation and progression but their involvement in hepatocellular carcinoma (HCC) is not clear. This study aimed to investigate the prognostic value and underlying mechanisms of ARS in HCC.

Data were obtained from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium, Gene Expression Omnibus and Human Protein Atlas databases. The prognostic model was constructed with the use of Cox regression and least absolute shrinkage and selection operator regression. Kaplan-Meier survival analysis, enrichment analysis, single sample gene set enrichment analysis and tumor mutation burden calculation were performed with R to evaluate the model and explore the underlying mechanism. Wilcoxon tests were used for comparisons between groups.

Aspartyl-tRNA synthetase 2 (DARS2), tyrosyl-tRNA synthetase 1 (YARS1) and cysteinyl-tRNA synthetase 2 (CARS2) were identified as prognostic biomarkers and enrolled in model construction. The area under receiver operating characteristic curve of the model was 0.775. The model was used to assign patients from TCGA into low- and high-risk groups. Those in the high-risk group had a worse prognosis (p<0.001). The clinical significance of the model was tested in different clinical subgroups. Genetic mutation analysis had a higher TP53 mutation frequency in high-risk group. Enrichment analysis and study of immune-related cells and molecules found that the high-risk group was characterized by immune-cell infiltration and immunosuppression states.

A novel ARS family-based model of HCC prognosis was constructed. TP53 mutation frequency and immune-suppressive status accounted for a worse prognosis in patients included in the high-risk group.

The outbreak of coronavirus disease 2019 (COVID-19) has resulted in significant morbidity and mortality worldwide. Vaccination against coronavirus disease 2019 is a useful weapon to combat the virus. Patients with chronic liver diseases (CLDs), including compensated or decompensated liver cirrhosis and noncirrhotic diseases, have a decreased immunologic response to coronavirus disease 2019 vaccines. At the same time, they have increased mortality if infected. Current data show a reduction in mortality when patients with chronic liver diseases are vaccinated. A suboptimal vaccine response has been observed in liver transplant recipients, especially those receiving immunosuppressive therapy, so an early booster dose is recommended to achieve a better protective effect. Currently, there are no clinical data comparing the protective efficacy of different vaccines in patients with chronic liver diseases. Patient preference, availability of the vaccine in the country or area, and adverse effect profiles are factors to consider when choosing a vaccine. There have been reports of immune-mediated hepatitis after coronavirus disease 2019 vaccination, and clinicians should be aware of that potential side effect. Most patients who developed hepatitis after vaccination responded well to treatment with prednisolone, but an alternative type of vaccine should be considered for subsequent booster doses. Further prospective studies are required to investigate the duration of immunity and protection against different viral variants in patients with chronic liver diseases or liver transplant recipients, as well as the effect of heterologous vaccination.

This study evaluates the association of haplotypes of vitamin D receptor (VDR) genes (BsmI-ApaI-TaqI) with blood lead (B-Pb) levels.

The VDR polymorphism results for 100 occupationally lead-exposed (LEx) workers in the battery industry and 100 non-lead-exposed controls (controls) from the Delhi-NCR region were analyzed for haplotypes. PCR-RFLP was used to identify three VDR polymorphisms (TaqI, BsmI and ApaI), and the VDR haplotype and linkage disequilibrium (D′) were analyzed in these subjects.

B-Pb, together with the total vitamin D, calcium and phosphorus levels, were reported in the previous study conducted by the investigators. Eight possible haplotypes were observed among the three single nucleotide polymorphisms (BsmI-ApaI-TaqI). Furthermore, significant differences in haplotype frequency were observed between LEx workers and controls for the “baT” haplotype (X2 = 4.9, p = 0.02). Importantly, higher B-Pb levels were observed for the “baT” haplotype of the BsmI-ApaI-TaqI polymorphism, and BsmI and ApaI had the highest D′ and r2 values. However, significant variations in vitamin D, calcium and phosphorus levels were not observed between these haplotypes.

The “baT” haplotype of VDR polymorphisms might be a potential risk factor for lead toxicity, especially in exposed individuals. Hence, this haplotype may be considered during the screening of occupationally exposed individuals, in order to identify those who are susceptible to developing lead toxicity.

Post-acute sequelae of SARS-CoV-2 (PASC) or long COVID is a major public health problem. The underlying mechanism(s) of this disease remains unclear, and there is a lack of effective therapies. We report a case of a 47-year-old patient who experienced breakthrough acute COVID-19 with PASC after two doses of COVID-19 vaccination, and its symptom resolution following a course of the novel combination of antiviral nirmatrelvir-ritonavir. One of several leading hypotheses on the pathogenesis of PASC is a persistent viral reservoir. This case report raises important questions on the potential role of antiviral therapies in long COVID, and the need for further research and clinical trials in this field of study.

As liquid biopsy attracts more attention for the clinical detection and diagnosis of cancer, the need to establish reliable biomarkers has emerged. Plasma has received extensive study. However, for genitourinary (GU) cancers, urine can be the ideal body fluid. Urine can be collected in large quantities for frequent biomarker analysis and disease monitoring with relative ease. New biomarker studies are of great importance due to the limitations of the present diagnostic tests used for cancer detection and monitoring. Recently, many promising studies have investigated the role of cell-free DNA, DNA methylation, extracellular RNAs, and exosome cargos as biomarkers for GU cancer detection. This review explores the recent literature on the discovery of novel urinary biomarkers and their utility in detecting GU cancers. In small-scale studies, several novel biomarkers have shown preliminary evidence of superior clinical sensitivity and specificity compared to conventional GU cancer screening methods. With the use of these new urinary biomarkers, routine non-invasive screening and tumor monitoring may be possible.

The COVID-19 pandemic has caused symptoms of anxiety, distress, and depression in the general population. In order to develop interventions that target psychological problems, it is necessary to determine individual factors that have an impact on the development of psychological problems. The present study examined the effects of emotion dysregulation, attachment style and perceived social support on psychological problems in the context of COVID-19 using a sample of people living in Türkiye.

The sample consisted of 517 participants. In addition to the Demographic and COVID-19-related Information Form, a number of questionnaires were used, including the Depression, Anxiety and Stress Scale (DASS-21), Experiences in Close Relationships Revised (ECR-R), Impact of Event Scale Revised (IES-R), Difficulties in Emotion Regulation Scale-Brief Form (DERS-16), and Multidimensional Scale of Perceived Social Support (MSPSS).

The findings revealed that perceived social support, emotion dysregulation and attachment anxiety did not have serial mediation effects in the relationship between the impact of COVID-19, and depression or stress. However, there were serial mediating effects of perceived social support, emotion dysregulation, and attachment anxiety in the relationship between the impact of COVID-19 and anxiety. That is, the effects of the impact of COVID-19 (X) on anxiety (Y) through emotion dysregulation (M2) and attachment anxiety (M3) (bootstrap = 0.007, 95% CI = −0.001, 0.015), and through perceived social support, emotion dysregulation, and attachment anxiety (bootstrap = 0.005, 95% CI = 0.001, 0.013) were significant.

These findings suggest the role of individual appraisals in the initial stages of the COVID-19 outbreak.

Growing scientific evidence has suggested the disrupted regulation of host cell cycle proteins in hepatitis C virus (HCV)-associated liver disease. Since the regulation of cell cycle proteins is closely associated with the control of the proliferation and survival of hepatocytes, any alteration in the regulation of these proteins would significantly contribute to the progression of the HCV disease and development of hepatocellular carcinoma (HCC). This mini-review aims to provide an overview of available information on hepatic cell cycle modulations during chronic HCV infection.

The recently proposed concept of metabolic dysfunction-associated fatty liver disease (MAFLD) has remained controversial. We aimed to describe the features and associated outcomes to examine the diagnostic ability of MAFLD for identifying high-risk individuals.

In this retrospective cohort study, we enrolled 72,392 Chinese participants between 2014 and 2015. Participants were classified as MAFLD, nonalcoholic fatty liver disease (NAFLD), non-MAFLD-NAFLD, and a normal control group. The primary outcomes were liver-related and cardiovascular disease (CVD) events. Person-years of follow-up were calculated from enrolment to the diagnosis of the event, or the last date of data (June, 2020).

Of the 72,392 participants, 31.54% (22,835) and 28.33% (20,507) qualified the criteria for NAFLD or MAFLD, respectively. Compared with NAFLD, MAFLD patients were more likely to be male, overweight, and have higher biochemical indices including liver enzyme levels. Lean MAFLD diagnosed with ≥2 or ≥3 metabolic abnormalities presented similar clinical manifestations. During the median follow-up of 5.22 years, 919 incident cases of severe liver disease and 2,073 CVD cases were recorded. Compared with the normal control group, the NAFLD and MAFLD groups had a higher cumulative risk of liver failure and cardiac-cerebral vascular diseases. There were no significant differences in risk between the non-MAFLD-NAFLD and normal group. Diabetes-MAFLD group had the highest incidence of liver-related and cardiac-cerebral vascular diseases, lean MAFLD came second, and obese-MAFLD had the lowest incidence.

This real-world study provided evidence for rationally assessing the benefit and practicability of the change in terminology from NAFLD to MAFLD. MAFLD may be better than NAFLD in identifying fatty liver with worse clinical features and risk profile.

Phenethyl isothiocyanate (PEITC), a phytochemical from cruciferous vegetables, is known to modulate detoxification enzymes. Fortification of PEITC into a complete nutrition gel, Nutri-PEITC jelly, has been shown to improve its bioavailability. This work aimed to study the effect of Nutri-PEITC jelly on active smokers’ detoxification of tobacco-derived carcinogens.

This pre-post trial was conducted on 30 healthy, male, regular smokers. During the pre-intervention period, they smoked regularly for three days. During the postintervention period, they smoked regularly and consumed Nutri-PEITC jelly for three days (40 mg PEITC/day). The total amounts of N-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol metabolites in 24-hour urine were measured by liquid chromatography-tandem mass spectrometry after deconjugation with β-glucuronidase and normalized to the urinary creatinine level. To ensure the consistency of smoking and the actual consumption of Nutri-PEITC jelly, the levels of urinary cotinine and PEITC were measured by using an enzyme-linked immunosorbent assay and liquid chromatography-tandem mass spectrometry, respectively.

After consuming Nutri-PEITC jelly, the level of total urinary NNN metabolites (mainly glucuronide conjugates) was significantly increased by up to 4-fold (p < 0.01). In contrast, the level of total urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol metabolites was not significantly altered (p = 0.325). The urinary cotinine level was similar (p = 0.8832), while the urinary PEITC level was greater than that of the pre-intervention period (p < 0.001).

The findings suggest that intake of Nutri-PEITC jelly may increase the detoxification of NNN, a tobacco-specific oral carcinogen, likely by promoting glucuronide conjugation. Future randomized controlled trials are warranted to confirm its potential for the primary prevention of smoking-related oral cancer.

Insulin is the cornerstone of type 1 diabetes therapy and a crucial component for controlling type 2 diabetes. Despite significant advancements in insulin therapy research, including the creation of innovative insulin formulations and delivery systems, there are still numerous difficulties and unknowns surrounding insulin therapy. The main issues with more recent pharmacological and technological methods are biocompatibility, degradation/clearance of delivery materials, immunogenicity, stability, the precision of dosing, reproducibility of an effect similar to that of endogenous insulin, predictability of performance, and safety over time. In order to achieve a protracted, flatter profile, with fewer instances of hypoglycemia and an improvement in postprandial glucose level, more recent insulin mutants have been developed. The “meal” (glucose-responsive) insulins, which are supplied in accordance with an endogenous glucose-sensing feedback mechanism, best represent the future generation of insulin treatment. Insulin delivery methods with novel jet injectors, smart pens, patch pumps, and other needle-free tools for subcutaneous doses are another area of ongoing advancements. Digital health has significantly advanced treatments in recent years. As such, insulin treatments should become more scalable and potentially more cost-effective.

Distinguishing alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH) with biopsy alone is often difficult without a reliable clinical context. A novel finding on liver imaging, perivascular branching heterogeneity, has shown promise in distinguishing between these chronic liver diseases. Our study investigated the role of this finding on imaging to differentiate between ASH and NASH. The aim of this study was to determine the utility and reproducibility of this novel radiographic marker to help distinguish ASH from NASH.

This was a retrospective cohort study conducted between 2016 and 2020 in patients with both liver biopsy-confirmed steatohepatitis/chronic hepatitis and abdominal magnetic resonance imaging within 13 months of each other. Two radiologists, blinded to patient clinical history and diagnosis, categorized the appearance of the liver as: 1- homogeneity, 2- mild heterogeneity, 3- moderate heterogeneity, 4- possible perivascular branching, 5- definite perivascular branching.

Of the 90 patients in the study, 60 were identified as NASH and 30 as ASH. The area under the curve (AUC) for both reader 1 and 2 when using the 5-point scale was 0.69 (CI: 0.56–0.82, p=0.006) and 0.72 (CI: 0.60–0.85, p=0.001), respectively. The positive predictive value (PPV) for identification of ASH when scoring 5 was 64.7% and 66.7% for reader 1 and 2, respectively. Interclass correlation coefficient was 0.74 in patients with ASH, indicating moderate reliability among both readers.

Identification of this perivascular branching pattern on imaging is a promising novel diagnostic marker that can be used with other methods to help distinguish between ASH and NASH.

Syntaxin 5 (STX5) is a member of the syntaxin or target-soluble SNAP receptor (t-SNARE) family and plays a critical role in autophagy. However, its function and molecular mechanism in tumor cell migration are still unknown. The role of STX5 in influencing hepatocellular carcinoma (HCC) is an important topic in our research.

By using quantitative reverse transcription polymerase chain reaction (qPCR), western blotting, and immunohistochemical analysis of RNA and protein in tissues, we comprehensively evaluated data sets from public databases and clinical patient cohorts for STX5. The correlation of STX5 expression with the clinicopathological characteristics of HCC patients were assessed. In addition, we predicted signal pathways from differentially expressed genes (DEGs) and the Cancer Genome Atlas (TCGA) databases, and confirmed the prediction using integrated transcriptome and RNA-seq. We further investigated the underlying mechanisms of STX5 in the migration and adhesion of HCC cells both in vitro and in vivo.

In the TCGA dataset and our patient cohort, STX5 levels were significantly higher in HCC tissues than in adjacent normal liver tissues. At the same time, high expression of STX5 predicted worse prognosis in patients with liver cancer. High expression of STX5 indicates the decrease of adhesion and the increase of migration of HCC cells, and the conversion of epithelial-mesenchymal transition (EMT) in vitro via PI3K/mTOR pathway activation. Conversely, when Sirolimus, a phosphoinositide 3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) inhibitor acts on cells simultaneously, STX5 overexpression-mediated enhancement of HCC metastasis is reversed. Double-negative regulation of STX5 and mTOR further enhanced the inhibitory effect of STX5 on HCC metastasis. In vivo, STX5 knockdown inhibited the metastasis of HCC cells.

Our study demonstrates a novel research result that STX5 promotes HCC metastasis through PI3K/mTOR pathway. We believe that combined inhibition of STX5 and mTOR is a potential treatment for effectively prolonging patient survival and inhibiting HCC metastasis.