Achalasia is a motility disorder of the esophagus, characterized by failure of relaxation of the lower esophageal sphincter and disordered peristalsis. Although it is a rare condition, its incidence is rising, likely due to advances in diagnostic techniques and the adoption of standardized definitions. Achalasia is associated with significant morbidity, and currently, there is no cure. Pharmacologic, endoscopic, and surgical interventions are aimed at symptom control. Laparoscopic Heller myotomy (LHM) has been the standard of care for achalasia since the 1990s. Over the past two decades, per-oral endoscopic myotomy (POEM) has emerged as a viable treatment option. Today, LHM and POEM represent the two most effective treatment modalities available for achalasia. This review aims to compare outcomes following LHM and POEM for achalasia and to explore patient characteristics and technical factors that guide optimal treatment selection. We examine the evidence regarding dysphagia relief, reflux, complications, and reintervention rates for both procedures, taking into account factors such as prior surgical history, achalasia subtype, and patient comorbidities.

Coronary heart disease is an ischemic condition characterized by vascular stenosis or obstruction caused by coronary atherosclerosis, resulting in myocardial ischemia, hypoxia, or necrosis. It is one of the leading causes of death in both urban and rural populations in China. Safflower yellow pigments, the main active components of the traditional Chinese herbal medicine safflower, are primarily composed of quinochalcone compounds, including hydroxysafflor yellow A and anhydrosafflor yellow B—of which hydroxysafflor yellow A is the principal component. Studies have demonstrated that these pigments can improve myocardial ischemia, reduce ischemia-reperfusion injury, alleviate atherosclerotic damage, and address risk factors associated with coronary heart disease. This review aimed to systematically and comprehensively summarize the mechanisms of action of safflower yellow pigments and their active components in the context of coronary heart disease and its related risk factors.

Gastrointestinal dysmotility commonly follows thermal injuries, such as burns. This study aimed to investigate the effects and mechanisms of electroacupuncture (EA) on burn-induced gastric dysmotility in rats.

Sprague-Dawley rats were divided into sham and thermal injury groups subjected to a 60% scald burn. Antagonists, including β-blockade (propranolol), α-blockade (phentolamine), or a selective cyclooxygenase (COX)-2 inhibitor (nimsulide), were administered to verify the pathways involved. Six hours after the burn, the animals were evaluated for gastric emptying and heart rate variability. Blood and gastric tissues were collected for assays of cytokines, hormones, and COX-2 levels. EA was performed at bilateral ST36 (Zusanli) acupoints for 45 m.

Burn injury delayed gastric emptying by 61% (P < 0.01), which was normalized by nimsulide or propranolol but not by phentolamine. EA improved gastric emptying by 87% (P = 0.03) in burned rats. Heart rate variability and plasma hormone (noradrenaline and pancreatic polypeptide) analyses indicated sympathetic hyperactivity in burned rats; EA improved burn-induced sympathovagal imbalance by enhancing vagal activity. Protein and mRNA expressions of COX-2 in the gastric fundus and antrum increased with burn but were normalized by propranolol. EA reduced the burn-induced increase in COX-2 expression in the gastric fundus but not in the antrum. EA also decreased burn-induced elevations in plasma interleukin (IL)-6 and IL-10. Negative correlations were found between gastric emptying and plasma IL-6 levels, as well as between gastric emptying and COX-2 mRNA levels.

These findings suggest that burn-induced gastric dysmotility is mediated via autonomic-COX-2 pathways. EA at acupoint ST36 improves burn-induced delays in gastric emptying by down-regulating COX-2 and pro-inflammatory cytokines through the autonomic nervous pathway.

Exophiala, a genus of saprotrophic black fungi commonly found in the environment, is typically associated with cutaneous infections in immunocompromised hosts and rarely manifests as pneumonia. Here, we report the first case of Exophiala pneumonia in Pakistan, occurring in an immunocompetent, middle-aged female with interstitial lung disease.

A 56-year-old female presented with a two-week history of malaise and a cough productive of black sputum. On auscultation, fine crackles were heard in the bilateral posterior middle and lower lung fields. Chest radiography showed features of usual interstitial pneumonia with patchy and dense reticular opacities in the middle and lower lung lobes bilaterally. Bronchoscopy was performed, and bronchoalveolar lavage was sent to the microbiology laboratory for culture. Gram stain findings revealed numerous pus cells, primarily neutrophils, along with septate hyphae, which were also confirmed on potassium hydroxide smear. The results were communicated to the treating physician, and the patient was started on intravenous voriconazole. After four days of incubation at 25°C and 37°C, colonies of mold were observed on the culture, which were identified as Exophiala jeanselmei on Lactophenol Cotton Blue staining. After one week of treatment, the patient showed clinical improvement and was discharged on oral voriconazole with outpatient follow-up.

Our findings suggest that bronchoalveolar lavage with an elevated neutrophil count and abnormal pulmonary imaging should be evaluated as signs of both fungal and bacterial pneumonia. Additionally, fungal culture should be considered in such cases, as it employs specific techniques and prolonged incubation for the isolation of fungi. Since Exophiala jeanselmei is a rare yet severe cause of pneumonia, early detection and the knowledge gained from treated infections are crucial for effective management.

Despite significant advances in Parkinson’s disease (PD) treatment, it remains incurable, with limited therapeutic options. Currently, repurposing already tested, safe drugs has emerged as an effective therapeutic strategy against various neurodegenerative diseases, including PD. Using a drug-repurposing approach, the current study investigated the neuroregenerative potential of polysialic acid mimicking compounds, 5-nonyloxytryptamine oxalate (5-NOT) and Epirubicin (Epi), an anti-cancer drug, in 1-methyl-4-phenylpyridinium (MPP+)-treated human neuroblastoma SH-SY5Y cells as a PD model.

The excitotoxic model was established by exposing SH-SY5Y cells to 500 µM of MPP+ and subsequently treating them with the test compounds. The effect of MPP+-induced toxicity on cellular and nuclear morphology, as well as on the expression of neuroplasticity and cell survival proteins, were studied by immunostaining, gelatin zymogram, and Western blot assays.

Treatment with 5-NOT and Epi significantly promoted the survival of MPP+-challenged SH-SY5Y cells and prevented changes in their cellular and nuclear morphology by regulating the expression of microtubule-associated protein (MAP-2) and polysialylated-neural cell adhesion molecule (PSA-NCAM) and NCAM synaptic plasticity proteins. Further, 5-NOT and Epi treatment also protected SH-SY5Y cells by restoring levels of nitric oxide, matrix metalloproteinase, and stress response proteins. Interstingly, 5-NOT attenuated MPP+-induced toxicity in SH-SY5Y cells by regulating the intrinsic protein kinase AKT/BAD apoptotic pathway and the P-38 MAP kinase synaptic plasticity pathway.

These preliminary findings suggest that 5-NOT, as a potential polysialic acid glycomimetic, may serve as a promising drug candidate for targeting neurodegeneration of dopaminergic neurons, a hallmark feature of PD.

Helicobacter pylori (H. pylori) infection plays a pivotal role in gastric carcinogenesis and poses a significant burden on global public health. Eradicating H. pylori infection is an important strategy for the primary prevention of gastric cancer but remains a challenge. This consensus, an update of The First Beijing Consensus on Holistic Integrated Medicine (HIM) Combining Traditional Chinese with Western Medicine for the Management of Helicobacter pylori-associated “Disease-Syndrome” released in 2018, aims to further incorporate the HIM perspective and the latest research advances into the management of H. pylori-associated “disease-syndrome”. Forty-three experts from 29 medical institutions were selected to vote and reach a consensus. The consensus consists of five sections addressing 19 key questions with corresponding statements. These cover the current status and challenges of managing H. pylori infection in China, refractory H. pylori infection, the role of HIM in H. pylori management, holistic and individualized assessment/treatment for refractory infections, and the integration of traditional Chinese medicine in treating H. pylori-associated “disease-syndrome”. Finally, three therapeutic schemes for traditional Chinese medicine in treating H. pylori-associated “disease-syndrome” were proposed. Taken together, this consensus incorporates the principles of HIM along with advanced medical knowledge and clinical practice into individualized treatment strategies. It is recommended as a guideline for the management of H. pylori-associated “disease-syndrome” in China.

Chronic hepatitis B virus (HBV) infection remains a major cause of liver diseases, including cirrhosis and hepatocellular carcinoma. Reliable biomarkers for assessing viral replication, liver damage, and predicting clinical outcomes are essential for effective patient management. This review focuses on two promising biomarkers: serum HBV RNA and hepatitis B core-related antigen, both of which show strong correlations with viral replication and disease progression. Serum HBV RNA levels reflect the quantity and transcriptional activity of intrahepatic covalently closed circular DNA, providing insights into viral replication. They also correlate with other markers of replicative activity and have predictive value for key clinical outcomes, including hepatitis B e antigen and hepatitis B surface antigen seroconversion, relapse after therapy cessation, and liver fibrosis. Similarly, hepatitis B core-related antigen is closely associated with covalently closed circular DNA levels, correlates with markers of viral replication, and shows promise in predicting liver fibrosis, cirrhosis, and the risk of hepatocellular carcinoma. This review highlights the potential of both biomarkers for monitoring disease progression and guiding therapeutic decisions, particularly in the context of personalized treatment strategies and risk assessment for liver-related complications.

Emergency department (ED) presentations are associated with higher cancer mortality. This study aimed to investigate the prevalence, frequency, and risk factors in Australian patients diagnosed with malignant skin cancers.

This data-linkage cohort study examined adult patients presenting to the ED at the Royal Melbourne and Western Health hospitals within 12 months of a malignant skin cancer diagnosis. Multivariable logistic and Poisson regressions were used to analyze factors influencing the prevalence and frequency of ED presentations.

A total of 3,873 patients were diagnosed with skin malignancies between 2010 and 2018, of which 631 were diagnosed with melanoma. The prevalence of ED presentation was 29%, representing 2,119 episodes of care (median: 0; range: 0–14). Risk factors for a higher prevalence and frequency included: age ≥75 years (odds ratio (OR) = 1.78 [95% confidence interval 1.47–2.15]; incidence risk ratio (IRR) = 1.52 [1.35–1.70]); male (OR = 1.17 [1.01–1.36]; IRR = 1.23 [1.12–1.35]); socioeconomic status levels of 0–30% (OR = 1.59 [1.24–2.03]; IRR = 1.69 [1.45–1.96]) and 71–100% (OR = 1.30 [1.07–1.58]; IRR = 1.27 [1.12–1.45]); preferred language other than English (OR = 1.47 [1.17–1.84]; IRR = 1.49 [1.32–1.69]); and experience with any systemic therapy or radiotherapy (OR = 3.77 [2.12–6.71]; IRR = 2.36 [1.82–3.05]). Age < 65 years was protective (OR = 0.72 [0.59–0.89]; IRR = 0.78 [0.68–0.90]). Other preferred languages and cancer treatment experience were also risk factors in the sub-cohort with melanoma.

This study reports the prevalence and frequency of ED presentations following a skin cancer diagnosis and their association with socioeconomic and linguistic factors in Australia. Increased awareness of these factors could help address health inequities and potentially reduce the need for ED presentations.

There are no intraepithelial eosinophils present in the normal esophageal mucosa. It is well established that gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EoE) individually can result in esophageal eosinophilia and that the two disorders frequently coexist in the same patient. Nevertheless, the first step in the diagnostic algorithm for patients with esophageal symptoms associated with esophageal eosinophilia is to exclude non-EoE disorders that can cause esophageal eosinophilia, including GERD. While it is clear that GERD without EoE can cause low-level esophageal eosinophilia, it is less clear whether GERD alone can induce EoE-level esophageal eosinophilia (i.e., ≥15 eosinophils per high-power field). In this report, we have reviewed mechanisms by which reflux might induce eosinophilia in the esophagus and assessed studies suggesting that GERD alone can induce EoE-level esophageal eosinophilia. Studies on the latter issue have suffered from numerous shortcomings, including the use of outmoded or dubious methods for identifying GERD. Many of these studies were published prior to the realization that EoE can respond to proton pump inhibitor treatment. Our review of these studies suggests that GERD alone rarely, if ever, causes EoE-level eosinophilia (perhaps <1% of cases). For patients with definitive evidence of GERD associated with EoE-level esophageal eosinophilia but without endoscopic or clinical features of EoE, it is impossible to determine whether the eosinophilia is caused solely by GERD, by underlying but unrelated EoE that does not manifest typical features, or by EoE driven by GERD-induced defects, such as impaired esophageal barrier function. Until better diagnostic tests for EoE become available, this situation will remain a clinical conundrum.

Incomplete immune reconstitution is characterized by chronic immune activation and systemic inflammation, which are not fully reversed by antiretroviral therapy. Dihydroartemisinin (DHA) has demonstrated anti-inflammatory and immunosuppressive properties, which may benefit individuals with incomplete immune reconstitution. This study aimed to investigate the biological mechanisms underlying incomplete immune reconstitution and evaluate the therapeutic potential of DHA in modulating immune activation in immunological non-responders (INRs). This study aimed to investigate the biological mechanisms underlying incomplete immune reconstitution and evaluate the therapeutic potential of DHA in modulating immune activation in immunological non-responders (INRs).

RNA sequencing data (GSE106792) was retrieved from the Gene Expression Omnibus database. R software and Bioconductor packages were used to identify differentially expressed genes (DEGs) among INRs, immune responders (IRs), and healthy controls (HCs). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, along with protein-protein interaction (PPI) network construction, were performed. Potential DHA-binding proteins were predicted using the STITCH server and molecular docking studies. Validation experiments were conducted on peripheral blood mononuclear cells from 18 INRs. Cells were treated with varying concentrations of DHA, and CD4+ and CD8+ T cell activation markers (CD38 and HLA-DR) were measured via flow cytometry.

Enrichment and PPI network analysis identified 119, 56, and 189 DEGs in the INR vs. HC, INR vs. IR, and IR vs. HC comparisons, respectively. Enrichment and PPI analyses showed that DEGs were mainly involved in immune response pathways. DHA was predicted to interact with multiple target proteins, indicating anti-inflammatory effects. In vitro, DHA significantly reduced the frequency of CD38− HLA-DR+ CD4+ T cells and CD38+ HLA-DR+ CD8+ T cells at 1,000 µM and 500 µM compared to the control.

This study provides insights into the biological mechanisms underlying incomplete immune reconstitution and supports DHA’s potential as a therapeutic agent. DHA effectively inhibits T cell activation in INRs, presenting a novel and promising treatment strategy.