Following complete peripheral nerve injury, collateral sprouting (CS) by adjacent nerves causes concentric shrinkage of the insensate area. Such take-over of insensate territory is unknown in proximal lesions such as stroke, spinal cord injury, and cauda equina syndrome, as peripheral nerves supplying insensate territories still maintain continuity from the cell body in the dorsal root ganglion (DRG) to the skin innervation territory. This preserved distal continuity opposes territory take-over by the expansion of adjacent sensate territories; sectioning peripheral nerves in insensate territories distal to DRGs disconnects nerve cell bodies from their skin territory, thus facilitating sensate territory expansion of adjacent nerves. Similar motor system applications in paralyzed territories include lower motor neurone lesioning and fasciectomies, facilitating motor territory expansion of adjacent nerves through CS. A search for evidence of previous conception of these hypotheses was conducted in the literature, using a combination of relevant terms from three categories (proximal neuraxial lesions, nerve-muscle interventions, collateral sprouting); however, this yielded no pertinent results, suggesting that these concepts are novel. Observations from the literature on peripheral nerve injury indicate a sound scientific basis for these hypotheses. Therefore, the suggested “weeding” interventions are likely to succeed in minimizing neurological deficits and improving patients’ quality of life. Various interventions to expand sensory/motor territories are considered; these include nerve lesioning distal to DRGs and removing fascial barriers between innervated and paralyzed muscles. Experience from such interventions will help expand our understanding of the speed and extent of CS-mediated neurological recovery as well as brain’s plastic abilities in reorienting after such procedures.

Cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/2B) deletions are frequently identified in patients with biliary tract cancer; however, standard treatment options for this genetic alteration are lacking. Here, we present the case of a 64-year-old woman diagnosed with intrahepatic cholangiocarcinoma and hilar lymph node metastasis who underwent radical surgery. Postoperative pathology confirmed moderately differentiated adenocarcinoma. The tumor recurred during the second cycle of adjuvant chemotherapy following surgery, and the metastatic sites included the cranial region, right lung, and right adrenal gland. Genetic analysis revealed a CDKN2A/2B deletion, indicating palbociclib sensitivity. Subsequently, the patient received palbociclib plus lenvatinib as systemic therapy, along with stereotactic radiotherapy for the intracranial lesion. Notably, the right pulmonary metastasis significantly regressed after 12 months of treatment, with the complete disappearance of the intracranial tumor. However, the disease progressed at 32.2 months, with significant enlargement of the right adrenal gland metastasis and new metastasis in the right lung. The progression-free survival and overall survival were 32.2 months and 34.4 months, respectively. In conclusion, our case demonstrates that palbociclib plus lenvatinib is a promising chemotherapy-free second-line treatment for intrahepatic cholangiocarcinoma with a CDKN2A/2B deletion.

The World Health Organization System for Reporting Pancreaticobiliary Cytopathology introduces a seven-tier category system to standardize terminology and nomenclature. This system includes the following categories: Insufficient/non-diagnostic, benign/negative for malignancy, atypia, pancreaticobiliary neoplasm low-risk/grade, pancreaticobiliary neoplasm high-risk/grade, suspicious for malignancy, and malignant categories. Adopting a standardized reporting scheme facilitates consistent diagnostic criteria among pathologists, thereby reducing report variability and enhancing communication with the clinical team for optimal patient management. The report also highlights the role of critical ancillary tests in improving diagnostic accuracy for pancreatic lesions and discusses practical approaches to managing solid and cystic pancreatic lesions.

The diagnostic value of primary biliary cholangitis (PBC)-specific antibodies in patients with elevated alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) levels, and other identifiable causes, was unclear. Our study aimed to determine whether etiological treatments in PBC-specific antibody-positive patients could improve liver biochemical tests, thereby distinguishing them from individuals with PBC.

We enrolled patients who were positive for PBC-specific antibodies and elevated ALP and/or GGT levels but with other identifiable etiologies. Changes in liver biochemistry following non-ursodeoxycholic acid etiological treatments were monitored.

A total of 155 patients with positive PBC-specific antibodies and elevated ALP and/or GGT levels due to non-PBC diseases were enrolled. Among them, 100 patients were diagnosed with non-PBC liver diseases, mainly metabolic-associated fatty liver disease, drug-induced liver injury, and autoimmune hepatitis. Additionally, 55 patients had non-liver diseases, predominantly connective tissue diseases. The median follow-up duration was 15.9 (4.7–25.6) months. Among 141 patients who completed follow-up after receiving etiological treatments, 85.1% (120/141) showed improvement in ALP and/or GGT levels, with 51.8% (73/141) achieving normalization of both ALP and GGT. However, 68 patients continued to exhibit elevated ALP and/or GGT, with 55 patients displaying isolated GGT elevation and 11 patients showing liver histological changes not consistent with PBC.

PBC-specific antibodies, along with elevated ALP and GGT levels, may occur in various non-PBC diseases. Etiological treatments may improve or even resolve cholestatic biochemistry. For these patients, initiating etiological treatment rather than immediately starting ursodeoxycholic acid therapy would be justified.

Harm caused by crude oil spillage and its associated environmental toxicants manifests slowly. This study examined the impact of crude oil environmental toxicants on neonates’ thyroid and cognitive functions in crude oil-producing communities.

The case-control study comprised 55 crude oil-exposed expectant mothers and 33 non-crude oil-exposed expectant mothers as controls. Serum Benzo Pyrene Dihydrodiol Epoxide (BPDE), triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) were assayed in expectant mothers and neonates. Intelligence quotient and APGAR scores were determined in the children using Fagan’s test of infant intelligence.

Serum TSH (p < 0.05) and BPDE (p < 0.001) were higher, while T3 and T3/T4 ratio were significantly lower (p < 0.001) in exposed pregnant women compared to the control. Cord blood TSH and T3/T4 ratio were lower (p < 0.001) while T4 and BDPE were higher (p < 0.001) in prenatally exposed neonates than prenatally non-exposed infants. Serum TSH correlated with BDPE (R2 = 0.080, p < 0.036) and APGAR score (R2 = 0.341, p < 0.012), while T3 and T4 were not associated with BDPE and APGAR score. TSH correlated with T3 (R2 = 0.0.082, p < 0.05), T3 correlated with T4 (R2 = 0.111, p < 0.013) and TSH (R2 = 0.082, p < 0.05). Exactly 54.5% (30/55) of prenatally exposed neonates had a low intelligence quotient compared to 36.4% (12/33) in prenatally non-exposed neonates.

Crude oil and associated environmental pollutants might significantly affect the thyroid function. Environmental surveillance, biomonitoring and environmental cleanup are emphasized. Future research on the mechanisms of the observed toxicological effects on thyroid hormones and targeted protection of pregnant women and their offspring is suggested.

Patients with corona virus disease 2019 (COVID-19) face not only physical strains but also significant psychological stress, highlighting the importance of addressing their mental health concerns. This study aimed to evaluate the impact of Lianhua Qingwen on the psychological well-being of asymptomatic and mildly symptomatic COVID-19 patients, providing empirical evidence to guide clinical practices.

Conducted in eight shelter hospitals in Shanghai, the study employed a cluster randomization method to allocate patients equally into either the Lianhua Qingwen group or the control group. The Lianhua Qingwen group received oral doses of four capsules or one packet of granules three times daily for 14 days. In contrast, the control group received standardized treatment according to the diagnostic and treatment plan, excluding Lianhua Qingwen. Mental health was assessed using the Self-rating Depression Scale and Self-rating Anxiety Scale, with symptom reporting on the 7th and 14th days, accompanied by nucleic acid test result screenshots. A follow-up investigation on new disease occurrence was conducted six months post-discharge.

Among the 2,652 valid questionnaire respondents, the Lianhua Qingwen group accounted for 1,665 cases, characterized by a higher proportion of females (32.7% vs. 26.9%), younger age (44.8 vs. 46.2 years), lower percentages of asymptomatic infections (27.6% vs. 38.5%), higher baseline Patient Health Questionnaire-9 scores (2.7 vs. 1.9), and higher Generalized Anxiety Disorder 7 scores (1.9 vs. 1.4). Further multivariate logistic regression analysis explored factors influencing the alleviation of depressive and anxiety symptoms during follow-up, revealing that Lianhua Qingwen use was an independent factor in reducing anxiety (odds ratio = 1.37, 95% confidence interval 1.14–1.65, p = 0.001) and depression (odds ratio = 1.42, 95% confidence interval 1.19–1.69, p < 0.0001). Lianhua Qingwen increased the likelihood of reducing anxiety by 37% and depression by 42%.

Lianhua Qingwen significantly alleviated anxiety and depression symptoms in COVID-19 patients, suggesting its potential therapeutic efficacy in mitigating these conditions.

Idiopathic pulmonary fibrosis is a chronic, progressive, incurable lung disease, leading to irreversible lung tissue remodeling. The Notch signaling pathway, essential for lung development, has gained attention for its role in pulmonary fibrosis. While Notch1 and Notch3 have been extensively studied, the involvement of other Notch receptors, especially Notch4, remains less explored. This study aimed to evaluate the impact of Notch4 on lung fibroblast activation and its potential interaction with the transforming growth factor-beta 1 (TGFβ1) signaling.

Primary human lung fibroblasts were transduced with lentivirus containing the intracellular domain of NOTCH4 (N4ICD). Changes in gene expression in transduced cells were assessed using real-time polymerase chain reaction, immunofluorescence staining, and Western blotting. Transcriptomic analysis was also performed on N4ICD-transduced lung fibroblasts.

N4ICD overexpression significantly upregulated key fibrotic markers such as ACTA2 and COL1A1. It also induced the TGFβ1 pathway, as evidenced by SMAD2 phosphorylation and elevated TGFβ1 mRNA level. Transcriptomic analysis revealed that N4ICD-induced cells exhibited characteristics of highly invasive myofibroblasts.

This study establishes Notch4 as a novel contributor to pulmonary fibrosis, by demonstrating its ability to induce myofibroblast differentiation and interact with the TGFβ1 pathway.

Tumor molecular analysis using next-generation sequencing (NGS) is the standard of care for guiding lung cancer treatment. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive technique used to sample mediastinal lymph nodes for diagnosing and staging lung cancer. This study aimed to determine if EBUS-TBNA provided adequate tissue samples for NGS.

We evaluated EBUS-TBNA samples from adult advanced non-small cell lung cancer patients who had both EBUS-TBNA and liquid biopsy samples analyzed by NGS between July 1, 2015 and June 30, 2021. Additionally, we compared the results with those from liquid biopsies performed on these patients.

Among the 44 evaluated patients, 43% were male, with a median age of 66 years at diagnosis. Seventy-five percent were smokers, 79.5% were White, 6.8% were Black, and 9.1% were Asian. EBUS-TBNA samples were sufficient for NGS in 95.5% of cases. The median turnaround time for EBUS-TBNA NGS was 38.5 days compared with eight days for NGS in liquid biopsies. Actionable genetic aberrations were detected in 71% of patients.

Our findings demonstrated that EBUS-TBNA provided sufficient tissue for identifying actionable genetic aberrations in patients with advanced non-small cell lung cancer.

Type 2 diabetes mellitus (T2DM) is a prevalent yet complex metabolic disorder that has shown a rising incidence over the past few decades. Recent research has identified flavonoids as compounds capable of both preventing and managing T2DM through various mechanisms. These mechanisms include enhancing insulin sensitivity, stimulating insulin secretion, modulating intestinal microbiota, inhibiting glucose absorption, and reducing gluconeogenesis. Moreover, numerous studies have suggested that flavonoids may influence gut hormones. Therefore, we propose that flavonoids could serve as effective therapeutic agents for T2DM by modulating intestinal hormone levels. This review aimed to elucidate the potential pathways through which flavonoids may impact T2DM, with a particular emphasis on their role in regulating the enteroendocrine system.