Background The high work intensity and possible subsequently increased susceptibility to occupational hazards of calcium carbide plants may lead to hypertension in workers, but there are few studies on the relationship between occupational hazard exposure and hypertension in workers involving the production process of calcium carbide. Objective To explore the influence of occupational hazards on the incidence of hypertension in calcium carbide plants. Methods Using historical cohort design, the employees of a calcium carbide factory in the western part of Inner Mongolia Autonomous Region were selected as research subjects. According to the pre-determined inclusion and exclusion criteria, the study population comprised an exposure group of 377 employees (including furnace workers, inspection workers, and maintenance workers) exposed to dust, noise & carbon monoxide, and a control group of 388 employees (including central control workers, electricians, and administrative personnel) without above-mentioned exposure. The total sample size was 765 participants. The follow-up period was from April 2011 to October 2022, and the study endpoint was defined as the conclusion of the follow-up period or diagnosed hypertension in annual occupational health examination. Information on general demographic characteristics, living habits, and work status was collected from all study subjects. Cox proportional hazards regression model was used to analyze the association between occupational hazard exposure and the risk of hypertension among the calcium carbide plant employees. Results The average age, mean systolic and diastolic blood pressure, proportion of males, smoking rate, and alcohol consumption rate in the exposure group were higher than those in the control group (P<0.05). Compared to baseline, both systolic and diastolic blood pressure levels increased in the exposure group and the control group at the end of the follow-up (P<0.05). At the end of the follow-up, the average differences between systolic/ diastolic blood pressure and baseline values in the exposure group were higher than those in the control group (P<0.05). During the follow-up period, a total of 223 cases of hypertension occurred, with a total follow-up of 2785 person-years, resulting in an incidence density of 8007.18 per 100000 person-years, an average age of onset of (35.90±8.22) years, and an average working age of onset of (2.69±1.97) years. The incidence density in the exposure group was 128.71% higher than that in the control group, and the risk of hypertension in the exposure group was 2.115 times that of the control group. The risk of hypertension was 2.199 times higher for men than for women, 1.344 times higher for those aged 30 and above than for those under 30, 1.546 times higher for smokers than for non-smokers, and 1.750 times higher for drinking workers than for non-drinking ones. The results of Cox proportional hazards regression modeling indicated that the hazard ratio (95%CI) of hypertension among the employees exposed to dust, noise, and carbon monoxide was 2.254 (1.703, 2.982), 1.594 (1.107, 2.295), and 1.567 (1.079, 2.274), respectively, when different covariates (gender, age, smoking, and alcohol consumption) were included. The results of Log-rank test showed that there were statistically significant differences in the distribution of disease-free survival between the exposure group and the control group (P<0.05). Conclusion Occupational exposures to dust, noise, and carbon monoxide may increase the risk of hypertension among calcium carbide plant workers.

This article discusses the important role and practical experience of Guangxi Zhuang Autonomous Region as a bridgehead between China and the Association of Southeast Asian Nations (ASEAN) in the joint prevention and control of cross-border infectious diseases between China and Vietnam. The cross-border transmission of infectious diseases has been effectively managed in Guangxi Zhuang Autonomous Region through a package of strategies, including government leadership, construction of the joint prevention and control mechanism, establishment of dialogue platforms, collaboration of scientific researches, and personnel exchange and training; however, there are still challenges. Further deepening of collaboration is required to meet future needs for infectious disease prevention and control.

This study aims to explore the role and mechanism of berberine in promoting the expression of aquaporin 4(AQP4) in astrocytes by regulating the expression of miR-383-5p in HepG2 cell-derived exosomes under insulin resistance(IR). The IR-HepG2 cell model was established with 1×10~(-6) mol·L~(-1) insulin. With metformin as the positive control, the safe concentrations of berberine and metformin were screened by cell counting kit-8(CCK-8) and lactate dehydrogenase(LDH) leakage assays, and the effect of berberine on the IR of HepG2 cells was evaluated by glucose consumption. NanoSight was used to measure the particle size and concentration of exosomes secreted by HepG2 cells in each group. HepG2 cell-derived exosomes in each group were incubated with astrocytes for 24 h, and the protein and mRNA levels of AQP4 in HA1800 cells were determined by Western blot and qRT-PCR, respectively. qRT-PCR was performed to determine the expression of miR-383-5p in HepG2 cell-derived exosomes and HA1800 cells after co-incubation. Western blotting was employed to determine the expression levels of miRNAs and proteins associated with exosome production and release in HepG2 cells. The results showed that 10 μmol·L~(-1) berberine and 1 mmol·L~(-1) metformin significantly alleviated the IR of HepG2 cells and reduced the concentration of exosomes in HepG2 cells. The exosomes of HepG2 cells treated with berberine and metformin significantly up-regulated the protein and mRNA levels of AQP4 in HA1800 cells. The mRNA level of miR-383-5p in HepG2 cell exosomes and HA1800 cells co-incubated with berberine and metformin decreased significantly. The intervention with berberine and metformin significantly down-regulated the expression of proteins associated with the production of miRNAs(Dicer, Drosha) as well as the production(Alix, Vps4A) and release(Rab35, VAMP3) of exosomes in IR-HepG2 cells. In conclusion, berberine can promote the expression of AQP4 in astrocytes by inhibiting the production and release of miR-383-5p in HepG2-derived exosomes under IR.
Humans ; MicroRNAs/metabolism* ; Berberine/pharmacology* ; Hep G2 Cells ; Exosomes/genetics* ; Aquaporin 4/metabolism* ; Insulin Resistance ; Astrocytes/drug effects*

Mechanical pain is one of the most common causes of clinical pain, but there remains a lack of effective treatment for debilitating mechanical and chronic forms of neuropathic pain. Recently, neurotoxin GsMTx4, a selective mechanosensitive (MS) channel inhibitor, has been found to be effective, while the underlying mechanism remains elusive. Here, with multiple rodent pain models, we demonstrated that a GsMTx4-based 17-residue peptide, which we call P10581, was able to reduce mechanical hyperalgesia and neuropathic pain. The analgesic effects of P10581 can be as strong as morphine but is not toxic in animal models. The anti-hyperalgesic effect of the peptide was resistant to naloxone (an μ-opioid receptor antagonist) and showed no side effects of morphine, including tolerance, motor impairment, and conditioned place preference. Pharmacological inhibition of TRPV4 by P10581 in a heterogeneous expression system, combined with the use of Trpv4 knockout mice indicates that TRPV4 channels may act as the potential target for the analgesic effect of P10581. Our study identified a potential drug for curing mechanical pain and exposed its mechanism.

Colorectal tumorigenesis generally progresses from adenoma to adenocarcinoma, accompanied by dynamic changes in the tumor microenvironment (TME). A randomized controlled trial has confirmed the efficacy and safety of Shen-Bai-Jie-Du decoction (SBJDD) in preventing colorectal tumorigenesis. However, the mechanism remains unclear. In this study, we employed single-cell RNA sequencing (scRNA-seq) to investigate the dynamic evolution of the TME and validated cell infiltration with multiplex immunohistochemistry and flow cytometry. Bulk RNA sequencing was utilized to assess the underlying mechanisms. Our results constructed the mutually verifiable single-cell transcriptomic atlases in Apc ^Min/+ mice and clinical patients. There was a marked accumulation of CCL22⁺ dendritic cells (DCs) and an enhanced immunosuppressive action, which SBJDD and berberine reversed. Combined treatment with cholesterol and lipopolysaccharide induced characteristic gene expression of CCL22⁺ DCs, which may represent "exhausted DCs". Intraperitoneal injection of these DCs after SBJDD treatment eliminated its therapeutic effects. TMEM131 derived CCL22⁺ DCs generation by TNF signaling pathway and may be a potential target of berberine in retarding colorectal tumorigenesis. These findings emphasize the role of exhausted DCs and the regulatory mechanisms of SBJDD and berberine in colorectal cancer (CRC), suggesting that the multi-component properties of SBJDD may help restore TME homeostasis and offer novel cancer therapy.

Objective:To explore the relationship between Epstein-Barr virus (EBV) infection, hepatitis B virus (HBV) reactivation and clinical features and prognosis in HBV-infected non-Hodgkin lymphoma (NHL) patients and influencing factors of HBV reactivation.Methods:A retrospective cohort study was conducted. A total of 80 NHL patients with hepatitis B surface antigen (HBsAg) positive (which was defined as HBV positive) who were admitted to the Second People's Hospital of Lianyungang and Jiangsu Province Hospital from December 2012 to October 2022 were selected. All patients were divided into EBV-positive group and EBV-negative group according to EBV DNA results, and further grouped into the HBV reactivation group and the non-reactivation group according to whether HBV were reactivated after chemotherapy. The clinical characteristics of patients among groups were compared. Multivariate logistic regression model was used to analyze the factors influencing HBV reactivation. The Kaplan-Meier method was used to evaluate the progression-free survival (PFS) and overall survival (OS) of patients, and the log-rank test was used for inter-group comparison.Results:Among NHL patients with HBV positive, 27 cases (33.8%) were EBV-positive and 29 cases (36.3%) were HBV reactivation. Compared with the EBV-negative group, the proportion of patients with Ann Arbor stage Ⅲ-Ⅳ [92.6% (25/27) vs. 66.0% (35/53)], elevated β 2-microglobulin level [88.9% (24/27) vs. 62.3% (33/53)], bone marrow involvement [40.7% (11/27) vs. 15.1% (8/53)], and HBV reactivation [51.9% (14/27) vs. 28.3% (15/53)] was higher in the EBV-positive group, and the differences were statistically significant (all P<0.05). There were no statistically significant differences in the composition of patients stratified by age, gender, pathological type, B symptom, lactate dehydrogenase level, international prognostic index score, number of extranodal involvements, liver involvement, hepatitis outbreak, prophylactic anti-HBV therapy, hepatitis B surface antibody (HBsAb), rituximab therapy, and the last chemotherapy effects between the 2 groups (all P > 0.05). Compared with the HBV non-reactivation group, the proportion of patients undergoing hepatitis outbreak [48.3% (14/29) vs. 17.6% (9/51)], not receiving prophylactic anti-HBV therapy [65.5% (19/29) vs. 39.2% (20/51)], HBsAb negative [79.3% (23/29) vs. 21.6% (11/51)], EBV positive [48.3% (14/29) vs. 25.5% (13/51)], receiving rituximab [82.8% (24/29) vs. 60.8% (31/51)] was higher in the HBV reactivation group, and the differenves were statistically significant (all P < 0.05); while there were no statistically significant differences in the composition of patients stratified by the other clinical characteristics between the 2 groups (all P > 0.05). Multivariate logistic regression analysis showed that EBV-positivity was an independent risk factor for HBV reactivation after chemotherapy in NHL patients with HBsAg positive ( OR = 7.073, 95% CI: 1.613-31.010, P = 0.009), while HBsAb positive ( OR = 0.038, 95% CI: 0.008-0.186, P < 0.001) and preventive anti-HBV therapy ( OR = 0.172, 95% CI: 0.039-0.756, P = 0.020) were independent protective factors. The last follow-up was in December 2023 and the median follow-up time was 36.5 months. There were no statistically significant differences in PFS and OS between the EBV-positive group and the EBV-negative group, HBV reactivation group and the non-reactivation group (all P > 0.05). Conclusions:Among HBV-infected NHL patients, those with concurrent EBV infection have a more advanced clinical stage and are very prone to bone marrow invasion, and they also show a higher probability of HBV reactivation; HBV reactivation may be related to whether receiving preventive anti-HBV therapy and rituximab therapy. EBV infection may increase the risk of HBV reactivation in NHL patients; EBV infection and HBV reactivation may not be relevant to the prognosis of patients.

Acute T-lymphoblastic leukemia (T-ALL) is a hematopoietic malignancy, and in recent years, with the advancement of combined chemotherapy and hematopoietic stem cell transplantation, the prognosis of T-ALL has improved significantly, but for patients with primary drug resistance or relapsed/refractory disease the prognosis is still poor. The plant homeodomain finger 6 (PHF6) is a tumor suppressor protein, it plays a pivotal role in T cell differentiation, epigenetic regulation and oncogenic pathway synergy, and its mutations and deletions are commonly associated with the development of T-lymphocytic leukemia. However, the underlying mechanism of PHF6 in the pathogenesis of T-ALL remains unclear. This article reviews the structure, function and mechanism of action of PHF6 in T-ALL, the important coexisting genes associated with the progression of T-ALL, and the research progress in targeted therapy.

Objective To explore the value of combined detection of serum mitogen-activated protein kinase 1(MAPK1)and lysyl oxidase-like protein 2(LOXL2)in early diagnosis of cervical cancer.Methods A total of 218 patients with cervical lesions were selected as study group(103 ca-ses in cervical cancer group,115 cases in benign tumor group).Additionally,100 patients with cer-vical intraepithelial neoplasia grade Ⅱ were selected as precancerous lesion group,and 79 healthy in-dividuals undergoing physical examinations during the same period were selected as control group.Se-rum levels of MAPK1 and LOXL2 were measured in each group.Pearson correlation analysis was used to evaluate the correlations of serum MAPK1 and LOXL2 levels in patients with cervical cancer.Logistic regression analysis was performed to screen influencing factors for the occurrence of cervical cancer.Receiver operating characteristic(ROC)curves were plotted to assess the diagnostic efficacy of serum MAPK1 and LOXL2 for cervical cancer.Results Serum MAPK1 and LOXL2 levels in the study group were higher than those in the precancerous lesion group and the control group,and those in the precancerous lesion group were higher than those in the control group,with statistically signif-icant differences(P＜0.05).The proportion of patients with high-risk human papillomavirus(HPV)infection and serum MAPK1 and LOXL2 levels in the cervical cancer group were higher than those in the benign tumor group,with statistically significant differences(P＜0.05).Serum MAPK1 and LOXL2 levels in patients with stage Ⅲ to Ⅳ cervical cancer were higher than those in patients with stage Ⅰ to Ⅱ cervical cancer,with statistically significant differences(P＜0.05).Pearson correlation analysis showed a positive correlation between serum MAPK1 and LOXL2 levels in patients with cervical cancer(r=0.468,P＜0.001).Logistic regression analysis showed that high-risk HPV infection,MAPK1 and LOXL2 were all influencing factors for the occurrence of cervi-cal cancer(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)for com-bined diagnosis of serum MAPK1 and LOXL2 was 0.911,which was significantly greater than the AUCs for individual diagnoses(0.848 and 0.843,respectively).Conclusion Serum MAPK1 and LOXL2 levels in patients with cervical cancer are significantly upregulated,and the two indicators were positively correlated.High-risk HPV infection,serum MAPK1 and LOXL2 levels were influen-cing factors for the occurrence of cervical cancer.Combined detection of MAPK1 and LOXL2 levels is expected to assist in the diagnosis of cervical cancer.

Objective:To investigate the short-term outcome of transoral robotic thyroidectomy.Methods:This is a retrospective case series study. The clinicopathologic characteristics and postoperative results of 107 patients who underwent transoral robotic thyroidectomies in the Department of Thyroid and Breast Surgery of the 960 th Hospital of People′s Liberation Army from May 2020 to August 2023 were retrospectively analyzed. There were 12 males and 95 females, with an age of (31.8±9.4) years (range: 11 to 55 years), including 20 benign tumors and 87 thyroid papillary carcinoma. Postoperative follow-up was carried out through returning visit and telephone, mainly to observe the recovery of postoperative complications, cosmetic effects and recurrence results. Results:All transoral robotic thyroidectomy was successfully completed without conversion to open surgery. The tumor size of thyroid papillary carcinoma patients was (5.6±2.7) mm (range: 2 to 15 mm). Furthermore, central cervical lymph node metastasis was found in 45 cases. The number of central cervical lymph nodes retrieved and metastasized ( M(IQR)) were 11 (8) (range: 3 to 26) and 1 (3) (range: 0 to 13), respectively. There was no recurrent laryngeal nerve injury and permanent hypoparathyroidism. The transient hypoparathyroidism after surgery was 8 cases. Other complications occurred as follows: postoperative infection ( n=1), left submandibular perforation ( n=1), skin scald ( n=1), and perioral numbness ( n=1), oral tear ( n=2). The postoperative stay was 6 (2) days (range: 3 to 11 days). No local lymph node recurrence or metastasis occurred after a follow-up of (22.6±10.0) months (range: 1.0 to 37.4 months). All patients were satisfied with the postoperative cosmetic results, the aesthetic effect score was 9.3 (0.2) (range: 8.4 to 9.6) one month after surgery. Conclusion:For highly screened patients with early thyroid cancer, experienced surgeons can perform a transoral robotic thyroidectomy that has excellent cosmetic results.

BackgroundThe development of executive function in adolescents is influenced by many environmental factors. Previous studies have found that perceived stress is closely related to executive function， whereas its role in the mediation of executive function remains poorly studied. ObjectiveTo explore the role of negative affect and self-hate in mediating the relationship between perceived stress and executive function in adolescents， so as to assist the improvement of executive function in adolescents. MethodsQuestionnaires were administered to 7 734 adolescents from five junior and five senior high schools in Rizhao city， Shandong province from 1 to 30 May 2022. Data were collected using a self-made questionnaire， and adolescents were assessed using Perceived Stress Scale （PSS）， Behavior Rating Inventory of Executive Function-Self Report Version （BRIEF-SR）， Patient Health Questionnaire （PHQ-4） and Self-Hate Scale （SHS）. Spearman correlation analysis was conducted to examine the correlation between variables. A Bootstrap method was chosen to examine the mediation effect of self-hate and negative affect on the relationship between perceived stress and executive function in adolescents. ResultsA total of 7 012 （90.66%） valid questionnaires were retrieved. BRIEF-SR score was positively correlated with PSS， PHQ-4 and SHS scores （r=0.564， 0.653， 0.597， P<0.01）. PSS score was positively correlated with PHQ-4 and SHS scores （r=0.615， 0.531， P<0.01）. PHQ-4 score was positively correlated with SHS score （r=0.566， P<0.01）. The value of mediation effect of perceived stress on executive function was 0.574 （95% CI： 0.555~0.594）. Self-hate （indirect effect value of 0.160， 95% CI： 0.145~0.175） and negative affect （indirect effect value of 0.143， 95% CI： 0.129~0.158）， separately from each other， mediated the relationship between perceived stress and executive function， and a chained mediation effect of self-hate and negative affect was also documented （indirect effect value of 0.065， 95% CI： 0.058~0.073）， accounting for 27.87%， 24.91% and 11.32% of the total effect， respectively. ConclusionThe perceived stress of adolescents may be a influencing factor of the executive function. Additionally， perceived stress can either directly affect executive function or indirectly through the separate or chained mediation via negative affect and self-hate.