Objective: To investigate the prevalence of hepatitis B and hepatitis C in Hotan Prefecture, Xinjiang Uygur Autonomous Region, so as to provide insights into prevention and intervention strategies for viral hepatitis for these populations. Methods: Data on hepatitis B and hepatitis C cases in Hotan Prefecture from 2016 to 2022 were collected through the Chinese Disease Prevention and Control Information System. The temporal, demographic and regional distribution characteristics of hepatitis B and hepatitis C incidence were analyzed using the descriptively epidemiological method. The trends in the incidence of hepatitis B and hepatitis C from 2016 to 2022 were analyzed using average annual percent change (AAPC). Results: A total of 8 910 hepatitis B cases and 4 106 hepatitis C cases were reported in Hotan Prefecture from 2016 to 2022, with average annual incidences of 55.60/105 and 25.61/105, respectively. The average annual incidence of hepatitis B in males was 66.78/105, which was higher than that in females (43.83/105, P<0.05). The average annual incidence of hepatitis C in males was 25.70/105, while in females it was 25.36/105, with no statistically significant difference (P>0.05). With increasing age, the incidence of hepatitis B showed an "M"-shaped trend, with the highest average annual incidence in the age group of 20-<30 years (97.20/105); the incidence of hepatitis C first increased and then decreased, with the highest average annual incidence in the age group of 70-<80 years (102.50/105). The majority of the cases were farmers/migrant workers, with 5 610 (62.96%) and 2 963 cases (72.16%), respectively. The top three counties with higher average annual incidences of hepatitis B were Minfeng County (84.78/105), Karakax County (81.69/105) and Lop County (72.20/105), and the top three counties with higher average annual incidences of hepatitis C were Pishan County (46.92/105), Karakax County (35.62/105) and Hotan County (26.31/105). The incidences of hepatitis B and hepatitis C in Hotan Prefecture showed downward trends from 2016 to 2022 (AAPC=-10.711% and -16.594%, both P<0.05), with consistent trends observed in Hotan City, Hotan County, Pishan County and Qira County (all P<0.05). Conclusions From 2016 to 2022, the incidences of hepatitis B and hepatitis C in Hotan Prefecture both showed downward trends. Young and middle-aged adults, males, and farmers/migrant workers were the high-risk populations for hepatitis B, while middle-aged and elderly adults and farmers/migrant workers were the high-risk populations for hepatitis C.

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Objective To investigate the toxicokinetic differences of 3,4-methylenedioxy-N-methylamphetamine(MDMA)and its metabolite 4,5-methylene dioxy amphetamine(MDA)in rats af-ter single and continuous administration of MDMA,providing reference data for the forensic identifica-tion of MDMA.Methods A total of 24 rats in the single administration group were randomly divided into 5,10 and 20 mg/kg experimental groups and the control group,with 6 rats in each group.The ex-perimental group was given intraperitoneal injection of MDMA,and the control group was given intraperi-toneal injection of the same volume of normal saline as the experimental group.The amount of 0.5 mL blood was collected from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.In the continuous administration group,24 rats were randomly divided into the experi-mental group(18 rats)and the control group(6 rats).The experimental group was given MDMA 7 d by continuous intraperitoneal injection in increments of 5,7,9,11,13,15,17 mg/kg per day,respectively,while the control group was given the same volume of normal saline as the experimental group by in-traperitoneal injection.On the eighth day,the experimental rats were randomly divided into 5,10 and 20 mg/kg dose groups,with 6 rats in each group.MDMA was injected intraperitoneally,and the con-trol group was injected intraperitoneally with the same volume of normal saline as the experimental group.On the eighth day,0.5 mL of blood was taken from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.Liquid chromatography-triple quadrupole tandem mass spectrometry was used to detect MDMA and MDA levels,and statistical software was employed for data analysis.Results In the single-administration group,peak concentrations of MDMA and MDA were reached at 5 min and 1 h after administration,respectively,with the largest detection time limit of 12 h.In the continuous administration group,peak concentrations were reached at 30 min and 1.5 h af-ter administration,respectively,with the largest detection time limit of 10 h.Nonlinear fitting equations for the concentration ratio of MDMA and MDA in plasma and administration time in the single-administration group and continuous administration group were as follows:T=10.362C-1.183,R2=0.974 6;T=7.397 3C-0.694,R2=0.961 5(T:injection time;C:concentration ratio of MDMA to MDA in plasma).Conclusions The toxicokinetic data of MDMA and its metabolite MDA in rats,obtained through single and continuous administration,including peak concentration,peak time,detection time limit,and the relationship between concentration ratio and administration time,provide a theoretical and data foundation for relevant forensic identification.

Objective To study the clinical and pathological characteristics,as well as diagnosis,treatment methods and prognosis of adult patients with chronic active Epstein-Barr virus infection(CAEBVI).Methods Clinical and pathological data of 8 adult patients with CAEBVI admitted to a hospital in Gansu Province from January 2017 to December 2022 were collected retrospectively,clinical and histopathological characteristics,EBV-related test re-sults,as well as treatment and prognosis of patients were analyzed.Results Among 8 CAEBVI patients,3 were males and 5 were females,with the median age of 21.5 years.The median time from onset to diagnosis of CAEBVI was 7 months.The main manifestations were fever,pancytopenia(involving two or three peripheral blood lines),as well as lymph node enlargement,hepatomegaly and splenomegaly.The quantifications of plasma EBV nucleic acid(DNA)were all＞1.0 × 103.The sorting results of EBV infected cells showed that 3 cases were T lymphocytes in-fection,2 were NK cell infection,and 3 were co-infection of T lymphocytes and NK cells.Bone marrow cytological examination of 8 patients showed no atypical lymphocytes,while 6 patients showed hemophagocytic cells.Flow cy-tometey(FCM)typing results showed that no abnormal cell population was detected in all the 8 patients,and no myeloid,B lymphocyte,T lymphocyte and NK cell markers were expressed.The positive rate of T cell receptor(TCR)gene rearrangement was 37.5％(n=3).Histopathology showed that most cases(n=6,75.0％)expressed CD3,partial cases expressed CD4,CD8,CD56,TIA-1,and EBV encoded RNA(EBER),all were positive.The survival rate of patients after treatment was 50.0％(n=4),the follow-up time was 6-51 months,the 1-year sur-vival rate was 85.7％,and the median survival time was 24 months.Conclusion CAEBVI is characterized by varia-ble clinical manifestations that may lead to fatal complications.Early diagnosis and individualized treatment should be performed to reduce mortality of patients.

ObjectiveThe purpose of this study was to investigate the effects of transcutaneous electrical acupoint stimulation (TEAS) on cognitive function of vascular dementia (VD) rats and its mechanism. MethodsVD rat model was established by modified two-vessel occlusion (2-VO). After modeling, TEAS and electroacupuncture (EA) were used to stimulate Baihui and Zusanli points of rats respectively for 14 d. After treatment, novel object recognition test, Morris water maze test, and Y maze test were used to evaluate the spatial memory and learning ability of rats. Hematoxylin and eosin staining was used to observe the morphology of hippocampal neurons. Transmission electron microscopy was used to observe the ultrastructure of hippocampal mitochondria. Enzyme-linked immunosorbent assay kits were used to detected the levels of SOD, CAT, GSH-Px, MDA and ROS in serum of rats. Western blot was used to detect the expression of PGC-1α, TFAM, HO-1, NQO1 proteins in the hippocampus, Keap1 protein in the cytoplasm and Nrf2, NRF1 proteins in the nucleus. ResultsAfter treatment for 14 d, compared to the model group, the escape latency of VD rats decreased, while the discrimination index, the times of rats crossing the original platform area, the residence time in the original platform quadrant, and the percentage of alternation increased. TEAS can improve the structure of hippocampal neurons and mitochondria of VD rats, showing that neurons were arranged more regularly and distributed more evenly, nuclear membrane and nucleoli were clearer, and mitochondrial swelling were reduced, mitochondrial matrix density were increased, and mitochondrial cristae were more obvious. The levels of SOD, GSH-Px and CAT in serum increased significantly, while the concentration of MDA and ROS decreased. TEAS also up-regulated the expression levels of PGC-1α TFAM, NQO1 and HO-1 proteins in the hippocampus and Nrf2, NRF1 proteins in the nucleus, but down-regulated the Keap1 protein in the cytoplasm. ConclusionTEAS can improve cognition, hippocampal neurons and mitochondrial structure of VD rats, and the effect is better than EA. The mechanism may be the activation of PGC-1α mediated mitochondrial biogenesis and antioxidant stress, which also provides a potential therapeutic technology and experimental basis for the treatment of VD.

Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria, Acinetobacter baumannii can still survive and acquire polymyxin resistance after complete loss of LPS. Previous studies of LPS-deficient Acinetobacter baumannii mostly focused on LPS-deficient strains induced by polymyxin, whose background was complex and unstable. To investigate LPS loss-mediated polymyxin resistant-Acinetobacter baumannii, this study constructed a stable and clear background LPS-deficient strain by knocking out lpxC gene in Acinetobacter baumannii ATCC 19606 with CIRSPR/Cas9, and then studied the phenotypic changes of the lpxC-deficient strain including morphology, growth rate, antibiotic susceptibility, virulence, membrane permeability, and membrane potential. Animal experiments were approved by the Animal Care and Welfare Committee Institute of Medicinal Biotechnology, CAMS and PUMC (approval number: IMB-20240119D₉). The results indicated that the lpxC gene of Acinetobacter baumannii ATCC 19606 was successfully knocked out. After losing the lpxC, the strain underwent the morphological change from rod-shaped to spherical. Furthermore, it leads to reduced growth rate, enhanced membrane permeability, decreased membrane potential, lower virulence, and increased antibiotic susceptibility to β-lactams, quinolones, aminoglycosides, macrolides, glycopeptides. The lpxC deletion results in significant changes in membrane homeostasis and adaptability of Acinetobacter baumannii. Understanding the phenotypic changes of colistin-resistant Acinetobacter baumannii mediated by LPS loss is useful for exploring the resistance mechanism of Acinetobacter baumannii and developing new therapeutic strategies.

A middle-aged man was presented with poor appetite, polyuria, polydrpsia, and headache. A sellar mass was found, along with total pituitary hypofunction and visual field defect. A biopsy of the lesion via the trans-sphenoidal approach showed inflammatory changes and granuloma formation. However, repeated cerebrospinal fluid and pathogenic examination of the pathological tissue showed no positive indications. The initial diagnosis considered autoimmune hypophysitis, and treatment of glucocorticoids combined with immunosuppressants was administered, which led to a temporary shrinkage of the lesion, but it gradually enlarged subsequently. After multidisciplinary discussion, a high possibility of pituitary tuberculosis infection was decided upon. After standardized anti-tuberculosis treatment was initiated, the lesion reduced noticeably and the patient′s condition improved. Pituitary tuberculosis infection is incredibly rare and extremely easy to misdiagnose. This case was diagnosed and treated in a timely and effective manner through a multidisciplinary approach, highlighting the importance of such an approach in dealing with rare diseases.

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

Phosphodiesterase 4 (PDE4) is an important member of the phosphodiesterase enzyme family that specifically catalyzes the hydrolysis of cyclic adenosine monophosphate (cAMP), activates the downstream phosphorylation cascade pathway by altering cAMP concentration, and is strongly associated with multiple diseases. Inhibition of PDE4 is clinically investigated as a therapeutic strategy in a broad range of disease areas, including respiratory system diseases, autoimmune disorders, central nervous system diseases, and dermatological conditions. However, the incidence of adverse reactions such as nausea and vomiting is relatively high in the marketed PDE4 inhibitors, which has stalled their clinical development. In this review, we provide an overview of the clinical progression and safety issues of the marketed PDE4 inhibitors. We also review the main causes underlying PDE4-mediated adverse effects by combining the structural analysis of the PDE4 protein, the mechanism of action of PDE4 inhibitors, and the related side effect mechanism research, aiming to provide a reference for the development of safe and effective PDE4 inhibitors.