Background: Malignant pleural effusion (MPE), a common complication of advanced cancers, is associated with poor prognosis and reduced quality of life. Although host–tumor interactions are known to drive MPE development, the associated immune dynamics during disease progression remain unclear. Using a Lewis lung carcinoma-induced MPE model in C57BL/6JNidfc mice, we systematically evaluated general parameters and immune cell changes at two-day intervals throughout disease progression. Results: The day of Lewis lung carcinoma cell injection into the pleural space was designated as day 0. By day 10 post-injection (p.i.), MPE-bearing mice exhibited ~ 10% body weight loss, marking the experimental endpoint. Pleural tumor mass and pleural effusion volume were minimal up to day 4 p.i. but increased sharply from day 6 onward.CD45⁺ immune cell counts rose over time, and days 6, 8, and 10 p.i. marked key stages of MPE progression. On day 6, B cells, T cells, and natural killer cells, but not macrophages and neutrophils, increased significantly compared to earlier timepoints. By day 8, all immune cell subsets except T cells exceeded day 6 levels, and at day 10, natural killer cell numbers declined while others continued to increase. Besides, the numbers of CD8⁺ T cells, Th1 cells, regulatory T cells, and M2 macrophages progressively increased from day 6 to 10. Based on these data, days 6 and 10 were defined as early and advanced MPE stages, respectively, with distinct immune phenotypes. In advanced MPE, CD8⁺ T cells displayed reduced IFN-γ, TNF-α, Granzyme B, Perforin, FasL, and Ki-67, but upregulated PD-1 and CTLA-4 relative to early stage. Similarly, Th1 cells showed decreased IFN-γ, TNF-α, and IL-2 production along with reduced Ki-67 expression. Advanced-stage M2 macrophages exhibited lower MHC-II levels and impaired phagocytosis, but higher PD-L1 and IL-10 production, while neutrophils showed reduced TNF-α release and phagocytic activity. Conclusions Our findings characterize the temporal immune dynamics associated with MPE progression in a mouse model, revealing a transition from an early immunostimulatory state to a late immunosuppressive state. This study enhances our understanding of MPE immunopathogenesis and provides a foundation for developing precise, stagespecific therapeutic strategies.

OBJECTIVE: To evaluate the clinical effect and safety of acupuncture manipulation on treatment of intractable facial paralysis (IFP), and verify the practicality and precision of the Anzhong Facial Paralysis Precision Scale (Eyelid Closure Grading Scale, AFPPS-ECGS). METHODS: A multicentre, single-blind, randomized controlled trial was conducted from October 2022 to June 2024. Eighty-nine IFP participants were randomly assigned to an ordinary acupuncture group (OAG, 45 cases) and a characteristic acupuncture group (CAG, 44 cases) using a random number table method. The main acupoints selected included Yangbai (GB 14), Quanliao (SI 18), Yingxiang (LI 20), Shuigou (GV 26), Dicang (ST 4), Chengjiang (CV 24), Taiyang (EX-HN 5), Jiache (ST 6), Fengchi (GB 20), and Hegu (LI 4). The OAG patients received ordinary acupuncture manipulation, while the CAG received characteristic acupuncture manipulation. Both groups received acupuncture treatment 3 times a week, with 10 times per course, lasting for 10 weeks. Facial recovery was assessed at baseline and after the 1st, 2nd and 3rd treatment course by AFPPS-ECGS and the House-Brackmann (H-B) Grading Scale. Infrared thermography technology was used to observe the temperature difference between healthy and affected sides in various facial regions. Adverse events and laboratory test abnormalities were recorded. The correlation between the scores of the two scales was analyzed using Pearson correlation coefficient. RESULTS: After the 2nd treatment course, the two groups showed statistically significant differences in AFPPS-ECGS scores (P<0.05), with even greater significance after the 3rd course (P<0.01). Similarly, H-B Grading Scale scores demonstrated significant differences between groups following the 3rd treatment course (P<0.05). Regarding temperature measurements, significant differences in temperatures of frontal and ocular areas were observed after the 2nd course (P<0.05), becoming more pronounced after the 3rd course (P<0.01). Additionally, mouth corner temperature differences reached statistical significance by the 3rd course (P<0.05). No safety-related incidents were observed during the study. Correlation analysis revealed that the AFPPS-ECGS and the H-B Grading Scale were strongly correlated (r=0.86, 0.91, 0.93, and 0.91 at baseline, and after 1st, 2nd, and 3rd treatment course, respectively, all P<0.01). CONCLUSIONS Acupuncture is an effective treatment for IFP, and the characteristic acupuncture manipulation enhances the therapeutic effect. The use of the AFPPS-ECGS can more accurately reflect the recovery status of patients with IFP. (Trial registration No. ChiCTR2200065442).
Humans ; Acupuncture Therapy/methods* ; Facial Paralysis/therapy* ; Female ; Male ; Middle Aged ; Adult ; Treatment Outcome ; Acupuncture Points ; Aged

Azvudine and nirmatrelvir/ritonavir (Paxlovid) are recommended for COVID-19 treatment in China, but their safety and efficacy in the elderly population are not fully known. In this multicenter, retrospective, cohort study, we identified 5131 elderly hospitalized COVID-19 patients from 32,864 COVID-19 patients admitted to nine hospitals in Henan Province, China, from December 5, 2022, to January 31, 2023. The primary outcome was all-cause death, and the secondary outcome was composite disease progression. Propensity score matching (PSM) was performed to control for confounding factors, including demographics, vaccination status, comorbidities, and laboratory tests. After 2:1 PSM, 1786 elderly patients receiving azvudine and 893 elderly patients receiving Paxlovid were included. Kaplan-Meier and Cox regression analyses revealed that compared with Paxlovid group, azvudine could significantly reduce the risk of all-cause death (log-rank P = 0.002; HR: 0.71, 95% CI: 0.573-0.883, P = 0.002), but there was no difference in composite disease progression (log-rank P = 0.52; HR: 1.05, 95% CI: 0.877-1.260, P = 0.588). Four sensitivity analyses verified the robustness of above results. Subgroup analysis suggested that a greater benefit of azvudine over Paxlovid was observed in elderly patients with primary malignant tumors (P for interaction = 0.005, HR: 0.32, 95% CI: 0.18-0.57) compared to patients without primary malignant tumors. Safety analysis revealed that azvudine treatment had a lower incidence of adverse events and higher lymphocyte levels than Paxlovid treatment. In conclusion, azvudine treatment is not inferior to Paxlovid treatment in terms of all-cause death, composite disease progression and adverse events in elderly hospitalized COVID-19 patients.

Prostate cancer is the second most common malignancy and the sixth leading cause of cancer-related death in men worldwide. Radical prostatectomy (RP) is the standard treatment for localized prostate cancer, but the procedure often results in postoperative erectile dysfunction (ED). The poor efficacy of phosphodiesterase 5 inhibitors after surgery highlights the need to develop new therapies to enhance cavernous nerve regeneration and improve the erectile function of these patients. In the present study, we aimed to examine the potential of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in preserving erectile function in cavernous nerve injury (CNI) mice. We found that HB-EGF expression was reduced significantly on the 1 st day after CNI in penile tissue. Ex vivo and in vitro studies showed that HB-EGF promotes major pelvic ganglion neurite sprouting and neuro-2a (N2a) cell migration. In vivo studies showed that exogenous HB-EGF treatment significantly restored the erectile function of CNI mice to 86.9% of sham levels. Immunofluorescence staining showed that mural and neuronal cells were preserved by inducing cell proliferation and reducing apoptosis and reactive oxygen species production. Western blot analysis showed that HB-EGF upregulated protein kinase B and extracellular signal-regulated kinase activation and neurotrophic factor expression. Overall, HB-EGF is a major promising therapeutic agent for treating ED in postoperative RP.
Animals ; Male ; Heparin-binding EGF-like Growth Factor/therapeutic use* ; Erectile Dysfunction/etiology* ; Mice ; Penis/drug effects* ; Nerve Regeneration/drug effects* ; Penile Erection/drug effects* ; Peripheral Nerve Injuries/drug therapy* ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Cell Movement/drug effects* ; Prostatectomy/adverse effects* ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism*

BACKGROUND:Neuregulin 1 has been shown to be characterized in cell proliferation,differentiation,and vascular growth.Human amniotic mesenchymal stem cells are important seed cells in the field of tissue engineering,and have been shown to be involved in tissue repair and regeneration. OBJECTIVE:To construct human amniotic mesenchymal stem cells overexpressing neuregulin 1 and investigate their proliferation and migration abilities,as well as their effects on wound healing. METHODS:(1)Human amniotic mesenchymal stem cells were in vitro isolated and cultured and identified.(2)A lentivirus overexpressing neuregulin 1 was constructed.Human amniotic mesenchymal stem cells were divided into empty group,neuregulin 1 group,and control group,and transfected with empty lentivirus and lentivirus overexpressing neuregulin 1,or not transfected,respectively.(3)Edu assay was used to detect the proliferation ability of the cells of each group,and Transwell assay was used to detect the migration ability of the cells.(4)The C57 BL/6 mouse trauma models were constructed and randomly divided into control group,empty group,neuregulin 1 group,with 8 mice in each group.Human amniotic mesenchymal stem cells transfected with empty lentivirus or lentivirus overexpressing neuregulin-1 were uniformly injected with 1 mL at multiple local wound sites.The control group was injected with an equal amount of saline.(5)The healing of the trauma was observed at 1,7,and 14 days after model establishment.Histological changes of the healing of the trauma were observed by hematoxylin-eosin staining.The expression of CD31 on the trauma was observed by immunohistochemistry. RESULTS AND CONCLUSION:(1)Human amniotic mesenchymal stem cells overexpressing neuregulin-1 were successfully constructed.The mRNA and protein expression of intracellular neuregulin 1 was significantly up-regulated compared with the empty group(P<0.05).(2)The overexpression of neuregulin 1 promoted the migratory ability(P<0.01)and proliferative ability of human amniotic mesenchymal stem cells(P<0.05).(3)Human amniotic mesenchymal stem cells overexpressing neuregulin 1 promoted wound healing in mice(P<0.05)and wound angiogenesis(P<0.05).The results showed that overexpression of neuregulin 1 resulted in an increase in the proliferative and migratory capacities of human amniotic mesenchymal stem cells,significantly promoting wound healing and angiogenesis.

BACKGROUND:Chronic myofascial trigger points can identify differential metabolite changes through non targeted metabolomics techniques,helping to understand and further explore the pathophysiological processes and pathogenesis of chronic myofascial trigger points from the perspective of endogenous small molecule metabolites. OBJECTIVE:To investigate potential biomarkers and related metabolic pathways based on urine metabolomics in the rat model of chronic myofascial trigger points. METHODS:Sixteen Sprague-Dawley rats were randomly divided into a model group and a normal group.The model group was used to establish a chronic myofascial trigger point animal model by combining blunt hitting with centrifugal exercise(treadmill slope:-16°,running speed:16 m/min,training time:90 minutes each),once a week for 8 continuous weeks,with 4 weeks off.After 12 weeks of modeling,the metabolic cage method was used to collect urine from rats at 24 hours after modeling.Liquid chromatography-mass spectrometry non-targeted metabolomics technology was used to detect metabolic profiles in the urine samples,screen common differential metabolites,and conduct bioinformatics analysis. RESULTS AND CONCLUSION:Compared with the normal group,there were 32 differential metabolic markers in the model group,of which 21 were upregulated and 11 were downregulated.A total of 14 differential metabolites were identified as potential biomarkers based on the value of variable important in projection greater than 3.The enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes indicated that the formation of chronic myofascial trigger points is closely related to metabolic pathways such as primary bile acid biosynthesis and arachidonic acid metabolism.

Acute pancreatitis(AP)is a frequently encountered acute abdominal syndrome in clinical settings,and the integrated model of traditional Chinese and Western medicine(TCM-WM)has demonstrated notable advantages in the diagnosis and treatment of AP.To systematize and standardize clinical practices related to develop clinical pathway for integrated TCM-WM diagnosis and treatment of AP,which enhances the efficiency and quality of patient care.This pathway focuses on AP,a common acute and life-threatening disease within the digestive system,and outlines that the central pathological mechanism involves pancreatic injury and localized inflammation resulting from the abnormal activation of pancreatic enzymes.It has the characteristics of rapid onset,multiple causes,and complex manifestations.Severe cases can be life-threatening.At present,conventional treatments encompass a diverse range of modalities.Moreover,traditional Chinese medicine(TCM)holds distinct advantages in alleviating relevant symptoms,and TCM-WM is gaining increasing prevalence.To enhance the standardization and consistency of diagnostic and therapeutic practices,this clinical pathway clearly delineates the target patient population,which includes individuals diagnosed with abdominal pain disorder according to TCM and with AP in accordance with WM criteria,as well as the corresponding inclusion standards.The diagnostic framework integrates both TCM and WM guidelines,and further incorporates disease staging,severity grading,and syndrome differentiation to support a comprehensive and integrated diagnostic strategy.The treatment integrates approaches from both TCM and WM.Within the WM framework,interventions consist of basic supportive care,infection control,nutritional support,and the management of complications.In the context of TCM,the protocol includes syndrome differentiation and corresponding therapeutic strategies(Distinct syndrome patterns are identified and managed during the acute and convalescent phases),such as acupuncture and retention enema.This clinical pathway addresses multiple key components,including preventive strategies,post-treatment follow-up,criteria for evaluating therapeutic efficacy,admission and discharge,admission examination protocols,discharge criteria,and the rationale for deviations or withdrawal from the pathway.It is designed to provide a systematic and standardized reference framework for relevant clinical practices.

Objective:To analyze the epidemiological characteristics and infection sources of cholera in China from 2005 to 2024.Methods:A total of 2 066 cholera cases were included in the study, which were obtained from the China Disease Control and Prevention Information System (CDPCIS) of China CDC. The information on cholera clusters was downloaded from the National Public Health Emergency Event Surveillance System (PHEESS) of China CDC. A total of 128 cholera clusters were included and analyzed in this study. The epidemiological characteristics and infection sources of cholera were analyzed. The Jointpoint model was applied to analyze the incidence trend, and annual percentage change (APC) was also quantified.Results:From 2005 to 2024, a total of 2 066 cholera cases were reported, with an average of 103 cases reported annually. Specifically, the incidence showed a marked downward trend from 2004 to 2015 ( APC=-26.78%, P=0.006). During 2015-2024, the disease remained at low endemic levels, with an average of 18 reported cases annually ( APC=-2.68%, P=0.807). Cholera peak season was from May to October. A total of 24 provinces reported cholera cases, which were mainly distributed in Zhejiang, Fujian, Beijing, Jiangsu, Anhui, Guangdong, and Hainan provinces, accounting for 78.03% of the total cases. Pathogen surveillance indicated an alternating prevalence of Vibrio cholerae serogroups O1 and O139 among laboratory-confirmed cases between 2005 and 2024. There was a disparity in the dominant serogroup of Vibrio cholerae by region. The results from 128 cholera clusters indicated that cholera outbreaks frequently occurred in rural banquets (64.84%), followed by regular restaurants (13.28%). Among these, 63 clusters (49.22%) with identified infection sources indicated that foodborne transmission (95.24%) was the primary mode of cholera transmission, which mainly through seafood and aquatic products, such as soft-shelled turtles, shrimp and shellfish. The characteristics of cholera clusters caused by Vibrio cholerae serogroups O1 and O139 showed statistically significant differences in scale, attack rate, place of residence, setting, and infection source ( P<0.05). Conclusion:Cholera incidence has remained consistently low since 2015 in China, mainly in sporadic cases. Rural gatherings (e.g., wedding banquets) are the main settings for cholera clusters. The main infection sources are predominantly caused by cross-contamination due to improper processing practices of aquatic products, such as soft-shelled turtles.

Objective:To investigate the prevalence and influencing factors of frailty among older adults diagnosed with non-ST-segment elevation acute coronary syndrome(NSTE-ACS).Methods:We conducted a cross-sectional study involving patients aged 65 years and older with NSTE-ACS, who were admitted to the Cardiology Center and the Department of Geriatrics at Beijing Friendship Hospital, Capital Medical University, between January 2020 and November 2021.Patients were categorized into non-frail, pre-frail, and frail groups based on the FRAIL scale.We collected clinical data, including general health conditions, comorbidities, laboratory results, treatments, and comprehensive geriatric assessments.Logistic regression analysis was employed to identify the influencing factors associated with frailty and pre-frailty in older adults with NSTE-ACS.Results:A total of 528 patients with NSTE-ACS were included in the study, comprising 308 males(58.3%)and 220 females(41.7%). The age range of participants was from 65 to 90 years, with a median age of 72(68, 76)years.The prevalence of frailty among older adults with NSTE-ACS was 11.4%(60/528), while pre-frailty was observed in 51.9%(274/528), and non-frailty in 36.7%(194/528). Compared to the non-frail and pre-frail groups, patients in the frail group were older, had a higher proportion of females, exhibited a greater prevalence of chronic diseases, and presented with elevated inflammatory markers.Additionally, frail patients demonstrated poorer nutritional status and reduced functional ability(all P<0.005). Risk factors for frailty in older adults with NSTE-ACS included older age( OR=1.110, 95% CI: 1.032-1.194, P=0.005), diabetes( OR=2.489, 95% CI: 1.091-5.679, P=0.030), cerebrovascular disease ( OR=4.151, 95% CI: 1.660-10.384, P=0.002), chronic kidney disease ( OR=42.874, 95% CI: 3.957-464.513, P=0.002), and elevated white blood cell levels( OR=1.424, 95% CI: 1.125-1.802, P=0.003). Conversely, being male( OR=0.252, 95% CI: 0.105-0.604, P=0.002)was identified as a protective factor against frailty in this patient population.For pre-frail older adults with NSTE-ACS, identified risk factors included diabetes( OR=1.882, 95% CI: 1.199-2.955, P=0.006), cerebrovascular disease( OR=1.938, 95% CI: 1.176-3.195, P=0.009), and chronic kidney disease ( OR=12.137, 95% CI: 1.536-95.934, P=0.018). Similarly, being male( OR=0.601, 95% CI: 0.376-0.961, P=0.033)was also a protective factor for pre-frailty in older adults with NSTE-ACS. Conclusions:The prevalence of frailty and pre-frailty among older adults with NSTE-ACS is notably high.Common risk factors for frailty and pre-frailty in this population include female gender, diabetes, cerebrovascular disease, and chronic kidney disease.

Objective:To characterize the vaginal flora of pregnant women during the second trimester using full-length 16S rRNA sequencing.Methods:A total of 142 pregnant women were systematically sampled from a pregnancy cohort. Vaginal swabs were collected for full-length 16S rRNA gene sequencing，and bioinformatics analysis was performed to characterize the vaginal microbiota and identify associated influencing factors.Results:Among the 142 pregnant women，the most frequently detected species were Lactobacillus iners（83.10%，118/142）and Lactobacillus crispatus（49.30%，70/142）. The majority of samples（90.85%，129/142）were classified as Lactobacillus-dominant vagitypes，with the Lactobacillus iners vagitype accounting for 48.59%（69/142）and the Lactobacillus crispatus vagitype accounting for 38.73%（55/142）. The vaginal microbiota was clustered into five community state types（CSTs）：Ⅰa，Ⅰb，Ⅲa，Ⅲb，and Ⅳ. The most prevalent CSTs were Lactobacillus iners-dominated CST-Ⅲ（51.41%，73/142）and Lactobacillus crispatus-dominated CST-Ⅰ（24.65%，35/142）. No samples were classified as CST-Ⅱ or CST-Ⅴ. A significant negative correlation was observed between Lactobacill and vaginosis-associated bacteria. Age，alcohol consumption，smoking，and vaginal treatments showed significant associations or trends toward significance with various Alpha diversity indices. Vaginal douching was associated with CST clustering，while obstetric history（primiparity，previous miscarriage history）was associated with vagitype classification. However，no significant associations were identified between maternal baseline characteristics and Beta diversity indices. Conclusions:Full-length 16S rRNA gene sequencing reveals that the vaginal microbiota of pregnant women is dominated by Lactobacillus iners and Lactobacillus crispatus. Maternal age，lifestyle factors such as smoking and alcohol consumption，and obstetric history are significantly associated with variations in vaginal microbiota composition.