The study focuses on the concept of multifunctional traditional Chinese medicine (TCM) formulas and aims to evaluate the efficacy of the classical formula Xiaoyao San (逍遥散). Study employs the integrated evidence chain (Eff-iEC) method to organize, integrate, and evaluate its therapeutic efficacy in treating different diseases with the same therapy, and to investigate the feasibility of using Eff-iEC to evaluate the multifunctionality of TCM formulas. The evaluation covered Xiaoyao San's therapeutic effects on depression, premenstrual syndrome, chronic hepatitis, irritable bowel syndrome, dyspepsia, and menopausal syndrome. Concurrently, the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system was used for evaluation, and authoritative medical documents were incorporated to corroborate the recognition of Xiaoyao San within the medical community. Depression and menopausal syndrome received higher ratings than other conditions in the Eff-iEC, GRADE, and Medical Community Recognition assessments. The Eff-iEC evidence grade for Xiaoyao San was rated as "High" or above for chronic hepatitis, irritable bowel syndrome, dyspepsia, and menopausal syndrome. Premenstrual syndrome received a "Moderate ⁺" rating. The GRADE evidence level was "Low-〇〇⨁⨁" for depression, premenstrual syndrome, and chronic hepatitis; "Moderate-〇⨁⨁⨁" for dyspepsia and menopausal syndrome; and "Very Low-〇〇〇⨁" for irritable bowel syndrome. Depression and menopausal syndrome had the highest inclusion frequency, appearing in all 4 categories. Premenstrual syndrome, chronic hepatitis, and dyspepsia are not recommended in Western medical guidelines, but they are included in TCM guidelines, the China National Basic Medical Insurance Drug List, and the China National Essential Drug List. Irritable bowel syndrome appears only in the China National Basic Medical Insurance Drug List and China National Essential Drug List. The evaluation results obtained using the Eff-iEC method align with Medical Community Recognition, providing an objective and comprehensive assessment of Xiaoyao San's efficacy. The findings suggest that Xiaoyao San has strong evidence for treating depression and menopausal syndrome. However, further experimental and clinical trials are needed to assess its efficacy in treating premenstrual syndrome, chronic hepatitis, irritable bowel syndrome, and dyspepsia. These results support the clinical efficacy and rational use of Xiaoyao San, expand the application scope of the Eff-iEC method, and offer valuable insights and methodological references for the comparative evaluation of multifunctional TCM formulas.

Objective:To explore the differences in resting-state brain functional activity in obsessive-compulsive disorder (OCD) patients with and without sensory phenomena (SP).Methods:Clinical data from 102 OCD patients (60 males, 42 females; age 18-50(27±8) years) who visited the OCD outpatient clinic at the Affiliated Brain Hospital of Nanjing Medical University between August 2021 and December 2022 were prospectively collected. Based on the presence of sensory phenomena, patients were categorized into 70 cases with sensory phenomena (Sensory Phenomena Group) and 32 cases without sensory phenomena (Non-Sensory Phenomena Group). Additionally, 50 age-matched healthy controls (Control Group, 24 males, 26 females; age 18-49(25±6) years) were recruited. Resting-state functional magnetic resonance imaging (rs-fMRI) was analyzed using the amplitude of low-frequency fluctuations (ALFF) and functional connectivity (FC) between differential brain regions. One-way ANOVA and post-hoc tests were used to compare group differences. Spearman correlation and binary logistic stepwise regression were applied to analyze the associations between SP and brain functional activity.Results:Compared to healthy controls, OCD patients showed decreased ALFF in bilateral middle frontal gyri, left superior frontal gyrus, right angular gyrus, and right supramarginal gyrus ( F=17.29-32.99, all P<0.05). The SP group exhibited increased ALFF in the right triangular part of the inferior frontal gyrus ( F=23.47, P<0.05) and decreased ALFF in the left superior parietal gyrus and left postcentral gyrus ( F=18.80, 15.04; both P<0.05). The non-SP group demonstrated increased ALFF in the left supramarginal gyrus and left postcentral gyrus ( F=19.64, 15.04; both P<0.05) and decreased ALFF in the left superior frontal gyrus, right middle frontal gyrus, and left angular gyrus ( F=17.29-35.52, all P<0.05). Reduced FC was observed between the left middle frontal gyrus and left angular gyrus, left middle frontal gyrus and right angular gyrus and left and right angular gyri ( F=17.29-23.47, all P<0.05). The SP group showed lower FC between the left middle frontal and left angular gyrus than the non-SP group ( F=23.47, P<0.05). Positive correlations with SP were found for ALFF in the right triangular part of the inferior frontal gyrus, left superior frontal gyrus, and right middle frontal gyrus (r=0.40, 0.35, 0.31; all P<0.05). Negative correlations were observed for ALFF in the left supramarginal gyrus, left superior parietal gyrus, and left postcentral gyrus (r=-0.38, -0.47, -0.52; all P<0.05) and FC between the left middle frontal gyrus-left angular gyrus and left middle frontal gyrus-right angular gyrus (r=-0.24, -0.21; both P<0.05). OCD patients with increased ALFF in the left superior frontal gyrus and right middle frontal gyrus, along with decreased ALFF in the left supramarginal gyrus, left superior parietal gyrus, left postcentral gyrus, and reduced FC between the left middle frontal gyrus-right angular gyrus, had a higher likelihood of SP (log OR (95% CI)=8.5(4.0-14.2), 8.0(1.7-16.4), -8.9(-15.2--4.4), -5.2 (-9.1--2.3), -4.1(-6.9--1.7), -7.0(-13.2--1.8); all P<0.05). Conclusion:Altered functional activity in the left superior frontal gyrus, right middle frontal gyrus, left supramarginal gyrus, left superior parietal gyrus, left postcentral gyrus, and abnormal FC between the left middle frontal gyrus and right angular gyrus represent key neuroimaging features of OCD patients with SP.

Objective:To compare the curative effect of local anesthesia Lichtenstein, modified Kugel and general anesthetic transabdominal preperitoneal(TAPP) hemioplasty in the treatment of primary unilateral inguinal hernia in elderly patients.Methods:Six hundred and twenty-one patients with unilateral primary inguinal hernia admitted at Second Hospital of Tianjin Medical University from January 2021 to December 2023 were randomly divided into 3 groups before operation: Lichtenstein group, Modified-Kugel group, TAPP group,207 patients in each group. The clinical data were compared.Results:The average operation time of the Lichtenstein and modified Kugel hernia repair groups was significantly shorter than that of TAPP group ( P<0.01), and the hospitalization cost was also significantly lower than that of TAPP group. The postoperative pain score, time spent in the ground and hospital stay in TAPP group were significantly lower than those in Lichtenstein and modified Kugel groups ( P<0.05). There were no serious complications in the 3 groups. Conclusions:Three kinds of hernia repair are all safe and effective in the treatment of elderly patients with unilateral primary inguinal hernia. TAPP has lighter postoperative pain and quicker recovery. Lichtenstein and Modified-Kugel hernia repair under local anesthesia are suitable for those who cannot tolerate general anesthesia.

Objective:To investigate the application and clinical efficacy of customized, 3D-printed femoral bone marrow stems in the revision of tumor prostheses.Methods:A retrospective analysis was performed for the data of 11 patients (7 males and 4 females) aged 53.1±11.7 years (range, 38-75 years), who underwent 3D-printed customized revision of femoral intramedullary stems due to loosening of femoral tumor prostheses at the 960th Hospital of the Joint Support Force of the PLA from June 2021 to June 2023. The pathological types of tumors associated with the initial surgeries included 4 cases of giant cell tumor of bone, 5 cases of osteosarcoma, 1 case of chondrosarcoma, and 1 case of plasma cell tumor. The tumor was located at the distal femur in 8 cases and the proximal femur in 3 cases. The procedures included 3 initial revisions, 7 secondary revisions, and 1 tertiary revision. The average limb shortening measured 4.6±2.2 cm (range, 2.5-9.0 cm). Prior to revision, all prostheses were fixed with bone cement, revealing enlargement of the femoral medullary cavity and cortical bone thinning. Among them, 5 cases had intramedullary stems permeabilizing the femoral cortex, and 1 case had femoral cleavage fractures. All 11 patients received personalized data for the design and 3D printing of femoral bone marrow stems.Results:The lengths and diameters of the 3D-printed porous femoral bone marrow stems ranged from 80 to 160 mm and 20 to 22 mm, respectively. Ten patients were fitted with cylindrical intramedullary handles, while one received a conical intramedullary handle. A successful revision with the 3D-printed stems was achieved in 10 patients; however, 1 case failed to accommodate the conical handle and was instead revised with a bone cement prosthesis. During the implantation of the intramedullary stems, three patients experienced minor cortical splitting, which was managed with bundling and fixation during the procedure. Immediate stability was attained for all prostheses during surgery, yet postoperative limb shortening did not undergo significant correction. All patients exhibited normal healing of their postoperative incisions. The visual analog scale for limb pain decreased significantly from 8.0±0.8 points before surgery to 1.0±0.4 points three months postoperatively ( t=25.957, P<0.001). By six months after the surgery, none of the patients reported any limb pain. Follow-up data for all 11 patients indicated an average follow-up duration of 25.2±7.5 months (range, 16-36 months), during which limb function improved satisfactorily. The Musculoskeletal Tumor Society (MSTS) score increased from 7.9±1.4 points preoperatively to 20.9±2.7 points at the last follow-up, with this change also being statistically significant ( t=14.229, P<0.001). Imaging evaluations revealed normal lower limb force lines, no rotation or longitudinal displacement of the prosthetic stem, and successful integration with the femur. Conclusion:Personalized intramedullary stems produced through 3D printing demonstrate significant clinical effectiveness in femoral tumor prosthesis revision surgery, making them a viable option for such procedures.

Objective:To analyze the proportion of nonobstructive azoospermia(NOA)patients opting for sperm bank donation under different sperm retrieval methods[percutaneous testicular sperm aspiration(TESA),microdissection testicular sperm extraction(mTESE)]and its influencing factors.Methods:Retrospective data from assisted reproductive technology(ART)cycles at the Center for Reproductive Medical,Peking University Third Hospital(from January 2019 to December 2023)were collected.Data-complete ART cycles involving NOA patients and their partners(using the last treatment cycle as the endpoint)were selected.Sperm donation utilization rates were compared across retrieval methods(fresh mTESE,fresh TESA,thawed mTESE,thawed TESA).Log-linear models were used to analyze the rela-tionship between sperm retrieval method and sperm source.Results:Among the 1 730 couples,the over-all sperm donation utilization rate was 12.66％.The highest rate occurred in the fresh mTESE group(23.42％),followed by the thawed mTESE group(5.87％).The rates for the fresh TESA and thawed TESA groups were 5.22％and 0％,respectively.Log-linear analysis demonstrated that sperm retrieval method was significantly associated with sperm source(mTESE:Estimate=4.499;TESA:Estimate=2.780;P＜0.001).Conclusion:The low overall sperm donation utilization rate in ART cycles may re-flect the efficacy of synchronous sperm retrieval ART.The proportion of NOA patients opting for sperm donation was influenced by the retrieval method.Compared with patients undergoing TESA,those under-going mTESE were more inclined to utilize donor sperm after retrieval failure.

Stroke, a major cerebrovascular disease, has high morbidity and mortality. Effective methods to reduce the risk and improve the prognosis are lacking. Currently, uric acid (UA) is associated with the pathological mechanism, prognosis, and therapy of stroke. UA plays pro/anti-oxidative and pro-inflammatory roles in vivo. The specific role of UA in stroke, which may have both neuroprotective and damaging effects, remains unclear. There is a U-shaped association between serum uric acid (SUA) levels and ischemic stroke (IS). UA therapy provides neuroprotection during reperfusion therapy for acute ischemic stroke (AIS). Urate-lowering therapy (ULT) plays a protective role in IS with hyperuricemia or gout. SUA levels are associated with the cerebrovascular injury mechanism, risk, and outcomes of hemorrhagic stroke. In this review, we summarize the current research on the role of UA in stroke, providing potential targets for its prediction and treatment.
Humans ; Uric Acid/metabolism* ; Stroke/drug therapy* ; Animals ; Hyperuricemia/drug therapy* ; Ischemic Stroke/blood* ; Biomarkers/blood*

Background and Aims:Currently,the treatment of hepatocellular carcinoma(HCC)faces significant challenges due to recurrence and metastasis,with tumor immune evasion being one of the key mechanisms underlying these issues.Signal transducer and activator of transcription 3(STAT3),an important transcription factor,is overactivated in many malignancies and is involved in both tumorigenesis and progression,closely associated with immune evasion.Programmed cell death ligand 1(PD-L1),a key immune checkpoint,helps tumor cells evade immune surveillance when its expression is upregulated,thereby suppressing anti-tumor immunity.Studies have shown that STAT3 may activate the MYC signaling pathway through interaction with DNA-activated protein kinase(PRKDC),thereby promoting PD-L1 expression and inducing immune evasion.However,the specific mechanism of the STAT3/PRKDC/MYC axis in HCC remains unclear.This study aims to elucidate the molecular mechanism by which STAT3 regulates PD-L1 expression through the PRKDC/MYC signaling pathway,potentially inducing immune evasion in HCC,with the goal of providing potential targets for HCC immunotherapy.Methods:The expressions of STAT3 in human normal liver cells(HL-7702)and human HCC cells(HuH-7,HepG2)were detected by qRT-PCR and Western blot.Plasmids with STAT3 knockdown(si-STAT3)and PRKDC overexpression(oe-PRKDC),along with their respective negative controls(si-NC,oe-NC),were constructed and transfected into HCC cells(HuH-7)according to the experimental design,with untreated HuH-7 cells as the blank control.Western blot was used to analyze the expression of STAT3,PRKDC,PD-L1,and MYC pathway-related proteins.Cell proliferation,invasion,migration,and apoptosis of HCC cells were assessed by CCK-8,Transwell,wound healing assay,and flow cytometry.After co-culturing HuH-7 cells with human peripheral blood mononuclear cells(hPBMCs),ELISA was used to detect the secretion of the immune regulatory factor interferon γ(IFN-γ).Co-immunoprecipitation and immunofluorescence co-localization were performed to verify the interaction between STAT3 and PRKDC proteins.Results:Results of qRT-PCR and Western blot showed that the mRNA and protein levels of STAT3 were significantly elevated in HCC cells(both P＜0.05).Functional experiments demonstrated that in the si-STAT3 group,HCC cell proliferation,migration,and invasion were significantly weakened,and cell apoptosis was notably increased;the expression of PD-L1 and MYC pathway-related proteins was significantly downregulated;the secretion of IFN-γ was significantly increased after co-culturing with hPBMCs(all P＜0.05).After co-culturing with oe-PRKDC plasmids,the effects of STAT3 knockdown on HCC cells were significantly reversed(all P＜0.05).Scansite 4.0 database analysis revealed that STAT3 and PRKDC have binding sites,and co-immunoprecipitation and immunofluorescence co-localization experiments confirmed the interaction between STAT3 and PRKDC proteins.Conclusion:STAT3 is highly expressed in HCC cells and can promote HCC cell proliferation,migration,invasion,and immune evasion through interaction with PRKDC,suppress cell apoptosis,activate the MYC pathway,and increase PD-L1 expression.The STAT3/PRKDC/MYC axis may serve as a potential target for HCC immunotherapy.

Objective: To investigate the epidemic situation of notifiable infectious diseases in Zhejiang Province in 2024, so as to summarize the epidemic characteristics. Methods: Data of notifiable infectious diseases cases in Zhejiang Province from January 1 to December 31, 2024 were collected from the Infectious Disease Surveillance System of Chinese Disease Prevention and Control Information System. The epidemiological characteristics were analyzed according to the classification and transmission routes using the descriptive epidemiological method. Results: A total of 32 types of notifiable infectious diseases with 1 858 695 cases and 392 deaths were reported in Zhejiang Province in 2024, with a reported incidence of 2 804.73/105 and a reported mortality of 0.591 5/100 000. A total of 238 infectious disease public health emergencies were reported, of which 218 (91.60%) occurred in schools and kindergartens. There were 22 types of class A and B notifiable infectious diseases reported, with incidence of 470.62/100 000 and mortality of 0.591 5/100 000. Totally 10 types of class C notifiable infectious diseases, with a reported incidence of 2 334.11/105, and no deaths were reported. Classified by transmission route, respiratory infectious diseases had the highest reported incidence of 2 423.87/100 000, among which influenza exhibited the highest reported incidence of 2 024.22/100 000. The reported incidence of intestinal infectious diseases was 312.94/105, among which the incidence of other infectious diarrhea and hand-foot-mouth disease (HFMD) were high, with reported incidences of 169.52/100 000 and 136.18/100 000, respectively. Blood-borne and sexually transmitted infectious diseases accounted for the largest number of reported deaths, among which AIDS had the highest mortality of 0.424 0/100 000. Natural and insect-borne infectious diseases exhibited a low reported incidence of 1.37/105. The reported incidence of dengue fever was 0.40/100 000, and 95.08% of the cases were imported. Conclusions The reported incidence of respiratory and intestinal infectious diseases and the reported mortality of AIDS were high in Zhejiang Province in 2024. It is recommended to strengthen the prevention and control of infectious diseases such as influenza, other infectious diarrhea, and HMFD in schools and kindergartens.

Objective:To analyze the proportion of nonobstructive azoospermia(NOA)patients opting for sperm bank donation under different sperm retrieval methods[percutaneous testicular sperm aspiration(TESA),microdissection testicular sperm extraction(mTESE)]and its influencing factors.Methods:Retrospective data from assisted reproductive technology(ART)cycles at the Center for Reproductive Medical,Peking University Third Hospital(from January 2019 to December 2023)were collected.Data-complete ART cycles involving NOA patients and their partners(using the last treatment cycle as the endpoint)were selected.Sperm donation utilization rates were compared across retrieval methods(fresh mTESE,fresh TESA,thawed mTESE,thawed TESA).Log-linear models were used to analyze the rela-tionship between sperm retrieval method and sperm source.Results:Among the 1 730 couples,the over-all sperm donation utilization rate was 12.66％.The highest rate occurred in the fresh mTESE group(23.42％),followed by the thawed mTESE group(5.87％).The rates for the fresh TESA and thawed TESA groups were 5.22％and 0％,respectively.Log-linear analysis demonstrated that sperm retrieval method was significantly associated with sperm source(mTESE:Estimate=4.499;TESA:Estimate=2.780;P＜0.001).Conclusion:The low overall sperm donation utilization rate in ART cycles may re-flect the efficacy of synchronous sperm retrieval ART.The proportion of NOA patients opting for sperm donation was influenced by the retrieval method.Compared with patients undergoing TESA,those under-going mTESE were more inclined to utilize donor sperm after retrieval failure.

Background and Aims:Currently,the treatment of hepatocellular carcinoma(HCC)faces significant challenges due to recurrence and metastasis,with tumor immune evasion being one of the key mechanisms underlying these issues.Signal transducer and activator of transcription 3(STAT3),an important transcription factor,is overactivated in many malignancies and is involved in both tumorigenesis and progression,closely associated with immune evasion.Programmed cell death ligand 1(PD-L1),a key immune checkpoint,helps tumor cells evade immune surveillance when its expression is upregulated,thereby suppressing anti-tumor immunity.Studies have shown that STAT3 may activate the MYC signaling pathway through interaction with DNA-activated protein kinase(PRKDC),thereby promoting PD-L1 expression and inducing immune evasion.However,the specific mechanism of the STAT3/PRKDC/MYC axis in HCC remains unclear.This study aims to elucidate the molecular mechanism by which STAT3 regulates PD-L1 expression through the PRKDC/MYC signaling pathway,potentially inducing immune evasion in HCC,with the goal of providing potential targets for HCC immunotherapy.Methods:The expressions of STAT3 in human normal liver cells(HL-7702)and human HCC cells(HuH-7,HepG2)were detected by qRT-PCR and Western blot.Plasmids with STAT3 knockdown(si-STAT3)and PRKDC overexpression(oe-PRKDC),along with their respective negative controls(si-NC,oe-NC),were constructed and transfected into HCC cells(HuH-7)according to the experimental design,with untreated HuH-7 cells as the blank control.Western blot was used to analyze the expression of STAT3,PRKDC,PD-L1,and MYC pathway-related proteins.Cell proliferation,invasion,migration,and apoptosis of HCC cells were assessed by CCK-8,Transwell,wound healing assay,and flow cytometry.After co-culturing HuH-7 cells with human peripheral blood mononuclear cells(hPBMCs),ELISA was used to detect the secretion of the immune regulatory factor interferon γ(IFN-γ).Co-immunoprecipitation and immunofluorescence co-localization were performed to verify the interaction between STAT3 and PRKDC proteins.Results:Results of qRT-PCR and Western blot showed that the mRNA and protein levels of STAT3 were significantly elevated in HCC cells(both P＜0.05).Functional experiments demonstrated that in the si-STAT3 group,HCC cell proliferation,migration,and invasion were significantly weakened,and cell apoptosis was notably increased;the expression of PD-L1 and MYC pathway-related proteins was significantly downregulated;the secretion of IFN-γ was significantly increased after co-culturing with hPBMCs(all P＜0.05).After co-culturing with oe-PRKDC plasmids,the effects of STAT3 knockdown on HCC cells were significantly reversed(all P＜0.05).Scansite 4.0 database analysis revealed that STAT3 and PRKDC have binding sites,and co-immunoprecipitation and immunofluorescence co-localization experiments confirmed the interaction between STAT3 and PRKDC proteins.Conclusion:STAT3 is highly expressed in HCC cells and can promote HCC cell proliferation,migration,invasion,and immune evasion through interaction with PRKDC,suppress cell apoptosis,activate the MYC pathway,and increase PD-L1 expression.The STAT3/PRKDC/MYC axis may serve as a potential target for HCC immunotherapy.