OBJECTIVE: To observe the effects of electroacupuncture (EA) on improving motor function and regulating microglial activation based on Notch receptor 1 (Notch1)/Hes family bHLH transcription factor 1 (Hes1) pathway in mice with Parkinson's disease (PD). METHODS: Thirty-six male C57BL/6 mice were randomly divided into a control group, a model group and an EA group, 12 mice in each group. PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days in the model group and the EA group. From the 1st day of modeling, EA was applied at "Baihui" (GV20) and bilateral "Shenshu" (BL23) in the EA group, with continuous wave, in frequency of 2 Hz and current of 2 mA, 15 min a time, once a day for 14 days continuously. The behavioral performance was evaluated by gait test, pole climbing test and hanging test, the number of positive cells of tyrosine hydroxylase (TH) and the co-expression positive cells of Notch1/ionized calcium binding adaptor molecule 1 (Iba-1) in the substantia nigra of midbrain was assessed by immunofluorescence, the protein expression of TH, α-synuclein (α-syn), Notch1, Hes1, Iba-1, inducible nitric oxide synthase (iNOS), Arginase-1 (ARG1), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and IL-10 was detected by Western blot, the mRNA expression of Notch1 and Hes1 was detected by real-time PCR. RESULTS: Compared with the control group, in the model group, the stride frequency was accelerated (P<0.001) and the stride length was shortened (P<0.001) for the four limbs, the pole climbing test time was prolonged (P<0.01) and the grip level was reduced (P<0.01); in the substantia nigra of midbrain, the number of positive cells of TH was decreased (P<0.001), the number of co-expression positive cells of Notch1/Iba-1 was increased (P<0.001), the protein expression of α-syn, Notch1, Hes1, Iba-1, iNOS, TNF-α, IL-1βand IL-6 was increased (P<0.01, P<0.05, P<0.001), the protein expression of TH, ARG1 and IL-10 was decreased (P<0.01, P<0.001), the mRNA expression of Notch1 and Hes1 was increased (P<0.01). Compared with the model group, in the EA group, the stride frequency was decelerated (P<0.001) and the stride length was increased (P<0.05, P<0.01, P<0.001) for the four limbs, the pole climbing test time was shortened (P<0.05) and the grip level was increased (P<0.05); in the substantia nigra of midbrain, the number of positive cells of TH was increased (P<0.01), the number of co-expression positive cells of Notch1/Iba-1 was decreased (P<0.001), the protein expression of α-syn, Notch1, Hes1, Iba-1, iNOS, TNF-α, IL-6 and IL-1β was decreased (P<0.05, P<0.01), the protein expression of TH, ARG1 and IL-10 was increased (P<0.05, P<0.001, P<0.01), the mRNA expression of Notch1 and Hes1 was decreased (P<0.05). CONCLUSION EA can improve the behavioral performance and protect the dopaminergic neurons in PD mice, its mechanism may relate to the inhibition of Notch1/Hes1-mediated neuroinflammation, thus inhibiting the microglial activation.
Animals ; Electroacupuncture ; Microglia/metabolism* ; Male ; Receptor, Notch1/metabolism* ; Parkinson Disease/physiopathology* ; Transcription Factor HES-1/metabolism* ; Mice ; Mice, Inbred C57BL ; Humans ; Signal Transduction

OBJECTIVE: To observe the effect of governor vessel moxibustion on improving cardiopulmonary fitness in patients with stable chronic obstructive pulmonary disease (COPD) of qi deficiency of lung and kidney. METHODS: A total of 40 patients with stable COPD of qi deficiency of lung and kidney were randomized into an observation group (20 cases) and a control group (20 cases). The routine basic treatment and nursing were adopted in the control group. In the observation group, on the basis of the treatment in the control group, governor vessel moxibustion was applied at the area from Dazhui (GV14) to Yaoshu (GV2) of the governor vessel, 1 hour a time, once a week. Both groups were treated for 8 weeks consecutively. The maximal oxygen uptake (VO₂max), 6-minute walking test (6MWT) and Borg score, pulmonary function indexes (forced expiratory volume in 1 second [FEV₁], forced vital capacity [FVC] and ratio of FEV₁ and FVC [FEV₁/FVC]), chronic obstructive pulmonary disease assessment test (CAT) score, and TCM syndrome score were observed in the two groups before and after treatment respectively. RESULTS: After treatment, the VO₂max, 6MWT, FEV₁, FVC and FEV₁/FVC were increased compared with those before treatment in the two groups (P<0.001, P<0.05), the above indexes in the observation group were higher than those in the control group (P<0.05, P<0.01). After treatment, the Borg, CAT and TCM syndrome scores were decreased compared with those before treatment in the two groups (P<0.05, P<0.001), the above indexes in the observation group were lower than those in the control group (P<0.05). CONCLUSION Governor vessel moxibustion can effectively improve the cardiopulmonary fitness, clinical symptoms and the quality of life in patients with stable COPD of qi deficiency of lung and kidney.
Humans ; Moxibustion ; Pulmonary Disease, Chronic Obstructive/physiopathology* ; Male ; Female ; Middle Aged ; Aged ; Qi ; Lung/physiopathology* ; Kidney/physiopathology* ; Acupuncture Points

OBJECTIVES: To explore the value of serum cystatin C (CysC) levels in evaluating renal prognosis in IgA nephropathy (IgAN) patients. METHODS: We retrospectively collected the clinical data of IgAN patients diagnosed by renal biopsy at Guangdong Provincial People's Hospital from January, 2014 to December, 2018. Based on baseline serum CysC levels, the patients were divided into high serum CysC (>1.03 mg/L) group and normal serum CysC (≤1.03 mg/L) group. The composite endpoint for poor renal prognosis was defined as ≥50% decline in estimated glomerular filtration rate (eGFR) and/or progression to end-stage renal disease (ESRD). Lasso regression, multivariate Cox regression and Kaplan-Meier survival analysis were used to identify the risk factors and compare renal survival rates between the two groups. Smooth curves fitting and threshold effect analysis were used to explore the relationship between serum CysC levels and the outcomes. A nomogram model was constructed and its predictive performance was evaluated using concordance index, calibration curve, receiver operating characteristic (ROC) curve and the area under curve (AUC). RESULTS: A total of 356 IgAN patients were enrolled, who were followed up for 4.65±0.93 years. The composite endpoint occurred in 74 patients. High serum CysC was identified as an independent risk factor for poor renal prognosis in IgAN (HR=2.142, 95% CI 1.222 to 3.755), and the patients with high serum CysC levels had a lower renal survival rate (Log-rank χ²=47.970, P<0.001). In patients with serum CysC below 2.12 mg/L, a higher CysC level was associated with an increased risk of poor renal prognosis (β=3.487, 95% CI: 2.561-4.413, P<0.001), while above this level, the increase of the risk was not significant (β=0.676, 95% CI: -0.642-1.995, P=0.315). The nomogram model based on serum CysC and 3 other independent risk factors demonstrated good internal validity with a concordance index of 0.873 (95% CI: 0.839-0.907) and an AUC of 0.909 (95% CI: 0.873-0.945). CONCLUSIONS Serum CysC levels are associated with renal prognosis in IgAN patients, and high serum CysC an independent risk factor for poor renal prognosis.
Humans ; Glomerulonephritis, IGA/diagnosis* ; Cystatin C/blood* ; Prognosis ; Risk Factors ; Retrospective Studies ; Glomerular Filtration Rate ; Kidney Failure, Chronic ; Male ; Female ; Adult ; Nomograms ; Middle Aged

OBJECTIVES: To investigate the subcellular localization and biological functions of transmembrane protein 240 (TMEM240). METHODS: NCBI BLAST and TMHMM bioinformatics software were used for protein sequence analysis and prediction of transmembrane domain of TMEM240. Brain tissues from male C57BL/6 mice (18-20 days old) were examined for distribution of TMEM240 using in situ hybridization, and qPCR and Western blotting were used to detect TMEM240 expression in different mouse tissues and in cortical neurons at different time points (n=3). In the in vitro experiment, HepG2 and Neuro-2a cells were transfected with plasmids for overexpression of TMEM240, and subcellular localization of TMEM240 was analyzed using cell imaging. In primary cultures of cortical neurons isolated from C57BL/6 mice, TMEM240 expression and its biological functions were investigated using qPCR, Western blotting, and immunofluorescence staining. RESULTS: Human and mouse TMEM240 proteins share a 97.69% similarity in the protein sequences, and both are transmembrane proteins with two transmembrane domains. TMEM240 mRNA and protein were highly expressed in mouse brain tissues and cortical neurons. In isolated mouse cortical neurons, TMEM240 expression reached the peak level after primary culture for 9 days and distributed in scattered spots within the cells. In HepG2 cells, TMEM240 was characterized as intracellular membrane structures and showed 80% colocalization with peroxisomes. In Neuro-2a cells, TMEM240 overexpression caused significant enhancement of the expressions of Rho GDP dissociation inhibitor β (ARHGDIB) at both the mRNA and protein levels. CONCLUSIONS TMEM240 is a novel intracellular subcellular structure specifically expressed in neurons with significant potential for targeted cellular function regulation.
Animals ; Humans ; Mice ; Peroxisomes/metabolism* ; Membrane Proteins/genetics* ; Mice, Inbred C57BL ; Neurons/metabolism* ; Male ; rho-Specific Guanine Nucleotide Dissociation Inhibitors ; Hep G2 Cells ; Brain/metabolism*

Objective: To explore the associations of moderate to vigorous intensity physical activity (MVPA) and sedentary behavior (SB) among primary and secondary school students and their parents, so as to provide a scientific basis for formulating targeted physical activity promotion strategies for children and adolescents. Methods: From 2021 to 2022, basic information and 24 h movement behaviors of 2 484 pairs of students and their parents were collected from five primary and secondary schools in Haizhu District, Guangzhou City, with a convenient sampling combining with cluster sampling method. Component regression models were constructed to analyze the relationship between parental MVPA, SB and primary and secondary school students MVPA and SB, and a component isochronous substitution model was used to explore the effects of mutual substitution between parental MVPA, residual components (time use components other than SB during the 24 h period), and SB on the behavioral activities of MVPA and SB in primary and secondary school students. Results: Parental MVPA and SB of students in grade 1 to 3 were positively correlated with both students MVPA and SB ( β=0.06, 0.12, P <0.01). The component isochronous substitution model showed that substituting 10 and 20 minutes of MVPA for SB by parents in grade 1 to 3 was associated with an increase in MVPA of students, and substituting 10 and 20 minutes of residual ingredients for SB was associated with a decrease in SB of students, with mean changes of 0.8 (95% CI =0.4-1.2) and 1.4 (95% CI =0.7-2.2) and -1.4 (95% CI =-1.7 to -1.1) and -2.9 (95% CI =-3.4 to -2.3)( P <0.05). No statistically significant associations were observed between parents of students in grades 4 to 6 and 7 to 9 and students physical activity and sedentary behaviour ( P >0.05). Conclusions Parents of students in grades 1 to 3 increases MVPA and decrease SB are beneficial to increase MVPA and decrease SB of students. Parents could promote physical activity among primary and secondary school students, and the intervention gateway should be advanced, with the low grades as the optimal intervention period.

Evidence serves as the driving force shifting medical practice from empirical medicine towards evidence-based medicine. In the current era of information explosion, it is challenging for clinical surgeons to extract evidence from the vast pool of primary research literature to address clinical issues. Literature reviews, as a form of synthesized evidence, are particularly crucial for precise and efficient evidence utilization. A new form of review within the framework of evidence-based medicine, systematic reviews, also has widespread application in the surgical domain. With the development of methodological approaches in evidence-based medicine, the types of systematic reviews continue to diversify. This paper outlines and summarizes the common types and methodologies of systematic reviews in the surgical field, aiming to provide a clear framework for surgical practitioners to select evidence for both confirming and innovating clinical practices in specific clinical challenges.

Autoimmune hepatitis （AIH） is a chronic inflammatory liver disease. The pathogenesis of AIH remains unclear， but it is mainly autoimmune injury caused by the breakdown of autoimmune tolerance due to the abnormal activation of the immune system， while the specific molecular mechanism remains unknown. Recent studies have shown that abnormal amino acid metabolism plays an important role in the development and progression of AIH. This article reviews the research advances in amino acid metabolic reprogramming in AIH， in order to provide a theoretical basis for amino acid metabolism as a new target for the clinical diagnosis and treatment of AIH.

Objective:To evaluate the effect of fiberoptic endoscopic evaluation of swallowing (FEES) on clinical functional outcomes of patients with intensive care unit-acquired swallowing disorders (ICU-ASD).Methods:This retrospective cohort study analyzed clinical data of patients diagnosed with post-extubation dysphagia (PED) in the intensive care unit (ICU) and respiratory intensive care unit (RICU) of the Affiliated Hospital of Inner Mongolia Medical University from February 2020 to February 2025. Patients were categorized into a FEES group of 60 cases [34 males, 26 females, aged 37-80 years (median age 62 years)] and a control group without FEES of 58 cases [32 males, 26 females, aged 39-77 years (median age 61 years)].The patients in two groups received swallowing function and feeding training based on the results of the FEES assessment and the Volume-Viscosity Swallow Test-Clinical Version (VVST-CV), respectively. Clinical functional outcome measures included pneumonia incidence, clinical pulmonary infection score (CPIS), pneumonia severity index (PSI), Functional Oral Intake Scale (FOIS), and dietary method at discharge. χ2 test, Mann-Whitney U test, and Wilcoxon signed-rank test, were employed for statistical analysis of the outcome measures. Results:Compared with the control group, the FEES group had significantly lower aspiration pneumonia incidence at discharge [3.3% (2/60) vs 15.5% (9/58), χ2=5.179, P=0.023]. Regarding dietary methods,a significantly higher proportion of patients in the FEES group achieved complete oral feeding compared with the control group [75.0% (45/60) vs 67.3% (39/58), χ2=8.065, P<0.05]. After training, the FEES group had higher median FOIS scores than the control group (7.00 vs 6.00, Z=-2.370, P=0.018), and lower CPIS scores (2.50 vs 5.00, Z=-2.216, P=0.027) and PSI scores (59.00 vs 73.00, Z=-2.251, P=0.024). Within-group comparisons revealed that FOIS scores significantly improved post-training in both groups (both P<0.001). Conclusion:Early FEES examination for ICU patients with acquired swallowing disorders is associated with a lower incidence of pneumonia, improved swallowing function, and superior clinical functional outcomes.

Objective To develop a nurse-led dynamic monitoring protocol for fluid responsiveness and to evaluate its effectiveness in preventing fluid accumulation syndrome in patients with septic shock.Methods A nurse-led dynamic monitoring protocol for fluid responsiveness was developed through literature review and expert panel discussion.Using convenience sampling,160 patients with septic shock admitted to the emergency department of a tertiary hospital in Hangzhou,Zhejiang Province,were enrolled.According to admission period,80 patients admitted from November 2023 to August 2024 were assigned to an intervention group,and 80 patients admitted from January 2023 to October 2023 were assigned to a control group.The intervention group received the nurse-led dynamic monitoring in addition to routine care,while the control group received routine care and conventional fluid responsiveness monitoring.The therapeutic outcomes and incidence of complications were compared between the 2 groups.Results All 80 patients in each group completed the study.The intervention group demonstrated higher lactate clearance rates at 6 and 24 hours after fluid resuscitation,lower incidences of acute pulmonary edema and fluid accumulation syndrome,and shortened durations of mechanical ventilation and ICU stay(all P＜0.05)compared to the control group.There was no statistically significant difference in 28-day mortality between the 2 groups(P=0.212).Conclusion The nurse-led dynamic monitoring protocol for fluid responsiveness in patients with septic shock is both scientific and practical.Its implementation can effectively improve lactate clearance,reduce the incidence of fluid accumulation syndrome and acute pulmonary edema,and shorten the duration of mechanical ventilation and ICU stay.

Objective:To evaluate the safety and effectiveness of fuzuloparib for the treatment of ovarian epithelial cancer patients in the real world setting.Methods:A retrospective analysis was conducted on the baseline data of 4 620 ovarian cancer patients who had received fuzuloparib monotherapy or combination therapy. Another 224 ovarian cancer patients who were willing to receive fuzuloparib monotherapy or combination therapy were prospectively enrolled, and their baseline characteristics, drug effectiveness, and safety data were analyzed.Results:(1) Among the 4 620 patients in the retrospective cohort, the median age of patients was 60 years; tumor types: 89.8% (4 149/4 620) had ovarian cancer. Among patients with clearly documented information, the vast majority had a histological type of serous carcinoma (82.9%, 3 770/4 546) and International Federation of Gynecology and Obstetrics (FIGO) staging of Ⅲ-Ⅳ (90.9%, 1 537/1 691). (2) Among the 224 patients in the prospective cohort, the median age of patients was 57 years; tumor types: 83.9% (188/224) had ovarian cancer. Among patients with clearly documented records, the predominant pathologic type was serous carcinoma (91.9%, 193/210), and FIGO stage was Ⅲ-Ⅳ in 79.9% (139/174). (3) Among the 224 prospective patients: 84 patients received first-line fluzoparib maintenance therapy, 92 patients received fluzoparib maintenance therapy after platinum-sensitive recurrence, 23 patients received direct fluzoparib treatment after platinum-sensitive recurrence, 19 patients received direct fluzoparib treatment after platinum-resistant recurrence. The median follow-up durations were 8.5, 8.7, 7.9, and 6.7 months, respectively. The median durations of fluzoparib treatment were 6.7, 4.8, 3.1, and 1.9 months, respectively. The median progression-free survival (PFS) times were not reached during follow-up, 12.6 months, not reached during follow-up, and 4.8 months, respectively. The 1-year PFS rates were 84.1%, 55.0%, 69.8%, and 45.5%, respectively. The remaining 6 patients received other fluzoparib regimens. (4) Among the 224 patients in the prospective dataset, 205 had safety data recorded. Of these, 127 patients (62.0%, 127/205) experienced treatment-related adverse events, with common events including anemia (24.4%, 50/205), thrombocytopenia (21.0%, 43/205), and leukopenia (19.5%, 40/205). Among the 205 patients, 43 (21.0%, 43/205) experienced grade 3 or higher treatment-related adverse events, with common events including anemia (8.3%, 17/205) and thrombocytopenia (8.3%, 17/205).Conclusions:The effectiveness of fuzuloparib in clinical application is generally consistent with other drugs in the same class, with good safety. This study provids new clinical evidence for the treatment of ovarian cancer with fuzuloparib.