OBJECTIVE: To reveal the effects and potential mechanisms by which synaptic vesicle glycoprotein 2A (SV2A) influences the distribution of amyloid precursor protein (APP) in the trans-Golgi network (TGN), endolysosomal system, and cell membranes and to reveal the effects of SV2A on APP amyloid degradation. METHODS: Colocalization analysis of APP with specific tagged proteins in the TGN, ensolysosomal system, and cell membrane was performed to explore the effects of SV2A on the intracellular transport of APP. APP, β-site amyloid precursor protein cleaving enzyme 1 (BACE1) expressions, and APP cleavage products levels were investigated to observe the effects of SV2A on APP amyloidogenic processing. RESULTS: APP localization was reduced in the TGN, early endosomes, late endosomes, and lysosomes, whereas it was increased in the recycling endosomes and cell membrane of SV2A-overexpressed neurons. Moreover, Arl5b (ADP-ribosylation factor 5b), a protein responsible for transporting APP from the TGN to early endosomes, was upregulated by SV2A. SV2A overexpression also decreased APP transport from the cell membrane to early endosomes by downregulating APP endocytosis. In addition, products of APP amyloid degradation, including sAPPβ, Aβ _1-42, and Aβ _1-40, were decreased in SV2A-overexpressed cells. CONCLUSION These results demonstrated that SV2A promotes APP transport from the TGN to early endosomes by upregulating Arl5b and promoting APP transport from early endosomes to recycling endosomes-cell membrane pathway, which slows APP amyloid degradation.
Amyloid beta-Protein Precursor/genetics* ; Membrane Glycoproteins/genetics* ; Animals ; Protein Transport ; Nerve Tissue Proteins/genetics* ; Humans ; Mice ; Endosomes/metabolism* ; trans-Golgi Network/metabolism*

OBJECTIVE: This study aimed to investigate the prevalence of HIV pretreatment drug resistance (PDR) and the transmission clusters associated with PDR-related mutations in newly diagnosed, treatment-naive patients between 2020 and 2023 in Dehong prefecture, Yunnan province, China. METHODS: Demographic information and plasma samples were collected from study participants. PDR was assessed using the Stanford HIV Drug Resistance Database. The Tamura-Nei 93 model within HIV-TRACE was employed to compute pairwise matches with a genetic distance of 0.015 substitutions per site. RESULTS: Among 948 treatment-naive individuals with eligible sequences, 36 HIV subtypes were identified, with unique recombinant forms (URFs) being the most prevalent (18.8%, 178/948). The overall prevalence of PDR was 12.4% (118/948), and resistance to non-nucleotide reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) was 10.7%, 1.3%, and 1.6%, respectively. A total of 91 clusters were identified, among which eight showed evidence of PDR strain transmission. The largest PDR-associated cluster consisted of six CRF01_AE drug-resistant strains carrying K103N and V179T mutations; five of these individuals had initial CD4+ cell counts < 200 cells/μL. CONCLUSION The distribution of HIV subtypes in Dehong is diverse and complex. PDR was moderately prevalent (12.4%) between 2020 and 2023. Evidence of transmission of CRF01_AE strains carrying K103N and V179T mutations was found. Routine surveillance of PDR and the strengthening of control measures are essential to limit the spread of drug-resistance HIV strains.
Humans ; HIV Infections/virology* ; China/epidemiology* ; Drug Resistance, Viral ; Male ; Adult ; Female ; Middle Aged ; HIV-1/genetics* ; Anti-HIV Agents/therapeutic use* ; Myanmar/epidemiology* ; Young Adult ; Prevalence ; Adolescent ; Mutation

OBJECTIVES: To investigate the etiological characteristics of bacterial meningitis (BM) in infants aged <90 days. METHODS: A retrospective analysis was conducted on the etiology and outcomes of BM in infants aged <90 days admitted to five collaborating hospitals between January 2007 and December 2021. The overall etiological profile was described, and pathogen distributions were compared across different age groups, regions, and years. The prognosis of BM caused by common pathogens was also evaluated. RESULTS: A total of 197 infants with bacteriologically confirmed BM were included. The most common pathogens were Escherichia coli (E. coli) (72 cases, 36.5%), group B Streptococcus (GBS) (49 cases, 24.9%), and Listeria monocytogenes (LM) (11 cases, 5.6%). The detection rate of E. coli was significantly higher in the neonatal group than in the infant group (40.2% vs 18.2%, P<0.05). E. coli was the predominant pathogen in Beijing (31.7%) and Kunming (54.1%), while GBS and E. coli were equally prevalent in Shenzhen (33.3%). From 2018 to 2021, the detection rates of E. coli were 46.4%, 47.2%, 45.2%, and 36.8%, respectively, whereas those of GBS were 25.0%, 27.8%, 22.6%, and 31.6%. No significant difference was observed in the overall complication rates among BM cases caused by E. coli, GBS, and LM (P>0.05). However, ventriculitis and hydrocephalus were more frequent in LM meningitis than in GBS meningitis (P<0.017). CONCLUSIONS E. coli is the most common pathogen in BM among young infants, particularly neonates. GBS is predominant in Shenzhen, with an increasing trend. LM meningitis accounts for a notable proportion of cases and is associated with poorer outcomes.
Humans ; Meningitis, Bacterial/microbiology* ; Infant ; Retrospective Studies ; Infant, Newborn ; Male ; Female

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

Objective To investigate the factors associated with coronary microvascular dysfunction(CMD)after percutaneous coronary intervention(PCI)in diabetic patients with multivessel disease and non-ST-segment elevation acute coronary syndrome(NSTE-ACS).Methods A single-center retrospective study was conducted,including 242 diabetic patients with NSTE-ACS and multivessel disease who underwent PCI between January 2021 and June 2024 at Hospital.Baseline characteristics,procedural parameters,and laboratory indicators were collected.CMD was defined based on immediate postoperative coronary functional measurements[computational pressure-flow dynamics derived angiography fractional flow reserve(caFFR)＞0.80 and coronary angiography-derived index of microcirculatory resistance(caIMR)≥25].Univariate and multivariate logistic regression analyses were performed to identify risk factors for CMD.Results Among the 242 patients,49(20.2%)were diagnosed with patient-level CMD after PCI.The CMD group showed significantly higher hemoglobin levels compared to the non-CMD group[136.00(130.00,150.00)g/L vs.130.00(119.00,145.00)g/L,P=0.012],as well as higher glutamic-pyruvic transaminase levels[20.00(16.00,31.00)U/L vs.18.00(13.00,26.00)U/L,P=0.047].However,there were no significant differences between the groups in terms of diabetes duration,traditional cardiovascular risk markers(hypertension,smoking history,low-density lipoprotein cholesterol),types of hypoalycemic agents,or procedural parameters(all P＞0.05).Univariate regression analysis indicated that hemoglobin(OR 1.025,95%CI 1.007-1.043,P=0.007)and urea(OR 0.897,95%CI 0.791-1.108,P=0.091)were associated with CMD.Multivariate logistic regression further confirmed that elevated hemoglobin concentration was an independent predictor of CMD after PCI in diabetic patients with NSTE-ACS and multivessel disease(OR 1.026,95%CI 1.007-1.045,P=0.006).According to the Youden index of the receiver operating characteristics curve,the optimal cutoff value for diagnosing hemoglobin content is 131 g/L(Youden Index=0.238,sensitivity 69.4%,specificity 54.4%).Conclusions Elevated hemoglobin concentration is an independent risk factor for CMD after PCI in diabetic patients with NSTE-ACS and multivessel disease,potentially linked to hyper-viscous blood-induced oxidative stress and endothelial injury.It is recommended to intensify postoperative microcirculatory monitoring in patients with preoperative hemoglobin≥131 g/L and to explore hemorheological intervention strategies.

Objective:To compare bowel function 12 months after surgery between side-to-end anastomosis (SEA) and end-to-end anastomosis (EEA) groups of patients who had undergone rectal cancer resection.Methods:This single-center, prospective, open-label, phase III randomized controlled trial was approved by the Ethics Committee of Peking University People's Hospital (2018PHB040-01) and registered at ClinicalTrials. org (NCT03669237). Inclusion criteria were as follows: (1) histologically confirmed rectal adenocarcinoma; (2) tumor located 0 to 12 cm from the anal verge; (3) age≥18 years; and (4) planned R0 resection with primary reconstruction. Exclusion criteria included: (1) emergency surgery; (2) cognitive impairment; (3) non-primary anastomosis; (4) history of left-sided colonic or anorectal surgery; and (5) preexisting chronic defecation dysfunction. Eligible rectal cancer patients scheduled for elective sphincter-preserving surgery at Peking University People's Hospital were prospectively enrolled between October 2018 and March 2021 and randomly assigned to either the EEA group or the SEA group via computer-generated numbers prior to entering the operating room. All patients underwent standard radical tumor resection. Bowel function was evaluated by the low anterior resection syndrome (LARS) questionnaire. It consists of five single-choice questions and yields a total score ranging from 0 to 42. Defecation function is categorized into three levels: no LARS (0-20 points), minor LARS (21-29 points), and major LARS (30-42 points). The primary endpoint was the LARS score 12 months after surgery. Secondary endpoints included LARS scores from 1 to 11 months and during long-term follow-up(>12 months). The final follow-up was completed in July 2022. All randomized patients were included in the intention-to-treat set (ITTS). The full analysis set (FAS) was defined as ITTS patients with valid outcome data. All primary statistical analyses were performed in the FAS, and results were further compared in the per-protocol set (PPS) based on the actual treatment received.Results:A total of 323 patients underwent eligibility assessment, of whom 71 did not meet the inclusion criteria and 52 declined to participate. Ultimately, 200 patients were randomized. Median age was 64 years and 85 were women. The SEA and EEA groups comprised 102 and 98 patients, respectively. A total of 181 patients (90.5%) were included in the FAS, and 170 (85.0%) were included in the PPS. Among these, the 12-month LARS score was evaluated in 178 patients (98.3%) in the FAS and in 167 (98.2%) in the PPS. Median LARS score at 1–12 months were significantly lower in the SEA group in both the FAS dataset [12 months:8 (interquartile range [IQR], 0–22) vs. 14 (IQR, 8–29); Z=2.687, P=0.007] and the PPS dataset [12 months: 8 (IQR, 0–22) vs. 14 (IQR, 6–29); Z=2.543, P=0.011]. During long-term follow-up, the median LARS score was also significantly lower in the SEA group in the FAS dataset [2 (IQR, 0–4) vs. 11 (IQR, 2–23); Z=2.968, P=0.003] and the PPS dataset [2 (IQR, 0–14) vs. 11 (2, 27); Z=2.687, P=0.007]. Conclusion:Compared with the EEA group, bowel function was superior in the SEA group 1 year after surgery and during long-term follow-up.

[Purpose]To analyze the trends in incidence,mortality and potential life loss of esophageal cancer in Linzhou City of Henan Province from 2010 to 2019.[Methods]The data of esophageal cancer incidence and mortality from 2010 to 2019 were collected from Linzhou cancer registries.The crude incidence and mortality rates,age-standardized rates(ASR)by sex and age group,the potential years of life lost(PYLL),average potential years of life lost(APYLL),and potential years of life lost rate(PYLLR)were calculated.The average annual percentage change(AAPC)from 2010 to 2019 were analyzed with Joinpoint software.[Results]From 2010 to 2019,there were a total of 8 447 newly diagnosed cases and 6 475 deaths of esophageal cancer in Linzhou.The ASR incidence and ASR mortality of esophageal cancer in the total population,males,females all showed significant downward trends,with AAPCs of-3.97％,-4.35％,-3.29％and-3.78％,-2.68％,-4.95％,respectively(all P＜0.05).The crude incidence and mortality rates in all age groups also showed significant downward trends.The AAPCs of incidence rate for the age groups of 0～49,50～59,60～69,and ≥70 years old were-9.92％,-8.27％,-1.41％,and-3.86％,respectively(all P＜0.05),and the AAPCs of mortality rate were-950％,-12.36％,-2.61％,and-2.98％,respectively(all P＜0.05).From 2010 to 2019,the total PYLL caused by esophageal cancer was 60 880 person years,APYLL was 13.73 person years,and PYLLR was 5.77‰.The PYLL,APYLL,and the PYLLR of the total population and those stratified by sex all showed a decreasing trend(all P＜0.05).[Con-clusion]From 2010 to 2019,the incidence,mortality and potential life loss of esophageal cancer in Linzhou City all decreased,and the long-term effect and screening programs is significant.How-ever,the risk of esophageal cancer among men and the elderly is still relatively high,indicating that more targeted prevention and control strategies should be developed.

[Purpose]To analyze the trends of incidence and mortality of malignant tumors in Linzhou City of Henan Province from 2010 to 2019.[Methods]The incidence and mortality data of malignant tumors of Linzhou cancer registration areas from 2010 to 2019 were collected and evaluated for data quality.The crude incidence/mortality rates and age-standardized incidence/mortality rates by Chinese standard population(ASIRC/ASMRC)were calculated by sex,age and can-cer type.Joinpoint software was used to calculate the average annual percentage change(AAPC)to analyze the trends from 2010 to 2019.[Results]From 2010 to 2019,the crude incidence of malig-nant tumors in Linzhou City showed an upward trend,with an AAPC of 2.09％(95％CI:0.58％～3.63％),while the ASIRC tended to be stable.The incidence of malignant tumors showed a signifi-cant upward trend in the 15～29 and 60～69 age groups,and a significant downward trend in the 70～79 age group.From 2010 to 2019,the ASIRC of esophageal cancer and stomach cancer in both men and women showed a significant downward trend,while that of lung cancer and prostate cancer increased in men,and the incidences of thyroid cancer,uterus cancer,cervical cancer,lung cancer and breast cancer increased significantly in women.From 2010 to 2019,the crude mortality of malignant tumors in Linzhou showed a significant upward trend,with an AAPC of 1.18％(95％CI:0.88％～1.48％),while ASMRC showed a significant downward trend,with an AAPC of-1.63％(95％CI:-1.86％～-1.40％).The mortality increased in the group aged 80 and above,while the other age groups remained in a downward or stable state.From 2010 to 2019,the ASMRC of stomach cancer and esophageal cancer in both men and women showed a down-ward trend,while those of prostate cancer,and malignant tumors of the lip,oral cavity and pha-ryngeal in men increased,and that of ovarian cancer in women increased significantly.[Conclu-sion]The disease burden of malignant tumors in Linzhou City is still heavy.The incidence of common cancer types such as thyroid cancer,prostate cancer and lung cancer shows a significant-ly increasing trends from 2010 to 2019.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.