Objective To analyze the situation of rapid antiretroviral therapy (ART) and death of HIV/AIDS in Wuhan from 1994 to 2023, and to provide a scientific basis for further rapid initiation of ART and reduction of mortality rate. Methods According to the case follow-up and treatment database of China AIDS Prevention and Control Information System, data were obtained from all the cases reported from January 1, 1994 to December 31, 2023 with the current address in Wuhan City and the review status of the final review card. The data were analyzed using Kaplan-Meier and Cox proportional hazards models. Results The total mortality rate of HIV/AIDS in Wuhan from 1994 to 2023 was 12.76%. The proportion of receiving antiretroviral therapy within 30 days increased year by year, and the mortality rate decreased year by year. After adjusting for sex, age, occupation, ethnicity, education level, mobile population, history of STD, route of infection, source of sample, and first CD4 value, receiving antiretroviral therapy within 30 days (HR=0.08, 95%CI: 0.07-0.10) was a protective factor for HIV/AIDS mortality. Conclusion Rapid antiretroviral therapy can significantly reduce the risk of HIV/AIDS death. A sustainable model of rapid initiation of antiretroviral therapy should be further established to increase the proportion of rapid antiretroviral therapy for HIV/AIDS in Wuhan.

Objective This study conducted molecular biological identification of the viruses carried by Culex pipiens pallens specimens collected in Shunyi District, Beijing in 2023, and observed the changes in the infection rate of the viruses carried by Cx. pipiens pallens at different collection times. Methods Cx. pipiens pallens were collected using carbon dioxide mosquito traps. The mosquito samples were ground in batches and analyzed by molecular biology technologies. The virus infection rate at different collection times was analyzed statistically. Results 17 strains of Culex pipiens pallens densovirus(CppDNV)were identified from Cx. pipiens pallens samples collected in Shunyi District, Beijing, in 2023. The nucleotide sequence analysis of the virus genome coding region showed that CppDNV was a single-stranded DNA virus with a total length of 3 335 nt, encoding 2 non-structural proteins(NS1, NS2)and 1 capsid protein(VP). The nucleotide(amino acid)sequence lengths of the three proteins were 2 376 nt(791 aa),1 092 nt(363 aa)and 1 071 nt(356 aa), respectively. Phylogenetic analysis showed that CppDNV was located in genus Brevihamaparvovirus. Statistical analysis showed no significant difference in infection rates across collection times(χ2=4.429, P=0.194). Conclusions CppDNV was identified in Cx. pipiens pallens in Beijing, and it was stably maintained in this natural population.

Objective To investigate the causes and management strategies for lower limb ischemic necrosis following xenogeneic heterotopic heart transplantation from a multigene-edited pig to a rhesus monkey. Methods A xenogeneic heterotopic heart transplantation was performed on December 16, 2023, at the Institute of Experimental Animals of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, using a quintuple-gene-edited pig as the donor and a rhesus monkey as the recipient. On postoperative day (POD) 9, the recipient monkey underwent left lower limb amputation due to ischemic necrosis. Blood samples were collected at various time points after transplantation for analysis of hematologic parameters, liver and renal function, myocardial enzymes, and coagulation profiles. Ultrasound and computed tomography (CT) were used to evaluate anastomotic patency and cardiac structure. Immunological assays, including complement-dependent cytotoxicity (CDC) and IgG/IgM antibody detection, combined with clinical observations, were employed to assess rejection type and therapeutic response. Results The recipient monkey survived for 46 days after transplantation. Echocardiography demonstrated preserved biventricular systolic function in the recipient’s native heart, with left ventricular ejection fraction (LVEF) consistently exceeding 50%. In the donor pig heart, left ventricular endocardial thickening was noted on POD 9, followed by right ventricular endocardial thickening on POD 24, while LVEF remained around 35%. No hyperacute or acute rejection was detected immunologically. CDC positivity ranged between 3.4% and 5.1%, with IgG/IgM antibody binding trends consistent with CDC results. Following amputation, the recipient exhibited elevated inflammatory markers, coagulopathy, and reactive thrombocytosis, which later normalized. Immunohistochemical staining of the necrotic limb revealed arterial and venous thrombosis; however, no T-cell or B-cell infiltration was observed in vascular structures, thrombi, nerves, muscles, fascia, or skin tissues, with CD3 and CD20 staining both negative. Conclusion Limb ischemia after xenogeneic heart transplantation may be associated with lower extremity vascular thrombosis triggered by local trauma in the context of transplantation-induced inflammatory activation and coagulation dysfunction. While no clear lymphocyte-mediated rejection was observed, further studies are needed to explore the potential role of non-lymphocyte-mediated immune mechanisms.

OBJECTIVE To evaluate the cost-effectiveness of brivaracetam （BRV） versus perampanel （PER） as add-on therapy for drug-resistant focal epilepsy in adults from the perspective of the Chinese healthcare system.METHODS A Markov model was established to simulate the progression of drug-resistant focal epilepsy in adults， with a simulation cycle of 5 months， a time horizon of 44 years， and a discount rate of 4.5%. Clinical data required for the model were derived from the phase Ⅲ clinical trial of BRV and a post hoc analysis of PER； cost data and utility data were obtained from Yaozh and related literature. The willingness-to-pay （WTP） threshold was set at twice China’s 2025 per capita gross domestic product （GDP） [199 330 yuan per quality-adjusted life year （QALY）]， and a cost-effectiveness analysis was adopted to compare the cost-effectiveness of the regimens. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to confirm the stability of the base-case analysis conclusions.RESULTS The incremental cost-effectiveness ratio （ICER） of BRV 50 mg/d as an add-on therapy versus PER 8 mg/d was 44 823.08 yuan/QALY， which was below the WTP threshold； the ICER of BRV 200 mg/d versus PER 12 mg/d was 238 783.00 yuan/QALY， which was above the WTP threshold. In the one-way sensitivity analysis， the direct medical cost of seizures ≥53 times/year and the health utility value of a seizure-free state per year had a relatively large impact on the two ICER results mentioned above， respectively. Probabilistic sensitivity analysis indicated that the above results were robust.CONCLUSIONS For the selection of add-on therapy for drug-resistant focal epilepsy in adults in China， when twice China’s per capita GDP is used as the WTP threshold， BRV 50 mg/d has a cost-effectiveness advantage over PER 8 mg/d， whereas BRV 200 mg/d not have a cost-effectiveness advantage over PER 12 mg/d.

Background: Adrenocortical hormones, particularly 11-oxygenated androgens, are pivotal in female reproductive health and fertility. Standardized detection kits and population-specific reference intervals are lacking in China, hindering related clinical applications. Methods: A HPLC-tandem mass spectrometry (HPLC-MS/MS) pipeline was developed, rigorously validated, and applied to simultaneously quantify corticosterone, cortisone, cortisol, 18-OH cortisol, androstenedione (A4), 11β-hydroxyandrostenedione (11-OH A4), dehydroepiandrosterone, and dehydroepiandrosterone sulfate in serum samples from 455 reproductive-aged women (18–45 yrs) in Guangxi, China. Age-dependent concentration trends were analyzed, and reference intervals stratified by age (2.5th to 97.5th percentiles) were established. Correlations with body-composition metrics, ethnicity, and the menstrual cycle were investigated. Results: The HPLC-MS/MS method demonstrated high precision (intra- and inter-assay CVs < 15%), accuracy, and sensitivity. All eight hormones exhibited significant age-related declines (P < 0.001 for seven hormones; P = 0.001 for 11-OH A4). Notably, 11-OH A4 levels were significantly lower in the 35–45-yr (3.05 nmol/L) and 25–34-yr (3.09 nmol/L) age groups than in the 18–24-yr (3.57 nmol/L) age group, whereas no significant difference was observed between the 35–45-yr and 25–34-yr age groups. Weak negative correlations were observed between the body mass index and corticosterone and cortisone levels, whereas ethnicity and the menstrual cycle showed no significant associations with hormone levels. Conclusions We developed an HPLC-MS/MS-based method for simultaneously quantifying eight adrenocortical hormones, including 11-OH A4, and defined age-specific reference intervals for reproductive-aged Chinese women. These findings advance the clinical utility of adrenocortical hormones in diagnosing and managing reproductive disorders.

Background/Aims: Acetyl coenzyme A (acetyl-CoA) is one of the most essential metabolites in cell metabolism but its function and concentration in hepatocellular carcinoma (HCC) remain elusive and controversial. Methods: A comprehensive analysis of acetyl-CoA levels and acetyl-CoA synthetase 2 (ACSS2) expression across a range of samples, including patient specimens from both hepatitis B virus (HBV) positive and HBV negative HCC individuals, HBV-transgenic mouse HCC models, and multiple cell lines. Furthermore, to evaluate the functional significance of ACSS2 in HBV-related HCC, we implemented both genetic and pharmacological inhibition strategies targeting ACSS2. Molecular mechanism and mitophagy assessment were revealed by cleavage under target and tagmentation sequencing, RNA sequencing, bioinformatic analyses, transmission electron microscopy and JC-1 staining. Results: Our study revealed a distinct metabolic signature of HBV-related HCC, marked by elevated acetyl-CoA, which was driven by ACSS2. ACSS2 was upregulated by the carbohydrate response element-binding protein in HBV-related HCC. Furthermore, ACSS2 improved tumor cell proliferation, an effect that was dependent on its enzymatic activity. Mechanistically, ACSS2-induced acetyl-CoA accumulation activated voltage-dependent anion channels 1 transcription through increased H3K27ac occupancy, which subsequently promoted mitophagy and HBV-related HCC tumorigenesis. Notably, targeting ACSS2 by depletion or inhibition with a catalytic inhibitor significantly suppressed tumor growth. Conclusions These findings not only illustrate the interplay between metabolic reprogramming, epigenetic modification, and tumorigenesis in the context of HBV infection, but also highlight ACSS2 as a novel metabolic vulnerability in HBV-related HCC. Therefore, targeting ACSS2 could be a novel strategy against HBV-related HCC.

OBJECTIVE To establish a method for simultaneous determination of plasma concentration of lamotrigine（LTG）， levetiracetam（LEV） and perampanel（PER） in children with epilepsy and apply this method in clinical practice. METHODS Plasma proteins were precipitated with acetonitrile. Using PER-D 5 as internal standard， ultra-high performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） method was adopted. The determination was performed on ACQUITY UPLC HSS T3 C 18 column with mobile phase consisted of 0.1% formic acid with 5 mmol/L ammonium acetate-acetonitrile （gradient elution） at the flow rate of 0.3 mL/min. The column temperature was 40 ℃， and sample size was 5 μL. The analysis time was 5 min. The electrospray ionization source and multiple reaction monitoring mode were used for positive ion scanning. The ion pairs used for quantitative analysis of LTG， LEV， PER and internal standard were m / z 255.9→144.9， m / z 171.1→126.1， m / z 350.1→219.0 and m / z 354.9→220.2， respectively. The steady-state trough concentrations of the aforementioned drugs in the plasma of 14 pediatric epilepsy patients receiving combination therapy were determined using the same UPLC-MS/MS method as above. RESULTS The linear ranges of LTG， LEV and PER were 0.15-24 μg/mL （ R 2 ＞0.993）， 0.312 5-50 μg/mL （ R 2 ＞0.997） and 6.25-1 000 ng/mL （ R 2 ＞0.997）， respectively. The lower limits of quantification were 0.15 μg/mL， 0.312 5 μg/mL and 6.25 ng/mL， respectively. RSDs of intraday and interday precision tests of the three drugs were no more than 9.83%， and the accuracies （relative errors） were between －9.33% and 13.72%（ n ＝6 or n ＝18）； the average extraction recovery rates were 86.4%-97.9%， and the average matrix effects were 86.9%-110.0% （ n ＝6）. The absolute values of the relative errors in the stability tests were all below 15%. The steady-state trough concentrations of LTG， LEV and PER were （5.64±4.03）μg/mL， （10.67±8.78）μg/mL and（450.20±251.27）ng/mL， respectively； the rates of achieving target trough concentrations were 71.4%， 37.5% and 84.6%， respectively. CONCLUSIONS The established UPLC-MS/MS method is specific， rapid and suitable for the plasma concentration monitoring in epileptic children receiving combination therapy.

Objective:To investigate the disease burden, clinical characteristics and independent risk factors affecting in-hospital outcomes of children with congenital heart disease (CHD) combined with heart failure (HF) in China.Methods:(1) Descriptive study: based on the global burden of disease study 2021, available data on children under 15 years of age with CHD and HF in China from 1990 to 2021 were collected. The prevalence and trends in different age subgroups (<1 year, 1-<2 years, 2-<5 years, 5-<10 years, 10-<15 years) were analyzed, and the annual percentage change (EAPC) was estimated using linear regression. (2) Retrospective cohort study: a total of 1 062 children with CHD and HF from a multicenter study on pediatric HF in China were included. The children were divided into two groups:<2 years group and 2-<18 years group. Data on demographics, clinical features, diagnosis, treatments, and in-hospital outcomes were analyzed. Mann-Whitney U test and chi-square test were used for group comparisons.Multivariable Logistic regression was applied to identify factors influencing outcomes (in-hospital mortality and adverse cardiovascular events). Results:(1) From 1990 to 2021, the number of children with CHD and HF in China increased from 333 000 (95% uncertainty interval ( UI) 271 000-405 000) to 368 000 (95% UI 296 000-459 000), a growth of 10.8% (95% UI 5.0%-16.6%). Concurrently the prevalence rate increased from 104.5 (95% UI 85.1-127.3) per 100 000 to 142.0 (95% UI 114.0-176.8) per 100 000, a growth of 35.9% (95% UI 28.7%-43.0%), with an EAPC of 1.5% (95% CI 1.2%-1.8%). Although the number of cases in the<1 year and 1-<2 years groups decreased by 41.0% and 25.6%, respectively, the prevalence in all age groups showed an upward trend:<1 year EAPC 0.6% (95% CI 0.5%-0.7%); 1-<2 years EAPC 0.9% (95% CI 0.8%-1.0%); 2-<5 years EAPC 1.2% (95% CI 1.0%-1.4%); 5-<10 years EAPC 1.5% (95% CI 1.2%-1.8%); 10-<15 years EAPC 2.1% (95% CI 1.9%-2.3%). (2) The multicenter study revealed that among 1 062 hospitalized children, 528 (49.7%) were male and 534 (50.3%) were female, with the age at admission of 5.4 (2.2,18.2) months. The majority of the children (77.9%, 827/1 062) were under 2 years of age, whereas 22.1% (235/1 062) were aged between 2-<18 years. Children with complex congenital heart defects accounted for the highest proportion (48.6%, 516/1 062), while those with isolated CHD made up 31.5% (335/1 062). Statistically significant differences were observed in several variables in demographics, clinical features, diagnosis, treatments, and outcomes between the two age groups (all P<0.05). The use of renin-angiotensin-aldosterone system inhibitors (41.1%, 436/1 062) and beta-blockers (8.7%, 92/1 062) was lower in hospitalized children with CHD and HF. Logistic regression identified complex CHD ( OR=7.73, 95% CI 2.24-26.63; OR=3.17, 95% CI 1.92-5.23), pulmonary hyperperfusion ( OR=2.15, 95% CI 1.01-4.18; OR=2.00, 95% CI 1.35-2.97), left ventricular ejection fraction<55% ( OR=2.13, 95% CI 1.08-4.21; OR=2.80, 95% CI 1.45-5.56), arterial oxygen partial pressure ( OR=0.99, 95% CI 0.98-0.99; OR=0.99, 95% CI 0.98-0.99), and serum calcium levels ( OR=0.31, 95% CI 0.17-0.58; OR=0.42, 95% CI 0.28-0.62) as independent risk factors for in-hospital mortality and cardiovascular events. Conclusions:The disease burden of CHD combined with HF in China has shown a continuous upward trend from 1990 to 2021, with higher growth rates in older age groups. Complex CHD, pulmonary hyperperfusion, left ventricular ejection fraction <55%, arterial oxygen partial pressure, and serum calcium concentration are independent risk factors for in-hospital mortality and cardiovascular events.

Objective:To observe the clinical effect of comprehensive reconstruction of grades Ⅰ-Ⅱ thumb and finger defects with hallux osteo-onychocutaneous flaps of great toe.Methods:This is a retrospective study. From June 2020 to December 2023, comprehensive reconstruction surgery for Grade Ⅰ-Ⅱ digital defect were performed with hallux osteo-onychocutaneous flaps of great toe for 3 thumbs and 7 fingers in 9 patients in the Department of Hand and Microsurgery of Baoji Third Hospital. Causes of digital injury were: 4 of machine crush, 3 of electric saw cut, 1 of door crush, and 1 of electrical burn. There were 6 grade I digital defects (beyond the nail root) and 4 grade Ⅱ defects (last segment of digit). The defects of the digits were reconstructed by taking references of the shape and structure of the contralateral normal thumbs and fingers. Then the hallux osteo-onychocutaneous flaps of great toe were designed and harvested accordingly from the left and right great toes. Donor sites were covered by skin grafting or local dressing change. One patient was treated in emergency surgery, 6 in sub-emergency surgery and 2 in elective surgery. Integrated perioperative patient management was provided to all of the patients. Postoperative follow-ups were conducted through the visit of outpatient clinic, telephone calls or WeChat interviews. Flap survival, appearance and sensation recovery were evaluated according to the Evaluation Standard of Upper Limb Functional of Hand Surgery of Chinese Medical Association.Results:Vascular insufficiency of 1 digit occurred in surgery, and relieved by local treatment with lidocaine and warm saline. All 10 digits successfully survived, and all donor sites healed spontaneously. The postoperative follow-up period was 10 to 30 months, with an average of 18 months. One transferred nail was found in poor appearance (not flat), the rest of the reconstructed digits were good in appearance and function. The nail, finger print and fine sensation (TPD 5~8 mm), as well as digital flexion, extension, grasping and opposition of the reconstructed digits were all good. According to the Evaluation Standard of Upper Limb Functional of Hand Surgery of Chinese Medical Association, at the last follow-up visit, 5 digits were in excellent, 4 in good and 1 in fair.Conclusion:The comprehensive reconstruction of grades Ⅰ-Ⅱ digital defects with hallux osteo-onychocutaneous flap of great toe is an ideal surgical technique that can reconstruct the nail, finger print and sensation of a digit, with good postoperative function as well as an aesthetic and realistic appearance.

Objective To explore the feasibility and safety of ultrasound-guided percutaneous microwave ablation for unresectable pancreatic cancer.Methods Totally 84 patients who underwent ultrasound-guided percutaneous microwave ablation for unresectable pancreatic cancer were enrolled,and the technical success rate,complete ablation rate,complication rate,pain relief rate and survival time,etc.were observed.Results The median age of 84 cases was 61.5 years.Totally 86 tumors,including 44.19％(38/86)at the head/neck and 55.81％(48/86)at the body/tail of pancreas were detected,and a total of 85 ablation sessions were performed with the median ablation energy applied per tumor of 9.90(1.08,21.60)kJ and the complete ablation rate of 42.86％(36/84).The technical success rate was 100％(85/85).Thirty-nine complication events occurred in 25 cases,no ablation-related death.Among 34 patients underwent ablation mainly for pain symptoms,the pain score decreased from(6.22±1.12)points before treatment to(1.94±1.64)points after treatment(P＜0.001).During 6.8(3.3,12.9)months' follow-up,the mean survival time was(8.5±6.7)months,and all 47 patients died due to tumor progression.Conclusion Ultrasound-guided percutaneous microwave ablation was safe and feasible for unresectable pancreatic cancer.