ObjectiveTo investigate the efficacy and safety of simplified diagnosis and treatment strategies and regimens in the treatment of patients with human immunodeficiency virus （HIV）/hepatitis C virus （HCV） co-infection. MethodsThis multicenter prospective real-world study was conducted among 198 patients with HIV/HCV co-infection who received hepatitis C treatment in 10 designated primary hospitals for hepatitis C in Yuxi， China from July 2023 to June 2024， and according to whether genotype detection was performed， they were divided into genotype detection group with 122 patients and non-genotype detection group with 76 patients. The patients were observed in terms of sustained virologic response at 12 weeks （SVR12）， safety， and liver biochemical parameters. Propensity score matching was used to match the two cohorts， using caliper matching （caliper value = 0.02） at a ratio of 1∶1. The independent-samples t test or the Wilcoxon signed-rank test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between groups. ResultsAmong the 122 patients in the genotype detection group， 63.11% （77/122） had genotype 3， while the non-genotype detection group had 76 patients； both groups achieved an SVR12 rate of 100%. From baseline to 12 weeks after treatment， both groups had a significant increase in the serum level of albumin， significant reductions in the serum levels of total bilirubin， alanine aminotransferase， aspartate aminotransferase， and alpha-fetoprotein， and a significant reduction in FibroScan value （all P<0.05）. A total of 54 patients （27.27%） experienced at least one adverse reaction， and anemia was the most common adverse reaction （38 patients， 19.19%）， with an incidence rate of 50.00% （33/66） in patients with liver cirrhosis. HIV viral load remained <50 IU/mL before and after treatment， and there was no significant change in CD4⁺ T lymphocyte count after treatment （Z=-0.969， P=0.202）. Compared with the genotype detection group， the non-genotype detection group had a significantly shorter time from positive HCV RNA testing to treatment initiation （4±2 days vs 19±4 days， t=5.321， P<0.05） and significantly lower testing costs （618±97 yuan vs 789±129 yuan， t=3.661， P<0.05）. ConclusionFor patients with HIV/HCV co-infection， the simplified diagnosis and treatment strategies can achieve a relatively high SVR12 rate， improve biochemical indicators， and effectively reduce time cost and economic burden， with a favorable safety profile.

ObjectiveTo generate cynomolgus and rhesus monkey models carrying the Booroola fecundity (FecB) variant of bone morphogenetic protein receptor type 1B (BMPR1B) gene (designated BMPR1B^FecB) using adenine base edit technology and to explore genetic improvement strategies for enhancing the reproductive performance of laboratory macaques. MethodsFour single-guide RNAs (sgRNAs) were designed to target the BMPR1B c.746A>G locus in cynomolgus and rhesus monkeys. The sgRNAs were combined with the ABE8e-SpRY base editor, and the resulting editing complexes were microinjected into zygotes of both macaque species. Following in vitro culture of the injected embryos, nested PCR amplification was performed to detect the base-editing efficiency at the target site to screen for highly efficient sgRNAs. Subsequently, normally developing gene-edited embryos were transferred into the oviducts of surrogates. Seven days after birth, ear skin or peripheral blood samples were collected from the newborn monkeys for genotyping and mosaicism analysis, and the growth, development, and health status of the gene-edited monkeys were monitored. ResultsAmong the four candidate sgRNAs, sgRNA4 was identified as achieving 100% editing efficiency at the c.746A>G site. A total of 17 live monkey offspring were obtained via embryo transfer, including 8 cynomolgus monkeys and 9 rhesus monkeys. Genotyping results showed that all 8 newborn cynomolgus monkeys carried the c.746A>G point mutation, with an editing efficiency of 100% (8/8), of which 37.50% (3/8) were mosaics. Among the 9 newborn rhesus monkeys, 8 individuals carried the c.746A>G mutation, with an editing efficiency of 88.89% (8/9), of which 75.00% (6/8) were mosaics. ConclusionThe ABE8e-SpRY base-editing system enables precise editing at the c.746A>G (p.Q249R) locus of the BMPR1B gene in both cynomolgus and rhesus monkey embryos, resulting in the successful establishment of laboratory monkey models carrying the BMPR1B^FecB variant. These models provide a valuable foundation for future studies of the regulatory role of the BMPR1B^FecB variant in reproductive performance at the non‑human primate level, as well as for exploring genetic improvement strategies to enhance reproductive performance in laboratory monkeys.

OBJECTIVE To investigate the ameliorative effects of Imperatae Rhizoma （RI） extract against doxorubicin （DOX）-induced myocardial injury and its potential molecular mechanisms. METHODS Network pharmacology was employed to screen for target overlap between the predicted core targets of RI’s active components and targets associated with myocardial injury， followed by gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses. Based on the network pharmacology results， a DOX-induced myocardial injury mouse model was established using male C57BL/6J mice to observe the effects of RI extract [1 g/（kg·d）] on the survival rate， body weight， and cardiac damage. A DOX-injured HL-1 cardiomyocyte model was established to assess the effects of different mass concentrations of RI extract （50， 100， 200 μg/mL） on mitochondrial membrane potential， adenosine triphosphate （ATP） production， reactive oxygen species （ROS） generation， apoptosis， and expression of the relevant target proteins. The mechanism was validated by transfecting with small interfering RNA of estrogen receptor 1 （ESR1）. RESULTS A total of 58 overlapping targets were screened， which were enriched in biological processes such as hormone response and hypoxia response， as well as pathways including apoptosis， tricarboxylic acid cycle， and pyruvate metabolism. Key target proteins， such as ESR1， were also identified. Animal experiments confirmed that the survival rate of mice in the DOX+RI group was obviously higher than that in the DOX group， with a slower rate of weight loss and improved pathological changes， such as cardiac atrophy and inflammatory cell infiltration， compared to the DOX group. Cell experiments showed that， compared with the DOX group， the DOX+RI groups exhibited significantly increased or upregulated mitochondrial membrane potential， relative ATP levels， and mRNA expressions of isocitrate dehydrogenase 3A （IDH3A）， succinate dehydrogenase A （SDHA） and peroxisome proliferators-activated receptor γ coactivator-1α （PGC-1α）， as well as mRNA and protein expressions of ESR1； conversely， relative ROS levels and apoptosis rates were significantly reduced （ P ＜0.05）. Following ESR1 knockdown， the anti-apoptotic effect of the RI extract on cardiomyocytes was significantly attenuated （ P ＜0.05）. CONCLUSIONS The RI extract may alleviate DOX-induced myocardial injury by activating the ESR1 signaling pathway， improving mitochondrial function， and inhibiting excessive ROS production and cardiomyocyte apoptosis.

Objective:To analyze the clinical characteristics and outcomes of Haemophilus influenzae (Hi) meningitis in children. Methods:This is a retrospective case series study. This study included 34 Hi meningitis patients who admitted to Beijing Children′s Hospital, Capital Medical University, from January 1, 2010, to December 31, 2023. Data on clinical presentations, laboratory tests, hearing assessment and outcomes at discharge were collected. Patients were divided into 2 groups according to the outcome at discharge: favorable outcome group and unfavorable outcome group. Mann-Whitney U test and Fisher exact test was used to estimate the risk factors for an unfavorable outcome at discharge. Results:Thirty-four patients were enrolled. There were 16 males and 18 females. The age at onset ranged from 3 months to 12 years. Fever (34 patients (100%)), convulsions (17 patients (50%)), and coma (21 patients (62%)) were the common clinical presentations. Twenty-four patients (71%) developed complications. There were 15 patients (44%) needed treatment in the intensive care unit, 5 patients (15%) received intubation, and 4 patients (12%) had developed shock. The favorable outcome group included 23 patients, and the unfavorable outcome group included 11 patients. Female, patients with limb movement disability, dystonia, ventriculomegaly or hydrocephalus, and a concentration of glucose in the initial cerebrospinal fluid lower than 1 mmol/L were risk factors of unfavorable outcome at discharge (all P<0.05). Among the 23 patients (68%) in favorable outcomes group, 13 patients (57%) had data available on their long-term follow-up results, including 12 patients with favorable long-term outcomes and 1 patient with unfavorable long-term outcome. Among the 11 patients (32%) in unfavorable outcomegroup, 1 patient died, the other 10 patients (91%) had data available on their long-term outcomes. Eight patients had unfavorable long-term outcomes and 2 patients with favorable long-term outcomes. Patients who had unfavorable outcomes at discharge were at a greater risk of experiencing unfavorable long-term outcomes ( P=0.001). Conclusions:It is common for patients with Hi meningitis to have intracranial complications or develop into critical conditions. Patients who have limb movement disability, dystonia, ventriculomegaly or hydrocephalus, and who exhibit a concentration of glucose in the initial cerebrospinal fluid lower than 1 mmol/L tend to have unfavorable outcomes; they need to be assessed for sequelae.

Objective:To establish a highly-sensitive method for the rapid measurement of 137Cs in seawater with an view to its preliminary application in eight coastal provinces of China. Methods:The method employed nickel potassium polyacrylonitrile (KNiFC-PAN), an organic polymer-based ion exchanged resin material, to filter and adsorb 137Cs from seawater at a rate of 60 ml/min via a peristaltic pump. The adsorption efficiency of KNiFC-PAN was determined by measuring the cesium ion concentration before and after adsorption in seawater, with the addition of stable cesium, using inductively coupled plasma mass spectrometry (ICP-MS). Three KNiFC-PAN matrix components of 137Cs standard samples were prepared for the efficiency calibration of well type high purity germanium gamma spectrometer to obtain its detection efficiency. Results:The established measuring method can complete the filtration and adsorption of 137Cs from 20 L seawater within 6-8 h, which was twice as fast as the co-precipitation method with phosphomolybdic acid-ammonium molybdate taking more than 12 h, as stipulated in the GB/T 16145-2022 standard. The cesium recovery rate was as high as 98.02%. The relative standard deviation of the efficiency calibration result for the three prepared standard samples was 1.30%, and the detection limit for 137Cs was 0.26 Bq/m 3. The activity concentrations of 137Cs in offcoast seawater in eight coastal provinces of China were detected ranging from 0.38 to 1.24 Bq/m 3. The activity concentration of 137Cs in coastal seawater of China was at the background level, while as reported in 2019 was 0.03-1.92 Bq/m 3 in the eastern Chinese seas and 1-2 Bq/m 3 in the Pacific Ocean. Conclusions:This method has high detection sensitivity and can quickly obtain the values of activity concentration of 137Cs in seawater, thus providing a rapid and feasible method for emergency monitoring of 137Cs in China.

Objective:To investigate the treatment strategies for vesicovaginal fistula（VVF）in women following cervical cancer radiotherapy.Methods:A retrospective analysis was performed on the clinical data of 33 female patients with post-radiotherapy VVF after cervical cancer treatment at Shanghai Sixth People’s Hospital between January 2020 and June 2024. The patients were categorized into three groups based on surgical approaches：Group A（11 patients）：Underwent prone-position VVF repair. Mean age：（50.0±9.6）years；mean radiotherapy sessions：（22.6±2.2）. All had simple VVF without concurrent intestinal or surrounding soft-tissue fistulas. Among them，1 patient previously received laparoscopic VVF repair，1 transvaginal VVF repair，and 2 gracilis muscle flap packing for VVF repair. One month prior to surgery，the average daily usage of urine pads was 16.7（12.8，25.7）pieces，and the quality of life（QOL）score stood at 4.0（4.0，5.0）points. Preoperative cystoscopy revealed that 8 cases had fistulas located in the trigonal region of the bladder，while 3 cases had fistulas on the posterior bladder wall. The diameter of the fistula openings，measured under a microscope，was 1.2（0.8，1.6）cm. Based on the Goh classification criteria for vesicovaginal fistulas，this group included 3 cases of type 1，4 cases of type 2，2 cases of type 3，and 2 cases of type 4；7 cases of type A and 4 cases of type B；as well as 3 cases of typeⅠ，7 cases of type Ⅱ，and 1 case of type Ⅲ.Group B（20 patients）：Underwent gracilis muscle flap packing for VVF repair. Mean age：（58.6±8.8）years；mean radiotherapy sessions：（29.8±3.9）. Three patients had concurrent rectovaginal fistulas and received colostomy for fecal diversion. History of previous interventions：3 had laparoscopic VVF repair，4 transvaginal VVF repair，and 1 both transvaginal and laparoscopic VVF repair. One month prior to surgery，the average daily usage of urine pads was 19.7（15.8，27.7）pieces，and the QOL score stood at 5.0（5.0，6.0）points. Preoperative cystoscopy revealed that 13 cases had fistulas located in the trigonal region of the bladder，while 7 cases had fistulas on the posterior bladder wall. The diameter of the fistula openings，measured under a microscope，was 1.8（1.0，3.2）cm. Based on the Goh classification criteria for vesicovaginal fistulas，this group included 4 cases of type 1，9 cases of type 2，3 cases of type 3，and 4 cases of type 4；6 cases of type A，11 cases of type B and 3 cases of type C；as well as 1 cases of type Ⅱ，and 19 case of type Ⅲ. Group C（2 patients）：Underwent ureterocutaneous diversion. Ages：67 and 73 years；radiotherapy sessions：51 and 60，respectively. Both had concurrent rectovaginal fistulas and bladder soft-tissue fistulas. The patient presented with recurrent thigh abscesses accompanied by fever. One month prior to surgery，the daily usage of urine pads was 29 and 23 pieces，respectively，and the QOL score was 6 points. Cystoscopic examination revealed that the vesicovaginal fistulas were located in the trigone of the bladder，with diameters of 3 cm and 4 cm，respectively. Additionally，partial defects were noted in the ventral wall of the urethra，while no bladder soft tissue fistulas were detected. According to the Goh classification for vesicovaginal fistulas，both cases were categorized as type 4，type C，and type Ⅲ. For Groups A and B，urinary catheters were indwelled for 3 weeks postoperatively，then removed to assess spontaneous urination and incontinence. QOL was evaluated，with a minimum 6-month follow-up. For confirmed postoperative VVF recurrence，re-repair was performed 3?6 months later based on patient preference. For Group C，double-J stents were placed in the ureters，and stoma bags were applied 3 days postoperatively. Stents were replaced every 1?2 months，with QOL assessment. Successful fistula repair in Groups A and B was defined as the absence of vaginal leakage confirmed by cystoscopy after six months of the procedure with no vaginal leakage. For Group C，surgical success was determined by the resolution of perineal urinary leakage and improvement in QOL.Results:All 33 patients completed surgery successfully. Group A：Follow-up duration：16.3（9.6，24.6）months. Surgical repair succeeded in 7 patients，with unobstructed spontaneous urination and no vaginal incontinence. Four patients had VVF recurrence：2 refused further treatment，and 2 underwent repeat gracilis muscle flap packing. One was successfully repaired，while one recurrence case refused further treatment. Group B：Follow-up duration：17.0（9.5，24.8）months（8?32 months）. Thirteen patients restored spontaneous urination without recurrence. Seven had recurrence：5 refused further surgery，and 2 underwent re-repair. One repair succeeded without incontinence，while one recurrence case refused treatment. Group C：Follow-up durations were 6 and 22 months. Perineum remained dry without incontinence（no urine pads needed），and no recurrence of thigh soft-tissue redness/infection occurred. QOL scores were 2 and 3，respectively.Conclusions:Post-radiotherapy VVF in women after cervical cancer presents complex and variable conditions. The primary goal of treatment should be to improve patients’ quality of life. Treatment approaches should be selected based on the complexity of urinary fistulas and local tissue conditions. In general，patients who are younger，have received lower doses of radiation therapy，present with smaller fistula diameters，have well-vascularized and elastic perifistular tissues，and have no concurrent tissue fistulas are candidates for prone-position VVF repair. Patients who do not meet the criteria for transvaginal repair，have a history of at least two previous repair attempts，or have concurrent vaginorectal fistulas require gracilis muscle flap packing for VVF repair. Patients with three or more types of concurrent tissue fistulas，extensive pale and inelastic perifistular tissues，and who are not amenable to repair surgery undergo ureterocutaneous diversion.

Background: The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies. Methods: MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function. Results: Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores. Conclusion Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To investigate the impact of different etiologies on the spatial distribution pattern of infarcts and the mapping pattern of focal symptoms in acute ischemic stroke (AIS) using a population-based standardized spatial analysis of MRI.Methods:This was a cross-sectional study. Clinical [age, sex distribution, admission National Institutes of Health Stroke Scale (NIHSS) score and 90-day modified Rankin Scale (mRS) score at discharge, etc.] and imaging data of 2 610 patients with AIS attending 9 Medical Centers from January 2015 to December 2021 were retrospectively analyzed. All patients were categorized into 1 718 cases of large artery atherosclerosis (LAA) type, 335 cases of cardioembolism (CE) type, and 557 cases of small artery occlusion (SAO) type according to TOAST typing. All patients underwent diffusion-weighted imaging, and the detected infarct lesions were segmented and aligned to the standardized space using artificial intelligence-assisted methods, and the spatial distribution frequency heatmaps of lesion locations in patients with different TOAST subtypes were plotted and compared with each other by χ2 test. Lesion-symptom image brain maps with different clinical symptoms were further plotted, and differences of lesion-symptom image relationships among different TOAST subtypes were observed and compared with each other by interaction effect. Results:In all patients, the favored sites of infarct lesions were the bilateral middle cerebral artery region in the anterior circulation and the occipital and brainstem regions in the posterior circulation. Compared with the LAA type, the CE type lesions were more likely to occur in the anterior cerebral artery region, the occipital lobe, and the cerebellum posterior, while the SAO type lesions were more likely to occur in the perforator artery supply area. The lesion-symptom mapping results showed that AIS patients with infarct lesions in the frontoparieto-temporal region in the presence of a left middle cerebral artery supply had higher admission NIHSS scores and higher discharge 90-day mRS scores for the LAA type than for the CE type( P<0.05); AIS patients with infarcted lesions in the brainstem region and some cerebellar regions in the presence of vertebrobasilar artery supply had higher admission NIHSS scores and higher discharge 90-day mRS scores for the CE type than for the LAA type( P<0.05). Conclusion:At the population level, brain mapping reveals specific infarct distribution patterns and differences in lesion-symptom mapping patterns of different etiologies AIS patients, providing imaging evidence for the understanding of AIS pathogenetic mechanisms and clinical management.

[Purpose]To analyze cancer incidence and mortality in Anhui cancer registration areas in 2019 and the trends from 2015 to 2019.[Methods]Data from 42 cancer registration areas in Anhui Province in 2019 meeting quality control requirements were collected.The incidence,mor-tality,age-standardized rates by Chinese standard population and world standard population,age-specific rate,accumulation rate(0～74 years old)and the top 10 cancers of high incidence and mortality were calculated by urban and rural areas,sexes and age groups.The standard population of China in 2000 was used for age-standardized incidence or mortality rate(ASIRC or ASMRC),and the Segi world standard population was used for age-standardized incidence or mortality rate(ASIRW or ASMRW),respectively.Joinpoint was used to analyze the incidence and mortality trends from 2015 to 2019,and the annual percentage change(APC)was estimated.[Results]In 2019,the reported incidence rate(crude rate)in Anhui cancer registration areas was 282.87/105(313.24/105 for male,251.19/105 for female),ASIRC and ASIRW were 183.85/105 and 178.94/105,respectively,with the cumulative incidence rate of 20.35％.There was no significant change in the incidence of malignant tumors from 2015 to 2019(APC=-1.00％,P＞0.05).The reported mortality rate(crude rate)was 167.20/105(214.67/105 for male,117.67/105 for female),ASMRC and ASMRW were 98.41/105 and 97.15/105,and the cumulative mortality rate was 10.68％.There was no significant change in the mortality rate of malignant tumors from 2015 to 2019(APC=-3.44％,P＞0.05).The incidence and mortality rate of lung cancer ranked the first in urban and rural popu-lations of all genders.The incidence rate of female breast cancer ranked the third and the mortali-ty rate ranked the sixth of all malignancies.The incidence and mortality of malignant tumors in men were higher than those in women,and higher in rural areas than those in urban areas,and the main cancer types of rural and urban areas tended to be the same.[Conclusion]From 2015 to 2019,there was no significant change in the incidence and mortality of malignant tumors in the cancer registration areas of Anhui Province,but it is still necessary to prevent and treat lung can-cer and female breast cancer.