OBJECTIVE To optimize the extraction process of Shenye buyi formula. METHODS Based on the quality by design （QbD） concept， the contents of rutin， nuciferine， sinapine thiocyanate， liquiritin，and glycyrrhizic acid ammonium salt， as well as the extract yield， were selected as the critical quality attributes （CQAs） for the extraction process of Shenye buyi formula. The fishbone diagram combined with the failure model and effect analysis method was adopted to determine the water addition， extraction time and extraction times as critical process parameters （CPPs）. High-performance liquid chromatography was employed to detect the contents of rutin， nuciferine， sinapine thiocyanate， liquiritin， and glycyrrhizic acid ammonium salt. The analytic hierarchy process-entropy weight method was used to comprehensively assign weights to the content of the five components including rutin and the extract yield. The Box-Behnken response surface method was employed to fit the mathematical model between CQAs and CPPs， screen the operational space of the extraction process， and validate it. RESULTS The optimal operational space of the extraction process was 9.5 to 12 times the amount of water added， the extraction time was 1 to 1.7 hours， and the extraction times were 3. Upon verification，the comprehensive scores of the optimal extraction process within the operational space were 89.79 and 84.93， respectively. CONCLUSIONS The extraction process of the Shenye buyi formula can be applied to the development and production of its granule preparations.

BackgroundAdverse childhood experiences （ACEs） are strong predictors of psychopathology across the lifespan， exerting extensive adverse effects on physical and mental health during early development. While ACEs increase the risk of childhood psychopathology， sleep quality and impair cognitive function， the early neurobiological mechanisms mediating ACE-induced cognitive impairment remain unclear. ObjectiveTo explore the association between ACEs exposure and the risk of psychopathology， sleep disorders， and cognitive function， and to examine the mediating role of the putamen volume in the relationship between ACEs and cognitive function from a neurodevelopment perspective. MethodsData were obtained from the Adolescent Brain Cognitive Development （ABCD） study， comprising 10 572 children aged 9 to 10. Participants were categorized into five groups based on the cumulative score of ACEs reported by their parents and the children themselves： no-exposure group （0 types of ACEs）， the one-exposure group， the two-exposure group， the three-exposure group， and the high-risk exposure group （≥ 4 types of ACEs）. Logistic regression analysis was employed to evaluate the association between ACEs and psychopathological symptoms ［T score of the Child Behavior Checklist （CBCL） ≥ 65］. Multiple linear regression analysis was ultilized to analyze the correlations between ACEs and the scores of the Sleep Disturbance Scale for Children （SDSC）， the NIH Toolbox Cognition Battery （NIHTB-CB）， as well as the multiple structures in the cerebral cortex and subcortex. The Bootstrap method was applied to test the mediating effect of the putamen volume between ACEs and neurocognitive function. ResultsAfter adjusting for confounders， ACEs cumulative score was correlated with children's psychopathological symptoms in a dose-response manner. Compared with the no-exposed group， the high-risk exposure group had a 2.08-fold （OR=2.080， 95% CI： 1.401–3.088） increased risk of internalizing problems and a 3.13-fold （OR=3.132， 95% CI： 1.703–5.760） increased risk of externalizing problems， and the risk of conduct problems was 4.68 times that of the no-exposed group （OR=4.681， 95% CI： 2.528–8.669）. ACEs cumulative score positively predicted the total score of SDSC （β=0.080， 95% CI： 0.059–0.102）， with relatively stronger predictive effects on sleep-wake transition disorder （β=0.086， 95% CI： 0.063–0.109） and sleep onset and maintenance disorder （β=0.066， 95% CI： 0.043–0.089）. In terms of neurocognition and brain structure， ACEs cumulative score negatively predicted the overall cognitive composite score （β=-0.025， 95% CI： -0.050–-0.001）， the crystallized cognitive composite score （β=-0.035， 95% CI： -0.060–-0.010）， the volume of the left putamen nucleus （β=-0.025， 95% CI： -0.046– 0.003）， and the volume of the right putamen nucleus （β=-0.023， 95% CI： -0.044– 0.003）. The total putamen volume played a partial mediating role between ACEs and the overall cognitive composite score， the effect value was -0.002 （95% CI： -0.004–-0.001）， accounting for 7.49% of the total effect. ConclusionACEs exposure may increase the risk of psychopathological and sleep disturbances in children and may impair neurocognitive function. Reduced putamen volume may serve a potential neurobiological pathway underlying the impact of ACEs on childhood cognition. ［Funded by National Natural Science Foundation of China-Young Scientists Program （number， 82401763）； Sichuan University West China Hospital Full-time Postdoctoral Research and Development Fund Project （number， 2023HXBH084）］

Booster vaccinations are highly recommended in combating the SARS-CoV-2 Omicron variant and its subvariants. However, the optimal booster vaccination strategies and related immune mechanisms with different prior vaccinations are under-revealed. In this study, we systematically evaluated the immune responses in mice and hamsters with different prime-boost regimens before their protective efficacies against Omicron were detected. We found that boosting with Ad5-nCoV, S_WT-2P or S_Omicron-6P induced significantly higher levels of neutralization activities against Omicron variants than CoronaVac and ZF2001 by eliciting stronger germinal center (GC) responses. Specifically, S_Omicron-6P induced even stronger antibody responses against Omicron variants in CoronaVac and Ad5-nCoV-primed animals than non-Omicron-specific vaccines but with limited differences as compared to Ad5-nCoV and S_WT-2P. In addition, boosting with a specific vaccine has the potential to remodel the existing immune profiles. These findings indicated that adenovirus-vectored vaccines and mRNA vaccines would be more effective than other types of vaccines as booster shots in combating Omicron infections. Moreover, the protective efficacies of the vaccines in booster vaccinations are highly related to GC reactions in secondary lymphatic organs. In summary, these findings provide timely important information on prime-boost regimens and future vaccine design.

Tuberculosis is a zoonotic disease posing a substantial public health threat.Immunological diagnosis and vaccine im-munization are both necessary to control tuberculosis prevalence.However,the identical antigenic components in diagnostic reagents and vaccines hinder the use of animal vaccines and limit the specificity of clinical diagnosis in humans.Differentiating infected from vaccinated animals can overcome these problems.This article reviews the progress in differential diagnosis research from three as-pects:the diagnostic effects of antigens,methods for discovering new antigens,and screening of new host immune markers,to provide a theoretical basis for future research.

Objective To establish a combined model of spectral CT multi-parameters and clinical features to distinguish between gastric poorly cohesive carcinoma and tubular adenocarcinoma.Methods A total of 87 patients with gastric cancer confirmed by postoperative pathology were retrospectively selected,including 26 patients with poorly cohesive carcinoma and 61 patients with tubular adenocarcinoma.Predictors were identified by univariate and multivariate logistic regression analyses,and a combined model was established.The area under the curve(AUC)of receiver operating characteristic(ROC)curve was used to evaluate the differential diagnostic efficiency of the parameters and the model.The AUC was compared by DeLong method.Results The gender[odds ratio(OR)5.124,P=0.004],normalized iodine density in the arterial phase(nIoDAP)(OR 5.789,P=0.017),arterial enhancement fraction(AEF)(OR 7.007,P=0.002)and ΔIoD(OR 0.025,P=0.021)were identified as independent predictors for poorly cohesive carcinoma by logistic regression analysis.The AUC of combined model established by four variables in distinguishing poorly cohesive carcinoma and tubular adenocarcinoma was 0.837[95％confidence interval(CI)0.716-0.907],which was significantly higher than that of single tumor spectral CT parameters(P＜0.01).Conclusion The combined model based on patients'gender and tumor spectral CT parameters(nIoDAP,AEF and ΔIoD)can effectively distinguish gastric poorly cohesive carcinoma and tubular adenocarcinoma,providing a basis for gastric cancer patients'individualized treatment strategy.

A porous composite scaffold is prepared through freeze-drying method using sodium alginate as the matrix and calcium citrate double salt as the functional enhancer.To thoroughly investigate the structure and properties of the composite scaffold,advanced instruments including Fourier transform infrared spectrometer,X-ray diffractometer,scanning electron microscope,and thermogravimetric analyzer are utilized for comprehensive structural characterization.Meanwhile,key properties such as porosity,mechanical performance,swelling ratio,gel fraction,and in vitro degradation rate are systematically tested and analyzed.The results show that the composite of sodium alginate and calcium citrate double salt is a physical complex.The porosity of the scaffold mainly ranges from 200 to 600 μm,and as the addition of double salt increases,the pore size firstly increases and then slightly decreases,while the pore distribution become more uneven.In terms of mechanical properties,with the gradual increase of the content of double salt in the scaffold,the mechanical properties of the scaffold are significantly improved.However,its swelling ratio and gel fraction exhibit decreasing trends.Additionally,the degradation rate of the alginate scaffold is relatively fast,while the addition of calcium citrate double salt does not significantly improve the degradation rate.This study not only provides valuable insights into the preparation and property research of porous composite scaffold composed of sodium alginate/calcium citrate double salt,but also offers important reference for their potential applications in biomedicine.

Objective To understand the current situation and dynamic changing trends of healthcare-associated infection(HAI)in a tertiary first-class hospital in the northwest of Hunan Province from 2015 to 2024,and provide scientific basis for optimizing infection control strategies.Methods A single-day cross-sectional survey method was employed to investigate the HAI prevalence rates of hospitalized patients on the given survey day each year from 2015 to 2024.The standardized survey protocol on prevalence rate issued by the National Medical Institution Infec-tion Surveillance Network was strictly adhered,lanqingting real-time HAI monitoring management platform was adopted to retrieve cases from the hospital information system,and R4.2.2 was applied for statistical analysis.Results From 2015 to 2024,the prevalence rate of HAI decreased from 3.03％in 2015 to 1.76％in 2024(Z=-3.37,P＜0.001),and the HAI case prevalence rate decreased from 3.55％in 2015 to 2.20％in 2024(Z=-2.81,P=0.005).Department of critical care medicine continuously had the highest HAI case prevalence rate,which presented a downward trend over time(Z=-2.84,P=0.004).The main site of HAI was lower respiratory tract,accounting for 39.36％to 48.15％,bloodstream infection increased from 3.57％in 2015-2016 to 10.60％in 2023-2024(Z=2.41,P=0.016).A total of 302 strains of HAI pathogens were detected,including 212 strains(70.20％)of Gram-negative bacteria,mainly Pseudomonas aeruginosa(n=55,18.21％),Escherichia coli(n=45,14.90％),Acinetobacter baumannii(n=33,10.93％),and Klebsiella pneumoniae(n=31i,10.26％).65 strains(21.52％)of Gram-positive bacteria were identified,with Enterococcus faecium(n=19,6.29％)and Staphylococcus aureus(n=18,5.96％)accounting for the highest proportions.25 fungal strains(8.28％)were detected,mainly Candi-da albicans(n=11,3.64％).The use rate of antimicrobial agents showed a downward trend over the past decade(Z=-4.01,P＜0.001).Therapeutic antimicrobial use accounting for 82.42％,and its proportion increased over time(Z=6.02,P＜0.001).Prophylactic antimicrobial use accounted for 16.42％,showing a decreasing trend(Z=-2.75,P＜0.001).The pathogen detection rate presented an upward trend over the past decade(Z=13.01,P＜0.001).Conclusion The prevalence rate and case prevalence rate of HAI present a downward trend in this hospi-tal.In the future,it is necessary to establish a monitoring data-based dynamic analysis mechanism,achieve timely feedback and intervention in data monitoring,pay attention to high-risk links in department of critical care medicine,implement precise prevention and control mearsures,perform targeted prevention and control for lower respiratory tract,urinary tract,and bloodstream infection,optimize diagnosis and treatment processes,use antimicrobial agents rationally,and pay attention to the prevalence trend of Gram-negative bacteria.

In recent decades,the incidence of human papillomavirus(HPV)-associated oropharyngeal squamous cell carcinoma(OPSCC)has shown a marked increase.Significant changes have also occurred in the OPSCC diagnosis and treatment paradigm.Deter-mining HPV status prior to treatment is now essential,and radiotherapy/chemotherapy,immunotherapy,and minimally invasive surgical techniques have progressively emerged as key modalities for managing OPSCC.However,alongside these paradigm shifts,a comprehen-sive technical consensus guiding the entire diagnostic and therapeutic process for OPSCC patients is currently lacking.Given China's large population base and the rising incidence of OPSCC,an expert panel convened to develop a clinical technical consensus on OPSCC diagno-sis and management tailored to China's specific context.This consensus aims to further enhance and standardize understanding of OPSCC management techniques among relevant healthcare professionals.

BACKGROUND: Chronic kidney disease (CKD)-associated anemia (CKD-anemia) is associated with poor survival, and hemoglobin targets are often not achieved with current therapies. Phase 3 trials have demonstrated the treatment efficacy of roxadustat for CKD-anemia. This phase 4 study aims to evaluate the long-term (52-week) safety and effectiveness of roxadustat in a broad real-world patient population with CKD-anemia with and without dialysis in China. METHODS: This Phase 4 multicenter, open-label, prospective study, conducted from 24 November 2020 to 11 November 2022, evaluated the long-term safety and effectiveness of roxadustat for CKD-anemia in China. Patients aged ≥18 years with CKD-anemia with or without dialysis were included. The initial oral dose was 70-120 mg (weight-based followed by dose adjustment) over 52 weeks. The primary endpoint was safety based on adverse events (AEs). The secondary endpoints were hemoglobin changes from baseline and the proportion of patients who achieved mean hemoglobin ≥100 g/L. Effectiveness evaluable populations 1 (EE1) and EE2 included roxadustat-naïve and previously roxadustat-treated patients, respectively. The safety analysis set (SAF) included all patients who received ≥1 occasion. RESULTS: The EE1, EE2, and SAF populations included 1804, 193, and 2021 patients, respectively. In the SAF, the mean age was 50 ± 14 years, and 1087 patients (53.8%) were male. Mean baseline hemoglobin was 96.9 ± 14.0 g/L in EE1 and 100.3 ± 12.9 g/L in EE2. In EE1, the mean (95% confidence interval) hemoglobin changes from baseline over weeks 24-36 and 36-52 were 14.2 (13.5-14.9) g/L and 14.3 (13.5-15.0) g/L, respectively. Over weeks 24-36 and 36-52, 83.3% and 86.1% of patients in EE1 and 82.7% and 84.7% in EE2 achieved mean hemoglobin ≥100 g/L, respectively. In the SAF, 1643 (81.3%) patients experienced treatment-emergent AEs (TEAEs). Overall, 219 (10.8%) patients experienced drug-related TEAEs. Thirty-eight (1.9%) patients died of TEAEs (unrelated to the study drug). Vascular access thrombosis was uncommon. CONCLUSIONS: Roxadustat (52 weeks) increased hemoglobin and maintained the treatment target in Chinese patients with CKD-anemia with acceptable safety, supporting its use in real-world settings. REGISTRATION Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100046322; CDE ( www.chinadrugtrials.org.cn ) CTR20201568.
Humans ; Male ; Female ; Anemia/etiology* ; Middle Aged ; Renal Insufficiency, Chronic/complications* ; Glycine/adverse effects* ; Isoquinolines/adverse effects* ; Aged ; Prospective Studies ; Adult ; Hemoglobins/metabolism* ; Treatment Outcome ; China ; Registries ; East Asian People

Tuberculosis is a zoonotic disease posing a substantial public health threat.Immunological diagnosis and vaccine im-munization are both necessary to control tuberculosis prevalence.However,the identical antigenic components in diagnostic reagents and vaccines hinder the use of animal vaccines and limit the specificity of clinical diagnosis in humans.Differentiating infected from vaccinated animals can overcome these problems.This article reviews the progress in differential diagnosis research from three as-pects:the diagnostic effects of antigens,methods for discovering new antigens,and screening of new host immune markers,to provide a theoretical basis for future research.