OBJECTIVE To investigate the ameliorative effects and potential mechanism of total secondary ginsenosides （TSG） on hypertrophic changes of primary cardiomyocytes stimulated by angiotensin Ⅱ （Ang Ⅱ）. METHODS Primary cardiomyocytes were isolated from the hearts of neonatal SD rats and divided into the following groups： control group， AngⅡ group （2 µmol/L）， TSG group （7.5 µg/mL）， PFK-015 group [6-phosphofructo-2-kinase/fructose-2， 6-bisphosphatase 3 （PFKFB3） inhibitor， 10 nmol/L]， and TSG+PFK-015 group （TSG 7.5 µg/mL+PFK-015 10 nmol/L）. The surface area， protein synthesis， energy metabolism-related indicators [free fatty acid （FFA）， coenzyme A （CoA）， acetyl coenzyme A （acetyl-CoA）]， and the expressions of glycolysis-related factors [hypoxia-inducible factor 1α （HIF-1α）， glucose transporter protein 4 （GLUT-4）， lactate dehydrogenase A （LDHA）， pyruvate dehydrogenase kinase 1 （PDK1） and PFKFB3] in primary cardiomyocytes of each group were measured. RESULTS Compared with the control group， the surface area of primary cardiomyocytes and protein synthesis were significantly increased， the content of FFA， protein and mRNA expressions of HIF-1α， LDHA， PDK1 and PFKFB3 were significantly increased or up-regulated in the AngⅡ group， while the contents of CoA and acetyl-CoA， the protein and mRNA expressions of GLUT-4 were significantly decreased or down-regulated （P＜0.05）. Compared with the AngⅡ group， both TSG group and PFK-015 group showed significant improvements in these indexes， with the TSG+PFK-015 group generally demonstrating superior effects compared to either treatment alone （P＜0.05）. CONCLUSIONS TSG can reduce the surface area of AngⅡ-induced primary cardiomyocytes， decrease protein synthesis， and inhibit their hypertrophic changes. These effects may be related to improving energy metabolism and the inhibition of glycolysis activity.

Combined with elastic network model (ENM), the perturbation response scanning (PRS) has emerged as a robust technique for pinpointing allosteric interactions within proteins. Here, we proposed the PRS analysis of drug-target networks (DTNs), which could provide a promising avenue in network medicine. We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework, for drug repurposing of multiple sclerosis (MS). First, the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes. Then, based on topological analysis and functional annotation, the neurotransmission module was identified as the "therapeutic module" of MS. Further, perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis, giving a list of repurposable drugs for MS. Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of serotonin 2B receptor (HTR2B). Finally, we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex. These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS. As a useful systematic method, our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

Objective To investigate the impact of virtual reality combined with body weight-supported treadmill training on phantom limb pain,lower limb dynamics,gait stability,balance func-tion,and quality of life in amputees.Methods A prospective study enrolled 100 unilateral lower limb amputees as participants,who were randomly divided into experimental group(n=50)and con-trol group(n=50).The experimental group received virtual reality combined with body weight-sup-ported treadmill training,while the control group received conventional rehabilitation training.Out-comes,including phantom limb pain intensity[Visual Analogue Scale(VAS),Douleur Neuropathique 4 Questions(DN4)scores],lower limb dynamics[vertical ground reaction force(Fz),anteroposterior ground reaction force(Fy),joint moments],gait parameters,static balance(Berg Balance Scale score),dynamic balance(stability time,proportion of gait support time),quality of life[12-Item Short-form Health Survey(SF-12)score],and activities of daily living[Modified Barthel Index(MBI)score]were assessed before intervention and at 4,8,and 12 weeks post-intervention.Results At 4,8,and 12 weeks post-intervention,the experimental group exhibited significantly lower VAS and DN4 scores compared to baseline and the control group(P＜0.05).Gait speed,stride length,ca-dence,stance time,Berg Balance Scale score,stability time,and proportion of gait support time improved in the experimental group compared to baseline and the control group(P＜0.05).SF-12 score,MBI score,peak Fz,peak Fy,knee flexion moment,ankle abduction moment,and stance phase proportion also increased significantly in the experimental group compared to baseline and the control group(P＜0.05).Conclusion Virtual reality combined with body weight-supported tread-mill training effectively alleviates phantom limb pain,improves lower limb dynamics,gait stability,and balance function,and enhances quality of life in amputees.

Objective:To investigate the epidemiological characteristics and genotype trends of rotavirus infection among the population with diarrhea in China, from 2009 to 2020 and provide evidence for strategic surveillance and prevention.Methods:Surveillance data on diarrhea syndrome from 252 sentinel hospitals across 28 provinces (municipalities, autonomous regions) were obtained from the information management system of the Infectious Disease Surveillance Technology Platform of the National Science and Technology Major Project. Descriptive epidemiological methods were employed to analyze the distribution of rotavirus diarrhea cases in different climatic zones, populations, and times from 2009 to 2020, as well as the genotyping characteristics and changing trends of group A rotavirus diarrhea cases.Results:From 2009 to 2020, a total of 114 606 diarrhea cases were tested for rotavirus, and the positive rate was 19.1% (21 872/114 606); group A rotavirus was dominant (98.2%, 21 471/21 872). The positive rate of rotavirus was the highest in 2009 (36.9%, 2 436/6 604) and 2010 (30.6%, 5 130/16 790), fluctuated between 14.0% to 18.0% from 2011 to 2017, raised slightly in 2018 (20.3%, 2 211/10 900), and declined continuously in the following two years (15.5%, 2 262/14 611 and 9.5%, 470/4 963). The positive rate of males (20.2%, 13 660/67 471) was significantly higher than that of females (17.4%, 8 212/47 135). Children under five had the highest positive rate (28.4%, 18 261/64 300), more than four times that of adults. The positive rate peaked from December to February in the mediate temperate zone, warm temperate zone, and subtropical zone, while there were two peaks from November to January and May to June in the frigid zone of the plateau. The dominant genotype of group A rotavirus gradually changed from G3P[8] and G1P[8] to G9P[8] during 2009-2020.Conclusions:The overall rotavirus infection rate in China was on a downward trend. Meanwhile, significant variations of positive rates were observed in seasonal epidemics and different age groups from 2009 to 2020. Rotavirus diarrhea in children was still a prominent concern. Vaccination of rotavirus vaccine should be promoted, and the epidemiological characteristics and genotypes of rotavirus diarrhea should be continuously monitored.

Objective:To establish an indicator system for surveillance of data sources to provide a theoretical basis for respiratory infectious disease surveillance and early warning.Methods:Indicators for data sources in the surveillance of acute respiratory infectious diseases were initially compiled through a literature search. Subsequently, two rounds of expert consultations were conducted with 22 experts using the Delphi method to refine the indicators.Results:The questionnaire recovery rates for the two rounds of expert consultation were 100.00% and 86.36%, respectively. The authority coefficient of the experts was 0.83. The coordination coefficient of the second round of Delphi expert consultation was 0.32, and the coefficient of variation of each indicator was less than 0.25. Finally, the indicators system of data source for the surveillance of acute respiratory infectious diseases includes 4 first-level indicators, 10 second-level indicators, and 26 third-level indicators.Conclusion:The indicator system of data sources for the surveillance of acute respiratory infectious diseases constructed in this study is reasonable and reliable, providing a valuable reference for surveillance, early warning and policy formulation of acute respiratory infectious diseases.

Objective:To analyze the nationwide epidemiological characteristics and trend of hand, foot and mouth disease (HFMD) fatal cases from 2008 to 2022 and provide evidence for the prevention and control of HFMD.Methods:The information on HFMD fatal cases during 2008 to 2022 was collected from the National Notifiable Disease Surveillance Reporting System of China. Data of the epidemiological characteristics was analyzed by R 4.2.2 software and the changing trends for the case fatality rates, mortality rates and their age-adjusted rates were analyzed by Joinpoint 4.9.10 software.Results:From 2008 to 2022, a total of 3 704 fatal HFMD cases were reported in China. The fatal cases were primarily observed in children aged <3 years (83.42%, 3 090/3 704). The male and female gender ratio was 1.82 ∶1 (2 389 ∶1 315). Regarding the age-adjusted case fatality rates over time, there was a rapid increase from 2008 to 2010 [annual percentage change (APC) =41.97%, P<0.05]. From 2010 to 2016, a steady decline was observed (APC=-28.57%, P<0.05), and the decline accelerated (APC=-39.66%, P<0.05) from 2016 to 2022. Since 2020, less than 10 fatal cases were reported annually nationwide. Among the 2 566 laboratory-confirmed deaths from 2008 to 2022, Enterovirus A71 (EV71) was the predominant pathogen (91.62%,2 351/2 566). There have been noticeable changes in the pathogen composition since 2017, decreasing in EV71 and increasing in the proportion of fatalities caused by Coxsackievirus A16 (CV-A16) and other enteroviruses. Conclusions:From 2008 to 2022, the HFMD case fatality rates and mortality rates continuously declined, peaked in 2010. Since 2017, the decline of HFMD case fatality rates has been noticeably accelerated. Along with the decrease in the proportion of EV71 in HFMD fatal cases, the proportion of other enteroviruses appeared increasing. It is essential to continuously monitor the etiological spectrum of the fatal cases.

Objective:Evaluation of the effectiveness of domestic ultrapulsed thulium laser ablation of isolated porcine kidneys.Methods:Forty-two fresh porcine kidneys were taken. One porcine kidney was dissected along the sagittal plane at the renal hilum, and then dissected along the coronal plane and divided into four pieces.A total of 168 pieces of renal tissues were obtained, of which 162 pieces were selected for the domestic hyperpulsed thulium laser ablation of isolated porcine kidneys using the single-needle method and the double-needle method, respectively. The ablation was carried out with different ablation modes (single-needle and double-needle methods), ablation power (4, 5, and 6 W), ablation modes (continuous, low-energy and high-frequency mode, and high-energy and low-frequency mode), and ablation time (10, 15, and 20 s). The size of the ablation area in terms of the long diameter, the short diameter, and the thick diameter were measured and recorded. The embedded tissues were sectioned and stained with HE to study the microscopic pathological characteristics of the ablation foci. The ablation foci volume and sphericity coefficient (Φ) were calculated, and the ablation foci volume and sphericity coefficient were statistically analyzed by analytic factorial design and one-way ANOVA.Results:The gross specimen showed that the single-needle ablation foci were elliptical in shape, containing black carbonized areas and gray-white necrotic areas with clear boundaries, and the peripheral renal tissues were pink, and the ablation focus was clearly demarcated from the normal tissues. The double-needle ablation foci were a large ellipse containing two small ellipse ablation foci, and the structure was similar to that of the single-needle method. Under the light microscope, the center of the ablation focus was a "cavity-like" carbonized area, outside of which was an area of coagulation necrosis, with deepened cell staining, reduced cell volume, disorganized arrangement, loose nuclei, nuclear consolidation, and some cell nuclei were cleaved and ablated. Ablation mode ( P<0.001), ablation pattern ( P <0.001), ablation time ( P <0.001), and ablation power ( P <0.001) all significantly affected ablation focus volume. The volume of the ablation foci increased with increasing number of needle feeds, longer ablation time, higher ablation power, and with the ablation mode being continuous mode. Single-needle ablation produced the largest volume of ablation foci (259.56 mm 3) in continuous mode, ablation time of 20 s, and ablation power of 6 W. Double-needle ablation produced the largest volume of ablation foci (452.00 mm 3) in continuous mode, ablation time of 20 s, and ablation power of 6 W. The analysis of the sphericity coefficient showed that in single-needle ablation, the sphericity coefficient was the largest (Φ=0.76) under the conditions of continuous mode, ablation power of 4 W, and ablation time of 15 s. The sphericity coefficient was the smallest (Φ=0.56) under the conditions of high-energy, low-frequency mode, ablation time of 10 s, and ablation power of 6 W, and the morphology of the ablation foci were more close to ellipsoid shape. When ablated by the double-needle method, the ablation foci morphology was closer to spherical shape (Φ=0.91) under the conditions of continuous mode, ablation time of 10 s, and ablation power of 5 W. The combined main effect and interaction results showed that ablation mode ( P<0.001), ablation pattern ( P<0.001), and ablation power ( P<0.001) significantly affected the sphericity coefficient of the ablation foci, and ablation time did not affect the ablation foci morphology. Conclusions:Domestic ultrapulsed thulium laser ablates isolated porcine kidney tissues with precise effect, the tissue morphology of the unablated area is normal, the thulium laser ablated foci have a definite safe boundary. Choosing double needle method, continuous mode, ablation power 6 W for 20 s, can ablate spherical cancer foci within 1 cm in diameter, which can be used for spherical small kidney cancer ablation. Selecting the single-needle method, high-frequency, low-energy mode and ablation power of 6 W, the ablation foci were similar to the oval volume, and could be used for the ablation of oval small renal cancer. However, this study is only limited to the animal ex vivo model, which needs to be confirmed by further study.

Objective:To identify the predictive validity of C-reactive protein to albumin ratio (CAR) in the early diagnosis of Kawasaki disease shock syndrome (KDSS).Methods:This was a retrospective case-control study.Children with KDSS hospitalized in the Children′s Hospital, Capital Institute of Pediatrics, from January 2019 to December 2022, were selected as the case group, and children with Kawasaki disease (KD) hospitalized in the same period were selected as the control group.After a 1︰4 propensity score matching (PSM) of age and gender, the demographic characteristics, laboratory and imaging examinations, and other clinical data of all the patients were analyzed and compared between the two groups.Multivariate Logistic regression was used to analyze the possible risk factors of KDSS.The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of risk factors for KDSS.Results:There were 45 KDSS children and 269 KD children included in the study.The KDSS patients were older than the KD patients at the onset [43(19, 51) months vs.24(14, 44) months, Z=2.791, P<0.05].After age- and gender-based PSM, there were 45 children in the KDSS group and 180 children in the KD group.The children with KDSS had a shorter duration of fever [6(4, 6) days vs.6(5, 7) days] and a higher risk of coronary artery lesions [42.22%(19/45) vs.25.56%(46/180)] compared to those with KD ( Z=2.184, χ2=4.868, all P<0.05).Multivariate Logistic regression analysis showed that CAR, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, D-dimer, platelet count, serum sodium and estimated glomerular filtration rate were the independent risk factors for KDSS.The area under the ROC curve for identifying KDSS based on CAR was 0.850.When the cutoff value of CAR was 2.73, the sensitivity and specificity were 77.80% and 81.67%, respectively.After subgroup analysis, each one-unit increment in CAR was associated with a 239.6% increased risk of KDSS in children ≥ 3 years old ( OR=3.396, 95% CI: 2.105-5.479, P<0.05). Conclusions:As one of the independent risk factors for KDSS, CAR has high predictive value for early diagnosis of KDSS.In KD patients ≥ 3 years old, the risk of developing KDSS increases significantly with increased CAR.

Objective:To explore the safety and effectiveness of laparoscopic Heller-Dor surgery in the treatment of achalasia.Methods:The clinical data of 53 patients with achalasia who underwent laparoscopic Heller-Dor surgery from Jan 2013 to Dec 2023 were retrospectively analyzed, including operation time, intraoperative blood loss, postoperative hospitalization , and short-term complications.Patients were followed up for 6 to 12 months after surgery. The preoperative and postoperative achalasia symptom scores (Eckardt score, Gerd-Q score) were compared.Results:All operations were successful, with an average operation time of (124±22) min, an average intraoperative blood loss of (15±5) ml, and an average postoperative hospital stay of (4.2±1.3) d. Compared with those before the operation, the Eckardt score and Gerd-Q score of the patients after the operation were improved compared with that before surgery (all P<0.05). The average postoperative follow-up was 12 months in all 53 cases. One patient with end-stage achalasia developed mild dysphagia 11 months after surgery, and the symptoms of the remaining 52 cases improved significantly. Among them, symptoms disappeared in 48 cases and improved in 5 cases. Conclusions:Laparoscopic Heller-Dor surgery can not only effectively improve the symptoms of achalasia, but also effectively prevent postoperative gastroesophageal reflux symptoms. The operation is simple, less invasive, and has fewer complications.

Objective To explore the mechanism of Huoxiang Zhengqi Dropping Pills in treating dampness encumbering the spleen and stomach type rats by metabolomics method based on gas chromatography-time of flight mass spectrometry(GC-TOF/MS).Methods Male SD rats were randomly divided into normal group,model group and Huoxiang Zhengqi Dropping Pills group(1 g·kg-1).The rat model of dampness encumbering the spleen and stomach was prepared by comprehensive physical modeling method combined with improper diet.Intragastric administration was performed once a day for 10 consecutive days.The macroscopic signs and behavioral indexes(body mass,body length,tail length,abdominal circumference index and spontaneous activities frequency)of rats were observed.GC-TOF/MS method was used to analyze the serum and urine metabolome of rats,identify potential biomarkers related to dampness encumbering the spleen and stomach,and analyze the metabolic pathway of Huoxiang Zhengqi Dropping Pills in rats with dampness encumbering the spleen and stomach.Results Compared with the normal group,the body mass,body length,tail length and spontaneous activities frequency of the rats in the model group were significantly reduced(P＜0.05),and the abdominal circumference index was significantly increased(P＜0.05).Compared with the model group,the body mass,body length and spontaneous activities frequency of the rats in the Huoxiang Zhengqi Dropping Pills group were significantly increased(P＜0.05),and the abdominal circumference index was significantly decreased(P＜0.05).A total of 38 and 44 potential biomarkers related to dampness encumbering the spleen and stomach were identified in rat serum and urine,respectively.Huoxiang Zhengqi Dropping Pills can effectively interfere with the serum and urine metabolic phenotypes of model rats,and can significantly reverse 17 and 13 potential biomarkers in serum and urine,involving a total of 7 metabolic pathways.Conclusion The intervention mechanism of Huoxiang Zhengqi Dropping Pills on rats with dampness encumbering the spleen and stomach syndrome may be related to the regulation of tryptophan metabolism,histidine metabolism,glutamate-glutamine metabolism,energy metabolism and intestinal flora.