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 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.

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.

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 se-rotonin 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 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:To explore the clinical efficacy of modified superomedial pedicle technique using an inverted T-shaped incision for reduction mammaplasty and mastopexy.Methods:A retrospective analysis was conducted on clinical data of patients who underwent modified superomedial pedicle technique for breast reduction surgery with inverted T-shaped incision between March 2021 and March 2023 at the Department of Plastic and Aesthetic (Burn) Surgery, Second Xiangya Hospital of Central South University. Preoperatively, a handheld Doppler ultrasound blood flow detector was used to detect and mark the exit points of the 2nd to 4th perforating vessels of the internal thoracic artery, and a superomedial pedicle containing at least two perforators was designed based on the perforator locations, with a pedicle width generally about 6 cm. Intraoperatively, the pedicle was rotated superolaterally, moving the nipple-areola complex (NAC) upwards to construct a fuller upper pole of the breast and removing excess skin in the lower fold to form a inverted T-shaped incision. Postoperatively, the blood supply of the NAC, breast morphology, and incidence of complications were observed and followed up. Canfield Mirror 7.1.1 software was utilized to measure pre- and post-operative breast morphology data from lateral photographs at 6 months, including total breast area, maximum breast protrusion, upper pole protrusion, lower pole height, and nipple elevation height. The BREAST-Q questionnaire was used to survey patient satisfaction with breast appearance, psychosocial well-being, sexual well-being, and physical health before surgery and 6-12 months after surgery, with each dimension scoring 0-100 points, where higher scores indicate greater satisfaction and health. SPSS 28.0 software was used for data analysis, with normally distributed measurement data expressed as Mean±SD, and paired t-test was applied for comparisons of pre- and post-operative breast morphology data (the first 4 indicators) and BREAST-Q scores, with P<0.05 considered statistically significant. Results:A total of 56 female patients were included, with an age of (32.0±6.7) years and a body mass index of (29.1±5.7) kg/m 2. Preoperative Doppler ultrasound blood flow detection showed that none of the patients had missing or significantly variant perforators of the superomedial pedicle. The volume of breast tissue removed ranged from 890 to 1 800 ml, averaging 1 250 ml, with an average pedicle width of 5.4 cm (4.0-7.0 cm). The follow-up period was (13.3±2.5) months, during which all patients exhibited good blood supply to the NAC and favorable breast morphology, with universal high satisfaction with surgical outcomes. Postoperatively, one case developed incisional seroma, which resolved naturally within 3 months; two cases experienced minor incision dehiscence, which healed well after dressing changes; all other patients recovered well without any complications such as flap necrosis or hematoma. Comparison of breast morphology data showed significant reductions in postoperative left and right total breast area ( P<0.05 for both), and increases in maximum breast protrusion and lower pole height postoperatively ( P<0.05 for both), while the difference in upper pole protrusion was not statistically significant ( P>0.05 for both); postoperative left and right nipple elevation heights were (6.30±1.84) cm and (6.52±1.66) cm, respectively. Among the 44 patients who completed the BREAST-Q survey both before and after surgery, scores showed significant improvements in postoperative breast satisfaction [(50.30±10.30) points vs. (83.20±6.02) points] ( t=5.17, P=0.008) and psychosocial well-being [(56.20±17.20) points vs. (89.70±2.70) points] ( t=5.09, P=0.010), while sexual well-being and physical health scores did not differ significantly from preoperative scores ( P>0.05 for both). Conclusion:Preoperative identification of perforator locations using a handheld Doppler blood vessel detector, followed by the design of a modified superomedial pedicle technique for reduction mammaplasty with inverted T-shaped incision, can not only ensure NAC blood supply, avoiding ischemic necrosis due to vascular anomalies, but also maximally reduce pedicle width and increase pedicle rotation flexibility, achieving desirable breast shaping effects.

The patient was a 29-year-old male with a history of hemophilia for more than 10 years. After 6 hours of botulinum toxin injection into the masseter muscle, the redness and swelling of the right face gradually worsened, accompanied by local pain, and restricted mouth opening, etc. The hematoma was absorbed and the swelling subsided significantly after the infusion of coagulation factor Ⅸ. Such cases of large-scale hematomas after botulinum toxin injection in hemophiliacs is rarely reported. This article summarized the diagnosis and treatment process of this case and combines with literature review to provide clinical experience for diagnosis, treatment and prevention of similar complications.

Objective:To investigate the application effects of a novel framework: the external septal retention bionic framework in East Asian rhinoplasty.Methods:A retrospective analysis was performed based on the clinical data of the patients who received treatments in Department of Plastic and Aesthetic ( Burn) Surgery, the Second Xiangya Hospital, Central South University from January 2022 to July 2023 using an external septal retention bionic framework with autologous costal cartilage rhinoplasty. The patients were all treated with a V-shaped incision at the nasal columella, which continued to both sides of the nose to form a bird-shaped incision. During the operation, the sixth or seventh costal cartilage was sculpted to form the nasal columella support grafts (sturt), external nasal septal graft, cap grafts, and shield grafts, in which the nasal column support graft and external nasal septal graft were implanted in a mortise-and-tenon joint structure to form a septum bionic retained external stent in order to lengthen the nasal columellar column and strengthen the septum. A capsular graft was used to shape the tip of the nose and the rectus abdominis fascia was covered to soften the tip of the nose, and the shield grafts were used to fill out the subnasal lobules. A bulb was sculpted, shaped and implanted in the dorsal space to elevate the nasal dorsum. To observe the postoperative results and complications, a postoperative satisfaction survey was completed using the rhinoplasty outcome evaluation (ROE) and the visual analogue scale (VAS) with regular follow-up. Comparison of preoperative and postoperative scale scores was performed using paired samples t-test. Nasal stent stability was assessed by measuring the patients’ preoperative and postoperative nasolabial angle and nasal tip protrusion. The comparison of preoperative and postoperative nasolabial angle was performed using the paired-sample t-test, and the comparison of nasal tip protrusion was performed using the Wilcoxon signed rank-sum test, P<0.05 considered a statistically significant difference. Results:A total of 33 patients were enrolled, including 4 males and 29 females, with average age of 23.8 years(15-42 years). The follow-up period is (14.52 ± 4.72) months (3 to 21 months). Thirty-three patients recovered well after surgery, and no short-term complications such as infection or bleeding occurred. The patients' nasal aesthetic problems such as saddle nose, deviated nasal columella, bilateral asymmetry of the nose, bilateral nasal base depression, and rounded shield of the nasal tip were improved after surgery. Satisfaction survey results: ROE and VAS scores were significantly higher than those before surgery, which were [(17.92±2.56) vs.(12.78±3.14)] and [(8.08±1.66)vs(5.15±1.99)], ( P<0.05), 87.9% (27/33)of the patients were satisfied with the aesthetic and functional outcomes of the nose. Comparisons of nasolabial angle [(87.28±2.58)° vs. (97.64±1.95)°] and tip protrusion [1.88 (1.78, 1.95) cm vs. 2.16(2.01, 2.32) cm] measurements between preoperative and postoperative period of the 33 patients, the differences were statistically significant ( P<0.05). Conclusion:Rhinoplasty for East Asians employs an external septal retention bionic framework to retain the nasal septum. This technique can avoid septal cartilage resorption caused by compression of grafts transplanted in the future, and cause less damage to the anatomy and physiology of the nose. The framework is relatively easy to construct, with a stable and strong stent, and good patient satisfaction. It can achieve a more desirable aesthetic effect of the nose.