Objective To analyze the virus subtypes, molecular evolutional and molecular transmission network features of the first confirmed mpox case in Huai’an City, Jiangsu Province, so as to provide insights into understanding of the transmission and evolution dynamics of mpox virus and formulation of the mpox control strategy in the city. Methods Genomic DNA was extracted from swabs of the first confirmed mpox case’s skin lesions in Huai’an City, and the amplicon sequencing library was constructed using the hypersensitive mpox virus whole-genome capture kit. High-throughput sequencing was performed using the GridION X5 nanopore sequencer on the Nanopore sequencing platform, and single nucleotide polymorphism (SNP) analysis of mpox virus genome sequences was performed following sequence assembly. In addition, phylogenetic analysis, genetic genealogy and molecular traceability analysis were performed. Results The virus whole genome sequence of the first confirmed mpox case was successfully obtained by high-throughput sequencing, with a full length of 197 182 bp, and was named hMpxV/China/JS-HA01/2023, which belonged to the clade IIb (West African clade) lineage B.1.3. Compared with the mpox virus reference sequence MPXV-M5312_HM12_Rivers-001 (GenBank accession number: NC_063383), the genome sequence of the Huai’an virus isolate carried 86 SNPs, including 40 SNPs in the coding region as non-synonymous mutations and 73 SNPs as nucleotide mutations caused by APOBEC3 (APOBEC3). Of the 97 mpox virus gene sequences, 79 sequences were included in the molecular network (81.44%), and the threshold of the genetic distance accessed to the network was 0.35/10⁵. There were two large molecular transmission clusters and one scattered cluster in the molecular transmission network of the mpox virus, andthehMpxV/China/JS-HA01/2023 sequence was located in the large cluster. The 97 gene sequences formed 92 haplotypes, including three shared haplotypes Hap_4, Hap_6 and Hap_38, and an exclusive haplotype Hap_1 of hMpxV/China/JS-HA01/2023 generated from mutation of the exclusive haplotype Hap_43, while the exclusive haplotype Hap_43 was generated from mutation of the shared haplotype Hap_38. Conclusions The whole genome sequence of the mpox virus isolated from the first confirmed mpox case in Huai’an City has been successfully obtained, and the molecular evolutionary and molecular transmission network characteristics of the virus have been preliminarily understood.

Objective To construct a module for drug-induced central nervous system adverse reactions(CNS-ADR)within the Clinical Adverse Drug Event Active Monitoring and Intelligent Assessment Alert System-Ⅱ(ADE-ASAS-Ⅱ),and to conduct a large-scale,real-world active monitoring and evaluation of CNS-ADR specifically related to imipenem/cilastatin.Methods Based on literature review,spontaneous report evaluation,and initial word set of CNS-ADR related descriptions in electronic medical records,text recognition technology was used to construct and optimize the condition settings of the CNS-ADR automatic monitoring module.Hospitalized patients using imipenem/cilastatin were retrospectively monitored from 2017 to 2021,and the positive patients which had CNS-ADR were statistically described in terms of the demographic characteristics,CNS symptoms,and hospital departments.Results Based on a repeated testing optimization using 1 185 manually monitored results,the best setting for the determined module includes 62 sets of keywords,with a positive predictive value(PPV)of 13.63％and a recall rate of 100％.Expanding the monitoring to 8 222 medication users using this module,281 cases of positive causality were identified,with an incidence rate of 3.42％.Among them,patients over 60 years old accounted for 50.17％,and the main manifestations of CNS-ADR were epileptic seizures,headaches,mania,and delirium.Conclusion The CNS-ADR automatic monitoring module established based on ADE-ASAS-Ⅱ provides fast and reliable text data mining support for conducting real-world research on CNS-ADR.

Background::Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure-response relationship of ANV among people living with HIV.Methods::Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses.Results::ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for clearance adjusted for bioavailability (CL/F) was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure-response model revealed no significant correlation between the virologic response (HIV-RNA <50 copies/mL) at 48 weeks and the exposure, but the incidence of adverse events increased with the increasing exposure ( P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141, respectively). Conclusions::Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV, requiring no dose adjustment for the studied factors. Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure.Trial registration::Chinese Clinical Trial Registry https://www.chictr.org.cn (Nos. ChiCTR1800018022 and ChiCTR1800019041).

Objective:To investigate the clinical efficacy of transfer of a free segment of the proximal second toe interphalangeal joint composite tissue flap in reconstruction of defects of interphalangeal joint of fingers, and simultaneously reconstruct the donor site defect left with the second toe by a transfer of a pedicled bone flap of the fibular proximal great toe.Methods:From December 2020 to April 2023, a total of 9 patients with interphalangeal joint defects of fingers were treated in the Department of Hand Microsurgery of Shunde Heping Surgery Hospital. The patients were 7 males and 2 females, aged 18-55 years old, with an average age of 31 years old. Firstly, transfers of a free segment of the proximal second toe interphalangeal joint composite tissue flap were performed to reconstruct the defects of finger joints. Simultaneously in the surgery, transfers of the fibular pedicled bone flap of the proximal great toe were conducted to reconstruct the donor site defects left in the second toe. Patients were instructed with appropriate postoperative functional exercises. K-wires were removed at 8-12 weeks after surgery. Outpatient visits, telephone and WeChat follow-ups were conducted to evaluate the appearance and functional recovery of the reconstructed interphalangeal joints and donor feet. Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association, Vancouver Scar Scale (VSS) and American Orthopedic Foot and Ankle Society (AOFAS) foot function scoring standards were employed in the evaluation.Results:Postoperative follow-up lasted for 6 to 30 months. All of the 9 interphalangeal joint composite tissue flaps in the fingers survived with complete and good appearance. Function of the reconstructed interphalangeal joints of the fingers recovered well. According to the Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association, the average score achieved 12 points, with 6 patients of excellent, 2 of good and 1 of fair. After surgery, the appearance and function of the donor great toes and second toes all recovered well. The average score of the scars in donor second toe evaluated by VSS was 4 points. All the donor feet were kept with 5 toes, with full, intact and good in appearance. According to the AOFAS foot function scoring standard, the average score achieved 95 points, and were excellent.Conclusion:Application of transfer of free proximal segment of interphalangeal joint composite tissue flap of the second toe in reconstruction of the interphalangeal joint defect of a finger, and simultaneously reconstruct the defect left with the donor second toe with a fibular proximal great toe flap pedicled with bone tissue can achieve good clinical efficacy in reconstruction of the defects of interphalangeal joint of fingers, restore the function of the interphalangeal joint of fingers and the appearance and function of the donor foot.

Objective:Employ Lasso regression to develop a nomogram model for predicting the risk of liver cirrhosis in patients with chronic hepatitis B (CHB).Methods:A retrospective analysis was conducted on age, gender, laboratory test results, and liver ultrasound results of 1218 patients diagnosed with CHB at the First Affiliated Hospital of Harbin Medical University between 1 January 2023 and 30 November 2023. Based on the R caret package, patients were divided into a training set ( n=853) and an internal validation set ( n=365) at a ration of 7∶3, and an additional 185 patients with CHB treated at the First Affiliated Hospital of Harbin Medical University Qunli campus during the same period was included as an external validation set. Lasso regression and multiple logistic regression were employed for variable selection and nomogram model construction. The discriminative ability, calibration, and clinical utility of the prediction model were evaluated using Receiver Operating Characteristic (ROC) curves, calibration curves, Decision Curve Analysis (DCA), respectively. Results:Age, platelet, gamma-glutamine transpeptidase, prealbumin, portal vein diameter, and spleen thickness were selected as predictive variables for the occurrence of liver cirrhosis in CHB patients ( P<0.05), and a nomogram model was constructed based on the aforementioned variables. The AUC values for the ROC curves in the internal validation set and external validation set were 0.934 (95% CI 0.910-0.959) and 0.881 (95% CI 0.820-0.942), respectively. The fitting degree of calibration curve was observed in both sets (Internal validation set P=0.881; External validation set P=0.478). DCA curves demonstrated the high clinical utility of the model. Conclusion:Age, platelet, gammaglutamine transpeptidase, prealbumin, portal vein diameter, and spleen thickness were risk factors for the occurrence of liver cirrhosis in CHB patients. The constructed nomogram model exhibits good predictive value and clinical utility.

Objective To understand the incidence and characteristics of adverse drug reactions(ADRs)of carbapenems,explore the relevant risk signals,and provide a reference for clinically safe drug use.Methods All spontaneous reports of carbapenem drug-related ADRs from January 2008 to October 2022 in the Adverse Drug Reaction Monitoring Center,PLA General Hospital's ADR database were retrieved,and information such as patients'general conditions,involved systems and organs damage,and the names of ADRs involved were retrospectively analysed.Using the reporting odd ratio method,the proportional reporting ratio method,the Medicines and Healthcare Products Regulatory Agency method,and information component method to obtain risk signals of carbapenem antimicrobial drug-related ADR.Results A total of 2 642 ADR reports of carbapenems were reported,of which 410 serious ADR reports(15.52％)were serious ADR reports,five cabapenem antimirobial drug species were mainly involved.In descending order of composition were imipenem cilastatin(51.28％),meropenem(32.13％),biapenem(8.10％),ertapenem(7.68％),and panipenem(0.79％).The male to female ratio of patients was 1.74:1,with the most age＞60 years(59.69％).A total of 14"drug-ADR name"combinations generated risk signals in all four data mining methods,with meropenem being the most signals,and imipenem cilastatin and ertapenem had a high number of reported ADR in nervous system.Conclusion The results of risk signal mining are basically consistent with the known carbapenem ADR information,during the use of carbapenem antimicrobial drugs in the clinic,it is recommended to monitor patients'liver and kidney functions as well as blood biochemical indexes,so as to strengthen the awareness of vigilance in the clinical use of carbapenem antimicrobial drugs,and timely recognize and deal with ADRs in a timely manner,and to avoid the occurrence of serious ADRs.

AIM:To investigate the impact of aquaporin 4(AQP4)expression inhibition on autophagy and apoptosis in a mouse model of cerebral ischemia-reperfusion(I/R)injury,and to elucidate its underlying mechanism.METHODS:Cerebral I/R injury was induced in mice via transient middle cerebral artery occlusion(tMCAO).Totally 60 mice were randomly divided into sham group,I/R group,AQP4 inhibition group,and 3-methyladenine(3-MA)group,with 15 mice in each group.Among them,the mice in sham and I/R groups received intraperitoneal injections of normal saline,while those in AQP4 inhibition group and 3-MA group received intraperitoneal injections of AER-271(2 mg·kg-1·d-1)and AER-271+3-MA(2 mg·kg-1·d-1)for 3 d,respectively,once per day.Longa score was adopted to assess the neu-rological function,and to record changes in body weight.Cerebral infarction volume and histopathological alterations were evaluated using hematoxylin-eosin staining.Western blot analysis was performed to determine the levels of AQP4,LC3-Ⅱ,P62 and cleaved caspase-3,while the LC3-Ⅱ,P62,cleaved caspase-3 and NeuN(neuronal marker)colocalization and expression assessment were conducted with immunofluorescence.RESULTS:The mice in I/R and AQP4 inhibition groups exhibited extensive cerebral infarction,cerebral edema,and elevated Longa scores.However,in comparision to I/R group,the mice in AQP4 inhibition group showed significantly reduced cerebral infarct volume,cerebral edema vol-ume,and Longa score(P<0.05).Additionally,in contrast to sham group,the mice in I/R group displayed increased ex-pression of AQP4,LC3-Ⅱ and cleaved caspase-3(P<0.01),accompanied by decreased body weight and P62 expression(P<0.05 or P<0.01).Furthermore,compared with I/R group,the mice in both AQP4 inhibition group and 3-MA group demonstrated a decrease in the expression levels of AQP4,LC3-Ⅱ and cleaved caspase-3(P<0.05 or P<0.01),along with increased body weight and P62 expression(P<0.05 or P<0.01).Nonetheless,no significant differences were ob-served between AQP4 inhibition group and 3-MA group regarding Longa score,cerebral infarct volume,body weight,and the expression of AQP4,LC3-Ⅱ,cleaved caspase-3 and P62.CONCLUSION:Inhibition of AQP4 expression signifi-cantly reduces cerebral infarction area and nerve injury severity in tMCAO mice.Moreover,AQP4 expression inhibition decelerates autophagy and apoptosis after cerebral infarction,with the additional autophagy inhibitor showing no notable impact on the protective effect of AQP4 inhibition.

Objective:To evaluate the practical value of the up-converting phosphor technology (UPT) in the field fast detection of plague, and to provide scientific basis for its promotion and application in the field work of plague monitoring.Methods:In September 2020, a total of 116 samples (including 4 samples for epidemic determination) were collected at the plague epidemic site in Menghai County, Yunnan Province, including 24 human blood and lymphatic fluid samples, 83 rat liver and muscle samples, and 9 rat blood samples. In March 2023, a total of 12 rat liver and muscle samples were collected from Lijiang City for on-site monitoring of plague outbreak (all of them were outbreak determination samples). All of the above samples were tested for Yersinia pestis antibody and antigen using the up-converting phosphor technology. At the same time, haemagglutination test, real-time fluorescence quantitative PCR and bacterial culture were conducted to compare the detection process and results of different experimental methods, the advantages and disadvantages of the up-converting phosphor technology for detecting Yersinia pestis were analyzed, and the feasibility of using this detection method in the field of plague epidemic monitoring was judged. Results:The plague epidemic samples site in Menghai County, Yunnan Province were tested by up-converting phosphor technology, and 19 samples were found to be positive for Yersinia pestis (1 antibody-positive and 18 antigen-positive). Among the samples determined, 4 samples with positive results of Yersinia pestis were detected by up-converting phosphor technology, and the results of their haemagglutination test, real-time fluorescence quantitative PCR and bacterial culture were all positive. All samples from Lijiang City were tested by up-converting luminescence technology, two samples were positive for Yersinia pestis(antigen-positive). The results of haemagglutination test and real-time fluorescence quantitative PCR were positive, and one sample was positive for bacterial culture. The time required for up-converting phosphor technology, haemagglutination test, real-time fluorescence quantitative PCR, and bacterial culture were 0.5, 4.0, 2.5 and 72.0 h, respectively. Conclusions:The results of Yersinia pestis detection by up-converting phosphor technology are basically consistent with the results of haemagglutination test, real-time fluorescence quantitative PCR and bacterial culture, but the time used is relatively short. When the number of samples is large, this method can be used preferentially in the field work of plague outbreak monitoring, which can quickly complete the preliminary judgement of plague outbreak, and save a lot of time and economic resources for the next step of plague prevention and control work.

Objective To investigate the clinical application of 3D printed bolus with specific density in breast cancer radiotherapy,and to evaluate its effects on dose distribution and positioning.Methods Forty post-mastectomy patients undergoing intensity-modulated radiotherapy were randomly enrolled for 3D printed bolus(n=20)and conventional bolus(n=20),and all patients were fixed in the supine position using styrofoam.Conventional positioning was performed based on in-room lasers and body markers,with daily Catalyst HD optical surface monitoring combined with weekly CBCT verification.The absolute dose,patients'skin surface dose,surgical incision,planned field,target area doses(VCTV50Gy,VPTV50Gy)and organs-at-risk doses in patients with different boluses were recorded,and the conformity index and homogeneity index were calculated,and the setup errors using CBCT and Catalyst HD were also analyzed.Results The difference in absolute dose between different boluses was trivial,but the skin surface dose with 3D printed bolus was significantly higher than with conventional bolus[(54.83±0.44)Gyvs(54.43±0.51)Gy,P<0.05].Patients with 3D printed boluses had a higher conformity index than with conventional boluses(0.69±0.04 vs 0.65±0.02).For different boluses,there was no significant difference in VCTV50 Gy,while the VPTV50 Gy and organs-at-risk doses were lower in those with 3D printed bolus than conventional boluses(P<0.05),with heart Vmean of 9.68%±3.24%vs11.43%±3.60%.In patients with 3D printed boluses,both planned field arrangement and surgical incision affected the target doses,and the doses of the target area without an internal breast wrap was greater than those with internal breast wrap(P<0.05).When the field was not wrapped around the internal breast,the surgical incisions only affected VPTV50 Gy,and the VPTV50 Gy was greater with the transverse fusiform incision than with the oblique vertical incision(P<0.05),which were 95.58%±0.51%vs95.44%±0.71%.The optical monitoring accuracies with different boluses differed only in the left-right direction(P<0.05),with(0.08±0.57)cm and(-0.15±0.46)cm for 3D printed and conventional boluses.Conclusion Compared with conventional bolus,3D printed bolus can improve dose distribution and optical monitoring accuracy.The surgical incision and planned field arrangement under 3D-printed bolus would exert effects on target doses.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.