Neurofibromatosis type 1 (NF1) presents with a diverse range of symptoms that can affect the skin, bones, eyes, central nervous system, and other organs. This article reports the diagnosis and treatment process of a patient with NF1 complicated by bilateral severe-to-profound sensorineural hearing loss. Genetic testing revealed a heterozygous variant of NF1 NM_ 000267.3: c.4054_ 4058del(p.Ser1352LeufsTer20, supporting the diagnosis of NF1. After thorough evaluation, a right cochlear implantation was performed, yielding satisfactory postoperative results. This case suggests that NF1 patients may exhibit phenotypic heterogeneity and atypicality, providing a reference for clinicians in the diagnosis and treatment of such patients.

Objective:To analyze the clinical characteristics and genetic basis of a male patient with primary infertility caused by Acephalic spermatozoa syndrome.Methods:A patient who had presented at the Henan Provincial People′s Hospital on October 1, 2022 was selected as the study subject. Clinical data and results of laboratory exams and sperm electron microscopy were collected. The patient was subjected to whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing and pathogenicity analysis.Results:WES revealed that the patient has harbored compound heterozygous variants of the PMFBP1 gene, namely c. 853del (p.Ala285Leufs*24) and c. 1276A>T (p.Lys426X), which were both unreported previously. Sanger sequencing suggested that the c. 853del (p.Ala285Leufs*24) variant has derived from his deceased mother, whilst the c. 1276A>T (p.Lys426X) variant has derived from his father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were classified as pathogenic (PVS1+ PM2_Supporting+ PP4). Conclusion:The compound heterozygous variants of the PMFBP1 gene probably underlay the Acephalic spermatozoa syndrome in this patient. The discovery of the novel variants has also enriched the mutational spectrum of Acephalic spermatozoa syndrome.

Objective To investigate the effects of electrical stimulation combined with muscle strength training on knee joint biomechanical characteristics in patients with patellofemoral pain(PFP).Methods Forty-six patients with PFP were recruited and randomly assigned to the muscle strength training(MST)and electrical muscle stimulation with strength training(EMS)groups.The intervention was performed three times a week for six weeks.The anterior knee pain scale(AKPS)was used to measure the knee pain degree.Knee kinematics,dynamics,and surface electromyography(sEMG)data were collected using an infrared motion capture system,force platform,and sEMG system during drop jumps before and after the intervention.Two-way analysis of variance with repeated measures was applied to determine the differences between the dependent variables of the two groups before and after the intervention.Results Compared with pre-intervention,the AKPS score,vastus medialis oblique(VMO)activation,VMO/vastus lateralis(VMO/VL)activation,maximum knee flexion angle,and peak knee extension moment increased significantly in the EMS group;the maximum knee abduction,external rotation angle,and peak knee external rotation moment decreased significantly in the EMS group after intervention.Compared with pre-intervention,the AKPS score,maximum knee flexion angle,and peak knee extension moment increased significantly in the MST group after intervention,the peak knee abduction and external rotation moment significantly decreased in the MST group after intervention.Post-hoc comparisons indicated that compared with the MST group,the AKPS score,VMO activation,VMO/VL activation were significantly higher and the maximum knee abduction angle was significantly lower in the EMS group.Conclusions EMS contributes to the better balance muscle activation of the VMO and VL and corrects the excessive knee abduction angle during jump landing,which may be helpful in relieving pain and improving lower limb function in patients with PFP.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

In order to understand the prevalence of Akabane disease(AKAD)in Guizhou Province and the molecular characteristics of the isolates,the whole-genome sequence of a strain of Akabane virus(AKAV)from a bovine AKAD-positive sample was determined and analyzed.The genotype and genetic variation of the strain were also explored.Based on the conserved S sequence,a fluores-cence quantitative PCR(qPCR)detection method was established and applied for the investigation of AKAV infection status in four large-scale beef cattle farms of Guizhou.Results showed that the S,M and L fragments of the bovine strain were highly homologous to the Tianjin strain(TJ2016/China/2016)and the Australian strain(JaLAB39/Australia/1959),where they were in the same evolutionary branch and belonged to genotype Ⅱ.Sensitivity assay found that the lowest detection limit was 2.5 X 101 copies/μL.Specificity assay showed the established method detected only AKAV with no amplification on bovine bluetongue virus(BLUV),Pasteurella multocida(PM),bovine infectious rhinotracheitis virus(IBRV)and bovine Mycoplasma bovis.The variation coefficients of inter-and intra batches in the repeatability test were both lower than 2.26％.These findings illus-trated that the established qPCR method had high sensitivity,good specificity and repeatability.A total of 298 serum samples from 4 large-scale beef cattle farms in Qianxi City and Huangping County of Guizhou Province were collected and tested for AKAV by the method.Out of 298 sam-ples,25 positive samples(25/298)were detected as positive with a positive rate of 8.39％.In sum-mary,this work provided the reference data for a deep understanding of the molecular prevalence of AKAV in Guizhou Province and laid foundation for the prevention and control of AKAD.

Objective:To predict and analyze the number of acute pancreatitis (AP) inpatients based on time series model, and to explore the predictive efficiency of the model.Methods:Clinical data of AP inpatients in the Affiliated Hospital of Southwest Medical University from January 2014 to December 2019 were collected. R software was used to collect the time series of AP inpatients, and the trend and seasonal characteristics of AP inpatients from 2014 to 2018 were analyzed. Furthermore, the autoregressive moving average (ARIMA) model was established through stationarity test, model ordering and model testing steps, and the best selected model was used to predict the monthly number of inpatients in 2019 to verify its prediction efficiency.Results:A total of 3 939 AP patients were included in the study. The most common etiology for AP was cholestrogenic (48.2%), followed by hyperacylglyceremia (36.3%). The peak age of hospitalization was from 40 to 60 years old. Time series analysis showed that the number of AP inpatients increased year by year. The highest peak of the disease was from February to March, followed by September to November; and there was seasonal variation and the incidence was relatively small in summer. The established original training set sequence did not pass the stationarity test ( P=0.061), so the ARIMA model was established after it was transformed into a stationarity sequence by first-order difference. According to the criterion of minimum AIC value, ARIMA(2, 1, 1)(1, 1, 1) 12 was selected as the best model. The model was used to predict the number of AP inpatients in 2019, showing that it could better fit the trend of onset time and had good short-term prediction effect. The mean root error and absolute error were 6.8790 and 4.7783, respectively. Conclusions:The number of AP inpatients increases year by year with seasonal changes. ARIMA model is effective in predicting the number of AP inpatients and can be used for short-term prediction.

Pulmonary fibrosis (PF) is the pathological structure of incurable fibroproliferative lung diseases that are attributed to the repeated lung injury-caused failure of lung alveolar regeneration (LAR). Here, we report that repetitive lung damage results in a progressive accumulation of the transcriptional repressor SLUG in alveolar epithelial type II cells (AEC2s). The abnormal increased SLUG inhibits AEC2s from self-renewal and differentiation into alveolar epithelial type I cells (AEC1s). We found that the elevated SLUG represses the expression of the phosphate transporter SLC34A2 in AEC2s, which reduces intracellular phosphate and represses the phosphorylation of JNK and P38 MAPK, two critical kinases supporting LAR, leading to LAR failure. TRIB3, a stress sensor, interacts with the E3 ligase MDM2 to suppress SLUG degradation in AEC2s by impeding MDM2-catalyzed SLUG ubiquitination. Targeting SLUG degradation by disturbing the TRIB3/MDM2 interaction using a new synthetic staple peptide restores LAR capacity and exhibits potent therapeutic efficacy against experimental PF. Our study reveals a mechanism of the TRIB3-MDM2-SLUG-SLC34A2 axis causing the LAR failure in PF, which confers a potential strategy for treating patients with fibroproliferative lung diseases.

Pancreatic cancer is a more aggressive and refractory malignancy. Resistance and toxicity limit drug efficacy. Herein, we report a lower toxic and higher effective miriplatin (MPt)-loaded liposome, LMPt, exhibiting totally different anti-cancer mechanism from previously reported platinum agents. Both in gemcitabine (GEM)-resistant/sensitive (GEM-R/S) pancreatic cancer cells, LMPt exhibits prominent anti-cancer activity, led by faster cellular entry-induced larger accumulation of MPt. The level of caveolin-1 (Cav-1) determines entry rate and switch of entry pathways of LMPt, indicating a novel role of Cav-1 in nanoparticle entry. After endosome-lysosome processing, in unchanged metabolite, MPt is released and targets mitochondria to enhance binding of mitochondria protease LONP1 with POLG and TFAM, to degrade POLG and TFAM. Then, via PINK1-Parkin axis, mitophagy is induced by POLG and TFAM degradation-initiated mitochondrial DNA (mtDNA) replication blocking. Additionally, POLG and TFAM are identified as novel prognostic markers of pancreatic cancer, and mtDNA replication-induced mitophagy blocking mediates their pro-cancer activity. Our findings reveal that the target of this liposomal platinum agent is mitochondria but not DNA (target of most platinum agents), and totally distinct mechanism of MPt and other formulations of MPt. Self-assembly offers LMPt special efficacy and mechanisms. Prominent action and characteristic mechanism make LMPt a promising cancer candidate.

Objective To investigate the status quo of health literacy,motivation and self-management behaviours of patients with knee osteoarthritis(KOA),to explore the influence of health literacy and motivation on self-management behaviours to the patients with KOA,and to clarify the relationships among the three factors.Methods Convenience sampling method was used to select 169 KOA patients who were treated in 3 tertiary hospitals in Xianyang between September and December 2021.General status table,chronic disease health literacy scale,patient motivation scale and chronic disease self-management behaviour scale were employed in the on-the-spot survey.Pearson correlation was used to analyze the correlation of health literacy,motivation and self-management behaviour of patients with KOA.Results Total scores of health literacy,motivation and self-management behaviour of the patients with KOA were 79.66±11.91,54.97±9.95 and 23.75±8.89,respectively.It was found that health literacy and motivation of the patients were positively correlated with their self-management behaviour(r=0.872,r=0.822,both P<0.01).Health literacy of the patients was positively correlated with motivation of patients(r=0.877,P<0.01).Health literacy of the patients could be used to directly predict self-management behaviour of patients(β=0.708,95%CI:0.539-0.876),as well as to predict self-management behaviour of the patients through the mediating effect of patient motivation(β=0.228,95%CI:0.676-0.787).The mediating effect accounted for 24.36%of the total effect.Conclusions The health literacy,motivation and self-management behaviours of patients with KOA are all poor and they should be further improved.Patient motivation is the mediating variable in health literacy and self-management behaviour of the patients.It is suggested that nursing staff could encourage the motivation of patients hence to improve the self-management behaviour in the patients with KOA based on an improvement of health literacy.

Objective To investigate the clinical effects of two methods of compressive coverage with aseptic gauze dressing and alginate dressing on haemostasis in placement of peripherally inserted central catheter(PICC)so as to provide a new dressing method for clinical application.Methods A total of 416 breast cancer patients undergoing PICC were randomly divided into two groups,with 208 per group.In the control group,the puncture sites for PICC were dressed with aseptic gauze immediately after the placement of PICC,with a daily aseptic gauze dressing change once per 24 hours.In the trial group,the puncture sites were dressed with alginate dressing immediately after the placement of PICC,with a weekly dressing change at the 7th day after PICC placement,while no local bleeding on the puncture site.The incidence,within 24 hours,of bleeding,degree of comfort,frequency and cost of dressing change as well as the infection rate within 7 days after the PICC placement were monitored and compared between the groups.Results A total of 205 patients in the control group and 208 in the observation group had completed the study.In the trial group,the incidence of bleeding at puncture sites within 24 hours after placement of PICC was significantly lower than that of the control group(27.88%vs.38.05%,χ2=4.829,P=0.028).The frequency of dressing change within 24 hours in the observation group was significantly less than that of the control group(Z=205.235,P<0.001).The cost of dressing change in the observed groups was also significantly less than that of the control group(56.94 vs.10.20 yuan in average,Z=-8.990,P<0.001).The incidence rates of local pain and itche reported by the patients in the observation group were significantly lower than those in the control group(Z=-12.079,P<0.001;Z=-12.194,P<0.001).No infection at the puncture site was observed in both groups.Conclusions Application of alginate dressing immediately after PICC placement in breast cancer patients can extend the time for initial dressing change up to 7 days in the patient without bleeding at the puncture site within 24 hours after the placement of PICC.An alginate dressing can reduce the incidence of bleeding at the puncture site,increase the comfort of patients,lower the frequency and cost of dressing change hence the nursing workload.