Objective:To investigate the clinical and genetic characteristics of spinal muscular atrophy (SMA) patients with SMN1 gene compound heterozygous mutations. Methods:Three SMA-Ⅲ pedigrees treated in Henan Provincial People′s Hospital from October 2019 to July 2020 were selected. The clinical data of 3 SMA-Ⅲ probands were retrospectively analyzed. Multiplex ligation-dependent probe amplification (MLPA) technology was used to detect the copy number of the SMN gene in the probands and their parents. Polymerase chain reaction amplification combined with microfluidic capillary electrophoresis were used to detect point mutations in the SMN1 gene of the probands. Sanger sequencing was used to validate candidate variant sites. Results:The 3 probands are all male, aged 19, 17 and 12 years, respectively. The main clinical manifestations were symmetrical muscle weakness mainly in the proximal lower limbs, mild to moderate elevation of serum creatine kinase, and neurogenic injury as determined by electromyography or muscle pathology. The genetic testing results showed that all 3 probands had heterozygous deletion in exon 7 of the SMN1 gene, and carried heterozygous variations c.275G>A (p.Trp92 *), c.689C>T (p.Ser230Leu), and c.708dupT (p.Pro237Serfs *19), respectively. The exon deletion and point mutation were inherited separately from their parents. c. 275G>A (p.Trp92 *) and c.708dupT (p.Pro237Serfs *19) variations had not been reported before. Conclusions:The clinical manifestations of SMA-Ⅲ patients are symmetrical muscle weakness, mainly in the proximal extremities of both lower limbs, and electromyography or muscle biopsy suggesting neurogenic lesions. The compound heterozygous variation of point mutation and heterozygous deletion in the SMN1 gene can lead to SMA-Ⅲ. Suspected SMA patients with SMN1 gene heterozygous deletion should take point mutation testing.

Objective:To analyze the clinical manifestations and muscular magnetic resonance imaging (MRI) features of 12 families with facioscapulohumeral muscular dystrophy (FSHD).Methods:Retrospective analysis was conducted on 12 FSHD families diagnosed by genetic testing at the Department of Neurology of Henan Provincial People′s Hospital from January 2017 to June 2021. Clinical data and lower limb muscle MRI results of the probands and related members of the families were collected, and the degree of muscle fatty degeneration shown in the MRI was scored using the modified Mercuri score.Results:There were 21 patients in 12 families, with the age of onset ranged from 10 to 47 years (mean 19.5 years). The course of disease ranged from 1 to 47 years (mean 23.1 years). The onset sites included unilateral upper extremity in 8 cases, bilateral proximal upper extremities in 9 cases, bilateral proximal lower extremities in 2 cases, unilateral proximal lower extremity in 1 case, and simultaneous onset in all 4 limbs in 1 case. Sixteen patients had limb weakness and bilateral asymmetry, and 11/16 cases were more severe on the right side than the left side. Winged scapular and facial muscle weakness were observed in all patients. The creatine kinase range was 85-1 038 U/L (461 U/L on average) in 12/21 cases. There were 10/21 cases of myogenic lesion in electromyography. Myodystroph-like pathological changes were found in 11/21 cases. The fragment length of the 4q35 subtelomere polymorphism EcoRI/p13E-11 was less than 38 kb in 20/21 cases; 1 case was confirmed based on clinical symptoms and family history. Fat infiltration occurred in at least one muscle of lower limbs in 9/10 cases, in thigh muscle in 9/10 cases and in calf muscle in 6/10 cases. The average score of fat infiltration in thigh muscle group was higher than that in calf muscle group. The muscles with higher fat infiltration scores were the vastus intermedius, the long head of the biceps femoris, the vastus medialis, the vastus lateralis, the semitendinosus, the semimembranosus, the vastus lateralis in the thigh (with score ≥2.15), the tibialis anterior, and the medial head of the gastrocnemius in the calf (with score ≥1.11). Fat infiltration in the medial and posterior thigh muscles was more common than in the anterior thigh muscles. There was asymmetry of bilateral muscle fat in 9/10 cases. There were edematous changes in thigh muscles in 1 case and in calf muscles in 3 cases.Conclusions:The age of onset of FSHD patients is mostly ≤30 years. Bilateral asymmetric involvement is the characteristic manifestation of FSHD. The FSHD patients ' muscles most affected by the disease in the thigh are the quadriceps femoris, the long head of the biceps femoris, the vastus medialis, the vastus lateralis, the semitendinosus, the semimembranosus, and the vastus intermedius. In the calf, the muscles most affected are the anterior tibial muscle and the medial head of the gastrocnemius. The MRI pattern of muscle involvement of patients with FSHD is bilateral asymmetrical lesions, with the right side having more severe lesions. The fatization of thigh muscles is more significant than that of calf muscles, and the asymmetry of fatization between bilateral muscles is also present.

Objective:To investigate clinical, lower limb muscle magnetic resonance imaging (MRI) and myopathological features in hereditary caveolinopathy patients.Methods:Clinical data, lower limb muscle MRI and pathological findings of 2 patients with caveolinopathy diagnosed by genetic examination in Henan Provincial People′ s Hospital in January 2020 and August 2022 were retrospectively analyzed. And the characteristics of patients with hereditary caveolinopathy reported in China were analyzed in combination with literature review.Results:Case 1 was a 14-year-old boy. At 4 years old, his right heel did not touch the ground while squatting, and at 11 years old, he experienced weakness in his lower limbs and muscle pain during running, as well as difficulty in lifting his feet while walking. Six months earlier, he underwent surgery for right high-arched foot. Physical examination revealed slight atrophy of both first interosseous muscles, hypertrophy of the left calf, decreased muscle strength in the right distal leg, percussion-induced muscle mounding, postoperation of right high-arched foot, left high-arched foot as well as bilateral ankle contracture, foot drop, and inversion. Case 2 was a 15-year-old girl. At 14 years old, she presented prolonged exercise myalgia. Physical examination showed no positive signs. Both patients had no family history. Creatine kinase was slightly elevated in the 2 patients. Electromyography in the 2 patients showed a myopathic pattern in distal and proximal muscles. T 1-weighted MRI of lower limb muscles showed significant fatty infiltration in the bilateral rectus femoris, bilateral semitendinosus muscles, right tibialis anterior, right peroneus and right gastrocnemius lateral head in case 1. Selective rectus femoris muscle fatty infiltration in the thighs and mild gastrocnemius fatty infiltration in the lower legs were observed in case 2. Short inversion recovery sequence showed edema-like changes in both patients. Muscle pathology of both patients showed dystrophic-like pathological changes. A total of 9 Chinese patients with hereditary caveolinopathy reported in previous literature and in this study had an onset age from early childhood to youth. The main clinical manifestations were slowly progressive distal limb muscle weakness and atrophy accompanied by myalgia or merely presenting as myalgia. The creatine kinase levels were mildly to moderately elevated. Electromyography could show myogenic damage, myogenic and neurogenic mixed damage or normality. The muscle pathology showed myopathy-like or muscular dystrophy-like changes. Conclusions:The clinical manifestations of hereditary caveolinopathy are heterogeneous, and exercise-induced myalgia is frequently the most prominent symptom. The rectus femoris and gastrocnemius muscles tend to show early fatty infiltration in legs on MRI. Muscle pathology lacks specificity.

Objective:To understand the species of mosquitoes and the status of important mosquito-borne viruses in the Ningxia surveyed regions, to identify the dominant mosquito species and virus types, and to analyze their genetic characteristics, providing a scientific basis for predicting and controlling mosquito-borne infectious diseases.Methods:Mosquitoes were collected using light traps in Yinchuan and Wuzhong cities of the Ningxia Hui Autonomous Region, and the collected mosquitoes were classified and identified. Real-time polymerase chain reaction (PCR) was used to detect the Japanese encephalitis virus (JEV), West Nile virus (WNV), Chikungunya virus (CHIKV), Sindbis virus (SINV) carried by mosquitoes. The positive sample was subjected to sequencing the whole genome, and the phylogenetic tree of virus strains was constructed using bioinformatics methods.Results:From June to August 2023, a total of 8 561 mosquitoes of 3 genera and 6 species were collected in Yinchuan and Wuzhong cities, Ningxia, among which Culex pipiens pallens was the dominant species with 3 050 individuals, accounting for 35.63%; Anopheles sinensis with 2 379 individuals, accounting for 27.79%; Culex tritaeniorhynchus with 1 489 individuals, accounting for 17.39%; Caspian Aedes with 1 468 individuals, accounting for 27.79%; Aedes vexans with 152 individuals, accounting for 1.78%; and Culex modestus with 23 individuals, accounting for 0.27%. JEV GIb type was detected in the specimens of Culex tritaeniorhynchus collected in Qingtongxia city. Conclusions:The dominant mosquito species in the surveyed areas of Ningxia are primarily Culex pipiens pallens, and JEV GIb virus was detected in Culex tritaeniorhynchus in Qingtongxia city. This study provides basic data for understanding the current status of mosquitoes and mosquito-borne viruses in the Ningxia region and offers scientific guidance for further public health prevention and control measures.

Objective:To investigate the clinical and genetic characteristics of patients with amyotrophic lateral sclerosis (ALS) caused by FUS gene mutations. Methods:A retrospective analysis was conducted on 7 families diagnosed with FUS gene related ALS in the Department of Neurology of Henan Provincial People′s Hospital from January 2018 to June 2024. Clinical data and neuroelectrophysiological results of the probands and family members were collected. Next generation sequencing or whole exome sequencing was conducted on the probands. The detected variants of the FUS gene were confirmed by Sanger sequencing. Results:Among the 7 probands, 4 were with familial ALS and 3 with sporadic ALS, including 6 males and 1 female. The average age of onset was 24.6 years (ranging from 21 to 30 years). The onset site included bulbar muscles in 1 case, proximal upper limbs in 3 cases, proximal lower limbs in 2 cases, and both upper and lower limbs in 1 case. Four patients presented both upper and lower motor neurons involvement on examination, and 3 had only lower motor neuron syndrome. Muscle atrophy and fasciculation were observed in 6 patients respectively, and dyspnea in 3 patients. Bilateral muscle strength was asymmetric in 5 patients. Proximal muscle weakness was predominant in 6 of the 7 patients with upper limb weakness, and 3 of the 5 patients with lower limb weakness. Electromyography showed neurogenic damage in all 7 cases. Five heterozygous variants of the FUS gene were detected in 7 patients, including 2 patients with c.1574C>T(p.P525L), 2 with c.1552A>G(p.R518G), 1 with c.1561C>T(p.R521C), 1 with c.1441delC(p.R481Efs *48), and 1 with both c.1574C>T(p.P525L) and c.430_447del(p.G144_Y149del) variants. The variant c.1441delC(p.R481Efs *48) had not been previously reported. During follow-up, 6 patients died of respiratory failure 6-18 months after onset, with an average of 11.8 months. Conclusions:Patients with FUS gene related ALS have an early age of onset, rapid progression, short survival period, asymmetric limb weakness, and more severe involvement of proximal limbs. The c.1574C>T(p.P525L) is a hotspot mutation, and the novel variant c.1441delC(p.R481Efs *48) enriches the mutation spectrum of the FUS gene.

Objective To identify potential biomarkers and establish a prediction model for chemotherapy-related hepatotoxicity susceptibility based on plasma endogenous metabolites of colorectal cancer(CRC)patients before chemotherapy.Methods The plasma samples of 50 CRC patients before capecitabine chemotherapy and the records of their chemotherapy-related hepatotoxicity during the follow-up were collected.An ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS)was used to perform untargeted metabolomic analysis.Based on bioinformatics analysis,differential analysis,correlation analysis,and random forest were used to screen for hepatotoxicity-related plasma endogenous metabolites.All samples were randomly assigned(7∶3)to training set or test set.A multivariate logistic regression model was established to predict the hepatotoxicity of capecitabine chemotherapy based on the training set data.The prediction effects of the model in the training,test and entire sets were evaluated by receiver operating characteristic(ROC)curve analysis.Results The endogenous metabolites related to hepatotoxicity in the plasma of CRC patients before chemotherapy were mainly lipid endogenous metabolites.A series of potentially important predictive biomarkers for hepatotoxicity susceptibility were identified,including sphingamine-1-phosphate,ceramide,galactose,arachidonic acid,tyrosine,biliverdin,myristic acid,phosphatidylcholine(35∶1),phosphatidylethanolamine(36∶1),and hexadecanoic acid.The area under curve values of the prediction model based on the above biomarkers in the training,test and entire sets were 0.946(95%confidence interval[CI]0.842-1.000),0.920(95%CI 0.720-1.000),and 0.912(95%CI 0.810-0.982),respectively.Conclusion The endogenous metabolites in the plasma of CRC patients before chemotherapy can effectively predict the hepatotoxicity of capecitabine chemotherapy.These hepatotoxicity biomarkers indicate that susceptible patients have characteristics related to lipid metabolism disorders.

Helicobacter pylori(Hp)is a major pathogen that causes peptic ulcer,mucosa-associated tissue lymphoma and gastric cancer.Adhesion colonization is a prerequisite for the pathogenesis of Hp.After infec-tion,Hp first uses urease to neutralize gastric acid,and then it adapts to the environment through motility and chemotactic swimming of flagella.Finally,Hp adheres to gastric epithelial cells through outer membrane pro-teins.Some outer membrane proteins have the biological effect of transporting virulence factors,mediating in-flammation and assisting Hp to produce pathological changes on human body.This paper reviews the mecha-nism of main colonization factors of Hp.

Abstract Breastfeeding has an irreplaceable effect on the growth and development of premature infants and the reduction of complications during hospitalization. In recent years, with the opening of China′s birth policy, the incidence of premature babies has increased, and the corresponding complications have also gradually increased. Breast milk not only carries a rich supply of nutrients, including rich proteins, lipids, sugars to support the normal growth and development of infants, but also contains a large number of immunoglobulins, hormones and other bioactive substances to promote the improvement of body immune function and the development of nervous system. In recent years, many studies have been carried out on the current situation of breast milk operation in breast milk bank, the collection and influencing factors of breast milk, the strategies of breast milk enrichment and its effects on the growth and development of premature infants and complications. Therefore, breast-feeding and intensive breast-feeding can effectively promote the growth and development of premature infants, and reduce the occurrence of complications.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.