Objective:To investigate the clinical features, molecular etiology, and treatment of a family with Treacher Collins Syndrome 2 (TCS2).Methods:Information of the proband (female, 8 years old) including medical history and family history was collected. Physical examination and examinations concerning laboratory, audiology, and radiology were performed on the proband. Physical examination was also performed on the family members. Genomic DNA of proband was extracted for whole exome sequencing, and then the genomic DNA of family members was extracted for Sanger sequencing. POLR1D and TCS2 related literatures published before August 31,2023 were searched and sifted in PubMed and CKNI databases. The clinical characteristics of TCS2 were summarized. Results:The proband had poor hearing since childhood, with pure tone audiometry indicating conductive hearing loss. She had a smaller jaw, bilateral preauricular fistulas and cup-shaped ear deformities. Temporal bone CT scan revealed deformities in the left external ear canal, bilateral middle ear and inner ear. A bone-conduction hearing aid device was surgically implanted, resulting in restoration of almost normal hearing levels. The proband′s mother also had a slightly smaller jaw. Genetic analysis revealed a novel heterozygous variant NM_015972.4:c.38_47del in the POLR1D gene in the proband, which was inherited from her mother. A review of the literature revealed no clear evidence of genotype-phenotype correlation in TCS2. Conclusions:Molecular diagnosis plays a vital role in the diagnosis of TCS2. Patients with normal facial phenotype may be carriers of pathogenic variants in the POLR1D gene and have the risk of passing it to the offsprings with complete penetrance. Proper bone conductive hearing devices can improve the quality of life of TCS2 patients.

Objective To investigate the effect of individual exercise training on the rehabilitation of patients with coronary heart disease(CHD)after percutaneous coronary intervention(PCI).Methods A total of 81 patients between January 2021 and December 2023 were randomly allocated into an observation group(n=41)and a control group(n=40)using a simple random number Tab.method.The control group received routine post-operative rehabilitation intervention,while the observation group received individualized exercise training as the core component of cardiac rehabilitation intervention.The study compared the effects of rehabilitation,cardiac function parameters[left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDD)],exercise endurance measures[6-minute walking distance(6MWD)],and quality of life assessed by Seattle Angina Pecina Scale(SAQ)scores between the two groups before and after a three-month intervention period.Results The total recovery response rate in the observation group was higher than that in the control group(P＜0.05).LVEF,LVEDD,6 MWD,maximum exercise load and SAQ scales(P＞0.05),LVEF were higher than before intervention(t=3.345,2.480,3.165,5.016,2.059,4.582,4.443,3.353,P＜0.05),and LVEDD was lower than before intervention(t=3.335,P＜0.05).Conclusion The individualized exercise training-based cardiac rehabili-tation program demonstrates potential for enhancing cardiac function and exercise endurance in patients with CHD following PCI,thereby improving their overall quality of life.This finding holds significant clinical implications.

Objective To study the causes of two Chinese families with Branchio-oto syndrome.Methods The clinical data of two families were collected,and the pathogenic genes and variants of Branchio-oto syndrome were screened and verified by whole exome sequencing and Sanger sequencing.Results Two proband patients were diagnosed with Branchio-oto syndrome.Proband 1 presented with preauricular and anterior cervical fistulas,as well as congenital severe sensorineural hearing loss.On the other hand,proband 2 displayed a preauricular fistula and an anterior cervical cyst.At the age of 5,progressive deterioration of binaural hearing was observed,leadingtothe cur-rent diagnosis of severe mixed deafness.Genetic analysis showed that proband 1 and 2 carried nonsense variants of EYA1 gene:NM_000503.6:c.1408G＞T(p.Glu470Ter),and c.889C＞T(p.Arg297Ter).According to the guide-lines of the American College of Medical Genetics and Genomics(ACMG),the above variants were rated as patho-genic variants.After reviewing the literature,the c.1408G＞T variant had not been previously reported,and the c.889C＞T is a known variant.Conclusion The variants c.1408G＞T(p.Glu470Ter)and c.889C＞T(p.Arg297Ter)of EYA1 gene are the cause of these two families with Branchio-oto syndrome.The first report of c.1408G＞T broadens the mutational spectrum of EYA1 gene and provids a clinical reference for the diagnosis of Branchio-oto syndrome.

Objective To explore the efficacy and safety of platelet-derived growth factor(PDGF)combined with allograft bone transplantation in the treatment of spinal tuberculosis.Methods A total of 177 patients with lumbar tuberculosis admitted to the 4th People's Hospital of Qinghai Province from August 2018 to August 2023 were selected as the research subjects.Patients were divided into control group(n=49)and observation group(n=128)based on the source of the transplanted bone.All patients underwent at least 2 weeks of standard quadruple anti-tuberculosis chemotherapy before surgery.Patients in the control group received PDGF combined with autograft bone transplantation,while patients in the observation group received PDGF combined with allograft bone transplantation.The surgical duration,intraoperative blood loss,and length of hospital stay of patients in the two groups were recorded;the erythrocyte sedimentation rate(ESR)and serum C-reactive protein(CRP)levels of patients in the two groups were compared before surgery and at 1,3,6 months after surgery.Preoperative CT and magnetic resonance imaging(MRI)examinations were performed,and postoperative CT and MRI were performed after bone fusion was completed to compare the changes in Cobb angle before and after surgery.The visual analogue scale(VAS)was used to assess the pain degree in the lumbar region before surgery and at 1,3,6 months after surgery.The VAS scores of patients in the two groups,VAS scores of male patients in the two groups,and VAS scores of female patients in the two groups were compared before and after surgery,respectively.Results There was no statistically significant difference in surgical duration and length of hospital stay between the observation group and the control group(P＞0.05).The intraoperative blood loss of patients in the observation group was significantly less than that in the control group(P＜0.05).There was no statistically significant difference in Cobb angle before and after surgery between the two groups(P＞0.05).The postoperative Cobb angle significantly decreased in both groups when compared to preoperative values(P＜0.05).The VAS scores of patients in both groups decreased sequentially before surgery and at 1,3,6 months after surgery,with statistically significant differences in intra-group pairwise comparisons(P＜0.05).The VAS scores of male patients in both groups decreased sequentially before surgery and at 1,3,6 months after surgery,with statistically significant differences in intra-group pairwise comparisons(P＜0.05).The VAS scores of female patients in both groups also decreased sequentially before surgery and at 1,3,6 months after surgery,with statistically significant differences in intra-group pairwise comparisons(P＜0.05).There was no statistically significant difference in VAS scores between the observation group and the control group before surgery and at 1,6 months after surgery(P＞0.05);the VAS score of patients in the observation group was significantly lower than that in the control group at 3 months after surgery(P＜0.05).There was no statistically significant difference in VAS scores between male patients in the observation group and male patients in the control group before surgery and at 1,3,6 months after surgery(P＞0.05);the VAS score of male patients in the observation group was significantly lower than that in the control group at 3 months after surgery(P＜0.05).There was no statistically significant difference in VAS scores between female patients in the observation group and female patients in the control group before surgery and at 1,6 months after surgery(P＞0.05);the VAS score of female patients in the observation group was significantly lower than that in the control group at 3 months after surgery(P＜0.05).The ESR of patients in both groups decreased sequentially before surgery and at 1,3,6 months after surgery,with statistically significant differences in intra-group pairwise comparisons(P＜0.05).The serum CRP levels of patients in both groups also decreased sequentially before surgery and at 1,3,6 months after surgery,with statistically significant differences in intra-group pairwise comparisons(P＜0.05).There was no statistically significant difference in ESR between the observation group and the control group before surgery and at 1,3,6 months after surgery(P＞0.05).There was no statistically significant difference in serum CRP level between the observation group and the control group before surgery and at 1,6 months after surgery(P＞0.05);the serum CRP level of patients in the observation group was significantly higher than that in the control group at 3 months after surgery(P＜0.05).Conclusion The effect of PDGF combined with allograft bone transplantation in the treatment of spinal tuberculosis is comparable to that of autograft bone transplantation,but PDGF combined with allograft bone transplantation can significantly reduce postoperative pain degree,improve patient comfort,avoid additional damage caused by autograft bone transplantation,and reduce the physical burden on patients.It can be considered a safe and reliable surgical method for bone grafting in lumbar tuberculosis surgery.

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.

Objective To investigate the distribution and antimicrobial resistance profiles of the common pathogens isolated from urine from 2015 to 2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods The bacterial strains were isolated from urine and identified routinely in 51 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Antimicrobial susceptibility was determined by Kirby-Bauer method,automatic microbiological analysis system and E-test according to the unified protocol.Results A total of 261 893 nonduplicate strains were isolated from urine specimen from 2015 to 2021,of which gram-positive bacteria accounted for 23.8％(62 219/261 893),and gram-negative bacteria 76.2％(199 674/261 893).The most common species were E.coli(46.7％),E.faecium(10.4％),K.pneumoniae(9.8％),E.faecalis(8.7％),P.mirabilis(3.5％),P.aeruginosa(3.4％),SS.agalactiae(2.6％),and E.cloacae(2.1％).The strains were more frequently isolated from inpatients versus outpatients and emergency patients,from females versus males,and from adults versus children.The prevalence of ESBLs-producing strains in E.coli,K.pneumoniae and P.mirabilis was 53.2％,52.8％and 37.0％,respectively.The prevalence of carbapenem-resistant strains in E.coli,K.pneumoniae,P.aeruginosa and A.baumannii was 1.7％,18.5％,16.4％,and 40.3％,respectively.Lower than 10％of the E.faecalis isolates were resistant to ampicillin,nitrofurantoin,linezolid,vancomycin,teicoplanin and fosfomycin.More than 90％of the E.faecium isolates were ressitant to ampicillin,levofloxacin and erythromycin.The percentage of strains resistant to vancomycin,linezolid or teicoplanin was＜2％.The E.coli,K.pneumoniae,P.aeruginosa and A.baumannii strains isolated from ICU inpatients showed significantly higher resistance rates than the corresponding strains isolated from outpatients and non-ICU inpatients.Conclusions E.coli,Enterococcus and K.pneumoniae are the most common pathogens in urinary tract infection.The bacterial species and antimicrobial resistance of urinary isolates vary with different populations.More attention should be paid to antimicrobial resistance surveillance and reduce the irrational use of antimicrobial agents.

Objective To understand the distribution and changing resistance profiles of clinical isolates of Enterococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Enterococcus according to the unified protocol of CHINET program by automated systems,Kirby-Bauer method,or E-test strip.The results were interpreted according to the Clinical & Laboratory Standards Institute(CLSI)breakpoints in 2021.WHONET 5.6 software was used for statistical analysis.Results A total of 124 565 strains of Enterococcus were isolated during the 7-year period,mainly including Enterococcus faecalis(50.7％)and Enterococcus faecalis(41.5％).The strains were mainly isolated from urinary tract specimens(46.9％±2.6％),and primarily from the patients in the department of internal medicine,surgery and ICU.E.faecium and E.faecalis strains showed low level resistance rate to vancomycin,teicoplanin and linezolid(≤3.6％).The prevalence of vancomycin-resistant E.faecalis and E.faecium was 0.1％and 1.3％,respectively.The prevalence of linezolid-resistant E.faecalis increased from 0.7％in 2015 to 3.4％in 2021,while the prevalence of linezolid-resistant E.faecium was 0.3％.Conclusions The clinical isolates of Enterococcus were still highly susceptible to vancomycin,teicoplanin,and linezolid,evidenced by a low resistance rate.However,the prevalence of linezolid-resistant E.faecalis was increasing during the 7-year period.It is necessary to strengthen antimicrobial resistance surveillance to effectively identify the emergence of antibiotic-resistant bacteria and curb the spread of resistant pathogens.

Objective To examine the changing antimicrobial resistance profile of Enterobacter spp.isolates in 53 hospitals across China from 2015 t0 2021.Methods The clinical isolates of Enterobacter spp.were collected from 53 hospitals across China during 2015-2021 and tested for antimicrobial susceptibility using Kirby-Bauer method or automated testing systems according to the CHINET unified protocol.The results were interpreted according to the breakpoints issued by the Clinical & Laboratory Standards Institute(CLSI)in 2021(M100 31st edition)and analyzed with WHONET 5.6 software.Results A total of 37 966 Enterobacter strains were isolated from 2015 to 2021.The proportion of Enterobacter isolates among all clinical isolates showed a fluctuating trend over the 7-year period,overall 2.5％in all clinical isolates amd 5.7％in Enterobacterale strains.The most frequently isolated Enterobacter species was Enterobacter cloacae,accounting for 93.7％(35 571/37 966).The strains were mainly isolated from respiratory specimens(44.4±4.6)％,followed by secretions/pus(16.4±2.3)％and urine(16.0±0.9)％.The strains from respiratory samples decreased slightly,while those from sterile body fluids increased over the 7-year period.The Enterobacter strains were mainly isolated from inpatients(92.9％),and only(7.1±0.8)％of the strains were isolated from outpatients and emergency patients.The patients in surgical wards contributed the highest number of isolates(24.4±2.9)％compared to the inpatients in any other departement.Overall,≤ 7.9％of the E.cloacae strains were resistant to amikacin,tigecycline,polymyxin B,imipenem or meropenem,while ≤5.6％of the Enterobacter asburiae strains were resistant to these antimicrobial agents.E.asburiae showed higher resistance rate to polymyxin B than E.cloacae(19.7％vs 3.9％).Overall,≤8.1％of the Enterobacter gergoviae strains were resistant to tigecycline,amikacin,meropenem,or imipenem,while 10.5％of these strains were resistant to polycolistin B.The overall prevalence of carbapenem-resistant Enterobacter was 10.0％over the 7-year period,but showing an upward trend.The resistance profiles of Enterobacter isolates varied with the department from which they were isolated and whether the patient is an adult or a child.The prevalence of carbapenem-resistant E.cloacae was the highest in the E.cloacae isolates from ICU patients.Conclusions The results of the CHINET Antimicrobial Resistance Surveillance Program indicate that the proportion of Enterobacter strains in all clinical isolates fluctuates slightly over the 7-year period from 2015 to 2021.The Enterobacter strains showed increasing resistance to multiple antimicrobial drugs,especially carbapenems over the 7-year period.

Objective To understand the changing distribution and antimicrobial resistance profiles of Proteus,Morganella and Providencia in hospitals across China from January 1,2015 to December 31,2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods Antimicrobial susceptibility testing was carried out following the unified CHINET protocol.The results were interpreted in accordance with the breakpoints in the 2021 Clinical & Laboratory Standards Institute(CLSI)M100(31 st Edition).Results A total of 32 433 Enterobacterales strains were isolated during the 7-year period,including 24 160 strains of Proteus,6 704 strains of Morganella,and 1 569 strains of Providencia.The overall number of these Enterobacterales isolates increased significantly over the 7-year period.The top 3 specimen source of these strains were urine,lower respiratory tract specimens,and wound secretions.Proteus,Morganella,and Providencia isolates showed lower resistance rates to amikacin,meropenem,cefoxitin,cefepime,cefoperazone-sulbactam,and piperacillin-tazobactam.For most of the antibiotics tested,less than 10％of the Proteus and Morganella strains were resistant,while less than 20％of the Providencia strains were resistant.The prevalence of carbapenem-resistant Enterobacterales(CRE)was 1.4％in Proteus isolates,1.9％in Morganella isolates,and 15.6％in Providencia isolates.Conclusions The overall number of clinical isolates of Proteus,Morganella and Providencia increased significantly in the 7-year period from 2015 to 2021.The prevalence of CRE strains also increased.More attention should be paid to antimicrobial resistance surveillance and rational antibiotic use so as to prevent the emergence and increase of antimicrobial resistance.

Objective To understand the changing distribution and antimicrobial resistance profiles of Klebsiella strains in 52 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Antimicrobial susceptibility testing was carried out according to the unified CHINET protocol.The susceptibility results were interpreted according to the breakpoints in the Clinical & Laboratory Standards Institute(CLSI)M100 document.Results A total of 241,549 nonduplicate Klebsiella strains were isolated from 2015 to 2021,including Klebsiella pneumoniae(88.0％),Klebsiella aerogenes(5.8％),Klebsiella oxytoca(5.7％),and other Klebsiella species(0.6％).Klebsiella strains were mainly isolated from respiratory tract(48.49±5.32)％.Internal medicine(22.79±3.28)％,surgery(17.98±3.10)％,and ICU(14.03±1.39)％were the top 3 departments where Klebsiella strains were most frequently isolated.K.pneumoniae isolates showed higher resistance rate to most antimicrobial agents compared to other Klebsiella species.Klebsiella isolates maintained low resistance rates to tigecycline and polymyxin B.ESBLs-producing K.pneumoniae and K.oxytoca strains showed higher resistance rates to all the antimicrobial agents tested compared to the corresponding ESBLs-nonproducing strains.The K.pneumoniae and carbapenem-resistant K.pneumoniae(CRKP)strains isolated from ICU patients demonstrated higher resistance rates to majority of the antimicrobial agents tested than the strains isolated from non-ICU patients.The CRKP strains isolated from adult patients had higher resistance rates to most of the antimicrobial agents tested than the corresponding CRKP strains isolated from paediatric patients.Conclusions The prevalence of carbapenem-resistant strains in Klebsiella isolates increased greatly from 2015 to 2021.However,the Klebsiella isolates remained highly susceptible to tigecycline and polymyxin B.Antimicrobial resistance surveillance should still be strengthened for Klebsiella strains.