OBJECTIVE To establish a determination method for the related substances of LPM3480392, a novel Gi protein-biased opioid receptor(MOR) agonist. METHODS The separation was carried out with Waters Symmetry Shield RP18 (150 mm×4.6 mm, 3.5 μm) by gradient elution method, using a mixture of 0.002 5 mol·L–1 sodium 1-octanesulfonate monohydrate in 0.01 mol·L–1 potassium dihydrogen phosphate-water solution(containing 0.1% triethylamine, adjusted pH to 2.50 with phosphate acid) and acetonitrile as the mobile phase at a flow rate of 1.0 mL·min–1 and the UV detection wavelength was set at 210 nm. RESULTS The chromatographic peaks of LPM3480392 and impurity A, impurity B, impurity C, impurity E and impurity F could be completely separated, the linear relationship of LPM3480392 was good in 0.064 9−5.191 2 μg·mL–1, while impurity A, impurity B, impurity C, impurity E and impurity F showed good linear relationship within 0.066 6−7.610 4 μg·mL–1, 0.166 0−3.794 0 μg·mL–1, 0.209 2−4.463 2 μg·mL–1, 0.167 9−7.672 6 μg·mL–1 and 0.016 4−7.505 7 μg·mL–1, respectively. The recovery rate was within 93.0%−103.2%. CONCLUSION The method is suitable for the determination of related substances in LPM3480392, and can provide valuable reference for the follow-up research and development of LPM3480392.

Objective:To explore the application value of renal artery resistance index in the diagnosist of intra-abdominal hypertension (IAH) in critically ill patients.Methods:89 patients with risk factors of IAH in the intensive care unit of Zhangzhou Hospital Affiliated to Fujian Medical University from February 2022 to June 2022 were retrospective analyzed. The intra-abdominal pressure (IAP) were measured by bladder, and patients divided into IAH group (IAP≥12 mmHg) and non-IAH group (IAP <12 mmHg). The resistance index (RI) of the right renal aorta, segment artery and interlobar artery were measured by color Doppler ultrasound. The difference between the measurement indicators of patients in the IAH and non-IAH groups and the correlation with IAP were analyzed. As for different indicators to predict the diagnostic efficacy of IAH, ROC curve analysis was used to evaluate the effect. And further multivariate logistic regression analysis was to find independent risk predictor.Results:A total of 89 patients were included in the study, including 44 patients with normal IAP and 45 patients diagnosed IAH. There were significant differences in the right renal aorta, segmental artery and interlobar artery RI (all P<0.01). The interlobar artery RI≥0.698 was the highest diagnostic cut-off,area under the curve was 0.914, sensitivity was 82.2%, specificity was 97.7%, and Jordon index was 0.799. The Spearman correlation analysis of IAP and the ultrasonographic measurements revealed a strong correlation between right renal interlobar artery RI and IAP ( r=0.741, P<0.01). The multivariate logistic regression analysis showed that the right renal interlobar artery RI ( OR= 24.472, 95% CI:5.122~116.919, P<0.01) was an independent risk predictor of IAH ( P<0.01). Conclusion:Right renal interlobar artery RI had better diagnostic efficacy of IAH,renal ultrasound could be used as an alternative, non-invasive technique for the diagnosis and follow-up of IAH.

Objective To analyze the hotspots and frontiers of researches related to exercise intervention for spinal curvature abnor-malities in children and adolescents. Methods Articles related to exercise intervention for spinal curvature abnormalities in children and adolescents were re-trieved from CNKI and Web of Science Core Collection,from January,2014 to December,2023.The literatures were analyzed wtih CiteSapce 6.2.R3 in terms of disciplines,countries,institutes and keywords. Results A total of 233 articles were retrived,including 71 articles in Chinese and 162 articles in English.The annual pub-lication volume was on the rise.China was the country with the highest number of publications.South Korea was seen a sudden increase in recent literature.For Chinese,the institutions with the largest number of publication were the Department of Health and Exercise Science in Tianjin University of Sport and Luoyang Orthopedic-Traumatological Hospital of Henan Province(Henan Provincial Orthopedic Hospital).While the institutions with the largest number of publication in English were Marmara University and Hong Kong Polytechnic University.The English literatures covered a wide range of disciplines,including clinical medicine,sports medicine,neurolo-gy and psychology.Common high-frequency keywords in both Chinese and English literatures were idiopathic scoliosis,Cobb's angle and Schroth exercise.The latest bursting words included physical health in Chinese,and health-related quality of life and respiratory muscle strength in English. Conclusion The research popularity related to exercise intervention for spinal curvature abnormality in children and ado-lescents is generally on the rise.The research hotspots focus on four main areas:disease,quality of life,research advances and clinical treatment.More attention should be paid to the effect and dosage of exercise intervention on the respiratory function,as well as the effect of Chinese medicine exercise therapy on pediatric patients with abnormal spinal curvature diseases.Future work should focus on constructing an evidence-based Chinese/West-ern medicine exercise prevention and treatment system in the context of China's national conditions,advancing high-quality randomized controlled trials,strengthening interdisciplinary and international collaborations,and fo-cusing on the development and evaluation of personalized exercise intervention programs.

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.

Background::There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients.Methods::In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12.Results::At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician’s Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs. 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs. 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab. Conclusion::Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.Trial registration::ClinicalTrials.gov, NCT05108766.

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.