Clopidogrel effectively inhibits platelet aggregation in response to ADP by irreversibly binding to the platelet P2Y₁₂ receptor through its active metabolite. However, the observed discrepancies between the pharmacokinetics (PK) and pharmacodynamics (PD) of clopidogrel present substantial challenges in individualizing of antiplatelet therapy. To address these challenges, a robust liquid chromatography-tandem mass spectrometry method has been developed to facilitate the real-time assessment of platelet P2Y₁₂ receptor occupancy. This method has been validated in animal models, providing a reliable link between individual PK profiles and PD effects. Target receptor occupancy offers a comprehensive overview of interindividual variations in clopidogrel metabolism, regulation of P2Y₁₂ receptor expression, and platelet turnover. Moreover, it directly correlates with the inhibitory effect on platelet aggregation. The levels of platelet P2Y₁₂ occupancy accurately reflect the extent of clinical factors influencing the PD of clopidogrel, including dosage, drug-drug interactions (DDI), and type 2 diabetes mellitus (T2DM). As a normalized metric, platelet P2Y₁₂ occupancy not only serves potential as a diagnostic tool for personalized clopidogrel therapy but also aids in elucidating the role of the P2Y₁₂ signaling pathway in cases of abnormal on-treatment platelet reactivity.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units，and the top five bacteria were Staphylococcus aureus（ n=1 147，36.3%），coagulase-negative Staphylococci（ n=928，29.3%）， Enterococcus faecalis（ n=369，11.7%）， Enterococcus faecium（ n=296，9.4%）and alpha-hemolyticus Streptococci（ n=192，6.1%）. The detection rates of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）were 26.4%（303/1 147）and 66.7%（619/928），respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome，rifampin，compound sulfamethoxazole，linezolid，minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%（2/369），and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions（ χ2=14.578， P=0.002），while the detection rate of MRCNS in northern China was significantly higher than that in other regions（ χ2=15.195， P=0.002）. The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals（ χ2=13.519 and 12.136， P<0.001）. The detection rates of MRSA and MRCNS in economically more advanced regions（per capita GDP≥92 059 Yuan in 2022）were higher than those in economically less advanced regions（per capita GDP<92 059 Yuan）（ χ2=9.969 and 7.606， P=0.002和0.006）. Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China， Staphylococci is the most common while the MRSA incidence decreases continuously with time；the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China，with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.

Recent studies have shown that stress can substantially facilitate breast cancer metastasis,which can be reduced by nonselective β1/β2-adrenergic receptor(β1/β2-AR)blocker.However,several side effects were identified.Thus,it is extremely warranted to explore more effective and better-tolerated β2-AR blocker.Currently,we demonstrated that baicalin(BA),a major bioactive component of Scutellaria bai-calensis Georgi,could significantly attenuate stress hormones especially epinephrine(Epi)-induced breast cancer cell migration and invasion in vitro.Mechanistically,we identified that β2-AR was a direct target of BA via the drug affinity responsive target stability(DARTS)combined with mass spectrum assay,and BA photoaffinity probe with pull-down assay,which was further confirmed by a couple of bio-physical and biochemical assays.Furthermore,we demonstrated that BA could directly bind to the Phe-193 and Phe-289 of β2-AR,subsequently inhibit cyclic adenosine monophosphate-protein kinase A-focal adhesion kinase(cAMP-PKA-FAK)pathway,and thus impede epithelial-mesenchymal transition(EMT),thereby hindering the metastatic progression of the chronic stress coupled with syngeneic and xenograft in vivo orthotopic and tail vein mouse model.These findings firstly identify BA as a potential β2-AR inhibitor in the treatment of stress-induced breast cancer metastasis.

Objective To investigate the Carabelli's traits on permanent maxillary molars in Han Chinese college students.Methods Intraoral photos and plaster models from 803 Han Chinese college students were observed and the Carabelli's traits on permanent maxillary molars were categorized by the Arizona State University Dental Anthropology System.Chi-square tests were performed for the comparison of the differences between male and female,permanent maxillary first and second molars.Kendall's tau-b correlation analy-ses were performed for the correlation between bilateral antimeric molars.Results The frequencies of Carabelli's traits on permanent maxillary first and second molars were 37.61％and 3.99％respectively,46.73％and 6.30％in males,27.95％and 1.54％in females,which were statistically significant between permanent maxillary first and second molars(P＜0.01),male and female(P＜0.01).In the positive expression,the low-grade expression(ASUDAS 1-4)was predominant and accounted for 67.37％and 59.52％on the perma-nent maxillary first and second molars.The correlation between bilateral antimeric teeth were statistically significant on permanent max-illary first molars(tau-b=0.756,P＜0.01)and second molars(tau-b=0.477,P＜0.01).Conclusion The Carabelli's traits on perma-nent maxillary molars in Han Chinese college students mostly occur on permanent maxillary first molars with low-grade expression,and understanding this has great anthropological and clinical significance.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Objective:To summarize the clinical and genetic characteristics of early-onset spinocerebellar ataxia type 5 (SCA5) caused by SPTBN2 gene mutation. Methods:The clinical and genetic data of a child with early-onset SCA5 diagnosed in the Department of Children′s Rehabilitation, Women and Children′s Hospital Affiliated to Qingdao University in February 2022 were retrospectively analyzed. The literatures related to early-onset SCA5 in major databases at home and abroad were retrieved and summarized.Results:The patient, a 4 years and 1 month old girl, was admitted to hospital because of "unable to stand independently at 2 years and 3 months", primarily presented with developmental delay, ataxia, hypotonia, and tendon hyperreflexia during infancy. Progressive cerebellar atrophy was observed on brain magnetic resonance imaging. A de novo heterozygous mutation of the SPTBN2 c.793G>C(p.Asp265His) was identified in the patient. Following hospitalization, the child received comprehensive rehabilitation therapy encompassing physical, occupational, language, educational interventions as well as bicycle ergometer training and transcranial magnetic stimulation. The patient was followed-up for more than 1 year to 4 years and 1 month old, whose motor function, cognitive abilities, and language skills were improved to some extent. A total of 13 English articles and 1 Chinese article were retrieved from the databases. A total of 20 early-onset SCA5 patients have been reported, with onset ages all within 12 months. Infants exhibited decreased muscle tone and delayed motor milestones, with the main clinical manifestations of ataxia, generalized developmental delay, and cerebellar atrophy. The previously reported cases involved 11 mutation sites in the SPTBN2 gene, and the main types of mutations were de novo missense mutations. The mutation site in this case has not been reported in the previous literature. Conclusions:Early-onset SCA5 is a rare autosomal dominant disorder caused by heterozygous mutations in the SPTBN2 gene. The main clinical manifestations include ataxia from infancy, developmental retardation and cerebellar atrophy. Early rehabilitation intervention can improve the degree of the dysfunction.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical bacterial isolates from bloodstream infections in China in 2021.Methods:The clinical bacterial strains isolated from blood culture from member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS) were collected during January 2021 to December 2021. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical Laboratory Standards Institute (CLSI). WHONET 5.6 was used to analyze data.Results:During the study period, 11 013 bacterial strains were collected from 51 hospitals, of which 2 782 (25.3%) were Gram-positive bacteria and 8 231 (74.7%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (37.6%), Klebsiella pneumoniae (18.9%), Staphylococcus aureus (9.8%), coagulase-negative Staphylococci (6.3%), Pseudomonas aeruginosa (3.6%), Enterococcus faecium (3.6%), Acinetobacter baumannii (2.8%), Enterococcus faecalis (2.7%), Enterobacter cloacae (2.5%) and Klebsiella spp (2.1%). The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus aureus were 25.3% and 76.8%, respectively. No glycopeptide- and daptomycin-resistant Staphylococci was detected; more than 95.0% of Staphylococcus aureus were sensitive to ceftobiprole. No vancomycin-resistant Enterococci strains were detected. The rates of extended spectrum B-lactamase (ESBL)-producing isolated in Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were 49.6%, 25.5% and 39.0%, respectively. The prevalence rates of carbapenem-resistance in Escherichia coli and Klebsiella pneumoniae were 2.2% and 15.8%, respectively; 7.9% of carbapenem-resistant Klebsiella pneumoniae was resistant to ceftazidime/avibactam combination. Ceftobiprole demonstrated excellent activity against non-ESBL-producing Escherichia coli and Klebsiella pneumoniae. Aztreonam/avibactam was highly active against carbapenem-resistant Escherichia coli and Klebsiella pneumoniae. The prevalence rate of carbapenem-resistance in Acinetobacter baumannii was 60.0%, while polymyxin and tigecycline showed good activity against Acinetobacter baumannii (5.5% and 4.5%). The prevalence of carbapenem-resistance in Pseudomonas aeruginosa was 18.9%. Conclusions:The BRICS surveillance results in 2021 shows that the main pathogens of blood stream infection in China are gram-negative bacteria, in which Escherichia coli is the most common. The MRSA incidence shows a further decreasing trend in China and the overall prevalence of vancomycin-resistant Enterococci is low. The prevalence of Carbapenem-resistant Klebsiella pneumoniae is still on a high level, but the trend is downwards.

Radical pelvic surgery is a surgical method mainly used to treat tumors in the pelvic cavity, and erectile dysfunction (ED) is a common sexual dysfunction after surgery. The incidence of ED after radical pelvic surgery is not uniformly understood due to differences in surgical approaches and methods of investigation. The main causes of postoperative ED include intraoperative neurovascular injury, psychosomatic factors and preoperative patient characteristics, with intraoperative injury to the neurovascular bundle being the most common. Studies have shown that the occurrence of postoperative ED can be prevented by active intervention, but still lack of effective treatment measures. This article reviews and summarizes the clinical epidemiological features and research progress in recent years on ED after radical pelvic surgery, and discusses specific measures for the prevention and treatment of postoperative ED.

Objective:To explore any effect of the single- and dual-task treadmill training on the functioning of children with bilateral spastic cerebral palsy.Methods:Fifty children with bilateral spastic cerebral palsy were randomly divided into a single-task treadmill training group (the control group, n=25) and a dual-task treadmill training group (the observation group, n=25). All of the children also received routine rehabilitation training, and the control and observation groups also conducted single- and dual-task treadmill training in addition to the routine rehabilitation training, respectively. Before and after 2 months of treatment, each child′s gross motor functioning was quantified using sections D (standing) and E (walking, running and jumping) of the Gross Motor Function Measurement-88 (GMFM-88) instrument. Balance was quantified using the Pediatric Balance Scale (PBS) and walking mobility was quantified using a 1 minute walking test (1MWT). Modified and dual task Timed Up and Go (mTUG) tests and dual-task effects (DTE) tests were also administered. Results:There were no significant differences in average test scores between the two groups before the treatment. After the treatment significant improvement was observed in both groups. There was no significant difference between the two groups in terms of average GMFM-88, PBS and 1MWT scores, but significantly greater improvement was observed in the average dual-task mTUG and DTE results of the observation group.Conclusion:Both single- and dual-task treadmill training are effective supplements to routine rehabilitation training for children with bilateral spastic cerebral palsy. Dual-task treadmill training is more effective than the single-task version.

Objective To preliminarily study and establish a method for measurement of the transuranic nuclide ²⁴¹Am in fecal samples, and to provide technical support for internal radiation monitoring of staff. Methods Fecal samples were collected with a self-made stool sampler and treated with a self-made carbonization and ashing furnace. DGA resin was used to separate and purify ²⁴¹Am from fecal samples. With ²⁴³Am as the tracer, the orthogonal method was used for condition optimization. Results The optimum conditions for separation and purification were: the acidity of HNO₃ added into the column, 6 mol/L; column flow rate, 0.6 mL/min; and the volume of analytical solution,12 mL. The method based on inductively coupled plasma mass spectrometry showed a detection limit of 9.79×10⁻⁴ Bq for ²⁴¹Am in fecal samples, which was satisfactory and feasible. Conclusion This method fills the vacancy of ²⁴¹Am measurement in fecal samples to some extent, which is of practical significance for internal radiation monitoring and protection for analysts.