Neonatal diabetes mellitus （NDM） is a rare monogenic disorder primarily caused by insufficient insulin secretion resulting from mutations in the KCNJ11 and ABCC8 genes. Sulfonylureas， represented by glibenclamide， have become the standard therapy for this type of NDM by precisely closing the mutated ATP-sensitive potassium channels in pancreatic β cells， thereby restoring insulin secretion. Clinical studies confirm that sulfonylureas enable over 90% of patients to successfully transition from insulin to oral treatment， achieving long-term stable glycemic control and improving neurological outcomes to a certain extent. In terms of safety， severe hypoglycemia induced by sulfonylureas is relatively rare and gastrointestinal reactions are mild； moreover， sulfonylureas show good long-term tolerability， and have no adverse effects on child growth and development. In the future， by further refining the full-chain management pathway of “rapid genetic diagnosis-early intervention-specialized dosage forms-long-term follow-up”， the clinical application of sulfonylureas is expected to provide NDM patients with an optimized treatment regimen and maximize their health benefits.

Objective To explore the number of peripheral blood regulatory T cells (Treg) in patients with chronic kidney disease (CKD) and its correlation with vascular calcification. Methods This was a single-center, cross-sectional, and observational study. Non-dialysis patients with CKD treated at Zhongshan Hospital, Fudan University from March 2021 to March 2022 were enrolled. Abdominal aortic calcification (AAC) was assessed using lateral abdominal X-ray. Number of Treg and cytokine levels were measured by flow cytometry. Logistic regression analysis was performed to evaluate the related factors for AAC in CKD patients. Results A total of 83 patients were included, aged 17–86 years, with 57 males (68.7%). The distribution of CKD stages was as follows: stage G1 in 7 patients (8.4%), stage G2 in 17 patients (20.5%), stage G3 in 21 patients (25.3%), stage G4 in 19 patients (22.9%), and stage G5 in 19 patients (22.9%). No AAC was observed in patients with stages G1 and G2, while the prevalence of AAC in patients with stages G3, G4, and G5 was 23.8%, 21.1%, and 26.3%, respectively. Compared with stage G1 patients, those with stages G3–5 showed decreased number of peripheral blood Treg and elevated levels of interleukin (IL)-6 and IL-17F (P＜0.05). The area under the receiver operating characteristic curve for number of peripheral blood Treg in predicting AAC in CKD patients was 0.766 (95%CI 0.652–0.879, P＝0.002). Logistic regression analysis showed that decreased number of Treg was related factor for AAC in CKD patients (OR＝0.957, 95%CI 0.922–0.992, P＝0.018). Conclusion As CKD progresses, number of peripheral blood Treg significantly decreases, which is correlated with AAC in CKD patients.

ObjectiveTo systematically compare the differential regulation of the maternal-fetal interface cell lineages and communication networks in the CBA/J×DBA/2 mouse model of recurrent pregnancy loss （RPL） by the two classic therapeutic methods-tonifying the kidney to stabilize the fetus and invigorating the spleen to stabilize the fetus （Shoutai Wan， Juyuan Jian）-of traditional Chinese medicine （TCM） at the single-cell resolution and clarify their modern scientific connotations. MethodsFemale non-pregnant CBA/J mice were caged with male BALB/c （blank group） and DBA/2 （modeling group） mice separately. Pregnant mice in the modeling group were randomly grouped as follows： high/low-dose Shoutai Wan， high/low-dose Juyuan Jian， model （RPL）， and positive control （dydrogesterone）， with 10 mice in each group. Starting from the day after the detection of the vaginal plug， mice were administrated with drugs or an equal volume of normal saline by gavage for 10 consecutive days. After the intervention， the following indicators were measured. ① Macroscopic evaluation： general conditions， uterine wet weight， embryo loss rate， four coagulation parameters ［prothrombin time （PT）， activated partial thromboplastin time （APTT）， fibrinogen （FIB）， and thrombin time （TT）］， and peripheral blood estradiol （E₂） and progesterone （Pg） levels. The decidua with embryos was stained with hematoxylin-eosin （HE） and evaluated by transmission electron microscopy （TEM）. The expression of B-cell lymphoma-2 （Bcl-2）， vascular endothelial growth factor （VEGF）， angiotensin Ⅱ （AngⅡ）， matrix metalloproteinase-2 （MMP-2）， interleukin-6 （IL-6）， leukemia inhibitory factor （LIF）， CXC chemokine ligand 12 （CXCL12）， and microtubule-associated protein 1 light chain 3 homolog （LC3）Ⅰ/Ⅱ was quantified by Western blot. ② Mechanism analysis at the single-cell level： The decidua with embryos from the blank， model， high-dose Shoutai Wan， and high-dose Juyuan Jian groups （6 mice per group， with 3 single-cell samples per group， totaling 24 mice） were analyzed by the BD Rhapsody™ platform， and the whole-cell atlas was drawn by uniform manifold approximation and projection （UMAP） dimensionality reduction clustering combined with the single-cell mouse cell atlas （scMCA）. The differentially expressed genes （DEGs） and cell interaction networks were analyzed via Gene Ontology （GO）， Kyoto Encyclopedia of Genes and Genomes （KEGG）， and CellChat， and the protein-protein interaction （PPI） map of subtype cells was constructed. The CytoTRACE pseudo-temporal analysis was performed to explore the developmental trajectories of core immune cells （natural killer cells， NK cells） from maternal and fetal sources. Results① Pathological and Western blot results indicated that compared with the blank group， the RPL group showed an increase in the embryo loss rate （P<0.01）， down-regulated expression of Bcl-2， LIF， MMP-2， and Vegf in the decidua with embryos （P<0.05）， up-regulated protein levels of CXCL-12， AngⅡ， and IL-6 （P<0.05）， blocked angiogenesis， apoptosis-inflammation imbalance， and coagulation dysfunction. Both prescriptions dose-dependently reduced the abortion rate and restored the angiogenesis-inflammation balance， and Shoutai pill showed superior performance in restoring the E₂ level to the Pg level （P<0.05）. ② Single-cell transcriptome analysis indicated that compared with the blank group， the RPL group showed differences in multiple key cell populations such as decidual cells， trophoblast cells， endothelial cells， erythroblasts， NK cells， and macrophages at the maternal-fetal interface. Immunity and angiogenesis were the key links in RPL. Compared with the RPL group， high-dose Shoutai Wan reversed the changes of NK cells in the embryonic layer （upregulating the mRNA levels of 17 genes and downregulating the mRNA levels of 29 genes） and macrophages （upregulating the mRNA levels of 117 genes and downregulating the mRNA levels of 53 genes） through the regulation of gene expression. High-dose Shoutai pill regulated the immune cells to affect unfolded proteins， cell adhesion， and programmed cell death， thereby promoting decidualization and angiogenesis and modulating embryo-membrane development. High-dose Juyuan Jian regulated the key subgroups of NK cells （up-regulating the mRNA levels of 9 genes and down-regulating the mRNA levels of 17 genes） and macrophages （up-regulating the mRNA levels of 110 genes and down-regulating the mRNA levels of 81 genes）， which affected decidual inflammation and apoptosis and intervened in glycolysis. ③ The pseudo-temporal analysis and communication network indicated that the communication frequency of the RPL group decreased. High-dose Shoutai Wan restored maternal-fetal tolerance through pathways such as NKG2D， CDH5， GDF， and FASLG. High-dose Juyuan Jian enhanced the IL-6/LIFR/JAK/signal transducer and activator of transcription 3 （STAT3） and desmosome/SEMA6/tumor necrosis factor-like weak inducer of apoptosis （TWEAK） signaling to improve endometrial receptivity. The RPL group showed an increased proportion of toxic dNK7， a decreased proportion of reparative dNK4， and blocked embryo fNK1. High-dose Shoutai Wan down-regulated dNK7 and up-regulated dNK4. High-dose Juyuan Jian inhibited the terminal differentiation of dNK7 and up-regulated LILRB1， thus restoring the balance of cytotoxicity and repair. ConclusionBoth the kidney-tonifying and spleen-invigorating methods are effective in treating RPL. NK and macrophages are the key immune cells in the interaction between the embryo and the membrane. The kidney-tonifying method （Shoutai Wan） has an advantage in regulating the phenotypes of unfolded protein， cell adhesion， and programmed cell death， and shows expression characteristics closer to the physiological state in the regulation of NKG2D and CDH5 signals. The spleen-invigorating method （Juyuan Jian） has an advantage in regulating epithelial-mesenchymal transition （EMT）， angiogenesis， and glycolysis and shows higher communication intensity in the IL-6 and LIFR pathways.

Objective:To understand the current status of family resilience in children with autism and explore its influencing factors, providing a basis for developing intervention measures to improve family resilience in these families.Methods:Convenience sampling was used to select children with autism and their caregivers who underwent rehabilitation training at the Department of Child Developmental Behavior, Third Affiliated Hospital of Zhengzhou University from March to September 2023. A cross-sectional survey was conducted using a general information questionnaire, the Chinese version of the Family Resilience Assessment Scale, the Chinese version of the Parenting Burnout Scale, and the Caregiver Stress Scale.Results:A total of 280 questionnaires were distributed, and 271 valid questionnaires were collected. Among the 271 children with autism, 210 were male and 61 were female, with the majority aged 3-5 years old (169 cases). Among the 271 caregivers, 21 were male and 250 were female, with the majority aged 30-39 years old (149 cases). The total score of the Chinese version of the Family Resilience Assessment Scale was (70.59 ± 14.08) points, with scores of (49.96 ± 10.23) points for family communication and problem-solving, (7.13 ± 1.62) points for social resource utilization, and (13.52 ± 3.31) points for maintaining a positive attitude. Multiple linear regression analysis showed that the child′s age, disease duration, reimbursement method, parenting burnout, and caregiver stress were influencing factors of family resilience in children with autism ( t values were -10.40-3.48, all P<0.05). Conclusions:The level of family resilience in children with autism needs improvement. Higher levels of parenting burnout and caregiver stress are associated with lower levels of family resilience. Future interventions should be developed based on these influencing factors to promote the physical and mental health of children with autism and their caregivers.

BACKGROUND:Through scientific research addressing the effect of calcined deer antler slices on promoting the proliferation of bone marrow mesenchymal stem cells,it aims to provide empirical support for the integration and innovation of traditional Chinese medicine and modern regenerative medicine,and promote the widespread application of traditional Chinese medicine in the treatment of skeletal system diseases.OBJECTIVE:To investigate the effect of calcined deer antler slices on bone marrow mesenchymal stem cell proliferation.METHODS:Different calcination samples were prepared by wrapping deer antler slices with materials such as clay,yellow clay,and salted yellow clay,resulting in seven different samples(clay-cotton cloth,yellow clay-cotton cloth,salted yellow clay-cotton cloth,yellow clay-tin foil,salted yellow clay-tin foil,yellow clay-honey roasted,salted yellow clay-honey roasted antler slices).Water-soluble extract content in deer antler slices was determined before and after calcination.CCK-8 assay was used to evaluate the effects of different aqueous extracts of calcined antler slices on the proliferation activity of bone marrow mesenchymal stem cells.RESULTS AND CONCLUSION:(1)Calcination significantly increased the water-soluble extract content of deer antler slices,with the highest content observed in samples treated with yellow clay and honey.(2)Calcined deer antler slices significantly promoted bone marrow mesenchymal stem cell proliferation,among which the yellow clay-honey roasted deer antler slices have the most significant effect on promoting the proliferation of bone marrow mesenchymal stem cells.

Acute lower respiratory infections in infants and young children, caused by respiratory syncytial virus (RSV), represent a significant global public health challenge, characterized by a substantial disease burden. During the winter and spring seasons, various respiratory viruses tend to co-circulate, leading to increased pressure on pediatric healthcare services due to heightened rates of visits and hospitalizations. Currently, there is no approved RSV vaccine available for children worldwide; however, the development and application of long-acting monoclonal antibodies present a promising avenue for the prevention of RSV in this vulnerable population. In June 2024, Tianjin released"Guidelines for the monoclonal antibody of respiratory syncytial virus in Tianjin (2024 version)", which outlines the promotion of monoclonal antibody administration in vaccination clinics throughout the region. The objective of this paper is to provide reference information that may assist in the formulation and implementation of a national RSV immunization strategy.

Objective To analyze the trends of suicide mortality and disease burden among the elderly aged 60 and above in Chongqing from 2012 to 2023,providing evidence for targeted interventions.Methods Death cases of elderly aged 60 and above were extracted from death registration between 2012 and 2023 according to death records(International Statistical Classification of Diseases and Related Health Problems,10th version:X60-X84,Y87).The data were analyzed to calculate indicators such as the mortality rate,standardized mortality rate,years of life lost(YLL)rate,and average years of life lost(AYLL),and the composition ratio of different causes of death with using Excel 2010 and SPSS 26.0.The comparison of mortality rates between male and female,urban and rural area was conducted using the x2 test.The trend changes of the rates were expressed by the annual percentage change(APC)and the average annual percentage change(AAPC).Results From 2012 to 2023,the suicide mortality rate and standardized mortality rate of the elderly aged 60 and above generally showed a downward trend,decreasing by 3.54%and 4.02%,respectively(P<0.05).From 2012 to 2016,the suicide mortality rate increased by an average of 4.53%per year,and from 2016 to 2021,it decreased by an average of 8.91%per year,and both trends were significant(P<0.05).Only in 2020 and 2022,the male suicide mortality rate was significantly higher than that of females(P<0.05).From 2012 to 2023,the suicide mortality rate and standardized mortality rate of males and females decreased by an average of 2.86%,3.44%,4.21%,and 4.69%per year respectively,and the trends were significant(P<0.05).The suicide mortality rate of the elderly aged 60 and above in rural areas was significantly higher than that in urban areas over the years(P<0.05).From 2012 to 2023,the suicide mortality rate and standardized mortality rate in urban areas remained relatively stable(P>0.05),while the suicide mortality rate and standardized mortality rate of the elderly aged 60 and above in rural areas decreased by an average of 3.44%and 4.02%per year respectively,and the trends were significant(P<0.05).The YLL rate and AYLL caused by suicide among the elderly aged 60 and above decreased from 3.03‰ and 18.54 years in 2012 to 2.26‰ and 17.50 years in 2023 respectively,and the AAPC were-4.02%and-0.60%respectively,and the trends were significant(P<0.05).By comparing the composition of deaths by different suicide methods over the years,it was found that the proportion of deaths due to pesticide poisoning showed a downward trend,while the proportions of deaths by hanging,jumping from a height,and drowning showed an upward trend.Conclusion The suicide mortality rate of the elderly aged 60 and above in Chongqing is relatively high.Although demonstrating an overall downward trend,enhanced efforts toward early identification and intervention for elderly suicide should be enhanced.

There is significant inter-individual variation of pharmacokinetics and pharmacody-namics in patients receiving tacrolimus(TAC)for an-ti-rejection therapy,which cause the rejection or toxic action.Based on results of therapeutic drug monitoring and pathophysiological index of trans-plant patients,the individualized dosing regimen can be designed and adjusted by using model in-formed precision dosing(MIPD).The patients'clini-cal outcome can be improved.In the consensus,the different methods of MIPD used for patients re-ceived TAC for anti-rejection therapy were intro-duced,which can be used for the designing and ad-justing doing regimen,predicting adverse drug reac-tion,improving medication adherence and econom-ics during therapy.

Objective:To analyze change trend of disease burden of chronic kidney disease (CKD) mortality between 2012 and 2023 in Chongqing, and provide suggestion for CKD prevention.Methods:The mortality data of CKD were collected from Chongqing death registration between 2012 and 2023 according to International Classification of Diseases 10 th. The data were analyzed to calculate mortality rate, standardized mortality rate, age specific mortality rate, and the rate of years of life lost (YLL) and proportion by using software SPSS 26.0. The mortality rate of CKD between men and women, urban area and rural area were compared by χ2 test. The change trend was described by average annual percent of change (AAPC). Results:The mortality rate and standardized mortality rate of CKD were 7.94/100 000 and 4.63/100 000 respectively in 2012 and 6.70/100 000 and 2.79/100 000 respectively in 2023 in Chongqing. The difference in change of CKD mortality rate was not significant (AAPC=-0.79%, t=-1.60, P=0.273). However, the standardized mortality rate of CKD decreased by 3.59% ( t=-3.98, P=0.003) from 2012 to 2023. The mortality rate of CKD was higher in men than in women in 2014 and 2022, the differences were significant (all P<0.05). The standardized mortality rate of CKD in men and women decreased by 3.17% and 4.11% respectively between 2012 and 2023, the difference was significant (all P<0.05). The mortality rate of CKD had been higher in urban area than in rural area since 2016 (all P<0.05). During this period, the mortality rate and standardized mortality rate of CKD in urban area remained stable, but the mortality rate and standardized mortality rate of CKD in rural area showed average annual decreases of 2.21% and 4.90%, the differences were significant (all P<0.05). The proportion of CKD due to hypertension decreased, but the proportion of CKD due to diabetes and other causes increased. The rate of age standardized YLL of CKD showed an average annual decrease of 2.83%, the differences were significant ( P=0.011). Conclusions:The standardized mortality rate and age standardized YLL of CKD decreased from 2012 to 2023 in Chongqing. Men, urban residents and the elderly are key populations in CKD prevention.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP