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.

ObjectiveTo systematically assess the public health governance capacity in Zhejiang Province, to conduct an in-depth analysis of its strengths and weaknesses, so as to provide scientific basis and strategic recommendations for further enhancement. MethodsA systematic collection of policy documents, public information reports, and research literature related to public health governance capacity in Zhejiang Province from 2002 to 2023 was conducted (encompassing a total of 1 263 policy documents, 138 pieces of information reports and 631 research articles). Based on the evaluation criteria suitable for public health systems previously developed by the research team, the basic status and magnitude of change in public health governance capacity in Zhejiang Province was evaluated. Additionally, normative gap analyses were employed to identify the strengths and weaknesses. ResultsZhejiang Province ranked 4th nationwide in terms of public health governance capacity with a score of 733.4 points (1 000.0-point maximum). The province has effectively implemented the principle of health first (scoring 698.5 points in the assessment of health-first strategy implementation) and attached sufficient importance to health-related goals (scoring 658.2 points in the scientific rationality of goal setting). However, the implementation of inter-departmental coordination and incentive mechanisms only scored 178.7 points, the feasibility of management and monitoring mechanisms scored even lower at only 144.0 points, and the coverage of incentive mechanisms scored 286.0 points. ConclusionZhejiang Province has effectively implemented its health first strategy and attached great importance to health targets, but still needs to strengthen cross-departmental coordination mechanisms and health-oriented incentives.

Anti-CD20 monoclonal antibodies for the treatment of refractory nephrotic syndrome （RNS） in children. The first- generation rituximab is the most widely used in clinical practice； it shows definite efficacy in children with RNS， is recommended by guidelines， particularly for achieving a high remission rate in minimal change nephrosis， and can significantly reduce the cumulative use of glucocorticoids and immunosuppressants. The second-generation ofatumumab has potential as an alternative treatment for patients who are intolerant or resistant to rituximab， while the third-generation obinutuzumab has shown efficacy in complex cases such as rituximab resistance or post-transplant recurrence. However， there is still controversy regarding the optimization of rituximab treatment dosage and whether ofatumumab and obinutuzumab offer greater advantages than rituximab for the treatment of RNS in children. The most common adverse reaction induced by anti-CD20 monoclonal antibodies is infusion reactions， and long-term adverse events mainly include increased risks of sustained immunosuppression and infections. Rituximab has significant economic advantages for the treatment of RNS， but additional pharmacoeconomic research based on China’s healthcare environment is needed to evaluate the cost-effectiveness of ofatumumab and obinutuzumab in this population. Given that the current use of ofatumumab and obinutuzumab in this field is considered off-label use， clinical application should only proceed after a rigorous evaluation of the patient’s benefits and risks.

A recombinant adenovirus(rAd)for expression of Mycobacterium tuberculosis(M.tb)c-di-AMP phosphodiesterase CnpB was constructed,and its induced humoral immune response was detected.The codon-optimized gene of M.tb CnpB was cloned into the adenoviral plasmid pcADV.The recombinant plasmid pcADV-CnpB was transfected into HEK293T cells,and expression was detected with Western blot.The recombinant plasmid pcADV-CnpB and the backbone plasmid were co-transfected into HEK293T cells to obtain the recombinant adenovirus rAd-CnpB.rAd-CnpB was amplified in HEK293T cells,and the target protein expression of rAd-CnpB was detected with Western blot and immunofluorescence.Mice were immunized with rAd-CnpB intranasally,and their sera and bronchoalveolar lavage fluid(BALF)were collected.ELISA was used to detect levels of antigen-specific antibodies.Restriction enzyme digestion and sequencing indicated that the recombinant plasmid pcADV-CnpB was successfully constructed and led to protein expression in eukaryotic cells.rAd-CnpB was packaged and produced in HEK293T cells.After amplification and purification,rAd-CnpB with a titer of 5.53×1010 PFU/mL was obtained.rAd-CnpB led to CnpB expression in HEK293T cells.Intranasal immunization with rAd-CnpB increased levels of IgG and secretory IgA in BALF and led to high levels of IgG in sera.rAd-CnpB,the recombinant adenovirus for expression of c-di-AMP phosphodiesterase CnpB was successfully constructed,and was found to induce antigen-specific humoral and mucosal immune responses through mucosal immunization.Thus,rAd-CnpB may be used in further research on new TB vaccine strategies.

Aim To investigate the effect of cordycepin(COR)on gentamicin(GEN)-induced nephrotoxicity and the molecular mechanism of inhibiting oxidative stress and ferroptosis induced by GEN.Methods The oral SD rats were divided into a control group,GEN group,and GEN+COR group.Following the success-ful setting up of the animal model,the serum creatinine(CR)and urea nitrogen(BUN)levels of rats were measured,and renal tissue injury was assessed using HE staining.In addition,the contents of malondialde-hyde and glutathione in kidney tissues of SD rats in each group were detected,and the expressions of fer-roptosis markers GPX4 and SLC7A11 were analyzed by Western blot.Results Compared with the control group,CR and BUN in GEN-stimulated group signifi-cantly increased(P＜0.01),and the level of CR and BUN was effectively reduced after 50 mg·kg-1 COR oral administration.HE results also showed that COR could alleviate the kidney tissue damage caused by GEN.COR could reverse the increase of malondialde-hyde level and the decrease of glutathione level caused by GEN in rat kidney tissue,and COR could restore the decrease of GPX4 and SLC7A11 protein levels induced by GEN.Conclusion COR can reduce GEN-induced kidney injury by inhibiting oxidative stress and ferrop-tosis.

OBJECTIVE: As an age-related neurodegenerative disease, the prevalence of mild cognitive impairment (MCI) increases with age. Within the framework of traditional Chinese medicine, spleen-kidney deficiency syndrome (SKDS) is recognized as the most frequent MCI subtype. Due to the covert and gradual onset of MCI, in community settings it poses a significant challenge for patients and their families to discern between typical aging and pathological changes. There exists an urgent need to devise a preliminary diagnostic tool designed for community-residing older adults with MCI attributed to SKDS (MCI-SKDS). METHODS: This investigation enrolled 312 elderly individuals diagnosed with MCI, who were randomly distributed into training and test datasets at a 3:1 ratio. Five machine learning methods, including logistic regression (LR), decision tree (DT), naive Bayes (NB), support vector machine (SVM), and gradient boosting (GB), were used to build a diagnostic prediction model for MCI-SKDS. Accuracy, sensitivity, specificity, precision, F1 score, and area under the curve were used to evaluate model performance. Furthermore, the clinical applicability of the model was evaluated through decision curve analysis (DCA). RESULTS: The accuracy, precision, specificity and F1 score of the DT model performed best in the training set (test set), with scores of 0.904 (0.845), 0.875 (0.795), 0.973 (0.875) and 0.973 (0.875). The sensitivity of the training set (test set) of the SVM model performed best among the five models with a score of 0.865 (0.821). The area under the curve of all five models was greater than 0.9 for the training dataset and greater than 0.8 for the test dataset. The DCA of all models showed good clinical application value. The study identified ten indicators that were significant predictors of MCI-SKDS. CONCLUSION The risk prediction index derived from machine learning for the MCI-SKDS prediction model is simple and practical; the model demonstrates good predictive value and clinical applicability, and the DT model had the best performance. Please cite this article as: Ai YT, Zhou S, Wang M, Zheng TY, Hu H, Wang YC, Li YC, Wang XT, Zhou PJ. Development of a machine learning-based risk prediction model for mild cognitive impairment with spleen-kidney deficiency syndrome in the elderly. J Integr Med. 2025; 23(4): 390-397.
Humans ; Cognitive Dysfunction/diagnosis* ; Aged ; Male ; Female ; Machine Learning ; Spleen ; Aged, 80 and over ; Kidney ; Medicine, Chinese Traditional

A recombinant adenovirus(rAd)for expression of Mycobacterium tuberculosis(M.tb)c-di-AMP phosphodiesterase CnpB was constructed,and its induced humoral immune response was detected.The codon-optimized gene of M.tb CnpB was cloned into the adenoviral plasmid pcADV.The recombinant plasmid pcADV-CnpB was transfected into HEK293T cells,and expression was detected with Western blot.The recombinant plasmid pcADV-CnpB and the backbone plasmid were co-transfected into HEK293T cells to obtain the recombinant adenovirus rAd-CnpB.rAd-CnpB was amplified in HEK293T cells,and the target protein expression of rAd-CnpB was detected with Western blot and immunofluorescence.Mice were immunized with rAd-CnpB intranasally,and their sera and bronchoalveolar lavage fluid(BALF)were collected.ELISA was used to detect levels of antigen-specific antibodies.Restriction enzyme digestion and sequencing indicated that the recombinant plasmid pcADV-CnpB was successfully constructed and led to protein expression in eukaryotic cells.rAd-CnpB was packaged and produced in HEK293T cells.After amplification and purification,rAd-CnpB with a titer of 5.53×1010 PFU/mL was obtained.rAd-CnpB led to CnpB expression in HEK293T cells.Intranasal immunization with rAd-CnpB increased levels of IgG and secretory IgA in BALF and led to high levels of IgG in sera.rAd-CnpB,the recombinant adenovirus for expression of c-di-AMP phosphodiesterase CnpB was successfully constructed,and was found to induce antigen-specific humoral and mucosal immune responses through mucosal immunization.Thus,rAd-CnpB may be used in further research on new TB vaccine strategies.

Aim To investigate the effect of cordycepin(COR)on gentamicin(GEN)-induced nephrotoxicity and the molecular mechanism of inhibiting oxidative stress and ferroptosis induced by GEN.Methods The oral SD rats were divided into a control group,GEN group,and GEN+COR group.Following the success-ful setting up of the animal model,the serum creatinine(CR)and urea nitrogen(BUN)levels of rats were measured,and renal tissue injury was assessed using HE staining.In addition,the contents of malondialde-hyde and glutathione in kidney tissues of SD rats in each group were detected,and the expressions of fer-roptosis markers GPX4 and SLC7A11 were analyzed by Western blot.Results Compared with the control group,CR and BUN in GEN-stimulated group signifi-cantly increased(P＜0.01),and the level of CR and BUN was effectively reduced after 50 mg·kg-1 COR oral administration.HE results also showed that COR could alleviate the kidney tissue damage caused by GEN.COR could reverse the increase of malondialde-hyde level and the decrease of glutathione level caused by GEN in rat kidney tissue,and COR could restore the decrease of GPX4 and SLC7A11 protein levels induced by GEN.Conclusion COR can reduce GEN-induced kidney injury by inhibiting oxidative stress and ferrop-tosis.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective:This study aimed to investigate the clinical features and prognosis of Pseudomonas aeruginosa infection in patients with hematologic malignancies.Methods:This study retrospectively analyzed the clinical data of 197 patients with hematologic malignancies complicated with P. aeruginosa infection who were hospitalized in the Department of Hematology from January 01, 2019, to December 31, 2021. Patients were categorized into a susceptible group (CSPA infection group) and a drug-resistant group (CRPA infection group) based on their sensitivity to carbapenems, comparing the differences in clinical features between the two groups, and analyzing the risk factors and prognosis of CRPA infection.Results:Logistic regression analysis revealed that hospitalization days of >50 days ( P=0.010, OR=3.581, 95% CI 1.356-9.457), history of antibiotic exposure ( P=0.008, OR=4.394, 95% CI 1.358-6.238), more than two courses of chemotherapy before infection ( P=0.006, OR=2.911, 95% CI 1.358-6.238) were independent risk factors for developing CRPA. The mortality rates were 12.8% (18/140) and 28.1% (16/57) in patients with CRPA and CSPA, respectively ( P=0.010). Logistic regression analysis revealed that bloodstream infection (BSI) ( P=0.039, OR=5.286, 95% CI 1.091-25.621) was an independent risk factor for hematologic malignancies and death from CRPA infection. Conclusion:Hospitalization for >50 days, history of antibiotic exposure, and >2 courses of chemotherapy before infection were independent risk factors for CRPA infection. Hematologic malignancies with CRPA infection had a high mortality rate, of which BSI was an independent risk factor for 30-day mortality from hematologic malignancies with CRPA infection.