OBJECTIVES: To evaluate the safety and efficacy of thiotepa (TT)-containing conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) in children with inborn errors of immunity (IEI). METHODS: Clinical data of 22 children with IEI who underwent HSCT were retrospectively reviewed. Survival after HSCT was estimated using the Kaplan-Meier method. RESULTS: Nine patients received a traditional conditioning regimen (fludarabine + busulfan + cyclophosphamide/etoposide) and underwent peripheral blood stem cell transplantation (PBSCT). Thirteen patients received a TT-containing modified conditioning regimen (TT + fludarabine + busulfan + cyclophosphamide), including seven PBSCT and six umbilical cord blood transplantation (UCBT) cases. Successful engraftment with complete donor chimerism was achieved in all patients. Acute graft-versus-host disease occurred in 12 patients (one with grade III and the remaining with grade I-II). Chronic graft-versus-host disease occurred in one patient. The incidence of EB viremia in UCBT patients was lower than that in PBSCT patients (P<0.05). Over a median follow-up of 36.0 months, one death occurred. The 3-year overall survival (OS) rate was 100% for the modified regimen and 88.9% ± 10.5% for the traditional regimen (P=0.229). When comparing transplantation types, the 3-year OS rates were 100% for UCBT and 93.8% ± 6.1% for PBSCT (P>0.05), and the 3-year event-free survival rates were 100% and 87.1% ± 8.6%, respectively (P>0.05). CONCLUSIONS TT-containing conditioning for allogeneic HSCT in children with IEI is safe and effective. Both UCBT and PBSCT may achieve high success rates.
Humans ; Retrospective Studies ; Transplantation Conditioning/methods* ; Thiotepa/therapeutic use* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child, Preschool ; Infant ; Child ; Transplantation, Homologous ; Graft vs Host Disease ; Adolescent

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Pharmaceutical cocrystals is an advanced technology to improve the physicochemical and biological properties of drugs. However, there are few studies on the in vivo metabolism of pharmaceutical cocrystals. In this study, the pharmacokinetics of wogonin cocrystal in normal rats was further studied on the basis of the previous preparation of wogonin-aloperine cocrystal. Firstly, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established for simultaneous determination of wogonin and its metabolite wogonoside in rat plasma, and to investigate the methodology. The method was applied to the pharmacokinetic study of wogonin-aloperine cocrystal (Wog-Alop) in rats. The results showed that wogonin and its metabolite wogonoside had a good linear relationship in the range of 1-800 ng·mL^-1, and the precision, accuracy, matrix effect and stability in this range met the requirements of biological analysis. Compared with direct administration of wogonin, the C_max of wogonin and its metabolite in rats increased to 7.44-fold and 9.15-fold, AUC_0-t increased to 1.67-fold and 3.72-fold, and oral bioavailability of wogonin increased to 187.66% after cocrystal administration. Wog-Alop cocrystal can significantly improve the C_max, AUC, and oral bioavailability of wogonin and its metabolite, which provides a new perspective for the clinical application of wogonin. This study was approved by the Experimental Animal Ethics Review Committee of Beijing University of Chinese Medicine (approval number: BUCM-2023032307-1148).

Photodynamic therapy is an emerging cancer therapy with clinical prospects, which plays a specific role in the tumor site and causes less harm to the human body. However, the toxicity of small molecules of hydrophobic photosensitizer, the tumor hypoxia microenvironment, and the biodegradability of nano-carrier systems affect its antitumor efficacy and metabolic clearance in vivo. In this paper, hexachloroplatinic acid was used as a novel oxidizing agent to initiate oxidative polymerization of pyrrole/amino pyrrole to achieve the amino functionalization; further reduced platinum acid anion in the nanostructures into platinum nanoclusters by sodium borohydride as a reducing agent to fabricate platinum nanocluster-doped polypyrrole nanoparticles (PtPPy); and finally, this functional nanoparticles delivering meso-tetra (4-carboxyphenyl) porphine (TCPP) were obtained by amide-bonded coupling of photosensitizers TCPP drug (PtPPy@T). The nanomedicine had a spherical structure, uniform morphology, a particle size of 91.93 ± 13.45 nm, and a zeta potential of -18.39 ± 1.4 mV. Experiments demonstrated that PtPPy@T could react with hydrogen peroxide overexpressed in the tumor to generate a large amount of oxygen, which could relieve the tumor hypoxia microenvironment, and at the same time, provided a sufficient substrate for the subsequent PDT; using 658 nm laser irradiation, the photodynamic effect of PtPPy@T was activated, which catalyzed the conversion of oxygen to singlet oxygen, thus triggering oxidative damage and inducing apoptosis in tumor cells; experimental studies showed that the PtPPy@T nanomedicine had a better tumor inhibitory effect in vivo and in vitro. All animal experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Radiological Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College (IRM/2-IACUC-2312-006).

Objective This study investigated the impact of occupational mercury(Hg)exposure on human gene transcription and expression,and its potential biological mechanisms. Methods Differentially expressed genes related to Hg exposure were identified and validated using gene expression microarray analysis and extended validation.Hg-exposed cell models and PTEN low-expression models were established in vitro using 293T cells.PTEN gene expression was assessed using qRT-PCR,and Western blotting was used to measure PTEN,AKT,and PI3K protein levels.IL-6 expression was determined by ELISA. Results Combined findings from gene expression microarray analysis,bioinformatics,and population expansion validation indicated significant downregulation of the PTEN gene in the high-concentration Hg exposure group.In the Hg-exposed cell model(25 and 10 μmol/L),a significant decrease in PTEN expression was observed,accompanied by a significant increase in PI3K,AKT,and IL-6 expression.Similarly,a low-expression cell model demonstrated that PTEN gene knockdown led to a significant decrease in PTEN protein expression and a substantial increase in PI3K,AKT,and IL-6 levels. Conclusion This is the first study to report that Hg exposure downregulates the PTEN gene,activates the PI3K/AKT regulatory pathway,and increases the expression of inflammatory factors,ultimately resulting in kidney inflammation.

Objective To understand the respiratory protection competency of staff in hospitals.Methods Staff from six hospitals of different levels and characteristics in Beijing were selected,including doctors,nurses,medical technicians,and servicers,to conduct knowledge assessment on respiratory protection competency.According to exposure risks of respiratory infectious diseases,based on actual cases and daily work scenarios,content of respira-tory protection competency assessment was designed from three aspects:identification of respiratory infectious di-seases,transmission routes and corresponding protection requirements,as well as correct selection and use of masks.The assessment included 6,6,and 8 knowledge points respectively,with 20 knowledge points in total,all of which were choice questions.For multiple-choice questions,full marks,partial marks,and no mark were given respective-ly if all options were correct,partial options were correct and without incorrect options,and partial options were correct but with incorrect options.Difficulty and discrimination analyses on question of each knowledge point was conducted based on classical test theory.Results The respiratory protection competency knowledge assessment for 326 staff members at different risk levels in 6 hospitals showed that concerning the 20 knowledge points,more than 60％participants got full marks for 6 points,while the proportion of full marks for other questions was relatively low.Less than 10％participants got full marks for the following 5 knowledge points:types of airborne diseases,types of droplet-borne diseases,conventional measures for the prevention and control of healthcare-associated infec-tion with respiratory infectious diseases,indications for wearing respirators,and indications for wearing medical protective masks.Among the 20 knowledge questions,5,1,and 14 questions were relatively easy,medium,and difficult,respectively;6,1,4,and 9 questions were with discrimination levels of ≥0.4,0.30-0.39,0.20-0.29,and ≤0.19,respectively.Conclusion There is still much room for hospital staff to improve their respiratory protection competency,especially in the recognition of diseases with different transmission routes and the indications for wearing different types of masks.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

This study aims to investigate the effect of salvianolic acid B (Sal B), the active ingredient of Salvia miltiorrhiza, on H9C2 cardiomyocytes injured by oxygen and glucose deprivation/reperfusion (OGD/R) through regulating mitochondrial fission and fusion. The process of myocardial ischemia-reperfusion injury was simulated by establishing OGD/R model. The cell proliferation and cytotoxicity detection kit (cell counting kit-8, CCK-8) was used to detect cell viability; the kit method was used to detect intracellular reactive oxygen species (ROS), total glutathione (t-GSH), nitric oxide (NO) content, protein expression levels of mitochondrial fission and fusion, apoptosis-related detection by Western blot. Mitochondrial permeability transition pore (MPTP) detection kit and Hoechst 33342 fluorescence was used to observe the opening level of MPTP, and molecular docking technology was used to determine the molecular target of Sal B. The results showed that relative to control group, OGD/R injury reduced cell viability, increased the content of ROS, decreased the content of t-GSH and NO. Furthermore, OGD/R injury increased the protein expression levels of dynamin-related protein 1 (Drp1), mitofusions 2 (Mfn2), Bcl-2 associated X protein (Bax) and cysteinyl aspartate specific proteinase 3 (caspase 3), and decreased the protein expression levels of Mfn1, increased MPTP opening level. Compared with the OGD/R group, it was observed that Sal B had a protective effect at concentrations ranging from 6.25 to 100 μmol·L^-1. Sal B decreased the content of ROS, increased the content of t-GSH and NO, and Western blot showed that Sal B decreased the protein expression levels of Drp1, Mfn2, Bax and caspase 3, increased the protein expression level of Mfn1, and decreased the opening level of MPTP. In summary, Sal B may inhibit the opening of MPTP, reduce cell apoptosis and reduce OGD/R damage in H9C2 cells by regulating the balance of oxidation and anti-oxidation, mitochondrial fission and fusion, thereby providing a scientific basis for the use of Sal B in the treatment of myocardial ischemia reperfusion injury.

Following the principles of evidence-based medicine,in accordance with the structure and drafting rules of standardized documents,based on literature research,according to the characteristics of chronic cough in children and issues that need to form a consensus,the TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children was formulated based on the Delphi method,expert discussion meetings,and public solicitation of opinions.The guideline includes scope of application,terms and definitions,eti-ology and diagnosis,auxiliary examination,treatment,prevention and care.The aim is to clarify the optimal treatment plan of Chinese medicine in the diagnosis and treatment of this disease,and to provide guidance for improving the clinical diagnosis and treatment of chronic cough in children with Chinese medicine.

Objective To explore the effect of Tongdu Tiaoshen acupuncture,a needling method for dredging governor vessel and regulating mind,on cerebral hemodynamics and oxygen free radicals in the patients with post-stroke epilepsy(PSE).Methods A total of 60 patients with PSE were randomly divided into a treatment group and a control group,with 30 cases in each group.Both groups were given basic treatment for lowering lipid level,controlling blood pressure and glucose contents,and counteracting platelet aggregation.Moreover,the control group was treated with Sodium Valproate Sustained-Release Tablets,and the treatment group was treated with Tongdu Tiaoshen acupuncture mainly on the acupoints of Baihui(GV20),Shenting(GV24),Shuigou(GV26),Fengfu(GV 16),Fengchi(GB20)based on the treatment for the control group.One month constituted a course of treatment,and the treatment for the two groups covered three courses of treatment.The number of epileptic seizures,the severity of electroencephalogram(EEG),the peak systolic velocity(Vs)and end diastolic velocity(Vd)of bilateral anterior cerebral arteries,middle cerebral arteries and posterior cerebral arteries detected by transcranial Doppler ultrasonography(TCD),and the changes in the peripheral levels of oxygen free radicals such as malondialdehyde(MDA),hydroxyl radical(OH),lipid peroxide(LPO)and superoxide dismutase(SOD)in the two groups were observed before and after treatment.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After three months of treatment,the total effective rate of the treatment group was 93.33％(28/30),and that of the control group was 73.33％(23/30).The intergroup comparison(tested by chi-square test)showed that the efficacy of the treatment group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the average monthly epileptic seizure frequency in the two groups was decreased when compared with that before treatment(P＜0.05),and the decrease in the treatment group was more significant than that in the control group(P＜0.05).(3)After treatment,the grading of EEG severity in the two groups was significantly improved when compared with that before treatment(P＜0.05),and the improvement in the treatment group was significantly superior to that in the control group(P＜0.05).(4)After treatment,the peripheral levels of oxygen free radicals of MDA,OH and LPO in the two groups were lower than those before treatment(P＜0.05),and the peripheral level of SOD was higher than that before treatment(P＜0.05).The decrease of MDA,OH and LPO levels and the increase of SOD level in the treatment group were significantly superior to those in the control group(P＜0.05 or P＜0.01).(5)After treatment,the values of cerebral hemodynamic indicators of Vs and Vd of both left and right anterior cerebral artery,middle cerebral artery and posterior cerebral artery in the two groups were higher than those before treatment(P＜0.05),and the increase in the treatment group was significantly superior to that in the control group,the differences being statistically significant(P＜0.05).(6)During the treatment,there were no fainting,sticking of needle,bleeding and rash occurring during acupuncture in the two groups,which indicated that the therapy had high safety.Conclusion Tongdu Tiaoshen acupuncture can significantly reduce the seizure frequency of PSE and improve the severity of epileptic EEG.Its therapeutic mechanism may be related with the decrease of the oxygen free radical levels and with the improvement of cerebral hemodynamics.