Objective To evaluate the in vitro effect of combinations of 5 β-lactam antibiotics with different β-lac-tamase inhibitors on the activity of multidrug-resistant Mycobacterium tuberculosis(MDR-TB),and identify the most effective combination of β-lactam antibiotics and β-lactamase inhibitors against MDR-TB.Methods MDR-TB strains collected in Henan Province Antimicrobial Resistance Surveillance Project in 2021 were selected.The mini-mum inhibitory concentrations(MIC)of 5 β-lactam antibiotics or combinations with different β-lactamase inhibitors on clinically isolated MDR-TB strains were measured by MIC detection method,and the blaC mutation of the strains was analyzed by polymerase chain reaction(PCR)and DNA sequencing.Results A total of 105 strains of MDR-TB were included in the analysis.MIC detection results showed that doripenem had the highest antibacterial activity against MDR-TB,with a MIC50 of 16 μg/mL.MIC values of most β-lactam antibiotics decreased significantly after combined with β-lactamase inhibitors.A total of 13.33％(n=14)strains had mutations in blaC gene,mainly 3 nu-cleotide substitution mutations,namely AGT333AGG,AAC638ACC and ATC786ATT.BlaC proteins Ser111 Arg and Asn213Thr enhanced the synergistic effect of clavulanic acid/sulbactam and meropenem on MDR-TB compared with synonymous single-nucleotide mutation.Conclusion The combination of doripenem and sulbactam has the strongest antibacterial activity against MDR-TB.Substitution mutations of BlaC protein Ser111 Arg and Asn213Thr enhances the sensitivity of MDR-TB to meropenem through the synergy with clavulanic acid/sulbactam.

Objective:To observe the genetic variation of SH2B3 in patients with myeloid neoplasms.Methods:The results of targeted DNA sequencing associated with myeloid neoplasms in the Department of Hematology,Xuanwu Hospital,Capital Medical University from November 2017 to November 2022 were retrospectively analyzed,and the patients with SH2B3 gene mutations were identified.The demographic and clinical data of these patients were collected,and characteristics of SH2B3 gene mutation,co-mutated genes and their correlations with diseases were analyzed.Results:The sequencing results were obtained from 1 005 patients,in which 19 patients were detected with SH2B3 gene mutation,including 18 missense mutations(94.74％),1 nonsense mutation(5.26％),and 10 patients with co-mutated genes(52.63％).Variant allele frequency(VAF)ranged from 0.03 to 0.66.The highest frequency mutation was p.Ile568Thr(5/19,26.32％),with an average VAF of 0.49,involving 1 case of MDS/MPN-RS(with SF3B1 mutation),1 case of MDS-U(with SF3B1 mutation),1 case of aplastic anemia with PNH clone(with PIGA and KMT2A mutations),2 cases of MDS-MLD(1 case with SETBP1 mutation).The other mutations included p.Ala567Thr in 2 cases(10.53％),p.Arg566Trp,p.Glu533Lys,p.Met437Arg,p.Arg425Cys,p.Glu314Lys,p.Arg308*,p.Gln294Glu,p.Arg282Gln,p.Arg175Gln,p.Gly86Cys,p.His55Asn and p.Gln54Pro in 1 case each.Conclusion:A wide distribution of genetic mutation sites and low recurrence of SH2B3 is observed in myeloid neoplasms,among of them,p.Ile568Thr mutation is detected with a higher incidence and often coexists with characteristic mutations of other diseases.

Excessive sodium/salt intake is the leading dietary risk factor for the loss of healthy life in the Chinese population. The "Healthy China 2030" Action Plan set the goal of reducing salt intake by 20% by 2030. However, salt intake in China is still at a very high level in the world, with adults reaching 11 g/d, more than twice the recommended limit of 5 g/d. The current policies and action plans of China have targeted catering workers, children, adolescents, and home chefs in salt, oil, and sugar reduction actions. However, there are still obvious deficiencies in the coordinated promotion and implementation. This study, therefore, proposed a set of comprehensive strategies (named CHRPS that is composed of communication and education, salt reduction in home cooking, salt reduction in restaurants, reducing salt content in pre-packaged food, and surveillance and evaluation) and key implementation points for further deepening the salt reduction action in China. These strategies were developed based on the main sources of dietary sodium for Chinese residents, the status of "knowledge, attitude and practice" in salt reduction, evidence of effective intervention measures, existing policies and requirements, and the salt reduction strategies of the World Health Organization and experience from some other countries. As a scientific reference, the CHRPS strategies will help the government and relevant organizations quickly implement salt reduction work and facilitate the earlier realization of China's salt reduction goal.
Adult ; Child ; Adolescent ; Humans ; Sodium Chloride, Dietary ; Sodium, Dietary ; Diet ; Food ; China

OBJECTIVE: To investigate the effects of miR-144-3p on cell proliferation, cell cycle and apoptosis of blast phase chronic myelogenous leukemia (CML) K562 cells. METHODS: K562 cells were cultured in vitro and mimics negative control, hsa-miR-144-3p mimics, inhibitor negative control and miR-144-3p inhibitor were respectively transfected into K562 cells with transfection reagents. The cells were divided into five groups including blank control, mimics negative control, miR-144-3p mimics, inhibitor negative control and miR-144-3p inhibitor. After transfection, the cell proliferation activity was detected by CCK-8 assay. The cell cycle distribution and apoptosis were detected by flow cytometry. RESULTS: Compared with the blank control and mimics negative control groups, the proliferation rate of miR-144-3p mimics group was significantly decreased (P<0.05), the proportion of S phase cells was markedly increased (P<0.05), while the proportion of G₁ phase cells was obviously decreased (P<0.05), and the apoptosis rate was significantly increased (P<0.05). Compared with the blank control and inhibitor negative control groups, the proliferation rate of miR-144-3p inhibitor group was obviously increased (P<0.05), the proportion of S phase cells was markedly decreased (P<0.05), while the proportion of G₁ phase cells was obviously increased (P<0.05), and the apoptosis rate was significantly decreased (P<0.05). CONCLUSION miR-144-3p can inhibit the proliferation and promote apoptosis of K562 cells, affect the cell cycle, and block K562 cells in S phase, which indicates that miR-144-3p is involved in the cell cycle activity of CML during blastic phase.
Humans ; Apoptosis/genetics* ; Cell Cycle/genetics* ; Cell Line, Tumor ; Cell Proliferation/genetics* ; K562 Cells ; MicroRNAs/metabolism*

OBJECTIVE: To investigate the safety and efficacy of reinforced radiculoplasty in the treatment of symptomatic sacral Tarlov cysts (TCs). METHODS: A retrospective analysis was performed on the clinical data and follow-up data of 71 patients with symptomatic sacral TCs who underwent reinforced radiculoplasty in the Neurosurgery Department of Peking University Third Hospital from June 2018 to March 2021. All the operations were performed under neuroelectrophysiological monitoring. Intraoperative cyst exploration, partial resection of the cyst wall, narrowing of the leak, nerve root sleeve radiculoplasty and artificial dural reinforcement were performed. The incidence of postoperative complications and new neurological dysfunction was analyzed. Visual analogue scale (VAS) was used to assess the changes of pain before and after surgery. The Japanese Orthopedics Association (JOA) low back pain score was used to evaluate the changes in nerve function before and after surgery. RESULTS: In the study, 71 patients had 101 TCs, 19 (18.8%) TCs originated from the left S1 nerve, 26 (25.7%) originated from the left S2 nerve, 3 (3.0%) originated from the left S3 nerve, 14 (13.9%) originated from the right S1 nerve, 33 (32.7%) originated from the right S2 nerve, 6 (5.9%) originated from the right S3 nerve, all the TCs underwent reinforced radiculoplasty. Deep infection (1 case), subcutaneous effusion (1 case), fat li-quefaction (1 case) and urinary tract infection (4 cases) were recorded postoperatively. The patients were followed up for 12-43 months (median, 26 months). Two cases had new urinary retention after operation, and the catheter was removed at the end of the first and second months respectively. One case had new fecal weakness, which improved after 3 months. Compared with preoperation, VAS decreased significantly at the last follow-up [median, 6 (4-9) vs. 1 (0-5), Z=-7.272, P < 0.001], JOA score increased significantly [median, 20 (16-25) vs. 27 (18-29), Z=-7.265, P < 0.001]. There were 18 cured cases (25.4%), 41 excellent cases (57.7%), 8 effective cases (11.3%), and 4 invalid cases (5.6%). The total efficiency was 94.4% (67/71). Two (1.98%) cysts recurred. CONCLUSION For patients with symptomatic sacral TCs, reinforced radiculoplasty can significantly improve the pain and nerve function, which is safe and reliable.
Humans ; Tarlov Cysts/epidemiology* ; Retrospective Studies ; Neoplasm Recurrence, Local/complications* ; Cysts/surgery* ; Pain

BackgroundType 1 diabetes is caused by a chronic immune response that destroys islet beta cells， resulting in elevated blood glucose. Mesenchymal stem cells can prevent and treat the development of diabetes and its complications. However， little is known about the effects and potential mechanisms of Gingival mesenchymal stem cells （GMSCs） in preventing diabetes. The aim of this study is to investigate the mechanism of GMSCs in preventing type 1 diabetes in mice and to find targets for clinical treatment of diabetes. MethodsWe injected human GMSCs into NOD mice to observe the trend of blood glucose， observed the survival of pancreatic β-cells by immunohistochemistry， and detected the change of immune cells in the spleen of mice by flow analysis. Finally， the immune cells in NOD mice were transfused into NOD-SCID mice to observe the onset of diabetes in NOD-SCID mice. ResultsGMSCs significantly reduced the incidence of diabetes in NOD mice， with 64% of control mice developing diabetes at 27 weeks of age compared with 35% in the GMSC group， P=0.013. The percentage of Follicular B cells（FO B cell） in the spleen of GMSCs-treated mice decreased from （52.2±4.1）% to （43.2±5.3）%， P=0.008， while other types of immune cells did not change significantly. The immunohistochemical results showed that GMSCs could effectively improve the survival of pancreatic β-cells， which could continuously produce insulin to control blood glucose. Finally， we found the spleen cells transfusion could prevent the development of diabetes in NOD-SCID mice. ConclusionGMSCs can reduce diabetes in mice by reducing FO B cells in the spleen.

The many-banded krait, Bungarus multicinctus, has been recorded as the animal resource of JinQianBaiHuaShe in the Chinese Pharmacopoeia. Characterization of its venoms classified chief phyla of modern animal neurotoxins. However, the evolutionary origin and diversification of its neurotoxins as well as biosynthesis of its active compounds remain largely unknown due to the lack of its high-quality genome. Here, we present the 1.58 Gbp genome of B. multicinctus assembled into 18 chromosomes with contig/scaffold N50 of 7.53 Mbp/149.8 Mbp. Major bungarotoxin-coding genes were clustered within genome by family and found to be associated with ancient local duplications. The truncation of glycosylphosphatidylinositol anchor in the 3'-terminal of a LY6E paralog released modern three-finger toxins (3FTxs) from membrane tethering before the Colubroidea divergence. Subsequent expansion and mutations diversified and recruited these 3FTxs. After the cobra/krait divergence, the modern unit-B of β-bungarotoxin emerged with an extra cysteine residue. A subsequent point substitution in unit-A enabled the β-bungarotoxin covalent linkage. The B. multicinctus gene expression, chromatin topological organization, and histone modification characteristics were featured by transcriptome, proteome, chromatin conformation capture sequencing, and ChIP-seq. The results highlighted that venom production was under a sophisticated regulation. Our findings provide new insights into snake neurotoxin research, meanwhile will facilitate antivenom development, toxin-driven drug discovery and the quality control of JinQianBaiHuaShe.

Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.

Objective:To explore the effects of informatization traceability management combined with performance assessment in the nursing management of Disinfection Supply Center.Methods:In March 2021, the Disinfection Supply Center of the First Affiliated Hospital of Zhengzhou University implemented the informatization traceability management combined with performance assessment. Convenient sampling method was used to select 172 medical devices disinfected and sterilized by the Disinfection Supply Center before implementation (from March 2020 to February 2021) and 166 medical devices disinfected and sterilized by the Disinfection Supply Center after implementation (from March 2021 to February 2022) for statistical analysis. We compared the cleaning qualified rate, sterilization qualified rate, packaging qualified rate, distribution qualified rate, management effects, adverse event rate of device management, and performance assessment results before and after the implementation of the informatization traceability management combined with performance assessment.Results:The cleaning qualified rate, packaging qualified rate and distribution qualified rate after implementation were higher than those before implementation, and the differences were statistically significant ( P<0.05) . The recovery and classification time, device information registration time, ex-warehouse inspection time and manual operation time after implementation were shorter than those before implementation, and the differences were statistically significant ( P<0.05) . The device damage rate, label error rate and device loss rate after implementation were lower than those before implementation with statistical differences ( P<0.05) . The scores of theoretical assessment and operational skill assessment after implementation were higher than those before implementation with statistical differences ( P<0.05) . Conclusions:The combination of informatization traceability management and performance assessment can improve the nursing management effects of the Disinfection Supply Center, significantly increase the qualified rate of cleaning, packaging and distribution, and boost the performance assessment results of nurses, which helps to reduce the incidence of adverse events in device management.

Objective: To investigate whether haplotype hematopoietic stem cell transplantation (haplo-HSCT) is effective in the treatment of pre transplant minimal residual disease (Pre-MRD) positive acute B lymphoblastic leukemia (B-ALL) compared with HLA- matched sibling donor transplantation (MSDT) . Methods: A total of 998 patients with B-ALL in complete remission pre-HSCT who either received haplo-HSCT (n=788) or underwent MSDT (n=210) were retrospectively analyzed. The pre-transplantation leukemia burden was evaluated according to Pre-MRD determinedusing multiparameter flow cytometry (MFC) . Results: Of these patients, 997 (99.9% ) achieved sustained, full donor chimerism. The 100-day cumulative incidences of neutrophil engraftment, platelet engraftment, and grades Ⅱ-Ⅳ acute graft-versus-host disease (GVHD) were 99.9% (997/998) , 95.3% (951/998) , and 26.6% (95% CI 23.8% -29.4% ) , respectively. The 3-year cumulative incidence of total chronic GVHD was 49.1% (95% CI 45.7% -52.4% ) . The 3-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) of the 998 cases were 17.3% (95% CI 15.0% -19.7% ) and 13.8% (95% CI 11.6% -16.0% ) , respectively. The 3-year probabilities of leukemia-free survival (LFS) and overall survival (OS) were 69.1% (95% CI 66.1% -72.1% ) and 73.0% (95% CI 70.2% -75.8% ) , respectively. In the total patient group, cases with positive Pre-MRD (n=282) experienced significantly higher CIR than that of subjects with negative Pre-MRD [n=716, 31.6% (95% CI 25.8% -37.5% ) vs 14.3% (95% CI 11.4% -17.2% ) , P<0.001]. For patients in the positive Pre-MRD subgroup, cases treated with haplo-HSCT (n=219) had a lower 3-year CIR than that of cases who underwent MSDT [n=63, 27.2% (95% CI 21.0% -33.4% ) vs 47.0% (95% CI 33.8% -60.2% ) , P=0.002]. The total 998 cases were classified as five subgroups, including cases with negative Pre-MRD group (n=716) , cases with Pre-MRD<0.01% group (n=46) , cases with Pre-MRD 0.01% -<0.1% group (n=117) , cases with Pre-MRD 0.1% -<1% group (n=87) , and cases with Pre-MRD≥1% group (n=32) . For subjects in the Pre-MRD<0.01% group, haplo-HSCT (n=40) had a lower CIR than that of MSDT [n=6, 10.0% (95% CI 0.4% -19.6% ) vs 32.3% (95% CI 0% -69.9% ) , P=0.017]. For patients in the Pre-MRD 0.01% -<0.1% group, haplo-HSCT (n=81) also had a lower 3-year CIR than that of MSDT [n=36, 20.4% (95% CI 10.4% -30.4% ) vs 47.0% (95% CI 29.2% -64.8% ) , P=0.004]. In the other three subgroups, the 3-year CIR was comparable between patients who underwent haplo-HSCT and those received MSDT. A subgroup analysis of patients with Pre-MRD<0.1% (n=163) was performed, the results showed that cases received haplo-HSCT (n=121) experienced lower 3-year CIR [16.0% (95% CI 9.4% -22.7% ) vs 40.5% (95% CI 25.2% -55.8% ) , P<0.001], better 3-year LFS [78.2% (95% CI 70.6% -85.8% ) vs 47.6% (95% CI 32.2% -63.0% ) , P<0.001] and OS [80.5% (95% CI 73.1% -87.9% ) vs 54.6% (95% CI 39.2% -70.0% ) , P<0.001] than those of MSDT (n=42) , but comparable in 3-year NRM [5.8% (95% CI 1.6% -10.0% ) vs 11.9% (95% CI 2.0% -21.8% ) , P=0.188]. Multivariate analysis showed that haplo-HSCT was associated with lower CIR (HR=0.248, 95% CI 0.131-0.472, P<0.001) , and superior LFS (HR=0.275, 95% CI 0.157-0.483, P<0.001) and OS (HR=0.286, 95% CI 0.159-0.513, P<0.001) . Conclusion: Haplo HSCT has a survival advantage over MSDT in the treatment of B-ALL patients with pre MRD<0.1% .
B-Lymphocytes ; Graft vs Host Disease ; HLA Antigens/genetics* ; Haplotypes ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Humans ; Leukemia, B-Cell/complications* ; Leukemia, Lymphocytic, Chronic, B-Cell/complications* ; Neoplasm, Residual ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Recurrence ; Retrospective Studies ; Siblings