OBJECTIVE: To analyze the distribution of thalassemia (referred to as "thalassemia") gene variant types in the population of the Wuhan area, aiming to provide a genetic basis for the precise prevention and control as well as clinical diagnosis of thalassemia in the Wuhan region. METHODS: In this study, 2 133 suspected thalassemia patients and individuals undergoing prenatal screening who visited the Department of Hematology, Obstetrics and Gynecology, Reproductive Medicine, Pediatrics, and Neurology at Wuhan First Hospital from October 2022 to October 2024 were selected as the research subjects. Peripheral blood samples were collected from the patients. The common 27 thalassemia genotypes of α- and β-thalassemia were initially screened using fluorescence PCR melting curve analysis technology. For samples where the fluorescence PCR melting curve results indicated unknown variants or where the clinical phenotype was inconsistent with the common genotypes, Sanger sequencing technology was used for review and verification. RESULTS: Among the 2 133 specimens analyzed, common thalassemia gene variants were detected in 210 cases (9.85%, 210/2 133). A total of 156 cases (8.05%, 156/1 938) of thalassemia gene variants were detected in females and 54 cases (27.69%, 54/195) in males. A total of 94 cases (4.41%, 94/2 133) of α-thalassemia were detected, including 46 cases (2.16%, 46/2 133) of silent α-thalassemia, 47 cases (2.20%, 47/2 133) of mild α-thalassemia, and 1 case (0.05%, 1/2 133) of intermediate α-thalassemia. Additionally, 111 cases of β-thalassemia were identified (5.20%, 111/2 133), including 51 cases of β/β⁺ thalassemia (2.39%, 51/2 133), 59 cases of β/β⁰ thalassemia (2.77%, 59/2 133), and 1 case of β⁺/HbE thalassemia (0.05%, 1/2 133). αβ-composite thalassemia gene variants were detected in 5 cases (0.23%, 5/2 133), including 1 complex variant with a genotype of --^SEA/αα combined with CD41-42 (-TTCT) and 29(A>G), representing a heterozygous variant of three genotypes. Rare globin gene variants were detected in 3 cases, including HBB:c.60C>T, HBB:c.-146G>T, and HBA2:c.*12G>A. CONCLUSION The Wuhan region exhibits a relatively high prevalence of thalassemia genes with notable gender disparities. While maintaining focus on thalassemia screening for females, enhanced males screening efforts and genetic counseling should be implemented in future prevention programs.
Humans ; Female ; Male ; Genotype ; beta-Thalassemia/genetics* ; China ; Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Genetic Variation

AIM:To investigate the clinical efficacy of phakic implantable collamer lens(ICL)implantation in correcting low-to-moderate myopia.METHODS: Retrospective study. A total of 48 patients(85 eyes)with low to moderate myopia who underwent ICL implantation were included in the study. The changes in uncorrected visual acuity(LogMAR), corrected visual acuity(LogMAR), refractive outcomes, intraocular pressure, vault and endothelial cell were observed at 1 a postoperatively.RESULTS: At 12 mo postoperatively, uncorrected and best-corrected visual acuity were -0.10(-0.20, -0.10)and -0.10(-0.20, -0.10), respectively, with an efficacy index of 1.07±0.13 and a safe index of 1.10±0.14. The difference between the actual corrected diopter and the expected corrected diopter was 91%(77/85)in the range of ±0.50 D, and 100%(85/85)in the range of ±1.00 D. The mean vault was 501.16±210.46 μm at 12 mo postoperatively. There was no significant difference in corneal endothelial cell density between preoperative and 6 and 12 mo postoperatively(F=1.050, P=0.352). All patients had no anterior subcapsular opacification, cataract, pupillary block, or other sight threatening complications during follow-up.CONCLUSION: ICL implantation for the correction of low to moderate myopia has good efficacy, safety and predictability.

The current situation of childrearing in the elderly and low birth rate showed that the prevention and treatment of infertility risk caused by the decline of male reproductive function are increasingly becoming prominent.The decline of male reproductive function is closely related to the hypothalamic-pituitary-gonadal axis,oxygen free radicals,blood-testis barrier,and the apoptosis of spermatogenic cells.Traditional Chinese medicine believes that the kidney stores essence and is in charge of reproduction,and the decline of reproductive function is closely related to the imbalance of yin and yang of the kidney.Therefore,kidney-supplementing method is helpful for treating the decline of reproductive function caused by kidney deficiency.Kidney-supplementing prescriptions were effective on systematically regulating the function of the hypothalamic-pituitary-gonadal axis,thus to significantly delay the decline of reproductive function,were effective on removing excessive oxygen free radicals in the body and protecting cells from oxidative damage,and were effective on improving spermatogenesis by restoring the blood-testis barrier and regulating the apoptosis of spermatogenic cells.The representative kidney-supplementing prescriptions for improving the decline of reproductive function caused by kidney deficiency include Wuzi Yanzong Pills,Shenqi Pills,Yougui Pills,Liuwei Dihuang Pills,Zuogui Pills and Guilu Erxian Soft Extract.The above formulas presented no single therapeutic mechanism but multiple-way,multiple-level and multiple-target mechanism,and the formulas can comprehensively regulate the internal environment of the body,so as to achieve the purpose of improving male reproductive function.The kidney-supplementing therapy of traditional Chinese medicine plays an irreplaceable role in the treatment of male reproductive function decline.The in-depth study of its therapeutic mechanism will provide guide for clinical practice and will supply theoretical basis for improving male reproductive function decline.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To compare the safety and efficacy of decitabine combined with unrelated umbilical cord blood transplantation and traditional regimen in the elderly patients with acute myeloid leukemia(AML)after achieving complete remission with induction therapy.Methods Fifty-two elderly AML patients who obtained complete remission(CR)after 1-2 cycles of induction therapy in the Department of Hematology of Yancheng First People's Hospital and the Huai'an First Hospital Affiliated to Nanjing Medical University from January 2019 to January 2022 were enrolled,and were divided into the observation group(n=24)and the control group(n=28).The observation group received decitabine combined with unrelated umbilical cord blood transplantation,and the control group received traditional consolidation therapy,including azacitidine+vinblastine,idarubicin+cytarabine(IA),or aclarubicin+cytarabine+granulocyte colony-stimulating factor,and so on.The hematopoietic recovery time,adverse reactions,relapse-free survival(RFS),and overall survival(OS)were compared between the two groups.Results The median recovery time of neutrophils was 12.54 d in the observation group and wes 18.64 d in the control group(P＜0.001);the median recovery time of platelets was 12.67 d in the observation group and was 19.71 d in the control group(P＜0.001).There was no difference in incidences of grade Ⅲ-Ⅳ myelosuppression and non-hematological toxicity between the two groups.There were statistical differences in the median RFS(33 months vs 11 months)and OS(36 months vs 24 months)between the observation group and the control group(P＜0.05).Conclusions Compared with the traditional consolidation regimen,decitabine combined with unrelated umbilical cord blood transplantation for consolidation of AML after achieving remission is more effective in elderly patients,could prolong survival,and has similar safety.

: AbstractObjective: To investigate the effect of γδ T cells on the proliferation, apoptosis and autophagy of multiple myeloma cells. METHODS: Peripheral blood mononuclear cells (PBMNC) were isolated from healthy volunteers, and stimulated with zoledronic acid (Zol) in combination with rhIL-2. Flow cytometry analysis was used to detected the purity of γδ T cells. γδ T cells were collected and co-cultured with RPMI-8226 or U-266 cells at different effector target ratios. The proliferation of RPMI-8226 or U-266 cell lines were detected by CCK-8. Cell cycle and cell apoptosis were detected by flow cytometry and Western blot．The expressions of autophagy-related proteins were detected by Western blot. RESULTS: γδ T cells can be expanded in vitro. γδ T cells could inhibit the proliferation of RPMI-8226 or U-266 cells, induced cell cycle arrest and promoted apoptosis in an effector target-dependent manner. In addition, γδ T cells could induce autophagy of myeloma cells, inhibited the expression of autophagy-related PI3K, P-AKT and P-mTOR, while increased the expression of AMPK and Beclin-1. CONCLUSION γδ T cells can inhibit the proliferation of RPMI-8226 and U-266 myeloma cells, induce cell cycle arrest, promote apoptosis, and enhance autophagy in vitro. The mechanism may be related to inhibition of PI3K/AKT/mTOR signaling pathway and/or activation of AMPK/Beclin-1 signaling pathway.
AMP-Activated Protein Kinases/pharmacology* ; Apoptosis ; Autophagy ; Beclin-1/pharmacology* ; Cell Proliferation ; Humans ; Leukocytes, Mononuclear/metabolism* ; Multiple Myeloma/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; T-Lymphocytes ; TOR Serine-Threonine Kinases/metabolism*

OBJECTIVE: To observe the occurrence time of neuralgia and the expression of purinergic ligand-gated ion channel 7 receptor (P2X7R) in the dorsal horn of the spinal cord after intraperitoneal injection of streptozotocin (STZ) in diabetic rats, and to explore the effect of electroacupuncture (EA) and pretreatment of EA on the heat pain threshold and expression of P2X7R in the spinal dorsal horn in rats with diabetic neuropathic pain (DNP), and to explore the possible mechanism of EA for DNP. METHODS: PartⅠ: Thirty male SD rats were randomly selected from 64 male SD rats as the control group; the remaining rats were given intraperitoneal injection of STZ (10 mg/mL) at a dose of 65 mg/kg to establish the diabetes model, and 30 rats were successfully modeled as the model group. The control group and the model group were divided into three subgroups respectively at 7, 14 and 21 days, with 10 rats in each subgroup. Body mass, fasting blood glucose (FBG) and thermal pain threshold were recorded at 7, 14 and 21 days after injection; the expression of P2X7R in spinal dorsal horn was detected by Western blot. PartⅡ: Eight SD rats were randomly selected from 35 male SD rats as the blank group, and the remaining 27 rats were given intraperitoneal injection of STZ (10 mg/mL) at a dose of 65 mg/kg to establish the diabetes model. The 24 rats with successful diabetes model were randomly divided into a DNP group, an EA group and a pre-EA group, 8 rats in each group. Fifteen to 21 days after STZ injection, the EA group received EA at "Zusanli" (ST 36) and "Kunlun" (BL 60), continuous wave, frequency of 2 Hz, 30 min each time, once a day; the intervention method in the pre-EA group was the same as that in the EA group. The intervention time was 8 to 14 days after STZ injection. The body mass, FBG and thermal pain threshold were recorded before STZ injection and 7, 14 and 21 days after STZ injection; the expression of P2X7R in spinal dorsal horn was detected by Western blot 21 days after injection. RESULTS: PartⅠ: Compared with the control group, in the model group, the body mass was decreased and FBG was increased 7, 14 and 21 days after STZ injection (P<0.01), and the thermal pain threshold was decreased 14 and 21 days after STZ injection (P<0.05), and the expression of P2X7R in spinal dorsal horn was increased 7, 14 and 21 days after STZ injection (P<0.05, P<0.01). PartⅡ: Compared with the blank group, in the DNP group, the body mass was decreased and fasting blood glucose were increased 7, 14 and 21 days after STZ injection (P<0.01). Compared with the DNP group, in the pre-EA group, the heat pain threshold was increased 14 and 21 days after STZ injection (P<0.05), while in the EA group, the heat pain threshold was increased 21 days after STZ injection (P<0.01), and the expression of P2X7R in the dorsal horn in the EA group and the pre-EA group was decreased (P<0.01). CONCLUSION The diabetic neuropathic pain is observed 14 days after STZ injection. EA could not only treat but also prevent the occurrence of DNP, and its mechanism may be related to down-regulation of P2X7R expression in the dorsal horn of the spinal cord.
Animals ; Diabetes Mellitus, Experimental/therapy* ; Electroacupuncture ; Male ; Neuralgia/therapy* ; Rats ; Rats, Sprague-Dawley ; Spinal Cord ; Spinal Cord Dorsal Horn

Objective: To examine the outcomes of Tiantan first-aid protocol on critically ill patients with primary central nervous system lymphoma (PCNSL). Methods: The clinical data of 18 patients with PCNSL who were treated according to Tiantan first-aid protocol at Department of Neurosurgery,Beijing Tiantan Hospital, Capital Medical University from November 2019 to December 2021 were retrospectively analyzed. There were 9 males and 9 females, aged (56.9±11.1)years (range: 29 to 77 years). The median Karnofsky performance status(KPS) score at admission was 40 (range: 20 to 60). Three patients were mild coma, 3 were lethargy and 12 were conscious. The mean midline shift was 0.7 cm (range: 0 to 1.8 cm). After admission, all patients were treated according to the plan of rapid biopsy, rapid routine pathology and rapid salvage chemotherapy. The treatment procedures, clinical and radiographic outcomes, KPS score and adverse reactions of patients after chemotherapy were collected. Results: All of the 18 patients completed the first-aid treatment. The median duration from admission to the biopsy was 1 day (range: 0 to 5 days), from biopsy to routine pathological diagnosis was 1 day (range: 1 to 4 days) and from routine pathology to salvage chemotherapy was 1 day (range: 0 to 4 days). All the patients were pathologically confirmed with diffuse large B cell lymphoma, 1 patient was double-hit lymphoma. Seventeen patients underwent clinical remission and 1 died of cardiac dysfunction. The successful salvage rate was 17/18. Radiologically, complete remission was observed in 1 case, partial remission in 16 cases, and stable disease in 1 case. The median KPS score at discharge was 60 (range: 30 to 80). The mild gastrointestinal, hematological and hepatic adverse effects were observed after chemotherapy. Conclusion: Tiantan first-aid protocol is effective for critically ill patients with PCNSL, which has the merit to be popularly used and improved.
Central Nervous System ; Central Nervous System Neoplasms/therapy* ; Critical Illness ; Female ; Humans ; Lymphoma/therapy* ; Male ; Retrospective Studies

Objective:To investigate the antimicrobial resistance characteristics of carbapenem-resistant Enterobacteriaceae （CRE） isolated from outpatients with diarrhea in Shanghai， and provide support for surveillance， prevention and control of CRE. Methods:A total of 800 fecal swabs of the outpatients with diarrhea were collected from 23 sentinel hospitals for diarrhea pathogen surveillance in Shanghai from January 2018 to December 2019. The drug-resistant strains were isolated using MacConkey plates containing 1 μg/μL meropenem. The collected strains were identified preliminarily by the VITEK-2 Compact system and VITEK mass spectrometry. The minimum inhibitory concentration （MIC） of the strain was determined by the broth microdilution method. The multi-locus sequence typing （MLST） method and pulsed-field gel electrophoresis （PFGE） were used to analyze the homology of drug-resistant strains. The transferability of the resistance gene was investigated by a junction experiment. High-throughput sequencing was used to characterize the isolates. Results:Seven non-repetitive CRE isolates were multi-drug resistant carbapenem-resistant Escherichia coli （CREC） strains that produce New Delhi metallo-β-lactamase （NDM） with resistance to several commonly used antibiotics in clinical therapy. The molecular typing results showed that the CRE strains had different sequence types， and diverse PFGE patterns. The stains were all positive for bla_NDM genes， including bla_NDM-5 and bla_NDM-13， with bla_NDM-5 as the main type. The carbapenem-resistant genes could be transferred to EC600 by conjugation. Conclusion:The intestinal carbapenem-resistant strains in this study are all NDM-producing Escherichia coli. The isolates carried bla_NDM and other resistance genes. The MLST analysis showed that they belonged to different cloning types. Antimicrobial resistance genes could be horizontally transferred to EC600 by conjugation.