OBJECTIVE: To retrospectively analyze the genetic differences of thalassemia gene mutations among ethnic groups in Hechi, Guangxi. METHODS: A total of 15 595 whole blood samples of residents of Hechi from January 1, 2020 to June 30, 2023 were screened for thalassemia, and the Gap-PCR method and RDB-PCR method were used to perform genetic testing on the positive samples. Gene sequencing was performed on the samples with positive screening results but negative genotyping results. RESULTS: Among the 15 595 samples, 10 501 cases were screened positively, and 8 506 cases were thalassemia gene carriers among the positive samples, with a positive coincidence rate of 81.00%. Among them, there were 5 374 cases of α-thalassemia, 2 531 cases of β-thalassemia, and 601 cases of α+β compound thalassemia. A total of 13 mutant types were detected in α-thalassemia, including --^SEA (48.57%), -α ^3.7 (31.31%), α ^CS (8.57%) and -α ^4.2 (8.07%). A total of 17 mutant types were detected in β-thalassemia, mainly CD17 (48.27%) and CD41-42 (41.24%). The thalassemia gene carriers were mainly from the Zhuang (6 106 cases), Han (969 cases), Yao (793 cases), Mulam (275 cases), and Maonan (228 cases) ethnic groups. The comparison of constituent ratios within the above five ethnic groups demonstrated that there were differences in the proportions of -- ^SEA, -α ^3.7, α ^CS , and -α ^4.2 among the Zhuang, Han, and Yao ethnic groups (P < 0.005). The proportion of α ^CS in the Mulam ethnic group was not significantly different from -α ^3.7 and -α ^4.2. The proportions of -- ^SEA, -α^3.7, and α ^CS in the Maonan ethnic group were not significantly different. There were no significant differences in the proportion of CD17 and CD41-42 among the Han, Yao, Mulam and Maonan ethnic groups. The proportion of --^SEA was the highest in the Mulam ethnic group (56.68%), which was statistically different from 35.92% in the Maonan ethnic group. The proportion of -α ^3.7 was the highest in the Zhuang ethnic group (33.25%), and the difference was statistically significant compared to the Mulam ethnic group which had the lowest proportion (18.72%). The proportion of α ^CS was the highest in the Maonan ethnic group (27.46%), and the differences were statistically significant compared with other ethnic groups. The proportions of CD17 in the Zhuang and Maonan ethnic groups (50.79%, 55.68%) were higher than those in the Han (39.12%), Yao (39.63%) and Mulam (30.00%), and the differences were statistically significant. There was no significant difference in the proportion of CD41-42 among the above five ethnic groups. CONCLUSIONS The mutation type and distribution differences of genes causing thalassemia among main ethnic groups in the minority inhabited areas of Hechi, Guangxi, show the characteristics of ethnic differentiation. The result is helpful to develop a special prevention and control plan for thalassemia in line with the population distribution characteristics, and provide reference for revealing the genetic background and geographical distribution of thalassemia in this area.
Humans ; China ; beta-Thalassemia/genetics* ; Ethnicity/genetics* ; alpha-Thalassemia/genetics* ; Mutation ; Genotype ; Retrospective Studies ; Asian People/genetics* ; Thalassemia/genetics* ; Male

Objective : To analyze the correlation between different laboratory biomarkers and disease activity in ankylosing spondylitis and to compare their specificity and sensitivity in assessing disease activity. Methods : Spearman correlation or Pearson correlation was used to analyze the correlation between disease activity and laboratory biomarkers. Receiver operating characteristic(ROC) was used to compare the sensitivity and specificity of each laboratory biomarker in evaluating disease activity. Results : Hypersensitive C-reactive protein, fibrinogen, D-dimer, erythrocyte sediment rate, C-reactive protein, immuno-inflammatory index(platelet count×neutrophil count/lymphocyte count), fibrinogen/albumin ratio, albumin and pro-albumin were correlated with disease activity. The ratio of fibrinogen to albumin, fibrinogen, erythrocyte sedimentation rate, immuno-inflammatory index, C-reactive protein and hypersensitive C-reactive protein had good values in determining the disease activity. Conclusion Different laboratory biomarkers are correlated with the disease activity of ankylosing spondylitis, and some of them have better discriminating values for the disease activity.

Objective To investigate the effects of miR-4531/CX3CL1 signaling pathway on the vascular injury in preeclampsia, and to search possible targets for early diagnosis and prevention of preeclampsia. Methods Placental tissue samples were obtained from 10 patients with late-onset preeclampsia and 10 normal pregnant women in the Obstetrics and Gynecology Department of Minhang Hospital, Fudan University from October 2021 to December 2022. The levels of miR-4531 and CX3CL1 were evaluated by qRT-PCR. Cell transfection was performed by lipofectamine 2000 in vitro. The binding relationship between miR-4531 and CX3CL1 was determined by luciferase reporter assay. The apoptosis of neutrophils, the migration, repair, colony formation and cell-free DNA (cfDNA) release of human umbilical vein endothelial cells (HUVECs) were detected. Results MiR-4531 was significantly downregulated, and CX3CL1 was upregulated in placental tissues of preeclampsia patients (P＜0.05). Luciferase report assay confirmed the direct binding relationship between miR-4531 and CX3CL1. Upregulation of miR-4531significantly promoted the migration, proliferation, repair, and inhibited cfDNA release of HUVECs and neutrophils apoptosis in medium under hypoxic condition (P＜0.05). However, downregulation of miR-4531 obviously inhibited the proliferation, migration, repair, and enhanced cfDNA release of HUVECs and neutrophils apoptosis in medium under hypoxic condition (P＜0.05). Conclusions The miR-4531is downregulated in placental tissues of preeclampsia parients and is a potential therapeutic target for preeclampsia. It might cause endothelial damage and an abnormal hypercoagulable state under hypoxic condition by targeting and regulating the CX3CL1 pathway.

Objective To explore the efficacy and safety of"ditching and ridge removal"with 450 nm semiconductor blue laser in the treatment of large volume benign prostatic hyperplasia(BPH),in order to promote the clinical application of this method.Methods A retrospective study was conducted on 30 patients with large volume BPH treated with"ditching and ridge removal"with 450 nm semiconductor blue laser in Yingsheng Branch of Tai'an Central Hospital during Sep.and Dec.2023.The laser operation time,level of hemoglobin before and after operation,bladder irrigation time after operation,urinary catheter indwelling time,postoperative hospital stay,and intraoperative and postoperative complications were recorded.The changes of international prostate symptom score(IPSS),quality of life scale(QoL)score,maximum urinary flow rate(Qmax)and post-void residual volume(PVR)were compared before and 1 month after operation.Results The volume of prostate was(104.5±14.52)mL,the laser operation time was(20.13±2.98)min,and the bladder irrigation time was(20.27±2.56)h.The catheter was removed in all patients 2 days after operation,and all patients were discharged 3 days after operation.One month after operation,the IPSS,QoL,Qmax and PVR were significantly improved as compared with those before operation(P＜0.05).No complications occurred during the follow-up.Conclusion"Ditching and ridge removal"with 450 nm semiconductor blue laser is a new,safe and effective method in the treatment of large volume BPH.

Objective To study the pharmacokinetic characteristics of etoricoxib tablets in healthy Chinese subjects and to evaluate the bioequivalence and safety of the test and reference formulations.Methods In a randomised,single-dose,two-period,two-sequence crossover trial,28 healthy subjects were enrolled under the fasting and fed conditions,respectively,who received a single oral dose of 60 mg of etoricoxib tablets in the test or reference formulation.The concentration of etoricoxib in plasma was detected by LC-MS/MS,and the main pharmacokinetic parameters were calculated to evaluate bioequivalence and using WinNonlin 8.2 software.Results The main pharmacokinetic parameters of the test and reference preparations were as follows:The fasting condition Cmax of etoricoxib were(1 176.96±287.95)and(1 164.93±189.65)ng·mL-1;AUC0-t were(18 651.95±6 100.27)and(19 241.39±6 107.48)ng·h·mL-1;and AUC0-∞ were(19 939.15±7 553.27)and(20 536.31±7 223.40)ng·h·mL-1.The fed condition Cmax of etoricoxib were(913.50±184.72)and(878.59±164.35)ng·mL-1;and AUC0-t were(19 085.22±5 155.01)and(18 669.54±4 508.21)ng·h·mL-1;AUC0-∞ were(20 103.77±5 567.02)and(19 528.05±4 989.74)ng·h·mL-1.The 90％confidence intervals for the geometric mean ratios of the main pharmacokinetic parameters in the fasting and fed conditions fell between 80.00％and 125.00％.The incidence of adverse events in the fasting and fed conditions were 28.57％and 21.43％,respectively.Conclusion Two kinds of etoricoxib tablets are bioequivalent,and have similar safety in healthy Chinese subjects.

ObjectiveTo observe the clinical effect of crocin tablets （CRO） combined with micropump infusion of doxorubicin in the prevention of acute cardiotoxicity in the patients with diffuse large B-cell lymphoma （DLBCL） and explore the related mechanism. MethodThe patients with DLBCL treated in the Huangshi Central Hospital from October 2022 to October 2023 were selected， and 92 patients who met the inclusion criteria were randomly assigned to a control group and an observation group at a ratio of 1∶1， with 46 patients in each group. The control group underwent conventional intravenous infusion of doxorubicin， and the observation group received CRO combined with micropump infusion of doxorubicin. The changes of abnormal ECG， myocardial injury markers， cardiac function indicators， oxidative stress， inflammatory mediators， and hemorheological indexes before and after chemotherapy were compared between the two groups. ResultThe incidence of abnormal ECG in the observation group was 23.91% （11/46）， which was lower than that （54.35%， 25/46） in the control group （χ²=8.944， P<0.01）. On day 8 after chemotherapy， the abnormal rates of creatine kinase-MB （CK-MB） and cardiac troponin I （cTnI） in the observation group were lower than those in the control group （χ²=4.423， 4.857， both P<0.05）. Compared with the control group after chemotherapy， the observation group showed lowered level of N-terminal pro-B-type natriuretic peptide， elevated left ventricular ejection fraction and levels of total antioxidant capacity and superoxide dismutase （P<0.01）， declined levels of interleukin-6 and tumor necrosis factor-α （P<0.01）， and decreased low whole blood viscosity， high whole blood viscosity， plasma viscosity， and fibrinogen （P<0.01）. ConclusionCRO combined with micropump infusion of doxorubicin can mitigate acute cardiotoxicity， reduce the incidence of abnormal ECG， protect cardiomyocytes， and improve the cardiac function by exerting the antioxidant and anti-inflammatory effects and improving blood flow.

Diabetic retinopathy(DR)is one of the major complications of diabetes mellitus, characterized by neurodegeneration and microangiopathy. Currently, the treatment of DR is mainly focused on the management of late complications and has not achieved the desired clinical outcome. Evidence suggests that the PI3K/AKT pathway, as one of the important intracellular signaling pathways during the cell cycle, is involved in the whole process of DR pathogenesis. This article focuses on the structural composition, activation and blocking pathways, conduction pathways, regulatory mechanisms and biological functions of the PI3K/AKT signaling pathway to review its role in DR and to explore the potential of targeting the PI3K/AKT pathway for the treatment of DR.

Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus.Angiogenesis is a major pathophysiology in endometriosis.Our previous studies have demon-strated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain unknown.In this study,we demonstrated that oral ProEGCG can be effective in preventing and treating endometriosis.Additionally,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,respectively.Computational simulation and BioLayer interferometry were used to confirm their binding affinity.Our results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)pathway.In vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling pathways.Moreover,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel anti-angiogenic therapy for endometriosis.

Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.