1.Pathogenesis of hepatitis B-associated intrahepatic cholangiocarcinoma
Qiyu TIAN ; Jian YU ; Gang HUANG
Journal of Clinical Hepatology 2024;40(4):797-803
Intrahepatic cholangiocarcinoma (ICC) is a type of primary liver cancer that accounts for about 10% — 15% of the total cases, and its incidence and mortality rates tend to increase significantly around the world, especially in Asian countries. At present, radical liver resection is the only possible cure for ICC, but with a fairly high postoperative recurrence rate and a poorer prognosis than hepatocellular carcinoma. Therefore, it is urgently needed to further investigate the mechanisms of the development and progression of ICC and search for more effective treatment methods. Some epidemiological data suggest that chronic hepatitis B virus infection is one of the most important predisposing factors for ICC, yet little is known about its oncogenic effects. This article summarizes the epidemiological evidence that links the two diseases and briefly elaborates on the mechanisms of the development and progression of HBV-associated ICC, so as to help to gain a better understanding of the role of HBV in the development and progression of ICC.
2.Efficacy of horizontal plate plus raft screws above the acetabulum in the treatment of acetabular fractures combined with dome impaction in the aged patients
Zhaojie LIU ; Jian JIA ; Haotian QI ; Yuxi SUN ; Gang LI ; Wei TIAN ; Hongchuan WANG ; Shucai BAI ; Pengfei LI
Chinese Journal of Trauma 2024;40(3):221-228
Objective:To compare the efficacy of the horizontal plate plus raft screws above the acetabulum and fixation with screws only for acetabular fractures combined with dome impaction in the aged patients.Methods:A retrospective cohort study was conducted to analyze the clinical data of 20 aged patients with acetabular fractures combined with dome impaction, who were admitted to Tianjin hospital between May 2013 and January 2023, including 5 males and 15 females, aged 61-84 years [(72.2±7.3)years]. According to Letournel and Judet classification, 13 patients had anterior column fracture, 5 anterior column fracture combined with posterior transverse fracture and 2 two-column fracture. All the patients underwent open reduction and internal fixation through an anterior approach. Of them, 11 patients were treated with the fixation with the horizonal plate plus raft screws above the acetabulum (plate plus raft screw group) and 9 with the screws only (screw only group). The operative time, intraoperative blood loss, and intraoperative fluoroscopy times were compared between the two groups. The quality of fracture reduction was evaluated with the Matta′s radiographic criteria at 3 days after surgery and the function of the hip joint was assessed with Merle D′Aubigné and Postel scoring system at 3 months after surgery and at the last follow-up as well as the excellent and good rate at te last follow-up. The occurrence of postoperative complications was observed.Results:All the patients were followed up for 6-18 months [(13.1±3.1)months]. There were no significant differences in the operative time, intraoperative blood loss or intraoperative fluoroscopy times between the two groups ( P>0.05). According to the Matta′s radiographic criteria at 3 days after surgery, patients with anatomical reduction and satisfactory reduction accounted 6 and 5 in the plate plus raft screw group, compared to 5 and 4 respectively in the screw only group ( P>0.05). The values of Merle D′Aubigné and Postel score at 3 months after surgery and at the last follow-up were (14.0±2.4)points and (15.8±2.2)points in the plate plus raft screw group, which were higher than those in the screw only group [(11.0±2.6)points and (13.0±3.1)points] ( P<0.01). The values of Merle D′Aubigné and Postel score at the last follow-up of both groups were further enhanced from those at 3 months after surgery ( P<0.01). At the last follow-up, 3 patients were rated excellent, 6 good, 1 fair and 1 poor in the plate plus raft screw group, with an excellent and good rate of 81.8%, while in the screw only group, 3 were rated good, 2 fair and 4 poor, with an excellent and good rate of 33.3% ( P<0.05). One patient in the plate plus raft screw group and 5 in the screw only group had displacement of the dome impaction fragment combined with traumatic arthritis after surgery ( P<0.05). Conclusion:For acetabular fractures combined with dome impaction in the aged patients, the horizontal plate plus raft screw above the acetabulum can effectively improve the function restoration of the hip joint and reduce the occurrence of the displacement of the dome impaction fragment and traumatic arthritis after surgery compared to the fixation with screws only.
3.A multi-center epidemiological study on pneumococcal meningitis in children from 2019 to 2020
Cai-Yun WANG ; Hong-Mei XU ; Gang LIU ; Jing LIU ; Hui YU ; Bi-Quan CHEN ; Guo ZHENG ; Min SHU ; Li-Jun DU ; Zhi-Wei XU ; Li-Su HUANG ; Hai-Bo LI ; Dong WANG ; Song-Ting BAI ; Qing-Wen SHAN ; Chun-Hui ZHU ; Jian-Mei TIAN ; Jian-Hua HAO ; Ai-Wei LIN ; Dao-Jiong LIN ; Jin-Zhun WU ; Xin-Hua ZHANG ; Qing CAO ; Zhong-Bin TAO ; Yuan CHEN ; Guo-Long ZHU ; Ping XUE ; Zheng-Zhen TANG ; Xue-Wen SU ; Zheng-Hai QU ; Shi-Yong ZHAO ; Lin PANG ; Hui-Ling DENG ; Sai-Nan SHU ; Ying-Hu CHEN
Chinese Journal of Contemporary Pediatrics 2024;26(2):131-138
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]
4.Treatment of Tile type C pelvic ring fracture using orthopedic robot combined with Starr pelvis reduction frame
Gang-Qiang JIANG ; Fu-De JIAO ; Ji-Chong YING ; Tian-Ming YU ; Jian-Lei LIU ; Yun-Qiang ZHUANG
China Journal of Orthopaedics and Traumatology 2024;37(5):445-450
Objective To investigate the clinical effect of orthopedic robot combined with Starr pelvic reduction frame in the treatment of Tile type C pelvic ring fracture.Methods From October 2019 to May 2021,14 patients with type C pelvic ring fracture were treated with robotic combined with Starr pelvic reduction frame,including 9 males and 5 females.The age ranged from 33 to 69 years.All the 14 patients had fresh closed fractures without femur,tibia and fibula fracture.Surgery was complet-ed from 4 to 7 d after hospital admission.During the operation,the X-ray carbon bed was used,the pelvic ring was reduced by Starr pelvis reduction frame,and pelvic ring fracture was treated by orthopedic robot.Operation time,bleeding volume,fluo-roscopy times of single screw placement,fracture reduction quality,affected limb function and complications were observed.Radiological reduction was evaluated using Matta scoring standard,and clinical efficacy was evaluated by Majeed pelvic func-tion scoring system at the final follow-up.Results All of 14 patients successfully completed the operation,the operation time was 84 to 141 min,the bleeding volume was 20 to 50 ml,and the fluoroscopy times of single screw insertion was 4 to 9 times.All of 14 patients were followed up for 12 to 24 months.The healing time was 3 to 7 months.No complications such as fracture of internal fixation,screw loosening,infection and nerve injury were found.According to the evaluation criteria of Matta imag-ing reduction,9 cases were excellent,4 cases were good,and 1 case was fair.At the final follow-up,Majeed pelvic function scoring system was used:10 cases were excellent,4 cases were good.Conclusion The treatment of type C pelvic ring fracture with robotic combined Starr pelvis reduction frame is simple,time-saving,less trauma,less complications and effective.
5.Effect of recombinant glycoprotein hormone beta5/alpha2 on promoting lipolysis via regulation of cAMP/PKA/CREB pathway in 3T3-L1 adipocytes and its mechanism
Ai-Jun QIAN ; Geng-Miao XIAO ; Zhuang LI ; Xue TIAN ; Xiao-Hong LIU ; Yu-Ping SONG ; Zheng-Gang ZHAO ; Zi-Jian ZHAO ; Fang-Hong LI
Chinese Pharmacological Bulletin 2024;40(7):1272-1278
Aim To investigate the effect of recombi-nant glycoprotein hormone β5/α2(rCGH)on lipolysis in 3T3-L1 adipocytes,and explore the underlying mechanism.Methods 3T3-L1 preadipocytes were cultured and induced to differentiate into mature adipo-cytes,then treated with different concentrations of rCGH for 24 h in vitro.Cell viability of 3T3-L1 adipo-cytes was evaluated by CCK-8 assay,the levels of in-tracellular triglyceride(TG)and glycerol in the culture supernatant were measured by enzymatic method,and the changes of lipid droplets were observed by oil red O staining.The expression levels of HSL and ATGL lipo-lytic proteins in adipocytes were detected by Western blot.To carry out the intervention experiment with dif-ferent concentrations of rCGH with or without the PKA inhibitor,H89,on the mature 3T3-L1 adipocytes,the cultured cells were divided into the control group,H89 pre treatment group,1 μmol·L-1 rCGH group,and(1 μmol·L-1 rCGH+H89)combined intervention group.The contents of intracellular TG and free glycer-ol were measured by enzymatic method,and the ex-pression of CREB and lipolysis-related proteins was de-tected using Western blot.Results Different concen-trations of rCGH(0.25,0.5,1,and 2 μmol·L-1)had no significant effect on the cell viability of adipo-cytes(P>0.05).Compared with the control group,the treatment with rCGH significantly decreased the size of lipid droplets and intracellular TG content,while significantly elevated glycerol concentration in cell supernatant.rCGH treatment also stimulated the protein expression of p-HSL,ATGL,and p-PKA.In addition,the addition of a PKA inhibitor,H89,atten-uated the effects of rCGH on free glycerol level,intra-cellular TG content,and the expression of p-HSL,p-PLIN1,and p-CREB.Conclusions rCGH enhances the lipolysis of 3T3-L1 adipocytes by up-regulating the activities of HSL,ATGL and PKA,promoting glycerol release,inhibiting TG synthesis and lipid accumula-tion,and its mechanism of action is related to the acti-vation of cAMP/PKA/CREB signaling pathway.
6.Exploration of the Mechanism of Toddalia asiatica in the Treatment of Ischemic Stroke:Based on Network Pharmacology and Experimental Validation
Jian-Hong GAO ; Dan YANG ; Gang WANG ; Tian-Ying SONG ; Fang-Yu ZHAO ; Xian-Bing CHEN
Chinese Pharmacological Bulletin 2024;40(7):1375-1383
Aim This study aims to investigate the therapeutic effect and underlying mechanism of Todda-lia asiatica in the treatment of ischemic stroke(IS),utilizing network pharmacology,molecular docking technology,and animal experiments.Methods To screen the chemical components of Toddalia asiatica and its targets related to IS,a database was utilized.A protein-protein interaction(PPI)network was con-structed,followed by KEGG pathway enrichment anal-ysis.Molecular docking was performed to investigate the interaction between the components and target pro-teins.Finally,the effects of the drug on the PI3K/AKT/mTOR pathway and autophagy were validated through animal experiments.We established a middle cerebral artery occlusion(MCAO)rat model and di-vided the rats into the model group,Donepezil hydro-chloride group,Toddalia asiatica group,and sham op-eration group randomly.Observed the pathological changes in neurons of the rat hippocampal and cortical regions induced by the drug,performed immunohisto-chemical analysis to detect and localize mTOR expres-sion,and used Western blot to assess the expression levels of PI3K,p-PI3K,AKT,p-AKT,mTOR,as well as autophagy markers(LC3-Ⅱ and p62).Re-sults A total of 22 active ingredients from Toddalia asiatica,including AKT1 and MAPK3,were identified through screening.Additionally,194 signaling path-ways,such as PI3K/AKT and MAPK,were analyzed.The active compounds in Toddalia asiatica demonstra-ted stable binding affinity with targets associated with ischemic stroke.The results of the animal experiment indicated that,compared to the sham-operated group,the neuronal distribution in the hippocampal and corti-cal regions of the model group rats became sparser and more disorganized.There was a decrease in the number of Nissl bodies and cytoplasmic vacuolization.The ex-pression of mTOR-positive cells in the hippocampal and cortical regions was reduced.Additionally,the ex-pression levels of p-PI3K,p-AKT,mTOR,and p62 in the rat hippocampal tissue decreased(P<0.05,P<0.01),while the expression of LC3-Ⅱ increased(P<0.01).Compared with the model group,the rats in the Toddalia asiatica and the Donepezil hydrochloride groups effectively improved the aforementioned indica-tors in rats.Conclusions Network pharmacology a-nalysis has revealed the promising potential of Toddalia asiatica in treating ischemic stroke,attributed to its di-verse components,targets,and pathways.The animal experiment showed that Toddalia asiatica can protect the neuronal structure in the hippocampal and cortical regions,which may be related to the inhibition of ex-cessive autophagy mediated by the PI3 K/AKT/mTOR pathway.
7.Epidemiological characteristics of pulmonary tuberculosis in the elderly people in Wuhan in 2016-2020
Zhou-qin LU ; Zheng-bin ZHANG ; Xiao-jun WANG ; Xin REN ; Dan TIAN ; Gang WU ; Qiong-hong DUAN ; Jian-jie WANG ; Mei-lan ZHOU ; Yue-hua LI
Journal of Public Health and Preventive Medicine 2023;34(1):35-38
Objective To analyze the epidemiological characteristics of pulmonary tuberculosis in the elderly people in Wuhan during 2016-2020, and to provide a basis for formulating effective prevention and control strategies and measures. Methods Using the National Tuberculosis Information Management System, a descriptive statistical analysis was performed on the medical records of elderly (≥60 years old) pulmonary tuberculosis patients registered in Wuhan from 2016 to 2020. Results A total of 9 427 elderly pulmonary tuberculosis patients were registered in Wuhan during 2016-2020, accounting for 32.07% of the total number of registrations in the whole population. The reported incidence rate of tuberculosis in the elderly was significantly higher than that in the total population, and the reported incidence rates in both the elderly and the general population showed declining trends (whole population χ2trend=216.97, P<0.05, elderly population χ2trend=153.57, P<0.05). The time distribution showed that more cases occurred from April to November (70.90%). The top three districts with the largest number of registered cases were far urban areas, namely Huangpi District (13.81%), Xinzhou District (11.55%), and Jiangxia District (9.82%). The ratio of male to female with pulmonary tuberculosis in elderly patients was 2.85:1. Among the elderly pulmonary tuberculosis, the most registered cases were in the age group of 60 ~ years old, followed by 65 ~ years old. The proportion of smear-positive in elderly patients with pulmonary tuberculosis retreatment was 16.83%. Conclusion From 2016 to 2020, the epidemic situation of elderly pulmonary tuberculosis showed a downward trend in Wuhan. However, the elderly population with tuberculosis registrations still accounted for a relatively high proportion of the total population. According to the epidemiological characteristics of pulmonary tuberculosis among the elderly, the city should carry out tuberculosis prevention and control work in a timely, appropriate and focused manner.
8.Epididymis cell atlas in a patient with a sex development disorder and a novel NR5A1 gene mutation.
Jian-Wu SHI ; Yi-Wen ZHOU ; Yu-Fei CHEN ; Mei YE ; Feng QIAO ; Jia-Wei TIAN ; Meng-Ya ZHANG ; Hao-Cheng LIN ; Gang-Cai XIE ; Kin Lam FOK ; Hui JIANG ; Yang LIU ; Hao CHEN
Asian Journal of Andrology 2023;25(1):103-112
This study aims to characterize the cell atlas of the epididymis derived from a 46,XY disorders of sex development (DSD) patient with a novel heterozygous mutation of the nuclear receptor subfamily 5 group A member 1 (NR5A1) gene. Next-generation sequencing found a heterozygous c.124C>G mutation in NR5A1 that resulted in a p.Q42E missense mutation in the conserved DNA-binding domain of NR5A1. The patient demonstrated feminization of external genitalia and Tanner stage 1 breast development. The surgical procedure revealed a morphologically normal epididymis and vas deferens but a dysplastic testis. Microfluidic-based single-cell RNA sequencing (scRNA-seq) analysis found that the fibroblast cells were significantly increased (approximately 46.5%), whereas the number of main epididymal epithelial cells (approximately 9.2%), such as principal cells and basal cells, was dramatically decreased. Bioinformatics analysis of cell-cell communications and gene regulatory networks at the single-cell level inferred that epididymal epithelial cell loss and fibroblast occupation are associated with the epithelial-to-mesenchymal transition (EMT) process. The present study provides a cell atlas of the epididymis of a patient with 46,XY DSD and serves as an important resource for understanding the pathophysiology of DSD.
Male
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Humans
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Epididymis
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Disorder of Sex Development, 46,XY/genetics*
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Disorders of Sex Development
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Mutation
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Mutation, Missense
;
Steroidogenic Factor 1/genetics*
9.Safety and feasibility of 120 min rapid infusion regimen of daratumumab in patients with multiple myeloma.
Tian Hang WANG ; Rui HAO ; Bao Nan XU ; Liang CHANG ; Zhao Bao LIU ; Jia Lin YAO ; Wen WANG ; Wen Jun XIE ; Wen qiang YAN ; Zhi Jian XIAO ; Lu Gui QIU ; Gang AN
Chinese Journal of Hematology 2023;44(8):696-699
10.Efficacy and safety of intermediate-dose cytarabine in the treatment of children with refractory high risk Langerhans cell histiocytosis.
Wen Qian WANG ; Jian GE ; Hong Hao MA ; Hong Yun LIAN ; Lei CUI ; Li ZHANG ; Zhi Gang LI ; Tian You WANG ; Rui ZHANG
Chinese Journal of Pediatrics 2023;61(12):1118-1123
Objective: To analyze the efficacy, safety, and long-term prognosis of intermediate-dose cytarabine (Ara-c) regimen in the treatment of children with refractory risk organ involvement Langerhans cell histiocytosis (LCH). Methods: Clinical data of 17 children with multisystem and risk organ involvement LCH who failed the first-line therapy and were treated with intermediate-dose Ara-c (250 mg/m2, twice daily) regimen in the Hematology Center, Beijing Children's Hospital from January 2013 to December 2016 were analyzed retrospectively. In addition to the basic treatment of vindesine and dexamethasone, the patients received two regimens: regimen A: the intermediate-dose Ara-c combined with cladribine and regimen B: the intermediate-dose Ara-c alone. The efficacy, safety and prognosis of the two regimens were analyzed. Results: Among all 17 patients, there were 11 males and 6 females, with the diagnosis age of 2.1 (1.6, 2.7) years. Ten children received regimen A, all of them achieved active disease-better (AD-B) after 8 courses of induction therapy. The disease activity scores (DAS) decreased from 5.5 (3.0, 9.0) to 1.0 (0, 2.3). Seven children received regimen B, and 6 of them achieved AD-B after 8 courses of induction therapy. The DAS decreased from 4.0 (2.0, 4.0) to 1.0 (0, 2.0). The follow-up time was 6.2 (4.9,7.2) and 5.2 (3.7,5.8) years in group A and B. The 5-year overall survival rate was 100.0% in both groups, and the 5-year event free survival rate was (88.9±10.5)% and (85.7±13.2)% in group A and B. Grade 3 or 4 myelosuppression was observed in 8 patients in group A and 2 patients in group B. Conclusions: The intermediate-dose Ara-c regimen (with or without cladribine) is effective and safe for patients with refractory high-risk LCH, with a good long-term prognosis.
Male
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Female
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Child
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Humans
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Cytarabine/adverse effects*
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Cladribine/adverse effects*
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Retrospective Studies
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Antineoplastic Combined Chemotherapy Protocols/adverse effects*
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Histiocytosis, Langerhans-Cell/drug therapy*
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Prognosis


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