1.Study on relationships of MS4A1 gene polymorphism with blood concentration and efficacy of rituximab in patients with non-Hodgkin’s lymphoma
Feng SHI ; Tao LIU ; He HUANG ; Caifu FANG ; Shaoxing GUAN ; Zhang ZHANG ; Zhao WANG ; Xiaojie FANG ; Zhuojia CHEN ; Shu LIU
China Pharmacy 2025;36(13):1641-1647
OBJECTIVE To explore the effects of CD20 coding gene (MS4A1) polymorphism on the blood concentration and efficacy of rituximab in patients with non-Hodgkin’s lymphoma. METHODS A prospective observational study was conducted on 160 newly diagnosed non-Hodgkin’s lymphoma patients who received the R-CHOP regimen at the Sun Yat Sen University Cancer Center from January 2016 to December 2020, with a minimum follow-up period of approximately 5 years. The blood concentration of rituximab was detected by enzyme-linked immunosorbent assay. MS4A1 tagSNPs were selected by Haploview4.2 software, including rs1051461, rs17155034, rs4939364, and rs10501385. The genotype of MS4A1 was detected by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Univariate linear regression analysis was employed to examine the correlation between various factors(demographic, clinical, and genotypic variables) in patients and the steady-state trough concentration of rituximab during the first course of treatment, followed by multivariate linear regression analysis. Kaplan-Meier curves were drawn to evaluate progression-free survival (PFS) and overall survival (OS). Using MS4A1 genotype and tumor stage as independent variables, Cox regression model was employed to evaluate the factors influencing patient prognosis. RESULTS The blood concentration of rituximab in MS4A1 rs10501385 CC carriers was 15.20 μg/mL,which was significantly lower than 21.95 μg/mL in AA+AC carriers (P<0.05). The multivariate linear regression model incorporating tumor stage and MS4A1 rs10501385 polymorphism explained 7.3% of the interindividual variability in rituximab concentrations. Compared with MS4A1 rs1051461 CC carriers, CT+TT carriers had significantly prolonged PFS and OS (P<0.05). The Cox proportional hazards regression model showed that the MS4A1 rs1051461 CC genotype (HR=4.406, 95%CI:1.743-11.137, P<0.05) and tumor Ⅲ&Ⅳ (HR=3.233, 95%CI: 1.413-7.399, P<0.05) were independent risk factors for PFS. CONCLUSIONS The tumor staging and MS4A1 rs10501385 polymorphism are key influencing factors for blood concentration of rituximab, and MS4A1 rs1051461 polymorphism significantly affects PFS in non-Hodgkin’s lymphoma patients.
2.Analysis of syncopal DRVR in blood donors: multicenter hemovigilance data (2020—2023)
Junhong YANG ; Qing XU ; Wenqin ZHU ; Fei TANG ; Ruru HE ; Zhenping LU ; Zhujiang YE ; Fade ZHONG ; Gang WU ; Guoqiang FENG ; Xiaojie GUO ; Jia ZENG ; Xia HUANG
Chinese Journal of Blood Transfusion 2025;38(8):1071-1076
Objective: Data on syncopal donation-related vasovagal reaction (DRVR) collected from 74 blood centers between 2020 and 2023 was statistically analyzed to provide a reference for developing preventive strategies against syncopal DRVR. Methods: Data on blood donation adverse reactions and basic information of donors from 2020 to 2023 were collected through the information management system at monitoring sentinel sites. Statistical analysis was performed on the following aspects of syncopal DRVR: characteristics of donors who experienced syncope, reported incidence, triggers, duration, presence and occurrence time of syncope-related trauma, clinical management including outpatient and inpatient treatment, and severity grading. Results: From 2020 to 2023, 45 966 donation-related adverse reactions were recorded. Of these, 1 665 (3.72%) cases were syncopal DRVR. The incidence of syncopal DRVR decreased with age, being the highest in the 18-22 age group. Incidence was significantly higher in female donors than male donors, in first-time donors than repeat donors, and in university and individual donors than group donors (all P<0.05). There was no statistically significant difference among different blood donation locations (P>0.05). The top three triggers were tension, fatigue, and needle phobia or fear of blood. Among syncopal DRVR cases, 60.36% occurred during blood collection, 87.63% lasted for less than 60 seconds, and 5.05% were accompanied by trauma. Notably, 57.14% of these traumas occurred after donor had left the blood collection site. Syncope severity was graded based on required treatment: grade 1 (fully recovered without treatment, 95.50%); grade 2 (recovered after outpatient treatment, 4.02%); and grade 3 (recovered after inpatient treatment, 0.48%). Conclusion: By analyzing the data of syncopal DRVR cases, it is possible to provide a reference for formulating blood donor safety policies.
3.Construction of a prediction efficacy model for PD-1 inhibitor in advanced esophageal squamous cell carcinoma
Shanshan WU ; Xiaojie HUANG ; Xiaochun XIE ; Shaokai HUANG ; Lina HUANG ; Xiaofen WANG
China Pharmacy 2025;36(17):2154-2159
OBJECTIVE To develop a prediction model for durable clinical benefit (DCB) in patients with advanced esophageal squamous cell carcinoma (ESCC) receiving programmed death-1 (PD-1) inhibitor. METHODS The clinical data of patients with advanced ESCC who received PD-1 inhibitor in Jieyang People’s Hospital were retrospectively collected between January 2020 to December 2023. Predictors were screened by least absolute shrinkage and selection operator (Lasso) regression, and a multivariable Logistic regression model was developed to predict DCB. A nomogram was constructed based on the model. Internal validation of the prediction model was performed by using the Bootstrap method, and the model was evaluated by the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis. RESULTS A total of 91 patients with advanced ESCC were included. The results of Lasso regression combined with Logistic regression analysis indicated that the baseline lymphocyte monocyte ratio (LMR) [odds ratio (OR)=1.97, 95% confidence interval (CI): 1.15-3.36, P=0.013], albumin (ALB) content (OR=1.35, 95%CI: 1.13-1.60, P<0.001), body mass index (BMI) category 1 [normal vs. low: OR= 0.28, 95%CI (0.09-0.96), P=0.042], BMI category 2 [overweight-obesity vs. low: OR=0.08, 95%CI (0.01-0.59), P=0.013], and treatment regimen [monotherapy vs. monotherapy combination therapy: OR=0.07, 95%CI (0.01-0.50), P=0.008] were predictive factors for patients with advanced ESCC to achieve DCB when treated with PD-1 inhibitor. A prediction model was constructed based on the above indicators. Internal validation of the model using the Bootstrap method showed an area under the curve of 0.831 (95%CI: 0.746-0.904), with specificity of 74.4% and sensitivity of 75.0%. The Hosmer-Lemeshow test yielded χ2= 9.930, P=0.270, and the calibration curve slope was close to 1. The decision curve analysis demonstrated that the model exhibited good clinical utility within a threshold range of 0.1 to 1.0. CONCLUSIONS The prediction model based on baseline LMR, ALB content, BMI, and treatment regimen demonstrates robust predictive performance and clinical utility for assessing therapeutic efficacy of PD-1 inhibitor in the treatment of advanced ESCC.
4. The application of positron emission tomography in the research and development of central nervous system drugs
Size LI ; Xiaojie WU ; Jing ZHANG ; Qi HUANG ; Yihui GUAN ; Fang XIE ; Qi HUANG ; Yihui GUAN ; Fang XIE ; Shaonan WANG ; Jing ZHANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(3):316-327
Positron emission tomography (PET) now plays an important role in the research and development (R&D) of central nervous system (CNS) drugs. PET could characterize the biodistribution, pharmacokinetics, and receptor binding of CNS drugs quantitatively. The present review summarized the quantitative methods of PET used in the pharmacokinetics and receptor occupancy analysis of CNS drugs. Moreover, the present review listed various applications of PET supporting R&D of CNS drugs, which could provide a new direction for the R&D of CNS drugs.
5.The molecular epidemiological characteristics of the gastroenteritis outbreaks caused by norovirusin Hainan Province,2020-2022
Yunting ZENG ; Haiyun CHEN ; Dandan LI ; Yanhui YANG ; Miao JIN ; Qiong HUANG ; Lei CUI ; Zhengfan PAN ; Lina REN ; Xiaojie YU
Acta Universitatis Medicinalis Anhui 2024;59(2):336-343
Objective To understand the molecular epidemiological characteristics of Norovirus outbreaks and the genome evolution of Norovirus epidemic strains in Hainan Province from 2020 to 2022.Methods The information and samples have been collected from the norovirus outbreaks from 2020 to 2022.Norovirus was detected by using the real-time PCR in these samples,then the detected sequences were amplified the analyzed.The Norovirus se-quences of 8 strains had been amplified and analyzed.Results From 2020 to 2022,39 gastroenteritis outbreaks were reported,and 25 outbreaks caused by Norovirus which mainly occurred in childcare institutions and schools(20/25,80%).The Norovirus outbreaks were mainly concentrated in counties around Haikou(northeast),which including Ding'an(5 cases),Wenchang(4 cases),Chengmai(4 cases),and Lingao(3 cases);following by western regions which included Baisha(2 cases),Ledong(2 cases),and Dongfang(3 cases).1 case was in Wanning in the southeast.Among individuals aged 2-17,the positive proportion of Norovirus in males was higher than that in females.Among individuals aged over 55,the proportion of Norovirus positive in females was higher than that in males.The gender of positive samples among individuals aged 18-40 was related to their profession.According to RT-PCR typing and sequencing,GⅡ group Norovirus were classified in13 outbreaks.There were 4 genotypes detected.GⅡ.2[P1 6]was the main epidemic strain with 60%(9/13),and the other three genotypes were GⅡ.4 Sydney[P31](15.4%,2/13)GⅡ.4 Sydney[P16](7.7%,1/13)and GⅡ.3[P12](7.7%,1/13).Further genic analysis of 8 Norovirus strains showed that all of them were still in the same branch as the previ-ous strain,and all exhibited a certain amount of amino acid variation.Conclusion Norovirus is the main pathogen of gastroenteritis outbreaks in Hainan province,and the main epidemic strain is GⅡ.2[P16].It is necessary to continue to strengthen the monitoring that provides scientific evidence for the prevention and control of norovirus out-breaks in Hainan region.
6.Construction of pancreatic cancer organoids and their sensitivity to chemotherapy drugs
Jingyu WANG ; Rong HUANG ; Yan LU ; Ziran CHEN ; Xiaojie ZHANG ; Hu REN ; Nan ZHANG ; Dongbing ZHAO ; Wei SONG ; Xingguang ZHANG
Journal of Clinical Hepatology 2024;40(9):1853-1858
Objective To construct and identify a patient-derived organoid model,and to investigate the sensitivity of chemotherapy drugs using this model.Methods Pancreatic cancer cells were obtained from the surgical specimens of two female patients with a confirmed diagnosis of pancreatic cancer after tumor tissue digestion,and then the cells were inoculated into a culture dish using matrigel for three-dimensional culture.Paraffin sections were prepared for HE staining and immunohistochemical staining and were compared with the parent tumor tissue to determine whether the histopathological features of the tumor in vivo were preserved.The pancreatic cancer organoids were treated with seven chemotherapy drugs at different concentrations;Cell Titer-Glo?3D reagent was used to measure cell viability,and the results of drug sensitivity were analyzed.Results Two patient-derived pancreatic cancer organoids were successfully constructed,and HE staining and immunohistochemical staining showed that the pancreatic cancer organoids had consistent histopathological features with the tumors of the corresponding patient.Both pancreatic cancer organoids were more sensitive to gemcitabine monotherapy and the combination of oxaliplatin+SN38+fluorouracil,and patient 1 was more sensitive than patient 2.There were individual differences in the response to drugs between the organoids from different patients.Conclusion The pancreatic cancer organoid model successfully constructed in this study can reflect the histological classification of parent pancreatic tumors and can be used for in vitro chemotherapy drug sensitivity test,which is expected to provide a reference for clinical medication.
7.Clinical study of transcatheter drug-loaded microsphere embolization in the treatment of patients with advanced bladder cancer with bleeding
Qihong CHEN ; Qingxian ZHANG ; Jianxiong LIN ; Jinqi HUANG ; Xiaojie GAO
Journal of Practical Radiology 2024;40(10):1699-1701,1716
Objective To investigate the feasibility,safety and efficacy of transcatheter drug-loaded microsphere embolization(DLME)in treating patients with advanced bladder cancer with bleeding(ABCB).Methods A total of 26 ABCB patients who underwent DLME for tumor supply arteries were retrospectively selected.The postoperative efficacy and related complications were observed.The recurrence of hematuria and survival situation were followed up.Results All 26 surgeries achieved success with a technical success rate of 100.0%.There were 21 cases(80.8%)of bilateral bladder artery embolism and 5 cases(19.2%)of unilateral bladder artery embolism.Three days after the operation,24 patients(92.3%)had hematuria remission.And the other two patients(7.7%)had no hematuria remission,they were relieved after interventional embolization again.Compared with that before operation,the blood transfusion rate,blood transfusion volume,hematocrit and hemoglobin at one week after operation were significantly improved(P<0.05).One month after the last intervention,there were 2 cases of complete response,19 cases of partial response,3 cases of stable disease,and 2 cases of progressive disease.The objective remission rate was 80.8%,and the disease control rate was 92.3%.Compared with that before operation,the T stage was significantly improved at one month after operation(P<0.05).No patients had severe complications such as ectopic embolism.After follow-up for 3-36 months,5 cases(19.2%)had a recurrence of hematuria.Conclusion Transcatheter DLME is feasible,safe,and effective in the treatment of patients with ABCB.It is an optional,minimally invasive palliative measure.
8.Preliminary application of virtual reality for pain management in patients undergoing peritoneal dialysis-related procedures
Sixiu CHEN ; Jianbo LI ; Jianwen YU ; Yujun ZHOU ; Youqi LI ; Xiaojie LIN ; Naya HUANG ; Zhong ZHONG ; Yunuo WANG ; Jianying LI ; Qinghua LIU ; Haiping MAO ; Fengxian HUANG ; Wei CHEN
Chinese Journal of Nephrology 2024;40(7):520-525
Objective:To investigate the application of virtual reality (VR) technology on intraoperative pain in patients undergoing peritoneal dialysis (PD)-related procedures with local infiltration anesthesia and the satisfaction.Methods:It was a single-center, prospective, concurrent controlled study. Patients were divided into two groups: VR group and control group. In the VR group, patients wore a VR headset to watch soothing audio and video content during surgery, while the control group underwent routine procedures. Intraoperative pain and satisfaction were assessed using the visual analog scale (VAS) and a 5-point satisfaction scale within 30 minutes of surgery. In addition, tolerance of the VR experience in the VR group was assessed using the VR sickness questionnaire.Results:A total of 43 patients were included in the study, including 25 males (58.1%). Chronic glomerulonephritis [17 cases (39.5%)] and diabetic nephropathy [6 cases (14.0%)] were the main primary diseases. There were 23 cases in the control group and 20 cases in the VR group. There were no significant differences between the two groups in age, sex ratio, proportion of primary disease, diabetes, hypertension, distribution of operation methods, preoperative vital signs and operation time (all P>0.05). VAS pain score was significantly lower in the VR group than that in the control group (5.90±2.38 vs. 7.43±1.67, t=2.469, P=0.018). The percentage of patients who were satisfied was 89.5% (17/19) in the VR group and 78.3% (18/23) in the control group, but there was no significant difference (chi-square test for continuity correction, χ2=0.308, P=0.579). Three patients in the VR group withdrew from the study due to severe discomfort, while the remaining participants found the VR experience to be tolerable. Common adverse effects included fatigue and blurred vision. Conclusions:The application of VR technology in PD-related procedures has been effective in reducing intraoperative pain when combined with local infiltration anesthesia. Furthermore, the utilization of VR technology in PD-related procedures is associated with a safe and tolerable outcome, despite the observation of some adverse effects.
9.Distribution pattern of the rectal circumferential fascia and its clinical significance: An anatomical study
Xiaojie WANG ; Yu DENG ; Zhifang ZHENG ; Ying HUANG ; Pan CHI
Chinese Journal of Gastrointestinal Surgery 2024;27(9):919-927
Objective:To investigate the pattern of distribution of the circumferential fascia of the rectum and elucidate its clinical implications.Methods:In this descriptive study, we examined the gross anatomy of four male hemipelvic cadaveric specimens from the Department of Anatomy at Fujian Medical University and the histological features of 16 fresh postoperative specimens from patients who had undergone total mesorectal excision for rectal cancer at the Department of Colorectal Surgery, Union Hospital, Fujian Medical University, between January and December 2022. The resultant combination of gross anatomical and histological features was employed to assess the following areas: (1)the morphology of the anterior mesorectum and fascia at the peritoneal reflection; (2)the caudal attachment point of Denonvilliers' fascia; (3) the fusion area of the pelvic plexus and the pre-hypogastric fascia; (4)the lateral and posterior attachment edges of the rectosacral fascia; and (5) selected histological features.Results:Our findings were as follows. (1) At the peritoneal reflection, the anterior mesorectum forms a triangular fat pad with a dense fascial structure. The base of this pad extends anteriorly across the most caudal point of the peritoneal reflection, with Denonvilliers' fascia originating from the anterior side of the triangle, near the bladder side of the peritoneum craniad to the peritoneal reflection. (2) The caudal attachment of Denonvilliers' fascia is at the angle between the seminal vesicles, the ampulla of the vas deferens, and the prostate. It adheres tightly to the prostatic capsule and vascular bundles pass through its cephalic side. (3) The pre-hypogastric fascia transitions laterally to merge with Denonvilliers' fascia; its middle part being inseparable from the main body of the pelvic plexus, which gives rise to the nerves that innervate the rectum. (4) The rectosacral fascia is formed by fusion of the fascia propria with the pre-hypogastric fascia. The resultant fused fascia bifurcates into two leaves on the right side; the outer leaf being the pre-hypogastric fascia and the inner leaf the fascia propria. (5) Histologically, the peritoneal reflection zone shows cuboidal epithelium of the peritoneum at its lowest point with no detectable origin of Denonvilliers' fascia. The anterior side of the peritoneal reflection, from which Denonvilliers' fascia originates, has a dense double-layered fascial structure comprising thick collagen fiber (16/16). The fascia propria exhibits a thinner and looser collagen fiber structure and its origin varies between individuals, 13/16 originating together with Denonvilliers' fascia from the craniad side of the peritoneal reflection, and 3/16 originating separately from the most caudal point of the peritoneal reflection. The caudal edge of Denonvilliers' fascia has a double-layered fascial structure with multiple S100-stained areas. The posterior edge of the rectosacral fascia has a fused fascial structure, thick nerve fibers being clearly observable between collagen fibers originating from the pre-hypogastric fascia under high magnification. The lateral edge of the rectosacral fascia extends interiorly, maintains the integrity of the fascia propria.Conclusions:In this study, we investigated the pattern of distribution of the circumferential fascia of the rectum by cadaveric dissection and histological examination of postoperative specimens. We found that the anterior mesorectum forms a triangular fat pad that can serve as a reference for dissection anterior to Denonvilliers' fascia, by making incisions 1 cm above the peritoneal reflection. The region of fusion of Denonvilliers' fascia with the prostatic capsule on the caudal side is rich in neurovascular bundles, contradicting the traditional view of a retroprostatic plane. This finding supports the practice of cutting Denonvilliers' fascia 0.5 cm above the base of the seminal vesicles. The fusion of the fascia propria with the pre-hypogastric fascia posteriorly forms the rectosacral fascia, which bifurcates into two leaves on both sides of the rectum, the inner leaf being the fascia propria and the outer leaf the pre-hypogastric fascia. These transition anteriorly to become Denonvilliers' fascia and fuse densely with the main body of the pelvic plexus on both sides. These findings provide a theoretical foundation for protecting the pelvic plexus and hypogastric nerve by transecting Denonvilliers' fascia and then dissecting in a top-to-bottom direction (i.e., from anterior to caudal), ultimately leading to the transection of the pre-hypogastric fascia.
10.Endovascular treatment of acute Stanford B-type aortic dissection involving the aortic arch
Qihong CHEN ; Xiaojie GAO ; Qingxian ZHANG ; Huang CHEN ; Jinqi HUANG
Journal of Practical Radiology 2024;40(12):2054-2057
Objective To explore the clinical effect of endovascular stent-graft exclusion in the treatment of acute Stanford B-type aortic dissection(AD)with distal left subclavian artery(LSA)rupture accompanied by arch intramural hematoma.Methods A total of 12 patients with acute AD treated by the endovascular stent-graft exclusion alone were retrospectively selected.All patients had primary rupture at the distal end of LSA with arch intramural hematoma and received endovascular treatment after 2 to 3 weeks of conservative treatment.The technique success rate and related complications were observed.Postoperative computed tomography angiography(CTA)of the aorta was reviewed to evaluate the remodeling of the true and false lumen,the absorption of the arch intramural hematoma,to observe whether there was a new rupture and endoleak,and to understand the position and shape of the stent and the blood supply of the branch arteries.Results All patients completed the operation with a technical success rate of 100%.Two patients partially blocked the opening of LSA,and one patient had type Ⅰ internal leakage after the operation,but the amount of internal leakage was small and was not treated.Other patients did not had serious complications such as aortic rupture,new rupture,paraplegia,stent displacement,stroke,upper limb ischemia or vertebral artery ischemia,internal leakage,and abdominal organ ischemia during and after the operation.The patients were followed up for 19 to 66 months,with an average follow-up of(36.7±13.9)months.During the follow-up period,no patient died.The aortic remodeling was satisfactory in all patients,the arch intramural hematoma was absorbed,and there were no new rupture,internal leakage,upper limb ischemia or vertebral artery ischemia,or other serious complications.One patient with type Ⅰ internal leakage showed no significant change in internal leakage after regular postoperative reexamination.Conclusion Endovascular stent-graft exclusion is safe and feasible in the treatment of acute AD patients with distal LSA rupture accompanied by arch intramural hematoma,and it is worth promoting and applying clinically.

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