1.The evaluation of alpha-fetoprotein response on efficacy and prognosis in targeted therapy combined with immunotherapy for intermediate-to-advanced hepatocellular carcinoma: a multicenter clinical study
Kongying LIN ; Qingjing CHEN ; Luobin GUO ; Yun YANG ; Yufeng CHEN ; Jianxi ZHANG ; Fuqun WEI ; Hui ZHANG ; Zhiqing CHENG ; Yuntong LI ; Congren WANG ; Yabin JIANG ; Kecan LIN ; Weiping ZHOU ; Yongyi ZENG
Chinese Journal of Digestive Surgery 2024;23(2):248-256
Objective:To investigate the evaluation efficacy and predictive prognostic value of alpha-fetoprotein (AFP) response in tyrosine kinase inhibitors (TKIs) in combination with PD-1 inhibitors (α-PD-1) for intermediate-to-advanced hepatocellular carcinoma (HCC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 205 patients with intermediate-to-advanced HCC who were admitted to 9 medical centers, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from March 2020 to July 2022 were collected. There were 178 males and 27 females, aged (52±12)years. Based on AFP response at 6-8 weeks after treatment, patients were divided into the AFP response group (AFP level decreased by ≥50% compared to baseline) and the AFP no response group (AFP level decreased by <50% compared to baseline). Observation indicators: (1) AFP response evaluation of anti-tumor efficacy; (2) comparison of patient prognosis; (3) analysis of factors affecting patient prognosis. Measurement data with normal distrubution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range) and M( Q1, Q3). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to draw survival curve and calculate survival rate, and the Log-Rank test was used for survival analysis. The COX proportional risk model was used for univariate analysis and the COX stepwise regression model was used for multivariate analysis. Results:(1) AFP response evaluation of anti-tumor efficacy. Before treatment, all 205 patients were positive of AFP, with a baseline AFP level of 1 560(219,3 400)μg/L. All 205 patients were treated with TKIs in combination with α-PD-1, and the AFP level was 776(66,2 000)μg/L after 6 to 8 weeks of treatment. Of the 205 patients, 88 cases were classified as AFP response and 117 cases were classified as AFP no response. According to the response evaluation criteria in solid tumors version 1.1, the objective response rate (ORR) and disease control rate (DCR) were 42.05%(37/88) and 94.32%(83/88) in patients of the AFP response group and 16.24% (19/117) and 64.10% (75/117) in patients of the AFP no response group, showing significant differences between them ( χ2=16.846, 25.950, P<0.05). According to the modified response evaluation criteria in solid tumors, the ORR and DCR were 69.32% (61/88) and 94.32% (83/88) in patients of the AFP response group and 33.33% (39/117) and 64.10% (75/117) in patients of the AFP no response group, showing significant differences between them ( χ2=26.030, 25.950, P<0.05). (2) Comparison of patient prognosis. All 205 patients were followed up for 12.4(range, 2.4-34.0)months after treatment. The median progression free survival time and total survival time were 5.5 months and 17.8 months, respectively. The 1-year, 2-year progression free survival rates were 20.8% and 7.2%, and the 1-year, 2-year overall survival rates were 68.7% and 31.5%, respectively. The median progression free survival time, 1-year and 2-year progression free survival rates were 9.7 months, 39.6% and 14.2% in patients of the AFP response group and 3.7 months, 7.8% and 2.0% in patients of the AFP no response group, showing a significant difference in progression free survival between them ( χ2=43.154, P<0.05). The median overall survival time, 1-year and 2-year overall survival rates were not reached, 85.2% and 56.3% in patients of the AFP response group and 14.6 months, 56.3% and 14.5% in patients of the AFP no response group, showing a significant difference in overall survival between them ( χ2=33.899, P<0.05). (3) Analysis of factors affecting patient prognosis. Results of multivariate analysis showed that invasion of large blood vessels, extrahepatic metastasis, combined hepatic artery intervention therapy, and AFP response were independent factors influencing progression free survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1 ( hazard ratio=1.474, 1.584, 0.631, 0.367, 95% confidence interval as 1.069-2.033, 1.159-2.167, 0.446-0.893, 0.261-0.516, P<0.05), and Eastern Cooperative Oncology Group score, invasion of large blood vessels, extrahepatic metastasis, and AFP response were independent factors influencing overall survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1 ( hazard ratio= 1.347, 1.914, 1.673, 0.312, 95% confidence interval as 1.041-1.742, 1.293-2.833, 1.141-2.454, 0.197-0.492, P<0.05). Conclusions:AFP response at 6-8 weeks after treatment can effectively evaluate anti-tumor efficacy of TKIs in combination with α-PD-1 for intermediate-to-advanced HCC. AFP response is the independent factor influencing progression free survival and overall survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1.
2.Effect of repetitive transcranial magnetic stimulation versus functional electrical stimulation on post-stroke complex regional pain syndrome
Rongrong PAN ; Xiahui ZHOU ; Mei YU ; Zhiqing CHENG ; Yinghao ZHI
Chinese Journal of Primary Medicine and Pharmacy 2024;31(2):196-200
Objective:To investigate the clinical efficacy of repetitive transcranial magnetic stimulation (rTMS) versus functional electrical stimulation (FES) in the treatment of post-stroke complex regional pain syndrome. Methods:The randomized controlled study included 60 patients with post-stroke complex regional pain syndrome who received treatment at the Wenzhou TCM Hospital of Zhejiang Chinese Medical University from July 2021 to February 2023. These patients were divided into an rTMS group ( n = 30) and an FES group ( n = 30) using a random number table method. Patients in the rTMS group were treated with rTMS, while those in the FES group were treated with FES. All treatments were performed once daily for 8 consecutive weeks. The clinical efficacy, total active movement score of the fingers, Fugl-Meyer assessment scale score, Activity of Daily Living score, modified Barthel Index score, shoulder joint range of motion, and safety were compared between the two groups. Results:The total response rate in the FES group was 86.7% (26/30), which was significantly higher than 83.3% (25/30) in the rTMS group ( Z = 0.09, P = 0.93). After treatment, there were no significant differences between the two groups in terms of total active movement score of the fingers and Fugl-Meyer assessment scale score ( P = 0.244, 0.262). No significant differences were found between the two groups in MBI score and ADL score (both P > 0.05). There was also no significant difference in shoulder joint range of motion between the two groups ( P > 0.05). Conclusion:Both rTMS and FES are highly effective for post-stroke complex regional pain syndrome. They can improve upper limb function, enhance daily living abilities, and remodel neurological functions of the brain.
3.Relationship of frailty with sarcopenia and subjective social isolation among elderly inpatients
Dan YANG ; Chenru CHI ; Mengqi CHEN ; Zhiqing ZHOU ; Huan LIU ; Cuizhen WANG
Journal of Shenyang Medical College 2024;26(3):287-291
Objective:To understand the status of frailty among elderly inpatients,analyze its influencing factors,and explore the relationship of frailty with sarcopenia,and subjective social isolation in elderly inpatients.Methods:A total of 518 elderly inpatients from a tertiary hospital in Wuhu were selected as the research subjects.General information questionnaire,Frail Scale,SARC-F Scale,and Subjective Social Isolation Scale were used for investigation.Logistic regression analysis was used to analyze the influencing factors of frailty among elderly inpatients.Results:The incidence of frailty in 518 elderly inpatients was 52.5%(272/518).Logistic regression analysis revealed that recent falls(OR=3.458,95%CI:1.454-8.229),sarcopenia(OR=5.622,95%CI:2.494-12.677),subjective social isolation(OR=181.165,95%CI:57.307-572.721),polypharmacy(OR=2.409,95%CI:1.336-4.346),and 80-89 years old(OR=8.982,95%CI:0.640-2.357)were risk factors for frailty in elderly inpatients(P<0.05).Conclusions:The prevalence of frailty is high among elderly inpatients.Healthcare professionals should pay attention to the assessment of frailty in elderly inpatients,and promptly implement targeted interventions to slow down or prevent the progression of frailty.
4.The mechanism of imatinib on the regulation of lipopolysaccharide-induced acute lung injury in mice through the Nrf2/HO-1 signaling pathway
Duanyang LI ; Yaru LIU ; Zhiqing ZHOU ; Hong YANG ; Xiaolong ZONG ; Zhenyu LI
Chinese Journal of Emergency Medicine 2024;33(8):1104-1109
Objective:To evaluate the effect of imatinib on the endotoxemia-induced acute lung injury in mice.Methods:Sixty SPF male, 8-12 weeks, C57BL/6 mice were randomly (random) divided into 4 groups ( n=15 each): control group (group C), imatinib group (groupⅠ), endotoxemia group (group LPS) and imatinib + endotoxemia group (group I+LPS). The endotoxemia model of acute lung injury was established. After 24 hours, the mice were sacrificed. The pathological changes of lung tissues were evaluated, the lung injury scores were calculated, and the wet/dry ratios of lung tissues were measured. ELISA was used to detect the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum. Detection kits were used to analyze the levels of malondialdehyde (MDA), glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and the ratio of reduced glutathione to oxidized glutathione (GSH/GSSG) in lung tissues; The expression levels of phosphorylated nuclear factor-kappa B (p-NF-κB), nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in lung tissues were analyzed by western blotting. Results:Compared with the group C, the wet/dry (W/D) ratio of lungs [(3.47±0.41) vs. (5.58±0.47)], lung injury scores [(1.25±0.89) vs. (10.25±1.75)], and the levels of TNF-α and IL-6 in serum increased in the group LPS ( P<0.05). The levels of SOD, CAT, GSH and GSH/GSSG decreased, the level of MDA increased, and the expression of p-NF-κB, Nrf2 and HO-1 protein up-regulated ( P<0.05). Compared with the LPS group, the W/D ratio of lungs [(5.58±0.47) vs.(4.62±0.38)] and lung injury scores [(10.25±1.75) vs. (7.00±1.31)] in the I+LPS group decreased ( P<0.05), and the levels of TNF-α and IL-6 in the serum decreased ( P<0.05). In lung tissues, the levels of SOD, CAT, GSH and GSH/GSSG increased (all P<0.05), the level of MDA decreased (all P<0.05), the expression of p-NF-κB protein decreased, and the expression of Nrf2 and HO-1 protein increased ( P<0.05). Conclusions:Imatinib improves sepsis-induced acute lung injury in mice, and the mechanism of actions behind may be related to the inhibition of oxidative stress.
5.Safety of high-carbohydrate fluid diet 2 h versus overnight fasting before non-emergency endoscopic retrograde cholangiopancreatography: A single-blind, multicenter, randomized controlled trial
Wenbo MENG ; W. Joseph LEUNG ; Zhenyu WANG ; Qiyong LI ; Leida ZHANG ; Kai ZHANG ; Xuefeng WANG ; Meng WANG ; Qi WANG ; Yingmei SHAO ; Jijun ZHANG ; Ping YUE ; Lei ZHANG ; Kexiang ZHU ; Xiaoliang ZHU ; Hui ZHANG ; Senlin HOU ; Kailin CAI ; Hao SUN ; Ping XUE ; Wei LIU ; Haiping WANG ; Li ZHANG ; Songming DING ; Zhiqing YANG ; Ming ZHANG ; Hao WENG ; Qingyuan WU ; Bendong CHEN ; Tiemin JIANG ; Yingkai WANG ; Lichao ZHANG ; Ke WU ; Xue YANG ; Zilong WEN ; Chun LIU ; Long MIAO ; Zhengfeng WANG ; Jiajia LI ; Xiaowen YAN ; Fangzhao WANG ; Lingen ZHANG ; Mingzhen BAI ; Ningning MI ; Xianzhuo ZHANG ; Wence ZHOU ; Jinqiu YUAN ; Azumi SUZUKI ; Kiyohito TANAKA ; Jiankang LIU ; Ula NUR ; Elisabete WEIDERPASS ; Xun LI
Chinese Medical Journal 2024;137(12):1437-1446
Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.
6.Effects of heparin on FAK/RhoA/ROCK signaling pathways during acute lung injury in septic mice
Xiaolong ZONG ; Tianyi ZHANG ; Duanyang LI ; Xiao WANG ; Yaru LIU ; Zhiqing ZHOU ; Zhenyu LI
Chinese Journal of Anesthesiology 2024;44(7):866-870
Objective:To evaluate the effects of heparin on focal adhesion kinase (FAK)/Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil-containing protein kinase (ROCK) signaling pathways during acute lung injury (ALI) in septic mice.Methods:Thirty SPF healthy adult male C57BL/6J mice, aged 6-8 weeks, weighing 20-23 g, were assigned into 3 groups ( n=10 each) using a random number table method: control group (group C), ALI group, and heparin group (group H). Septic ALI model was prepared by intraperitoneal injection of lipopolysaccharide 15 mg/kg, while group C received the equal volume of normal saline. In group H, heparin sodium solution 10 U was injected via the tail vein at 30 min before developing the model. The equal volume of normal saline was injected in C and ALI groups. Venous blood samples were collected from the eyeballs under deep anesthesia at 24 h after lipopolysaccharide injection. The mice were subsequently sacrificed and lung tissues were obtained for determination of the serum concentrations of interleukin-1beta (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) (using enzyme-linked immunosorbent assay), wet/dry lung weight (W/D) ratio, expression of vascular endothelial adhesion factor 1 (VCAM-1) (by immunohistochemical staining) and expression of FAK, phosphorylated FAK (p-FAK), RhoA, GTP-bound RhoA (RhoA-GTP) and ROCK (by Western blot) and for examination of the pathological changes. The lung injury was assessed and scored. Results:Comparison with group C, the serum concentrations of IL-1β, IL-6 and TNF-α, W/D ratio and lung injury scores were significantly increased, and the expression of VCAM-1, p-FAK, RhoA-GTP and ROCK was up-regulated in ALI group ( P<0.05). Compared with ALI group, the serum concentrations of IL-1β, IL-6 and TNF-α, W/D ratio and lung injury scores were significantly decreased, and the expression of VCAM-1, p-FAK, RhoA-GTP and ROCK was down-regulated in H group ( P<0.05). Conclusions:The mechanism through which heparin mitigates ALI is associated with the inhibition of the FAK/RhoA/ROCK signaling pathway in septic mice.
7.Clinical characteristics of choledocholithiasis combined with periampullary diverticulum and influencing factor analysis for difficult cannulation of endoscopic retrograde cholangiopan-creatography: a report of 1 920 cases
Ping YUE ; Zhenyu WANG ; Leida ZHANG ; Hao SUN ; Ping XUE ; Wei LIU ; Qi WANG ; Jijun ZHANG ; Xuefeng WANG ; Meng WANG ; Yingmei SHAO ; Kailin CAI ; Senlin HOU ; Kai ZHANG ; Qiyong LI ; Lei ZHANG ; Kexiang ZHU ; Haiping WANG ; Ming ZHANG ; Xiangyu SUN ; Zhiqing YANG ; Jie TAO ; Zilong WEN ; Qunwei WANG ; Bendong CHEN ; Yingkai WANG ; Mingning ZHAO ; Ruoyan ZHANG ; Tiemin JIANG ; Ke LIU ; Lichao ZHANG ; Kangjie CHEN ; Xiaoliang ZHU ; Hui ZHANG ; Long MIAO ; Zhengfeng WANG ; Jiajia LI ; Xiaowen YAN ; Ling'en ZHANG ; Fangzhao WANG ; Wence ZHOU ; Wenbo MENG ; Xun LI
Chinese Journal of Digestive Surgery 2023;22(1):113-121
Objective:To investigate the clinical characteristics of choledocholithiasis com-bined with periampullary diverticulum and influencing factor for difficult cannulation of endoscopic retrograde cholangiopancreatography (ERCP).Methods:The retrospective case-control study was conducted. The clinical data of 1 920 patients who underwent ERCP for choledocholithiasis in 15 medical centers, including the First Hospital of Lanzhou University, et al, from July 2015 to December 2017 were collected. There were 915 males and 1 005 females, aged (63±16)years. Of 1 920 patients, there were 228 cases with periampullary diverticulum and 1 692 cases without periampullary diverticulum. Observation indicators: (1) clinical characteristics of patients with choledocholithiasis; (2) intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis; (3) influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and com-parison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Logistic regression model was used for univariate and multivariate analyses. Results:(1) Clinical characteristics of patients with choledocholithiasis. Age, body mass index, cases with complications as chronic obstructive pulmonary disease, diameter of common bile duct, cases with diameter of common bile duct as <8 mm, 8?12 mm, >12 mm, diameter of stone, cases with number of stones as single and multiple were (69±12)years, (23.3±3.0)kg/m 2, 16, (14±4)mm, 11, 95, 122, (12±4)mm, 89, 139 in patients with choledocholithiasis combined with periampullary diverticulum, versus (62±16)years, (23.8±2.8)kg/m 2, 67, (12±4)mm, 159, 892, 641, (10±4)mm, 817, 875 in patients with choledocholithiasis not combined with periampullary diver-ticulum, showing significant differences in the above indicators between the two groups ( t=?7.55, 2.45, χ2=4.54, t=?4.92, Z=4.66, t=?7.31, χ2=6.90, P<0.05). (2) Intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis. The balloon expansion diameter, cases with intraoperative bleeding, cases with hemorrhage management of submucosal injection, hemostatic clip, spray hemostasis, electrocoagulation hemostasis and other treatment, cases with endoscopic plastic stent placement, cases with endoscopic nasal bile duct drainage, cases with mechanical lithotripsy, cases with stone complete clearing, cases with difficult cannulation, cases with delayed intubation, cases undergoing >5 times of cannulation attempts, cannulation time, X-ray exposure time, operation time were 10.0(range, 8.5?12.0)mm, 56, 6, 5, 43, 1, 1, 52, 177, 67, 201, 74, 38, 74, (7.4±3.1)minutes, (6±3)minutes, (46±19)minutes in patients with choledocholithiasis combined with periampullary diverticulum, versus 9.0(range, 8.0?11.0)mm, 243, 35, 14, 109, 73, 12, 230, 1 457, 167, 1 565, 395, 171, 395, (6.6±2.9)minutes, (6±5)minutes, (41±17)minutes in patients with choledocholithiasis not combined with periampullary diverticulum, showing significant differences in the above indicators between the two groups ( Z=6.31, χ2=15.90, 26.02, 13.61, 11.40, 71.51, 5.12, 9.04, 8.92, 9.04, t=?3.89, 2.67, ?3.61, P<0.05). (3) Influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Results of multivariate analysis showed total bilirubin >30 umol/L, number of stones >1, combined with periampullary diverticulum were indepen-dent risk factors for difficult cannulation in patients with periampullary diverticulum who underwent ERCP for choledocholithiasis ( odds ratio=1.31, 1.48, 1.44, 95% confidence interval as 1.06?1.61, 1.20?1.84, 1.06?1.95, P<0.05). Results of further analysis showed that, of 1 920 patients undergoing ERCP for choledocholithiasis, the incidence of postoperative pancreatitis was 17.271%(81/469) and 8.132%(118/1 451) in the 469 cases with difficult cannulation and 1 451 cases without difficult cannula-tion, respectively, showing a significant difference between them ( χ2=31.86, P<0.05). In the 1 692 patients with choledocholithiasis not combined with periampullary diverticulum, the incidence of postopera-tive pancreatitis was 17.722%(70/395) and 8.250%(107/1 297) in 395 cases with difficult cannula-tion and 1 297 cases without difficult cannulation, respectively, showing a significant difference between them ( χ2=29.00, P<0.05). In the 228 patients with choledocholithiasis combined with peri-ampullary diverticulum, the incidence of postoperative pancreatitis was 14.865%(11/74) and 7.143%(11/154) in 74 cases with difficult cannulation and 154 cases without difficult cannulation, respectively, showing no significant difference between them ( χ2=3.42, P>0.05). Conclusions:Compared with patients with choledocholithiasis not combined with periampullary divertioulum, periampullary divertioulum often occurs in choledocholithiasis patients of elderly and low body mass index. The proportion of chronic obstructive pulmonary disease is high in choledocholithiasis patients with periampullary diverticulum, and the diameter of stone is large, the number of stone is more in these patients. Combined with periampullary diverticulum will increase the difficult of cannulation and the ratio of patient with mechanical lithotripsy, and reduce the ratio of patient with stone complete clearing without increasing postoperative complications of choledocholithiasis patients undergoing ERCP. Total bilirubin >30 μmol/L, number of stones >1, combined with periampullary diverticulum are independent risk factors for difficult cannulation in patients of periampullary diverticulum who underwent ERCP for choledocholithiasis.
8.Effectiveness and security of anisodine hydrobromide tablets in treating nonarteritic anterior ischemic optic neuropathy: a Chinese multicenter nonrandomized controlled study
Mo YANG ; Honglu SONG ; Huanfen ZHOU ; Mengying LAI ; Quangang XU ; Mingming SUN ; Ke FAN ; Hongpei CUI ; Haiyan WANG ; Xin JIN ; Chuanbin SUN ; Qing XIAO ; Ying WANG ; Zide ZHAO ; Minglian ZHANG ; Yongye CHANG ; Mengping CHEN ; Zhanxing SHEN ; Hui YANG ; Xiaoyu XU ; Zhiqing LI ; Dongjun XING ; Yu DONG ; Jinrun YANG ; Qian REN ; Li LI ; Wenfang ZHANG ; Li SUN ; Zhengpei ZHANG ; Suyan LI ; Danyan LIU ; Nalei ZHOU ; Nali LUO ; Yadong LIU ; Shihui WEI
Chinese Journal of Experimental Ophthalmology 2023;41(7):646-653
Objective:To evaluate the efficacy and safety of oral anisodine hydrobromide tablets in the treatment of nonarteritic anterior ischemic optic neuropathy (NAION).Methods:A multicenter nonrandomized controlled trial was conducted.A total of 282 acute NAION patients (282 eyes) were recruited from 16 hospitals in China from July 2020 to May 2021.Patients were divided into two groups according to treatment methods, which were control group (124 cases, 124 eyes) receiving regular treatment including citicoline sodium plus Ginkgo biloba leaf liquid extract or Ginkgo biloba leaf extract tablets plus mecobalamin, and experimental group (158 cases, 158 eyes) receiving treatment in control group plus oral anisodine hydrobromide tablets 1 mg, twice daily for 2 to 3 months.Best corrected visual acuity (BCVA), visual field index (VFI), peripapillary retinal nerve fiber layer (pRNFL) and radial peripapillary capillary vessel density (RPC) were assessed at 1, 2, 3, and 6 months after enrollment using the standard decimal visual acuity chart, 750i Humphery visual field analyzer, Cirrus HD-OCT 4000/Cirrus HD-OCT 5000, RTVue-XR optical coherence tomography respectively.The primary outcomes were BCVA and VFI, and the secondary outcomes were pRNFL, RPC, and the side effects during the follow-up.The study adhered to the Declaration of Helsinki.All patients were fully informed about the treatment and purpose of this study and voluntarily signed the informed consent form.The study protocol was approved by Chinese PLA General Hospital (No.S2020-021-01). Results:In all, 242 patients (242 eyes) completed the follow-up of BCVA, and 98 patients (98 eyes) completed the VFI follow-up.In terms of visual function, BCVA and VFI improved significantly over time in the two groups, and BCVA and VFI were better in experimental group than in control group at various follow-up time points (all at P<0.05). In terms of structure, pRNFL gradually decreased in both groups with the extension of treatment, and pRNFL was significanthy thinner in experimental group than in control group at various follow-up time points (all at P<0.05). There was no significant difference in RPC between the two groups at the last follow-up ( P>0.05). There were two cases with side effects and one case was discontinued due to side effects 25 days after enrollment. Conclusions:Oral anisodine hydrobromide can improve visual acuity and visual field in NAION and accelerate the regression of optic disc edema, with good safety.
9.Lateral septum adenosine A2A receptors control stress-induced depressive-like behaviors via signal-ing to hypothalamus and habenula
Muran WANG ; Peijun LI ; Zewen LI ; SILVA S.da BEATRIZ ; Wu ZHENG ; Zhenghua XIANG ; Yan HE ; Tao XU ; CORDEIRO CRISTINA ; Lu DENG ; Yuwei DAI ; Mengqian YE ; Zhiqing LIN ; Jianhong ZHOU ; Xuzhao ZHOU ; Fenfen YE ; CUNHA A RODRIGO ; Jiangfan CHEN ; Wei GUO
Chinese Journal of Pharmacology and Toxicology 2023;37(7):547-548
Depressive disorder ranks as a major bur-den of disease worldwide,yet the current antidepressant medications are limited by frequent non-responsiveness and significant side effects.The lateral septum(LS)is thought to control of depression,however,the cellular and circuit substrates are largely unknown.Here,we identified a subpopulation of LS GABAergic adenosine A2A receptors(A2AR)-positive neurons mediating depres-sive symptoms via direct projects to the lateral habenula(LHb)and the dorsomedial hypothalamus(DMH).Activa-tion of A2AR in the LS augmented the spiking frequency of A2AR-positive neurons leading to a decreased activation of surrounding neurons and the bi-directional manipula-tion of LS-A2AR activity demonstrated that LS-A2ARs are necessary and sufficient to trigger depressive pheno-types.Thus,the optogenetic modulation(stimulation or inhibition)of LS-A2AR-positive neuronal activity or LS-A2AR-positive neurons projection terminals to the LHb or DMH,phenocopied depressive behaviors.Moreover,A2AR are upregulated in the LS in two male mouse mod-els of repeated stress-induced depression.This identifica-tion that aberrantly increased A2AR signaling in the LS is a critical upstream regulator of repeated stress-induced depressive-like behaviors provides a neurophysiological and circuit-based justification of the antidepressant poten-tial of A2AR antagonists,prompting their clinical transla-tion.
10.Effects of colpotomic approaches on prognosis and recurrence sites of stage Ⅰa2-Ⅱa2 cervical cancer after laparoscopic radical hysterectomy
Dan ZHOU ; Yudi LI ; Kaijian LING ; Ruiwei WANG ; Yanzhou WANG ; Shuai TANG ; Zhiqing LIANG
Chinese Journal of Obstetrics and Gynecology 2023;58(1):49-59
Objective:To investigate the factors affecting the prognosis of stage Ⅰa2-Ⅱa2 cervical cancer after laparoscopic radical hysterectomy (LRH), and to compare the prognosis and recurrence sites of patients with different colpotomy paths.Methods:The clinical data of 965 patients with stage Ⅰa2-Ⅱa2 cervical cancer who underwent LRH in the First Affiliated Hospital of Army Medical University from January 2015 to December 2018 were collected. The median age was 47.0 years of all patients with a median follow-up of 62 months (48-74 months). Cox regression was used to perform the univariate and multivariate analysis of the clinicopathological factors associated with the prognosis that included disease-free survival (DFS) and overall survival (OS). Patients were categorized into LRH through vaginal colpotomy (VC group, n=475) and LRH through intracorporeal colpotomy (IC group, n=490) according to the colpotomic approaches. The prognosis and recurrence sites of patients in each group were compared. Results:(1) During the follow-up period, 137 cases recurred (14.2%, 137/965) and 98 cases died (10.2%, 98/965). The 5-year DFS and OS were 85.8% and 89.9%, respectively. In univariate analysis, positive vaginal margin (PVM) was significantly affected the 5-year OS of patients with cervical cancer ( P=0.023), while clinical stage, maximum diameter of tumor, degree of pathological differentiation, lymph node metastasis (LNM), depth of cervical stromal invasion, parametrium involvement, and uterine corpus invasion (UCI) were significantly associated with 5-year DFS and OS in patients with cervical cancer (all P<0.05). In multivariate analysis, clinical stage ( HR=1.882, 95% CI: 1.305-2.716), LNM ( HR=2.178, 95% CI: 1.483-3.200) and UCI ( HR=3.650, 95% CI: 1.906-6.988) were independent risk factors of 5-year DFS (all P<0.001). Clinical stage ( HR=2.500, 95% CI: 1.580-3.956), LNM ( HR=2.053, 95% CI: 1.309-3.218), UCI ( HR=3.984, 95%C I: 1.917-8.280), PVM ( HR=3.235, 95% CI: 1.021-10.244) were independent risk factors of 5-year OS (all P<0.05). (2) Different colpotomy paths did not significantly affect the 5-year DFS and OS of patients with stage Ⅰa2-Ⅱa2 cervical cancer. The 5-year DFS in VC group and IC group were 85.9% and 85.6% ( P=0.794), and the 5-year OS were 90.8% and 89.3% ( P=0.966), respectively. Recurrence patterns consisted of intraperitoneal recurrence, pelvic recurrence, vaginal stump recurrence, and lymph node and distant metastasis. The intraperitoneal recurrence rate of VC group was significantly lower than that of IC group [0.6%(3/468) vs 2.3% (11/485), P=0.037], while the rates of pelvic recurrence, vaginal stump recurrence, lymph node and distant metastasis and overall recurrence were not significantly different between two groups (all P>0.05). Subgroup analysis of patients with different clinical stages, LNM and UCI showed that statistical differences of the intraperitoneal recurrence rates between two groups were only in patients without LNM (0.5% vs 2.3%, P=0.030) or without UCI (0.7% vs 2.3%, P=0.037). Conclusions:Clinical stage, LNM, PVM and UCI are independent risk factors for the prognosis of patients with stage Ⅰa2-Ⅱa2 cervical cancer. For patients without LNM or UCI, LRH through VC could reduce the intraperitoneal recurrence rate, while it is not enough to improve 5-year DFS and OS of patients. Low proportion of intraperitoneal recurrence, intra-operative tumor cells spillage to vagina stump and pelvic cavity might be the explanation.

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