1.Effect of Hirudo on autophagy in atherosclerotic mice
Qian-Qian HAN ; Yun-Yun PAN ; Zi-Yun WEN ; Qing LÜ ; Liang WEI ; Meng-Yi LI ; Min HONG
The Chinese Journal of Clinical Pharmacology 2024;40(5):688-692
Objective To explore the anti-atherosclerosis mechanism of Hirudo and its effect on autophagy in mice.Methods Forty healthy male ApoE-/-mice were randomly divided into model group,control group(3 × 10-3 g·kg-1·d-1 simvastatin)and experimental-L,experimental-M,experimental-H groups(0.45,0.9,1.8 g·kg-1· d-1,Maixuekang capsule).Eight healthy male C57BL/6J mice were divided into blank group.The mice were fed with common diet for 1 week.Then,except blank group,other groups were fed with high-fat diet.After 8 weeks of modeling,the atherosclerosis(AS)mice were given drugs orally once a day for 12 weeks,and fed with high-fat diet in the meantime.The levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)in serum were determined by enzyme-linked immunosorbent assay(ELISA).The levels of Beclin-1,LC3 autophagy protein were detected by Western blot method.Results The IL-6 contents in the experimental-H,experimental-M,experimental-L,control,model and blank groups were(107.59±3.03),(99.31±5.12),(103.52±2.28),(98.68±4.68),(112.66±6.08),(93.98±3.43)pg·mL-1;the TNF-α contents were(538.41±30.26),(504.49±21.51),(538.51±19.05),(494.05±25.08),(578.53±26.32),(467.35±21.53)pg·mL-1.For the above indexes,the differences between model group and experimental-H group,experimental-M group,experimental-L group,control group,blank group were all statistically significant(all P<0.05).The Beclin-1 protein expression levels in the experimental-H,experimental-M,experimental-L,control and model groups were 1.48±0.05,1.72±0.05,1.19±0.02,1.51±0.04,0.66±0.03;the LC3 Ⅱ protein expression levels were 1.53±0.01,1.83±0.02,1.16±0.01,1.90±0.01,0.49±0.01,and the differences between model group and experimental-H group,experimental-M group,experimental-L group,control group were all statistically significant(all P<0.05).Conclusion Hirudo can significantly reduce the area of atherosclerotic plaque by regulating the level of autophagy.
2.Protective effect and mechanism of Hirudo on mice with non-alcoholic fatty liver disease
Ziyun WEN ; Qianqian HAN ; Qing LYU ; Liang WEI ; Wenqiang NIE ; Min HONG ; Yunyun PAN
China Pharmacy 2024;35(10):1193-1197
OBJECTIVE To explore the protective effects and potential mechanisms of Hirudo on mice with non-alcoholic fatty liver disease (NAFLD) in mice. METHODS The male ApoE-/- mice were randomly divided into the model group and Hirudo low- dose and high-dose groups (0.45, 0.9 g/kg), with 10 mice in each group; another 10 wild-type male C57BL/6J mice were chosen as the control group. The control group was fed with basal maintenance chow and the remaining groups were fed with high-fat chow for 12 weeks to establish the NAFLD model. Each administration group was given corresponding solution intragastrically, once a day, for 8 consecutive weeks. In the 13th week, the body weight and liver weight of mice in each group were measured after the last medication, and the liver index was calculated; the serum levels of nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF- α), interleukin-1β (IL-1β), IL-6, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were detected; the liver pathomorphological changes were observed; the protein expressions of peroxisome proliferator-activated receptor γ(PPARγ) and silence information regulator type 1 (SIRT1) were detected. RESULTS Compared with the control group, the liver tissue of mice in the model group showed more fat vacuoles and infiltration of inflammatory cells, with significant lipid accumulation; the body weight, liver weight and liver index of the mice, and serum levels of NF-κB, TNF-α, IL-1β, IL-6, TC, TG and LDL-C significantly increased, while the serum level of HDL-C, the protein expressions of PPARγ and SIRT1 in liver tissues significantly decreased (P<0.01). Compared with the model group, the pathological changes in liver tissue of mice were all relieved in Hirudo low-dose and high-dose groups; the body weight, liver weight and liver index, the serum levels of NF-κB, TNF-α, IL-1β, IL-6, TC, TG and LDL-C decreased significantly, while the serum level of HDL-C, the protein expressions of PPARγ and SIRT1 in liver tissue all increased significantly (P<0.05 or P<0.01). CONCLUSIONS Hirudo can regulate liver lipid metabolism and inhibit inflammation by activating the protein expressions of PPARγ and SIRT1, thus having a significant ameliorative effect on NAFLD.
3.Quantitative Analysis of Lithium Element in Whole Blood Using Laser-induced Breakdown Spectroscopy
Wen-Xin REN ; Liang YANG ; Han ZHAO ; Yi-Meng WANG ; Da HUANG ; Xin-Hua DAI ; Qing-Yu LIN ; Yi-Xiang DUAN
Chinese Journal of Analytical Chemistry 2024;52(4):559-565
Lithium(Li)salts are commonly used as psychotropic medications for the treatment of major depressive disorders.However,long-term use of Li salts poses a high risk of toxicity,necessitating continuous monitoring of Li concentration in patient blood to ensure medication safety,which is crucial for clinical treatment.Laser-induced breakdown spectroscopy(LIBS),as a rapid analytical technique,has been widely applied in the elemental analysis of complex matrices in various practical scenarios.In this study,LIBS technology combined with partial least squares(PLS)was employed for quantitative analysis of Li elements in blood matrix.A total of 45 clinical blood samples were utilized,and the quantitative models for plasma and whole blood matrices were separately investigated.The number of latent variables in the PLS algorithm was optimized using a five-fold cross-validation method.Results revealed that the PLS quantitative model constructed on the basis of plasma matrix achieved a predictive determination coefficient(R2)of 0.992,a predictive root mean square error(RMSEP)of 0.204 μg/mL,and a relative standard error(RSD)of 2.14%.In contrast,for the PLS quantitative model constructed on the basis of whole blood matrix,the R2 was 0.984,the RMSEP was 0.728 μg/mL,and the RSD was 3.45%Consequently,the LIBS model constructed on the basis of plasma calibration values demonstrated superior performance in quantitative analysis of Li element in whole blood,and LIBS technology provided a new possibility for rapid assessment of blood Li levels in clinical practice,with promising prospects for application.
4.Effects of Different Test Positions on Quantitative Muscle Strength of Wrist and Finger Flexor Muscle Groups and Its Standardization
Ze-Ren YANG ; Dong GAO ; Qing XIA ; Dan RAN ; Yan-Liang SHENG ; Wen-Tao XIA
Journal of Forensic Medicine 2024;40(3):237-244,253
Objective To explore the effects of different test positions on quantitative muscle strength of wrist and finger flexor muscle groups and to establish a standardized muscle strength test protocol for each muscle group.Methods Forty healthy subjects (12 males and 28 females) were recruited.A portable digital quantitative muscle strength tester,Micro FET2TM,was used to measure the flexor muscle strength of each finger and the wrist joint at the 30° extension,0° neutral,and 30° flexion,respectively.Palmar abduction strength of the thumb was measured at 30° and 60°,respectively.Ten subjects were randomly selected from the 40 subjects,and the quantitative muscle strength of each muscle group was tested again by the same operator after an interval of 10 to 15 days.Results Except for the fact that in males,there was no significant difference in flexor muscle strength of thumb and wrist joint between 30° of wrist extension and neutral 0° position,the muscle strength of the other fingers flexion and wrist palmar flexor showed the following characteristics:30° of wrist extension>neutral 0° posi-tion>30° of flexion,and the PAST was 30°>60°;The flexor muscle strength of all the subjects was thumb>index finger>middle finger>ring finger>little finger;All muscle strength values of male were greater than those of female,and the difference was statistically significant (P<0.05);There was no significant difference between the left and right side muscle strength values of all subjects (P>0.05).The reliability of muscle strength values measured at different times in 10 subjects was good.Conclu-sion The quantitative muscle strength of each muscle group of the hand and wrist is affected by the test position,and a standardized and uniformed test position should be adopted in the actual identification.Micro FET2TM has good reliability for hand and wrist quantitative muscle strength testing.The 30° ex-tension of the wrist can be used as the best standardized test position for the flexion muscle strength of each finger and wrist joint.The 30° position can be used as the best standardized test position for PAST.
5.Clinical Observation on the Shugan Tiaoshen Acupuncture in the Treatment of Mild-to-Moderate Perimenopausal Depressive Disorder
Zi-Qing LIANG ; Cheng-Cheng CHAI ; Wen-Bin FU ; Ding LUO
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(5):1226-1232
Objective To observe the clinical efficacy of Shugan Tiaoshen Acupuncture in the treatment of mild-to-moderate perimenopausal depressive disorder(PDD).Methods A total of 66 patients with mild-to-moderate PDD were randomly divided into the observation group and the control group,with 33 cases in each group.The observation group was treated with Shugan Tiaoshen Acupuncture,and the control group was treated with conventional western medicine for 8 weeks.After 2 months of treatment,the clinical efficacy of the two groups was evaluated,and the changes in Hamilton Depression Scale(HAMD-17)scores before and after treatment,as well as the scores of Menopausal Quality of Life Scale(MENQOL)were observed in the two groups.The changes in serum luteinising hormone(LH),follicle-stimulating hormone(FSH)and oestradiol(E2)levels were compared before and after treatment between the two groups,and the safety and the occurrence of adverse reactions in the two groups were evaluated.Results(1)During the study,3 cases in the observation group and 2 cases in the control group were lost to followup.Finally,30 cases in the observation group and 31 cases in the control group were included in the efficacy statistics.(2)After treatment,the total score of HAMD-17 and the scores of each factor in the two groups were significantly improved(P<0.05),and the total score of HAMD-17 and the scores of anxiety/somatization factor and sleep factor in the observation group were significantly superior to those in the control group,the differences were statistically significant(P<0.05).(3)After treatment,the total score of MENQOL and the scores of vascular dimension,physiological dimension and sexual life dimension in the two groups were significantly improved(P<0.05),and the total score of HAMD-17 and the scores of vascular dimension and physiological dimension in the observation group were significantly superior to those in the control group,the differences were statistically significant(P<0.05).(4)After treatment,the levels of LH,FSH and E2 in the two groups were significantly improved(P<0.05),and the improvement of LH,FSH and E2 levels in the observation group was significantly superior to that in the control group(P<0.05).(5)The total effective rate was 93.33%(28/30)in the observation group and 74.19%(23/31)in the control group.The curative effect of the observation group was superior to that of the control group,and the difference was statistically significant(P>0.05).Conclusion Shugan Tiaoshen Acupuncture in the treatment of mild-to-moderate PDD can significantly improve the clinical symptoms of patients,improve the quality of life of patients,regulate the level of sex hormones,and have a significant effect.
6.Standardized operational protocol for the China Human Brain Bank Consortium(2nd edition)
Xue WANG ; Zhen CHEN ; Juan-Li WU ; Nai-Li WANG ; Di ZHANG ; Juan DU ; Liang YU ; Wan-Ru DUAN ; Peng-Hao LIU ; Han-Lin ZHANG ; Can HUANG ; Yue-Shan PIAO ; Ke-Qing ZHU ; Ai-Min BAO ; Jing ZHANG ; Yi SHEN ; Chao MA ; Wen-Ying QIU ; Xiao-Jing QIAN
Acta Anatomica Sinica 2024;55(6):734-745
Human brain banks use a standardized protocol to collect,process and store post-mortem human brains and related tissues,along with relevant clinical information,and to provide the tissue samples and data as a resource to foster neuroscience research according to a standardized operating protocols(SOP).Human brain bank serves as the foundation for neuroscience research and the diagnosis of neurological disorders,highlighting the crucial rule of ensuring the consistency of standardized quality for brain tissue samples.The first version of SOP in 2017 was published by the China Human Brain Bank Consortium.As members increases from different regions in China,a revised SOP was drafted by experts from the China Human Brain Bank Consortium to meet the growing demands for neuroscience research.The revised SOP places a strong emphasis on ethical standards,incorporates neuropathological evaluation of brain regions,and provides clarity on spinal cord sampling and pathological assessment.Notable enhancements in this updated version of the SOP include reinforced ethical guidelines,inclusion of matching controls in recruitment,and expansion of brain regions to be sampled for neuropathological evaluation.
7.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.
8.Feasibility study on the evaluation of parieto-occipital sulcus of normal fetuses by simplified grade of prenatal ultrasound
Yue QIN ; Dandan LUO ; Huaxuan WEN ; Qing ZENG ; Meiyu ZHENG ; Meiling LIANG ; Yimei LIAO ; Xin WEN ; Zhixuan CHEN ; Bocheng LIANG ; Shengli LI
Chinese Journal of Ultrasonography 2024;33(9):776-783
Objective:To validate the morphological changes of the parieto-occipital sulcus on the transcalvarial axial plane between 20 and 32 weeks of gestation, simplify grade for assessing fetal parieto-occipital sulcus development, and confirm its clinical feasibility.Methods:This was a cross-sectional study analysis that included 550 cases of normal singleton fetuses between 20 and 32 weeks of gestation, who underwent routine ultrasound examinations at Shenzhen Maternity and Child Healthcare Hospital from September 2019 to June 2022. The morphological changes of the bilateral parieto-occipital sulci on the transcalvarial axial plane were observed. The development of the parieto-occipital sulcus was classified into 6 grades based on the developmental features of angulation, progressive closure, and curvilinear growth: straight or shallow arcuate (Grade 0), shallow and wide V-shaped (Grade 1), deep and narrow V-shaped (Grade 2), Y-shaped (Grade 3), I-shaped (Grade 4), and curvilinear (Grade 5). The gestational age at examination and pregnancy outcomes were recorded. The distribution of gestational weeks for fetuses with different grades of parieto-occipital sulci on the left and right sides was analyzed. The symmetry between bilateral parieto-occipital sulcus gradings within individuals, as well as the inter-observer and intra-observer reliability were assessed using the Weighted Kappa coefficient. The gender differences in asymmetry of parieto-occipital sulci grades between the left and right sides was analyzed. Moreover, a model for predicting the grade of the parieto-occipital sulcus based on gestational week was established.Results:Grade for the left parieto-occipital sulcus was obtained for 549 fetuses, while grade for the right was obtained for 550 fetuses. From 20 to 32 weeks of gestation, the morphology of the fetal parieto-occipital sulcus was divided into Grade 0-5, progressing from low to high with gestational development. Grade 0 showed that the sulcus was not visible or only had a slight arcuate indentation, occurring at 20-22 weeks; Grade 1 presented as a shallow and wide "V" shape with an obtuse angle at the top, appearing from 20 to 27 weeks; Grade 2 was a deep and narrow "V" shape with an acute angle at the top, appearing from 24 to 29 weeks; Grade 3 appeared as a "Y" shape with the top part partially closed and the bottom still open, occurring between 26 to 30 weeks; Grade 4 was a fully closed "I" shape, appearing at 29-32 weeks; Grade 5 presented as a curved shape, indicating the parieto-occipital sulcus was approaching maturity, appearing from 31 to 32 weeks. There was no statistically significant difference in the distribution of gestational weeks for bilateral parieto-occipital sulcus developmental grade ( P>0.05). Bilateral parieto-occipital sulcus grade could be assessed in 549 fetuses, of which 43 cases (7.83%) exhibited grade asymmetry with a one-grade difference between sides; such asymmetry showed no significant difference between male and female genders ( P=0.647). The weighted kappa coefficient analysis results indicated a strong consistency in the development of the parieto-occipital sulci on both sides within individuals, generally demonstrating symmetrical development ( P<0.001). The intra-observer and inter-observer weighted kappa coefficients were 0.92 and 0.75, respectively, with good consistency. Conclusions:Prenatal ultrasound via the transcalvarial axial plane enables a preliminary and rapid assessment of the development of bilateral parieto-occipital sulci, facilitating early evaluation of fetal cortical maturation.
9.A cross-sectional study of simplified grade of the transcalvarial axial plane in evaluating the convexity sulci of normal fetuses
Yue QIN ; Huaxuan WEN ; Dandan LUO ; Qing ZENG ; Meiyu ZHENG ; Meiling LIANG ; Yimei LIAO ; Xin WEN ; Bocheng LIANG ; Ying YUAN ; Shengli LI
Chinese Journal of Ultrasonography 2024;33(10):884-890
Objective:To study the stability and morphological changes of the convexity sulci in normal fetuses between 20 and 32 weeks, and to explore the simplified grade for evaluating the convexity sulci development and analyzing its clinical significance.Methods:This study was a cross-sectional analysis. A total of 551 cases of normal singleton pregnancies between 20 and 32 weeks of gestation were retrospectively collected, who underwent routine ultrasound examinations at Shenzhen Maternity and Child Healthcare Hospital from September 2019 to June 2022. The display of the far-field convexity sulci on the transcalvarial axial plane was observed as 0 for not displayed and 1 for displayed.Further, based on the morphology and number of convexity sulci, they were classified into five grades: no sulcus displayed (grade 0), one sulcus (grade 1), two sulci (grade 2), three sulci (grade 3), and four or more sulci (grade 4). The gestational age at examination and pregnancy outcomes were recorded. The distribution characteristics of gestational weeks for each grade of the convexity sulci were analyzed, and the gestational week distribution of the left and right convexity sulci was compared to analyze bilateral symmetry. The Weighted Kappa coefficient was used to analyze inter-observer and intra-observer consistency, and curve regression analysis was employed to establish a model for predicting grade based on gestational weeks.Results:Before 25 weeks of gestation, the convexity of the fetal cranial vertex was completely smooth.The central sulcus consistently appeared after 26 weeks, while the superior frontal sulcus, intraparietal sulcus, postcentral sulcus, and precentral sulcus consistently appeared between 28 and 31 weeks. Among these, the superior frontal sulcus had a lower display rate before 29 weeks. By 32 weeks, all convexity sulci of the cranial vertex should be visible. Three hundred and eleven fetuses were graded for the left, and 240 fetuses were graded for the right. The developmental grade of the convexity sulci increased from Grade 0 to Grade 4 as the gestational age progressed. Grade 0 appeared between 20-26 weeks, grade 1 between 25-28 weeks, grade 2 between 26-28 weeks, grade 3 between 27-30 weeks, and grade 4 between 27-32 weeks. The distribution of grade did not differ significantly between the left and right sides of grade 0, 1, 3 and 4 (all P>0.05), while there was a significant difference in the distribution of gestational age between the convexity sulci of grade 2 ( P<0.05). The Weighted Kappa coefficients for intra-observer and inter-observer consistency were 0.94 and 0.86, respectively, indicating strong consistency. Conclusions:The simplified grade for assessing the development of convexity sulci in normal fetuses on the transcalvarial axial plane via prenatal ultrasound can provide a preliminary evaluation of the maturation of convexity sulci in fetuses between 20 and 32 weeks of gestation.
10.Efficacy, safety, and pharmacokinetics of capsid assembly modulator linvencorvir plus standard of care in chronic hepatitis B patients
Jinlin HOU ; Edward GANE ; Rozalina BALABANSKA ; Wenhong ZHANG ; Jiming ZHANG ; Tien Huey LIM ; Qing XIE ; Chau-Ting YEH ; Sheng-Shun YANG ; Xieer LIANG ; Piyawat KOMOLMIT ; Apinya LEERAPUN ; Zenghui XUE ; Ethan CHEN ; Yuchen ZHANG ; Qiaoqiao XIE ; Ting-Tsung CHANG ; Tsung-Hui HU ; Seng Gee LIM ; Wan-Long CHUANG ; Barbara LEGGETT ; Qingyan BO ; Xue ZHOU ; Miriam TRIYATNI ; Wen ZHANG ; Man-Fung YUEN
Clinical and Molecular Hepatology 2024;30(2):191-205
Background/Aims:
Four-week treatment of linvencorvir (RO7049389) was generally safe and well tolerated, and showed anti-viral activity in chronic hepatitis B (CHB) patients. This study evaluated the efficacy, safety, and pharmacokinetics of 48-week treatment with linvencorvir plus standard of care (SoC) in CHB patients.
Methods:
This was a multicentre, non-randomized, non-controlled, open-label phase 2 study enrolling three cohorts: nucleos(t)ide analogue (NUC)-suppressed patients received linvencorvir plus NUC (Cohort A, n=32); treatment-naïve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-α (Peg-IFN-α). Treatment duration was 48 weeks, followed by NUC alone for 24 weeks.
Results:
68 patients completed the study. No patient achieved functional cure (sustained HBsAg loss and unquantifiable HBV DNA). By Week 48, 89% of treatment-naïve patients (10/10 Cohort B; 24/28 Cohort C) reached unquantifiable HBV DNA. Unquantifiable HBV RNA was achieved in 92% of patients with quantifiable baseline HBV RNA (14/15 Cohort A, 8/8 Cohort B, 22/25 Cohort C) at Week 48 along with partially sustained HBV RNA responses in treatment-naïve patients during follow-up period. Pronounced reductions in HBeAg and HBcrAg were observed in treatment-naïve patients, while HBsAg decline was only observed in Cohort C. Most adverse events were grade 1–2, and no linvencorvir-related serious adverse events were reported.
Conclusions
48-week linvencorvir plus SoC was generally safe and well tolerated, and resulted in potent HBV DNA and RNA suppression. However, 48-week linvencorvir plus NUC with or without Peg-IFN did not result in the achievement of functional cure in any patient.

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