1.Dynamic Monitoring and Correlation Analysis of General Body Indicators, Blood Glucose, and Blood Lipid in Obese Cynomolgus Monkeys
Yanye WEI ; Guo SHEN ; Pengfei ZHANG ; Songping SHI ; Jiahao HU ; Xuzhe ZHANG ; Huiyuan HUA ; Guanyang HUA ; Hongzheng LU ; Yong ZENG ; Feng JI ; Zhumei WEI
Laboratory Animal and Comparative Medicine 2025;45(1):30-36
ObjectiveThis study aims to investigate the dynamic changes in general body parameters, blood glucose, and blood lipid profiles in obese cynomolgus monkeys, exploring the correlations among these parameters and providing a reference for research on the obese cynomolgus monkey model. Methods30 normal male cynomolgus monkeys aged 5 - 17 years old (with body mass index < 35 kg/m² and glycated hemoglobin content < 4.50%) and 99 spontaneously obese male cynomolgus monkeys (with body mass index ≥35 kg/m² and glycated hemoglobin content < 4.50%) were selected. Over a period of three years, their abdominal circumference, skinfold thickness, body weight, body mass index, fasting blood glucose, glycated hemoglobin, and four blood lipid indicators were monitored. The correlations between each indicator were analyzed using repeated measurement ANOVA, simple linear regression, and multiple linear regression correlation analysis method. Results Compared to the control group, the obese group exhibited significantly higher levels of abdominal circumference, skinfold thickness, body weight, body mass index, and triglyceride (P<0.05). In the control group, skinfold thickness increased annually, while other indicators remained stable. Compared with the first year, the obese group showed significantly increased abdominal circumference, skinfold thickness, body weight, body mass index, triglyceride, and fasting blood glucose in the second year(P<0.05), with this increasing trend persisting in the third year (P<0.05). In the control group, the obesity incidence rates in the second and third years were 16.67% and 23.33%, respectively, while the prevalence of diabetes remained at 16.67%. In the obese group, the diabetes incidence rates were 29.29% and 44.44% in years 2 and 3, respectively. Among the 11-13 year age group, the incidence rates were 36.36% and 44.68%, while for the group older than 13 years, the rates were 28.13% and 51.35%. Correlation analysis revealed significant associations (P<0.05) between fasting blood glucose and age, abdominal circumference, skinfold thickness, body weight, and triglyceride in the diabetic monkeys. Conclusion Long-term obesity can lead to the increases in general physical indicators and fasting blood glucose levels in cynomolgus monkeys, and an increase in the incidence of diabetes. In diabetic cynomolgus monkeys caused by obesity, there is a high correlation between their fasting blood glucose and age, weight, abdominal circumference, skinfold thickness, and triglyceride levels, which is of some significance for predicting the occurrence of spontaneous diabetes.
2.Carvedilol to prevent hepatic decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by new non-invasive model (CHESS2306)
Chuan LIU ; Hong YOU ; Qing-Lei ZENG ; Yu Jun WONG ; Bingqiong WANG ; Ivica GRGUREVIC ; Chenghai LIU ; Hyung Joon YIM ; Wei GOU ; Bingtian DONG ; Shenghong JU ; Yanan GUO ; Qian YU ; Masashi HIROOKA ; Hirayuki ENOMOTO ; Amr Shaaban HANAFY ; Zhujun CAO ; Xiemin DONG ; Jing LV ; Tae Hyung KIM ; Yohei KOIZUMI ; Yoichi HIASA ; Takashi NISHIMURA ; Hiroko IIJIMA ; Chuanjun XU ; Erhei DAI ; Xiaoling LAN ; Changxiang LAI ; Shirong LIU ; Fang WANG ; Ying GUO ; Jiaojian LV ; Liting ZHANG ; Yuqing WANG ; Qing XIE ; Chuxiao SHAO ; Zhensheng LIU ; Federico RAVAIOLI ; Antonio COLECCHIA ; Jie LI ; Gao-Jun TENG ; Xiaolong QI
Clinical and Molecular Hepatology 2025;31(1):105-118
Background:
s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model.
Methods:
Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort.
Results:
In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM).
Conclusions
Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.
3.Carvedilol to prevent hepatic decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by new non-invasive model (CHESS2306)
Chuan LIU ; Hong YOU ; Qing-Lei ZENG ; Yu Jun WONG ; Bingqiong WANG ; Ivica GRGUREVIC ; Chenghai LIU ; Hyung Joon YIM ; Wei GOU ; Bingtian DONG ; Shenghong JU ; Yanan GUO ; Qian YU ; Masashi HIROOKA ; Hirayuki ENOMOTO ; Amr Shaaban HANAFY ; Zhujun CAO ; Xiemin DONG ; Jing LV ; Tae Hyung KIM ; Yohei KOIZUMI ; Yoichi HIASA ; Takashi NISHIMURA ; Hiroko IIJIMA ; Chuanjun XU ; Erhei DAI ; Xiaoling LAN ; Changxiang LAI ; Shirong LIU ; Fang WANG ; Ying GUO ; Jiaojian LV ; Liting ZHANG ; Yuqing WANG ; Qing XIE ; Chuxiao SHAO ; Zhensheng LIU ; Federico RAVAIOLI ; Antonio COLECCHIA ; Jie LI ; Gao-Jun TENG ; Xiaolong QI
Clinical and Molecular Hepatology 2025;31(1):105-118
Background:
s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model.
Methods:
Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort.
Results:
In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM).
Conclusions
Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.
4.Carvedilol to prevent hepatic decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by new non-invasive model (CHESS2306)
Chuan LIU ; Hong YOU ; Qing-Lei ZENG ; Yu Jun WONG ; Bingqiong WANG ; Ivica GRGUREVIC ; Chenghai LIU ; Hyung Joon YIM ; Wei GOU ; Bingtian DONG ; Shenghong JU ; Yanan GUO ; Qian YU ; Masashi HIROOKA ; Hirayuki ENOMOTO ; Amr Shaaban HANAFY ; Zhujun CAO ; Xiemin DONG ; Jing LV ; Tae Hyung KIM ; Yohei KOIZUMI ; Yoichi HIASA ; Takashi NISHIMURA ; Hiroko IIJIMA ; Chuanjun XU ; Erhei DAI ; Xiaoling LAN ; Changxiang LAI ; Shirong LIU ; Fang WANG ; Ying GUO ; Jiaojian LV ; Liting ZHANG ; Yuqing WANG ; Qing XIE ; Chuxiao SHAO ; Zhensheng LIU ; Federico RAVAIOLI ; Antonio COLECCHIA ; Jie LI ; Gao-Jun TENG ; Xiaolong QI
Clinical and Molecular Hepatology 2025;31(1):105-118
Background:
s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model.
Methods:
Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort.
Results:
In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM).
Conclusions
Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.
5.Modified Lianpoyin Formula Treats Hp-associated Gastritis by Regulating Mitochondrial Autophagy and NLRP3 Inflammasome Signaling Pathway
Siyi ZHANG ; Haopeng DANG ; Wenliang LYU ; Wentao ZHOU ; Wei GUO ; Lin LIU ; Lan ZENG ; Yujie SUN ; Luming LIANG ; Yi ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):178-187
ObjectiveTo explore the effect of modified Lianpoyin formula (LPYJWF) in the treatment of Helicobacter pylori (Hp)-associated gastric mucosal damage based on mitochondrial autophagy and NLRP3 inflammasome signaling pathway. MethodsA total of 60 eight-week-old Balb/c male mice were assigned via the random number table method into control, model, high-dose LPYJWF (LPYJWF-H, 27.3 g·kg-1·d-1), medium-dose LPYJWF (LPYJWF-M, 13.65 g·kg-1·d-1), low-dose LPYJWF (LPYJWF-L, 6.83 g·kg-1·d-1), and quadruple therapy groups. Except the control group, other groups were modeled for Hp infection. Mice were administrated with LPYJWF at corresponding doses by gavage. Quadruple therapy group was given omeprazole (6.06 mg·kg-1·d-1) + amoxicillin (303 mg·kg-1·d-1) + clarithromycin (151.67 mg·kg-1·d-1) + colloidal pectin capsules (30.3 mg·kg-1·d-1) by gavage. The control group was given an equal volume of 0.9% NaCl for 14 days. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of gastric mucosa, and Warthin-Starry (W-S) silver staining was used to detect Hp colonization. Transmission electron microscopy was employed to observe the mitochondrial ultrastructure of the gastric tissue, and immunofluorescence co-localization assay was adopted to detect the expression of mitochondrial transcription factor A (TFAM) and translocase of the outer mitochondrial membrane member 20 (TOMM20). The water-soluble tetrazolium salt method and thiobarbituric acid method were used to determine the levels of superoxide dismutase (SOD) and malondialdehyde (MDA), respectively, in the gastric tissue. Western blot was employed to measure the protein levels of PTEN-induced kinase 1 (PINK1), Parkin, p62, microtubule-associated protein 1 light chain 3 (LC3), NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), interleukin-1β (IL-1β), and interleukin-18 (IL-18). Real-time quantitative PCR was employed to assess the mRNA levels of PINK1, Parkin, p62, and LC3. ResultsCompared with the control group, the model group presented obvious gastric mucosal damage, colonization of a large number of Hp, severe mitochondrial damage, vacuolated structures due to excessive autophagy, reduced TOMM20 and TFAM co-expression in the gastric mucosal tissue, and reduced SOD and increased MDA (P<0.01). In addition, the gastric tissue in the model group showed up-regulated protein and mRNA levels of PINK1, Parkin, and LC3 and down-regulated protein and mRNA levels of p62 (P<0.01, as well as increased expression of inflammasome-associated proteins NLRP3, ASC, IL-1β, and IL-18 (P<0.01). Compared with the model group, the LPYJWF and quadruple therapy groups showed alleviated pathological damage of gastric mucosa, reduced Hp colonization, mitigated mitochondrial damage, and increased co-expression of TOMM20 and TFAM. The SOD level was elevated in the LPYJWF-L group (P<0.01), and the MDA levels became lowered in the LPYJWF and quadruple therapy groups (P<0.05, P<0.01). Furthermore, the LPYJWF and quadruple therapy groups showed down-regulated mRNA levels of PINK1, Parkin, and LC3 and protein levels of PINK1 and Parkin, and up-regulated mRNA level of p62 (P<0.01). The LPYJWF-M, LPYJWF-H, and quadruple therapy groups showcased down-regulated LC3 Ⅱ/LC3 Ⅰ level (P<0.05, P<0.01) and up-regulated protein level of p62 (P<0.01). The expression of inflammasome-associated proteins NLRP3, ASC, IL-1β, and IL-18 were reduced in the LPYJWF and quadruple therapy groups (P<0.05, P<0.01). ConclusionLPYJWF ameliorates gastric mucosal damage and exerts mucosa-protective effects in Hp-infected mice, which may be related to the inhibition of excessive mitochondrial autophagy, thereby inhibiting the activation of the NLRP3 inflammasome pathway.
6.Modified Lianpoyin Formula Treats Hp-associated Gastritis by Regulating Mitochondrial Autophagy and NLRP3 Inflammasome Signaling Pathway
Siyi ZHANG ; Haopeng DANG ; Wenliang LYU ; Wentao ZHOU ; Wei GUO ; Lin LIU ; Lan ZENG ; Yujie SUN ; Luming LIANG ; Yi ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):178-187
ObjectiveTo explore the effect of modified Lianpoyin formula (LPYJWF) in the treatment of Helicobacter pylori (Hp)-associated gastric mucosal damage based on mitochondrial autophagy and NLRP3 inflammasome signaling pathway. MethodsA total of 60 eight-week-old Balb/c male mice were assigned via the random number table method into control, model, high-dose LPYJWF (LPYJWF-H, 27.3 g·kg-1·d-1), medium-dose LPYJWF (LPYJWF-M, 13.65 g·kg-1·d-1), low-dose LPYJWF (LPYJWF-L, 6.83 g·kg-1·d-1), and quadruple therapy groups. Except the control group, other groups were modeled for Hp infection. Mice were administrated with LPYJWF at corresponding doses by gavage. Quadruple therapy group was given omeprazole (6.06 mg·kg-1·d-1) + amoxicillin (303 mg·kg-1·d-1) + clarithromycin (151.67 mg·kg-1·d-1) + colloidal pectin capsules (30.3 mg·kg-1·d-1) by gavage. The control group was given an equal volume of 0.9% NaCl for 14 days. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of gastric mucosa, and Warthin-Starry (W-S) silver staining was used to detect Hp colonization. Transmission electron microscopy was employed to observe the mitochondrial ultrastructure of the gastric tissue, and immunofluorescence co-localization assay was adopted to detect the expression of mitochondrial transcription factor A (TFAM) and translocase of the outer mitochondrial membrane member 20 (TOMM20). The water-soluble tetrazolium salt method and thiobarbituric acid method were used to determine the levels of superoxide dismutase (SOD) and malondialdehyde (MDA), respectively, in the gastric tissue. Western blot was employed to measure the protein levels of PTEN-induced kinase 1 (PINK1), Parkin, p62, microtubule-associated protein 1 light chain 3 (LC3), NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), interleukin-1β (IL-1β), and interleukin-18 (IL-18). Real-time quantitative PCR was employed to assess the mRNA levels of PINK1, Parkin, p62, and LC3. ResultsCompared with the control group, the model group presented obvious gastric mucosal damage, colonization of a large number of Hp, severe mitochondrial damage, vacuolated structures due to excessive autophagy, reduced TOMM20 and TFAM co-expression in the gastric mucosal tissue, and reduced SOD and increased MDA (P<0.01). In addition, the gastric tissue in the model group showed up-regulated protein and mRNA levels of PINK1, Parkin, and LC3 and down-regulated protein and mRNA levels of p62 (P<0.01, as well as increased expression of inflammasome-associated proteins NLRP3, ASC, IL-1β, and IL-18 (P<0.01). Compared with the model group, the LPYJWF and quadruple therapy groups showed alleviated pathological damage of gastric mucosa, reduced Hp colonization, mitigated mitochondrial damage, and increased co-expression of TOMM20 and TFAM. The SOD level was elevated in the LPYJWF-L group (P<0.01), and the MDA levels became lowered in the LPYJWF and quadruple therapy groups (P<0.05, P<0.01). Furthermore, the LPYJWF and quadruple therapy groups showed down-regulated mRNA levels of PINK1, Parkin, and LC3 and protein levels of PINK1 and Parkin, and up-regulated mRNA level of p62 (P<0.01). The LPYJWF-M, LPYJWF-H, and quadruple therapy groups showcased down-regulated LC3 Ⅱ/LC3 Ⅰ level (P<0.05, P<0.01) and up-regulated protein level of p62 (P<0.01). The expression of inflammasome-associated proteins NLRP3, ASC, IL-1β, and IL-18 were reduced in the LPYJWF and quadruple therapy groups (P<0.05, P<0.01). ConclusionLPYJWF ameliorates gastric mucosal damage and exerts mucosa-protective effects in Hp-infected mice, which may be related to the inhibition of excessive mitochondrial autophagy, thereby inhibiting the activation of the NLRP3 inflammasome pathway.
7.Bone remodeling in the Masquelet-induced membrane model of rat femur by modulation of H-type vessels by total flavonoids of rhizome drynariae
Zhikui ZENG ; Wei XIONG ; Weidong LIANG ; Guowen QIAN ; Chaoyi LIANG ; Bin PAN ; Ling GUO ; Wenqiang WEI ; Xunxiang QIU ; Wenfang DENG ; Lingmei YUAN
Chinese Journal of Tissue Engineering Research 2024;28(32):5130-5135
BACKGROUND:Several studies have found that the total flavonoids of rhizome drynariae can promote neovascularization in the induced membrane,improve the biological properties of the induced membrane,and accelerate bone remodeling in the induced membrane,but the related molecular mechanisms still need to be further explored. OBJECTIVE:To explore the effect of total flavonoids of rhizome drynariae on bone remodeling in rat femoral Masquelet-induced membrane model by regulating H-type blood vessels. METHODS:Thirty-six male Sprague-Dawley rats were stratified by body mass and then randomly divided into blank group,model group and traditional Chinese medicine group,with 12 rats in each group.A 4-mm femoral bone defect model was established in all the rats.Bone defects in the model group and traditional Chinese medicine group were filled with polymethylmethacrylate bone cement.At 6 weeks after modeling,the tail bone of the rats was implanted in the blank group,as well as in the other two groups after removal of bone cement.The traditional Chinese medicine group was given 157.5 mg/kg per day of total flavonoids of rhizome drynariae at 3 days after bone implantation,while the model and blank groups were given the same amount of saline by gavage until the 8th week after bone implantation.Bone graft samples were taken for relevant testing at 8 weeks after implantation. RESULTS AND CONCLUSION:X-ray films showed that in the blank group,the fracture line in the defect area was clear,and only a small amount of bone callus formed;in the model group,the bone defect area still existed,where discontinuous cortical bone was visible;in the traditional Chinese medicine group,the defect area was filled with newborn bone tissues,the bone marrow cavity and part of the cortical bone formed,and the fracture line disappeared.Micro-CT scans showed that the amount of new bone in the defect area was low in the blank group,the number of bone trabeculae in the defect area was significantly increased in the model group,and a large amount of new bone tissue was filled in the bone defect area in the traditional Chinese medicine group.Hematoxylin-eosin staining results showed that in the blank group,only a small amount of new bone formed in the defect area and the quality of osteogenesis was poor;in the model group,there was more new bone tissue in the defect area,but some fibrous connective tissues were interspersed within the bone tissue;and in the traditional Chinese medicine group,a large amount of new bone formed in the defect area and the quality of osteogenesis was the best.CD31/Emcn immunofluorescence double-labeling staining results showed that the number of H-type blood vessels in the newborn bone tissue in the bone defect area of the blank group was sparse and sparsely distributed;compared with the blank group,there were more H-type blood vessels in the bone tissue in the bone defect area of the model group,and the blood vessels were distributed in relatively regular strips;the number of H-type blood vessels in the bone defect area of the traditional Chinese medicine group was the highest and the blood vessels were densely distributed.To conclude,the total flavonoids of rhizoma drynariae can upregulate the expression of H-type blood vessels to enhance the angiogenic-osteogenic effect,improve the osteogenic efficiency of the rat femoral Masquelet induced membrane model,and promote bone remodeling.
8.Helicobacter pylori in patients with gastric upset in Yuexiu Dongshan community,Guangzhou:an epi-demiological study
Wei CHENG ; Jing ZENG ; Junfeng GUO
Modern Hospital 2024;24(2):297-299
Objective To analyze and summarize the epidemiological characteristics of gastric Helicobacter pylori in pa-tients experiencing gastric discomfort in Yuexiu Dongshan Community,Guangzhou.Methods A total of 312 patients who visited Yuexiu District Dongshan Community Health Service Center for stomach upset testing between April 2023 and July 2023 were en-rolled in the study.The distribution characteristics of positive Helicobacter pylori were analyzed among the patients of different age and gender.Results Out of the 312 cases in the population,93 cases tested positive and 219 tested negative,with a positive de-tection rate of 29.81%.Specifically,28 cases tested positive,and 74 cases tested negative in the male population,with a positive detection rate of 27.45%.In the female population,65 cases tested positive,and 145 cases tested negative,with a positive detec-tion rate of 30.95%.The difference in positive rates by gender was not statistically significant(X2 =0.402,P=0.526).Among the male patients infected with Helicobacter,the mean value of delta over baseline of the C13 urea breath test(DOB)was(17.31±11.84).The DOB value was insignificantly higher in the males than in the females(t =1.430,P=0.156).There was no signifi-cant increasing or decreasing trend in the distribution of positive rates by age.The composition ratio of positive patients was predom-inant in the group aged 40 and above,accounting for 79.57%of the total number of positive cases.Among the individuals aged less than 60 infected with Helicobacter pylori,the mean duration of the breath test was(14.95±11.87),while among those aged over 61,the mean duration of the breath test was(24.66±22.71).The disparity between the two groups was statistically significant(t =2.643,P=0.009 7).Conclusion Gastric Helicobacter pylori can be detected in individuals of all genders and ages,and it is a primary cause of gastric discomfort.Community-based C13 breath tests can detect the presence of infections of helicobacter py-lori at an early stage.Antibiotics can be administered to treat the infections,thereby reducing the incidence of gastric tumors.
9.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.
10.Analysis of the causes of cage subsidence after oblique lateral lumbar interbody fusion
Zhong-You ZENG ; Ping-Quan CHEN ; Xing ZHAO ; Hong-Fei WU ; Jian-Qiao ZHANG ; Xiang-Qian FANG ; Yong-Xing SONG ; Wei YU ; Fei PEI ; Shun-Wu FAN ; Guo-Hao SONG ; Shi-Yang FAN
China Journal of Orthopaedics and Traumatology 2024;37(1):33-44
Objective To observe the cage subsidence after oblique lateral interbody fusion(OLIF)for lumbar spondylo-sis,summarize the characteristics of the cage subsidence,analyze causes,and propose preventive measures.Methods The data of 144 patients of lumbar spine lesions admitted to our hospital from October 2015 to December 2018 were retrospectively ana-lyzed.There were 43 males and 101 females,and the age ranged from 20 to 81 years old,with an average of(60.90±10.06)years old.Disease types:17 patients of lumbar intervertebral disc degenerative disease,12 patients of giant lumbar disc hernia-tion,5 patients of discogenic low back pain,33 patients of lumbar spinal stenosis,26 patients of lumbar degenerative spondy-lolisthesis,28 patients of lumbar spondylolisthesis with spondylolisthesis,11 patients of adjacent vertebral disease after lumbar internal fixation,7 patients of primary spondylitis in the inflammatory outcome stage,and 5 patients of lumbar degenerative scoliosis.Preoperative dual-energy X-ray bone mineral density examination showed 57 patients of osteopenia or osteoporosis,and 87 patients of normal bone density.The number of fusion segments:124 patients of single-segment,11 patients of two-seg-ment,8 patients of three-segment,four-segment 1 patient.There were 40 patients treated by stand-alone OLIF,and 104 patients by OLIF combined with posterior pedicle screw.Observed the occurrence of fusion cage settlement after operation,conducted monofactor analysis on possible risk factors,and observed the influence of fusion cage settlement on clinical results.Results All operations were successfully completed,the median operation time was 99 min,and the median intraoperative blood loss was 106 ml.Intraoperative endplate injury occurred in 30 patients and vertebral fracture occurred in 5 patients.The mean follow-up was(14.57±7.14)months from 6 to 30 months.During the follow-up,except for the patients of primary lumbar interstitial in-flammation and some patients of lumbar spondylolisthesis with spondylolisthesis,the others all had different degrees of cage subsidence.Cage subsidence classification:119 patients were normal subsidence,and 25 patients were abnormal subsidence(23 patients were grade Ⅰ,and 2 patients were grade Ⅱ).There was no loosening or rupture of the pedicle screw system.The height of the intervertebral space recovered from the preoperative average(9.48±1.84)mm to the postoperative average(12.65±2.03)mm,and the average(10.51±1.81)mm at the last follow-up.There were statistical differences between postop-erative and preoperative,and between the last follow-up and postoperative.The interbody fusion rate was 94.4%.The low back pain VAS decreased from the preoperative average(6.55±2.2 9)to the last follow-up(1.40±0.82),and there was statistically significant different.The leg pain VAS decreased from the preoperative average(4.72±1.49)to the final follow-up(0.60± 0.03),and the difference was statistically significant(t=9.13,P<0.000 1).The ODI index recovered from the preoperative av-erage(38.50±6.98)%to the latest follow-up(11.30±3.27)%,and there was statistically significant different.The complication rate was 31.3%(45/144),and the reoperation rate was 9.72%(14/144).Among them,8 patients were reoperated due to fusion cage subsidence or displacement,accounting for 57.14%(8/14)of reoperation.The fusion cage subsidence in this group had obvious characteristics.The monofactor analysis showed that the number of abnormal subsidence patients in the osteopenia or osteoporosis group,Stand-alone OLIF group,2 or more segments fusion group,and endplate injury group was higher than that in the normal bone mass group,OLIF combined with pedicle screw fixation group,single segment fusion group,and no endplate injury group,and the comparison had statistical differences.Conclusion Cage subsidence is a common phenomenon after 0-LIF surgery.Preoperative osteopenia or osteoporosis,Stand-alone OLIF,2 or more segments of fusion and intraoperative end-plate injury may be important factors for postoperative fusion cage subsidence.Although there is no significant correlation be-tween the degree of cage subsidence and clinical symptoms,there is a risk of cage migration,and prevention needs to be strengthened to reduce serious complications caused by fusion of cage subsidence,including reoperation.

Result Analysis
Print
Save
E-mail