1.Research Progress on the Role of Programmed Cell Death in Flap Ischemia-Reperfusion Injury
Jiwei ZHANG ; Jie ZHANG ; Xinshan WANG ; Xingzhang YAO ; Zhenxing JIANG ; Zhijun HE ; Tao LIU ; Jianliang LI ; Hui YAO ; Jie AN ; Qiuyue ZHAO ; Xiaotao WEI ; M Rayan GHAZI
Medical Journal of Peking Union Medical College Hospital 2026;17(3):851-861
Flap transplantation is a critical surgical strategy for the reconstruction of tissue defects caused by trauma, tumor resection, and congenital malformations, and its survival rate directly determines surgical efficacy and patient prognosis. Following transplantation, flaps inevitably undergo ischemia-reperfusion (I/R) injury, during which oxidative stress, inflammatory responses, and metabolic disturbances are intricately intertwined, ultimately leading to cellular injury and tissue necrosis. Recent studies have demonstrated that multiple forms of programmed cell death—including apoptosis, pyroptosis, ferroptosis, necroptosis, and PANoptosis—play central roles in flap I/R injury. The extensive crosstalk and molecular interactions among these pathways form a highly complex cell death network. Specifically, apoptosis is mediated by the imbalance of Bcl-2 family proteins and the activation of cysteine-dependent aspartate-specific protease (caspase) cascades; pyroptosis is driven by the NLRP3-caspase-1-GSDMD axis, resulting in membrane pore formation and the release of pro-inflammatory cytokines; ferroptosis is characterized by iron-dependent lipid peroxidation and dysfunction of glutathione peroxidase 4 (GPX4); necroptosis is triggered by the receptor-interacting serine/threonine-protein kinase 1 (RIPK1)-RIPK3-MLKL signaling complex, leading to membrane rupture; and PANoptosis represents an integrated form of inflammatory cell death that coordinates multiple death pathways. Importantly, these forms of programmed cell death are not independent but are interconnected through extensive signaling crosstalk. Key regulatory molecules, including caspase-8, reactive oxygen species (ROS), nuclear factor-κB (NF-κB), and nuclear factor erythroid 2-related factor 2 (Nrf2), collectively modulate the dynamic balance among these pathways. Therefore, the multidimensional interplay and spatiotemporal dynamics of programmed cell death constitute a fundamental pathological basis of flap I/R injury. This review systematically summarizes the latest advances in the mechanisms and interactions of various programmed cell death pathways in flap I/R injury, aiming to elucidate the underlying regulatory network. These insights may provide novel theoretical foundations for optimizing flap protection strategies, improving flap survival, and promoting tissue repair.
2.Effect and Mechanism of Icariin on Improving Spermatogenesis in Exercise-induced Fatigue Model Mice Through Regucalcin
Kunyang TANG ; Min XIAO ; Xiaocui JIANG ; Xiaoxue TAO ; Yue ZOU ; Chunchun ZHAO ; Zhipeng FANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):117-127
ObjectiveThis paper aims to investigate the effects of icariin on spermatogenesis in mice with exercise-induced fatigue and explore the underlying mechanisms. MethodsICR male mice were screened by swimming and randomly divided into normal group, model group, vitamin C group, icariin groups with low, medium, and high doses, and medium-dose icariin+N-nitro-L-arginine methyl ester (L-NAME) group, with 10 mice per group. Except for the normal group, all the other groups underwent weighted swimming training to establish an exercise-induced fatigue model. No gavage was administered during the first two weeks of the weighted training. From week three to four, the icariin groups with low, medium, and high doses received 0.03, 0.06, and 0.12 g·kg-1 icariin via gavage, respectively. The vitamin C group received 0.2 g·kg-1 vitamin C. The L-NAME group received 0.06 g·kg-1 icariin and 0.01 g·kg-1 L-NAME via intraperitoneal injection. The normal and model groups received equivalent physiological saline. After the experiment, body weight and the last exhaustive swimming time were recorded. Blood urea nitrogen (BUN), lactate (LA), lactate dehydrogenase (LDH), malondialdehyde (MDA), testicular testosterone (T), testicular Ca2+/Mg2+-adenosine triphosphatase (ATPase) (micro-assay), and the levels of testicular cyclic guanosine monophosphate (cGMP) were measured by using kits. Sperm CD46 levels were detected by flow cytometry. Testicular seminiferous tubules were observed via hematoxylin-eosin (HE) staining, and the testicular morphometric score (TMS) was used to evaluate the spermatogenic function. Protein expression of regucalcin (RGN, SMP30), cGMP-dependent protein kinase 1 (PKG), and cGMP-dependent protein kinase anchoring protein (GKAP1) was detected by Western blot. Testicular regucalcin expression was examined by immunofluorescence (IF). The epididymal sperm quality of mice was observed under a microscope. Fluorescence-stained sections of stimulated by retinoic acid gene 8 (STRA8), synaptonemal complex protein 3 (SCP3), and transition protein 1(TNP1) in testicular seminiferous tubules were assessed by immunohistochemistry (IHC). ResultsCompared with the normal group, the model group showed decreased body weight and exhaustive swimming time (P<0.01), significantly increased fatigue markers (LA, LDH, and BUN) and lipid peroxidation product MDA (P<0.01), reduced testicular RGN, PKG, GKAP1, testosterone, Ca2+/Mg2+-ATPase, and cGMP levels (P<0.01), decreased sperm motility, sperm count, and TMS scores, and downregulated the expression of STRA8, SCP3, and TNP1. Compared with the model group, the icariin group with high dose exhibited increased exhaustive swimming time (P<0.01), reduced LA, LDH, BUN, and MDA levels (P<0.01), elevated superoxide dismutase (SOD) (P<0.01), upregulated testicular RGN, PKG, GKAP1, testosterone, Ca2+/Mg2+-ATPase, and cGMP levels (P<0.01), improved sperm motility, sperm count, and TMS scores, and enhanced STRA8, SCP3, and TNP1 expression. Compared with the L-NAME group, the icariin group with medium dose showed increased expression of STRA8, SCP3, and TNP1 in the testicular tissue (P<0.01) and elevated cGMP and GKAP1 levels (P<0.01). ConclusionExercise-induced fatigue reduces the expression of RGN and cGMP/PKG/GKAP1 in mice, thereby causing abnormal spermatogenesis and impairing reproductive function in mice. Icariin ameliorates spermatogenic dysfunction in exercise-induced fatigue mice by promoting the expression of RGN and cGMP/PKG/GKAP1, thereby mitigating the damage of exercise-induced fatigue to the reproductive system.
3.Effect and Mechanism of Icariin on Improving Spermatogenesis in Exercise-induced Fatigue Model Mice Through Regucalcin
Kunyang TANG ; Min XIAO ; Xiaocui JIANG ; Xiaoxue TAO ; Yue ZOU ; Chunchun ZHAO ; Zhipeng FANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):117-127
ObjectiveThis paper aims to investigate the effects of icariin on spermatogenesis in mice with exercise-induced fatigue and explore the underlying mechanisms. MethodsICR male mice were screened by swimming and randomly divided into normal group, model group, vitamin C group, icariin groups with low, medium, and high doses, and medium-dose icariin+N-nitro-L-arginine methyl ester (L-NAME) group, with 10 mice per group. Except for the normal group, all the other groups underwent weighted swimming training to establish an exercise-induced fatigue model. No gavage was administered during the first two weeks of the weighted training. From week three to four, the icariin groups with low, medium, and high doses received 0.03, 0.06, and 0.12 g·kg-1 icariin via gavage, respectively. The vitamin C group received 0.2 g·kg-1 vitamin C. The L-NAME group received 0.06 g·kg-1 icariin and 0.01 g·kg-1 L-NAME via intraperitoneal injection. The normal and model groups received equivalent physiological saline. After the experiment, body weight and the last exhaustive swimming time were recorded. Blood urea nitrogen (BUN), lactate (LA), lactate dehydrogenase (LDH), malondialdehyde (MDA), testicular testosterone (T), testicular Ca2+/Mg2+-adenosine triphosphatase (ATPase) (micro-assay), and the levels of testicular cyclic guanosine monophosphate (cGMP) were measured by using kits. Sperm CD46 levels were detected by flow cytometry. Testicular seminiferous tubules were observed via hematoxylin-eosin (HE) staining, and the testicular morphometric score (TMS) was used to evaluate the spermatogenic function. Protein expression of regucalcin (RGN, SMP30), cGMP-dependent protein kinase 1 (PKG), and cGMP-dependent protein kinase anchoring protein (GKAP1) was detected by Western blot. Testicular regucalcin expression was examined by immunofluorescence (IF). The epididymal sperm quality of mice was observed under a microscope. Fluorescence-stained sections of stimulated by retinoic acid gene 8 (STRA8), synaptonemal complex protein 3 (SCP3), and transition protein 1(TNP1) in testicular seminiferous tubules were assessed by immunohistochemistry (IHC). ResultsCompared with the normal group, the model group showed decreased body weight and exhaustive swimming time (P<0.01), significantly increased fatigue markers (LA, LDH, and BUN) and lipid peroxidation product MDA (P<0.01), reduced testicular RGN, PKG, GKAP1, testosterone, Ca2+/Mg2+-ATPase, and cGMP levels (P<0.01), decreased sperm motility, sperm count, and TMS scores, and downregulated the expression of STRA8, SCP3, and TNP1. Compared with the model group, the icariin group with high dose exhibited increased exhaustive swimming time (P<0.01), reduced LA, LDH, BUN, and MDA levels (P<0.01), elevated superoxide dismutase (SOD) (P<0.01), upregulated testicular RGN, PKG, GKAP1, testosterone, Ca2+/Mg2+-ATPase, and cGMP levels (P<0.01), improved sperm motility, sperm count, and TMS scores, and enhanced STRA8, SCP3, and TNP1 expression. Compared with the L-NAME group, the icariin group with medium dose showed increased expression of STRA8, SCP3, and TNP1 in the testicular tissue (P<0.01) and elevated cGMP and GKAP1 levels (P<0.01). ConclusionExercise-induced fatigue reduces the expression of RGN and cGMP/PKG/GKAP1 in mice, thereby causing abnormal spermatogenesis and impairing reproductive function in mice. Icariin ameliorates spermatogenic dysfunction in exercise-induced fatigue mice by promoting the expression of RGN and cGMP/PKG/GKAP1, thereby mitigating the damage of exercise-induced fatigue to the reproductive system.
4.Applicability of a new pilot anti-G capability assessment trainer
Tao JIANG ; Jiao YIN ; Lijun WEN ; Bin LI ; Jiyu DANG ; Xi ZHAO ; Wen DONG ; Haixia WANG ; Yan XU
Chinese Journal of Aerospace Medicine 2025;36(1):38-43
Objective:To evaluate the applicability of a new anti-G capability assessment trainer (AG-CAT) in high-performance (HP) anti-G maneuver training and positive pressure breathing for high-G (PHP) training for pilots.Methods:A total of 142 fighter pilots who were subjected to anti-G maneuver training at Dujiangyan Special Crew Sanatorium of PLA Air Force between January and November 2023 were enrolled. According to the Guidelines for Aviation Physiological Training, 123 pilots underwent both HP anti-G maneuver training and PHP positive pressure breathing training, 15 received only HP training, and 4 received only PHP training. Based on the training devices used, these pilots were divided into AG-CAT group and an anti-G and anti-hypoxia capability detection instrument (GHyCDI) group. The 2 groups were compared regarding the pedal force of lower limbs, blood pressure, and improvement of +G z tolerance during training. Results:Of the 138 pilots undergoing HP training, 88 used AG-CAT and 50 used GHyCDI. One hundred and twenty-seven pilots participated in PHP training, with 73 in the AG-CAT group and 54 in the GHyCDI group. During HP training, the pedal force of left lower limbs in the AG-CAT group was greater than that of the right limbs and of the GHyCDI group ( t=4.38, 2.64, P<0.001, =0.009). In PHP training, the AG-CAT group exhibited greater pedal force in left limbs than in right ones, while the GHyCDI group showed an opposite trend ( t=2.25, 3.37, P=0.029, 0.002). Systolic and diastolic blood pressures during HP training (with or without anti-G suits) were higher in the AG-CAT group than in the GHyCDI group ( t=3.50, 3.72, 2.55, 4.21, P=0.001,<0.001,=0.012,<0.001). Similarly, during PHP training, both systolic and diastolic pressures were higher in the AG-CAT group ( t=2.03, 3.81, P=0.045,<0.001). The AG-CAT group demonstrated superior improvements in +G z tolerance during HP training (without/with anti-G suits: Z=2.14, 3.21, P=0.049, 0.001) and PHP training ( Z=2.56, P=0.010) compared with the GHyCDI group. Conclusions:AG-CAT shows excellent applicability in aviation physiological training of pilots. Its ergonomic design, practical functionalities and enhanced compatibility with personnel protective equipment can better meet training requirements compared to conventional devices.
5.Analysis of the efficacy of lamb′s tripe extract and vitamin B 12 capsule on chronic atrophic gastritis at different sites
Dongdong XIA ; Huahong XIE ; Bo JIANG ; Hong XU ; Zhanguo NIE ; Chengwei TANG ; Qiang GUO ; Xiaoping ZOU ; Shuisheng SHI ; Tao SUN ; Shourong SHEN ; Guoqing LI ; Xiaozhong GUO ; Xiaoyan ZHAO ; Jiaming QIAN ; Weixing CHEN ; Guiying ZHANG ; Aijun LIAO ; Jingyuan FANG ; Daiming FAN ; Kaichun WU
Chinese Journal of Digestion 2025;45(3):162-168
Objective:To evaluate the efficacy of lamb′s tripe extract and vitamin B 12 capsule (LTEVB 12C) on chronic atrophic gastritis (CAG) at different locations (antrum lesser curvature, antrum greater curvature, gastric angle, corpus lesser curvature, and corpus greater curvature). Methods:From August 2011 to January 2013, 715 patients with CAG in a multicenter, randomized, double-blind, placebo-controlled trial were enrolled from 16 tertiary first-class hospitals across the country, including the First Affiliated Hospital of Air Force Medical University, Nanfang Hospital of Southern Medical University, the First Hospital of Jilin University, West China Hospital of Sichuan University, etc., there were 476 cases in the LTEVB 12C group and 239 cases in the placebo group. The patients of the LTEVB 12C group received LTEVB 12C, and the patients of placebo group received LTEVB 12C mimetic, all the medications were taken 3 capsules each time and 3 times a day after meals, and the treatment course of 2 groups were both 6 months. The efficacy evaluation criteria included the effective rate (a decrease of ≥1 in histopathological score compared with baseline after 6 months of treatment) and the reversal rate (a decrease of ≥ 2 in histopathological score compared with baseline after 6 months of treatment in the patients with moderate to severe CAG). The impact of lesion sites on the therapeutic effects of LTEVB 12C was analyzed by logistic regression analysis. The two-way unordered Cochran-Mantel-Haenszel chi-square test considering the center effect and Pearson chi-square test were used for statistical analysis. Results:The effective rates of chronic inflammation at the antrum greater curvature and corpus greater curvature (23.3%, 110/473 vs. 13.0%, 31/239; 20.3%, 96/472 vs. 12.6%, 30/239), the effective rates of atrophy at the antrum lesser curvature, antrum greater curvature, gastric angle, corpus lesser curvature, and the corpus greater curvature (27.0%, 118/437 vs. 15.7%, 34/216; 29.2%, 126/432 vs. 18.5%, 38/205; 27.8%, 121/435 vs. 16.7%, 36/216; 32.5%, 127/391 vs. 19.8%, 37/187; 33.0%, 119/361 vs. 21.8%, 39/179), and the effective rates of intestinal metaplasia at the antrum lesser curvature, antrum greater curvature, gastric angle, and the corpus lesser curvature (45.0%, 112/249 vs. 29.8%, 31/104; 53.8%, 86/160 vs. 33.9%, 21/62; 45.8%, 103/225 vs. 24.0%, 25/104; 51.9%, 83/160 vs. 28.3%, 17/60) of the LTEVB 12C group were all higher than those of the placebo group, and the differences were statistically significant ( χ2=10.76, 6.39, 9.69, 7.91, 11.05, 9.62, 8.57, 5.20, 7.11, 12.45, and 6.73; all P<0.05). The reversal rates of chronic inflammation at the corpus lesser curvature and corpus greater curvature (5.2%, 12/231 vs. 0, 0/123; 4.7%, 8/170 vs. 0, 0/88), the reversal rates of atrophy at the antrum lesser curvature, antrum greater curvature, corpus lesser curvature, and the corpus greater curvature (6.8%, 22/323 vs. 1.3%, 2/151; 9.2%, 29/315 vs. 1.4%, 2/144; 14.2%, 38/267 vs. 2.5%, 3/121; 20.8%, 35/168 vs. 5.8%, 4/69), and the reversal rates of intestinal metaplasia at the antrum lesser curvature, antrum greater curvature, gastric angle, and the corpus lesser curvature (29.8%, 39/131 vs. 9.1%, 4/44; 41.0%, 32/78 vs. 12.5%, 3/24; 33.3%, 44/132 vs. 4.8%, 3/63; 50.0%, 37/74 vs. 8.7%, 2/23) of the LTEVB 12C group were all higher than those of the placebo group, and the differences were statistically significant ( χ2=6.58, 5.12, 5.60, 8.61, 11.43, 6.59, 7.30, 4.95, 15.92, 7.62; all P<0.05). There were no statistically significant differences in the effective rates and reversal rates of active inflammation at different locations between the LTEVB 12C group and the placebo group (all P>0.05). The results of logistic regression analysis (taking the antrum lesser curvature as the reference) further confirmed that the reversal rates of chronic inflammation ( OR=0.22, 95% confidence interval (95% CI): 0.07 to 0.67; OR=0.24, 95% CI: 0.07 to 0.80), atrophy ( OR=0.28, 95% CI: 0.16 to 0.49; OR=0.28, 95% CI: 0.16 to 0.49), and intestinal metaplasia ( OR=0.42, 95% CI: 0.24 to 0.77; OR=0.20, 95% CI: 0.08 to 0.52) at the corpus lesser curvature and corpus greater curvature were all higher than those at the antrum lesser curvature, and the differences were statistically significant (all P<0.05). There were no statistically siginificant differences in the reversal rates of the aforementioned pathological features between the antrum greater curvature, gastric angle, and the antrum lesser curvature (all P>0.05). Conclusion:LTEVB 12C can achieve good efficacy in the treatment of CAG, and the chronic inflammation, atrophy, and intestinal metaplasia at multiple locations are improved, especially at the corpus lesser curvature and the corpus greater curvature.
6.Association of Body Mass Index with All-Cause Mortality and Cause-Specific Mortality in Rural China: 10-Year Follow-up of a Population-Based Multicenter Prospective Study.
Juan Juan HUANG ; Yuan Zhi DI ; Ling Yu SHEN ; Jian Guo LIANG ; Jiang DU ; Xue Fang CAO ; Wei Tao DUAN ; Ai Wei HE ; Jun LIANG ; Li Mei ZHU ; Zi Sen LIU ; Fang LIU ; Shu Min YANG ; Zu Hui XU ; Cheng CHEN ; Bin ZHANG ; Jiao Xia YAN ; Yan Chun LIANG ; Rong LIU ; Tao ZHU ; Hong Zhi LI ; Fei SHEN ; Bo Xuan FENG ; Yi Jun HE ; Zi Han LI ; Ya Qi ZHAO ; Tong Lei GUO ; Li Qiong BAI ; Wei LU ; Qi JIN ; Lei GAO ; He Nan XIN
Biomedical and Environmental Sciences 2025;38(10):1179-1193
OBJECTIVE:
This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study.
METHODS:
A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants.
RESULTS:
Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m 2) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m 2) and obesity (≥ 28.0 kg/m 2) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m 2 ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses.
CONCLUSION
This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans
;
Body Mass Index
;
China/epidemiology*
;
Male
;
Female
;
Middle Aged
;
Prospective Studies
;
Rural Population/statistics & numerical data*
;
Aged
;
Follow-Up Studies
;
Adult
;
Mortality
;
Cause of Death
;
Obesity/mortality*
;
Overweight/mortality*
7.Applicability of a new pilot anti-G capability assessment trainer
Tao JIANG ; Jiao YIN ; Lijun WEN ; Bin LI ; Jiyu DANG ; Xi ZHAO ; Wen DONG ; Haixia WANG ; Yan XU
Chinese Journal of Aerospace Medicine 2025;36(1):38-43
Objective:To evaluate the applicability of a new anti-G capability assessment trainer (AG-CAT) in high-performance (HP) anti-G maneuver training and positive pressure breathing for high-G (PHP) training for pilots.Methods:A total of 142 fighter pilots who were subjected to anti-G maneuver training at Dujiangyan Special Crew Sanatorium of PLA Air Force between January and November 2023 were enrolled. According to the Guidelines for Aviation Physiological Training, 123 pilots underwent both HP anti-G maneuver training and PHP positive pressure breathing training, 15 received only HP training, and 4 received only PHP training. Based on the training devices used, these pilots were divided into AG-CAT group and an anti-G and anti-hypoxia capability detection instrument (GHyCDI) group. The 2 groups were compared regarding the pedal force of lower limbs, blood pressure, and improvement of +G z tolerance during training. Results:Of the 138 pilots undergoing HP training, 88 used AG-CAT and 50 used GHyCDI. One hundred and twenty-seven pilots participated in PHP training, with 73 in the AG-CAT group and 54 in the GHyCDI group. During HP training, the pedal force of left lower limbs in the AG-CAT group was greater than that of the right limbs and of the GHyCDI group ( t=4.38, 2.64, P<0.001, =0.009). In PHP training, the AG-CAT group exhibited greater pedal force in left limbs than in right ones, while the GHyCDI group showed an opposite trend ( t=2.25, 3.37, P=0.029, 0.002). Systolic and diastolic blood pressures during HP training (with or without anti-G suits) were higher in the AG-CAT group than in the GHyCDI group ( t=3.50, 3.72, 2.55, 4.21, P=0.001,<0.001,=0.012,<0.001). Similarly, during PHP training, both systolic and diastolic pressures were higher in the AG-CAT group ( t=2.03, 3.81, P=0.045,<0.001). The AG-CAT group demonstrated superior improvements in +G z tolerance during HP training (without/with anti-G suits: Z=2.14, 3.21, P=0.049, 0.001) and PHP training ( Z=2.56, P=0.010) compared with the GHyCDI group. Conclusions:AG-CAT shows excellent applicability in aviation physiological training of pilots. Its ergonomic design, practical functionalities and enhanced compatibility with personnel protective equipment can better meet training requirements compared to conventional devices.
8.Analysis of the efficacy of lamb′s tripe extract and vitamin B 12 capsule on chronic atrophic gastritis at different sites
Dongdong XIA ; Huahong XIE ; Bo JIANG ; Hong XU ; Zhanguo NIE ; Chengwei TANG ; Qiang GUO ; Xiaoping ZOU ; Shuisheng SHI ; Tao SUN ; Shourong SHEN ; Guoqing LI ; Xiaozhong GUO ; Xiaoyan ZHAO ; Jiaming QIAN ; Weixing CHEN ; Guiying ZHANG ; Aijun LIAO ; Jingyuan FANG ; Daiming FAN ; Kaichun WU
Chinese Journal of Digestion 2025;45(3):162-168
Objective:To evaluate the efficacy of lamb′s tripe extract and vitamin B 12 capsule (LTEVB 12C) on chronic atrophic gastritis (CAG) at different locations (antrum lesser curvature, antrum greater curvature, gastric angle, corpus lesser curvature, and corpus greater curvature). Methods:From August 2011 to January 2013, 715 patients with CAG in a multicenter, randomized, double-blind, placebo-controlled trial were enrolled from 16 tertiary first-class hospitals across the country, including the First Affiliated Hospital of Air Force Medical University, Nanfang Hospital of Southern Medical University, the First Hospital of Jilin University, West China Hospital of Sichuan University, etc., there were 476 cases in the LTEVB 12C group and 239 cases in the placebo group. The patients of the LTEVB 12C group received LTEVB 12C, and the patients of placebo group received LTEVB 12C mimetic, all the medications were taken 3 capsules each time and 3 times a day after meals, and the treatment course of 2 groups were both 6 months. The efficacy evaluation criteria included the effective rate (a decrease of ≥1 in histopathological score compared with baseline after 6 months of treatment) and the reversal rate (a decrease of ≥ 2 in histopathological score compared with baseline after 6 months of treatment in the patients with moderate to severe CAG). The impact of lesion sites on the therapeutic effects of LTEVB 12C was analyzed by logistic regression analysis. The two-way unordered Cochran-Mantel-Haenszel chi-square test considering the center effect and Pearson chi-square test were used for statistical analysis. Results:The effective rates of chronic inflammation at the antrum greater curvature and corpus greater curvature (23.3%, 110/473 vs. 13.0%, 31/239; 20.3%, 96/472 vs. 12.6%, 30/239), the effective rates of atrophy at the antrum lesser curvature, antrum greater curvature, gastric angle, corpus lesser curvature, and the corpus greater curvature (27.0%, 118/437 vs. 15.7%, 34/216; 29.2%, 126/432 vs. 18.5%, 38/205; 27.8%, 121/435 vs. 16.7%, 36/216; 32.5%, 127/391 vs. 19.8%, 37/187; 33.0%, 119/361 vs. 21.8%, 39/179), and the effective rates of intestinal metaplasia at the antrum lesser curvature, antrum greater curvature, gastric angle, and the corpus lesser curvature (45.0%, 112/249 vs. 29.8%, 31/104; 53.8%, 86/160 vs. 33.9%, 21/62; 45.8%, 103/225 vs. 24.0%, 25/104; 51.9%, 83/160 vs. 28.3%, 17/60) of the LTEVB 12C group were all higher than those of the placebo group, and the differences were statistically significant ( χ2=10.76, 6.39, 9.69, 7.91, 11.05, 9.62, 8.57, 5.20, 7.11, 12.45, and 6.73; all P<0.05). The reversal rates of chronic inflammation at the corpus lesser curvature and corpus greater curvature (5.2%, 12/231 vs. 0, 0/123; 4.7%, 8/170 vs. 0, 0/88), the reversal rates of atrophy at the antrum lesser curvature, antrum greater curvature, corpus lesser curvature, and the corpus greater curvature (6.8%, 22/323 vs. 1.3%, 2/151; 9.2%, 29/315 vs. 1.4%, 2/144; 14.2%, 38/267 vs. 2.5%, 3/121; 20.8%, 35/168 vs. 5.8%, 4/69), and the reversal rates of intestinal metaplasia at the antrum lesser curvature, antrum greater curvature, gastric angle, and the corpus lesser curvature (29.8%, 39/131 vs. 9.1%, 4/44; 41.0%, 32/78 vs. 12.5%, 3/24; 33.3%, 44/132 vs. 4.8%, 3/63; 50.0%, 37/74 vs. 8.7%, 2/23) of the LTEVB 12C group were all higher than those of the placebo group, and the differences were statistically significant ( χ2=6.58, 5.12, 5.60, 8.61, 11.43, 6.59, 7.30, 4.95, 15.92, 7.62; all P<0.05). There were no statistically significant differences in the effective rates and reversal rates of active inflammation at different locations between the LTEVB 12C group and the placebo group (all P>0.05). The results of logistic regression analysis (taking the antrum lesser curvature as the reference) further confirmed that the reversal rates of chronic inflammation ( OR=0.22, 95% confidence interval (95% CI): 0.07 to 0.67; OR=0.24, 95% CI: 0.07 to 0.80), atrophy ( OR=0.28, 95% CI: 0.16 to 0.49; OR=0.28, 95% CI: 0.16 to 0.49), and intestinal metaplasia ( OR=0.42, 95% CI: 0.24 to 0.77; OR=0.20, 95% CI: 0.08 to 0.52) at the corpus lesser curvature and corpus greater curvature were all higher than those at the antrum lesser curvature, and the differences were statistically significant (all P<0.05). There were no statistically siginificant differences in the reversal rates of the aforementioned pathological features between the antrum greater curvature, gastric angle, and the antrum lesser curvature (all P>0.05). Conclusion:LTEVB 12C can achieve good efficacy in the treatment of CAG, and the chronic inflammation, atrophy, and intestinal metaplasia at multiple locations are improved, especially at the corpus lesser curvature and the corpus greater curvature.
9.Phase Ⅲ, multicenter, randomized comparative study of LY01005 and Zoladex ? for patients with premenopausal breast cancer
Xiying SHAO ; Qingyuan ZHANG ; Zhaofeng NIU ; Man LI ; Jingfen WANG ; Zhanhong CHEN ; Ruizhen LUO ; Guangdong QIAO ; Jianguo WANG ; Liyuan QIAN ; Ronghua YANG ; Zhendong CHEN ; Jian WANG ; Yumin YAO ; Jianghua OU ; Tao SUN ; Qiao CHENG ; Yongsheng WANG ; Jian HUANG ; Hongying ZHAO ; Wuyun SU ; Zhong OUYANG ; Yu DING ; Lilin CHEN ; Sumei YANG ; Mengsheng CUI ; Aimin ZANG ; Enxiang ZHOU ; Peizhi FAN ; Jing ZHANG ; Qiang LIU ; Yuee TENG ; Hui LI ; Jianyun NIE ; Jin YANG ; Xiaojia WANG ; Zefei JIANG
Chinese Journal of Oncology 2025;47(4):340-348
Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.
10.Study about the role of long noncoding RNA CCDC18-AS1 in primary hyerparathyroidism
Dongxue ZHANG ; Teng ZHAO ; Jian HUANG ; Bojun WEI ; Tao JIANG
Chinese Journal of Endocrinology and Metabolism 2025;41(3):219-225
Objective:To explore the role of long noncoding RNA(lncRNA) CCDC18-AS1 in parathyroid carcinoma(PC) diagnosis.Methods:This cross-sectional study included 55 patients with primary hyperparathyroidism treated at Beijing Shijitan Hospital from 2013 to 2024. Of these, 12 patients were diagnosed with PC and 43 with parathyroid adenoma(PA). Tissue samples and clinical data were collected, and lncRNA CCDC18-AS1 expression were measured using real-time quantitative PCR(RT-qPCR).Results:LncRNA CCDC18-AS1 expression was significantly higher in the PC group than that in the PA group( P=0.003). It was identified as an independent risk factor for PC, independent of age, sex, or serum calcium levels. Among patients with hypophosphatemia, no significant differences in lncRNA CCDC18-AS1 expression was observed between the PC and PA groups. However, in patients with normal serum phosphate levels, lncRNA CCDC18-AS1 expression was significantly higher in the PC group( P<0.001) and showed a positive correlation with serum phosphorus concentration( P=0.001). The area under the receiver operating characteristic(ROC) curve(AUC) for lncRNA CCDC18-AS1 in PC diagnosis was 0.758(95% CI 0.620-0.866, P=0.005), comparable to that of lncRNA plasmacytoma variant translocation 1(PVT1). Among patients with normal serum phosphate, the AUC for lncRNA CCDC18-AS1 increased to 0.969(95% CI 0.835-0.999, P<0.001), with 100% sensitivity and 92.31% specificity, suggesting superior diagnostic performance compared to PVT1(0.840, 95% CI 0.653-0.950, P=0.001). Conclusions:LncRNA CCDC18-AS1 may serves as a potential biomarker for PC diagnosis, with greater diagnostic value in patients with normal serum phosphorus levels.

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