1.Xianglian Huazhuo Prescription Regulates GP73/PERK/ATF4 Signaling Pathway to Influence Endoplasmic Reticulum Stress and Ameliorate Chronic Atrophic Gastritis
Pengli DU ; Yuxi GUO ; Yican WANG ; Ziqi JIN ; Xin KANG ; Xuemei JIA ; Weichao XU ; Yanru CAI ; Qian YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):19-28
ObjectiveTo explore the mechanism by which Xianglian Huazhuo prescription ameliorates chronic atrophic gastritis (CAG) through regulating the Golgi protein 73 (GP73)/protein kinase R-like endoplasmic reticulum kinase (PERK)/activating transcription factor 4 (ATF4) signaling pathway and modulating endoplasmic reticulum stress (ERS). MethodA mouse model of CAG was induced by multiple factors, including ranitidine, N-methyl-N′-nitro-N-nitrosoguanidine (MNNG), and irregular feeding. The CAG mice were randomized into five groups: model, Morodan (2.0 g·kg-1), and high-dose, medium-dose, and low-dose (7.6, 3.8, 1.9 g·kg-1, respectively) Xianglian Huazhuo prescription, with 10 mice in each group. At the same time, 10 mice in normal group were set up. The mice in the Morodan group and the high-dose, medium-dose, and low-dose groups of Xianglian Huazhuo prescription were administrated with corresponding agents by gavage, and those in the normal group and the model group were administrated with an equal volume of normal saline. All the mice were intervened once a day for 60 consecutive days. After the last administration, the overall morphological changes of the gastric tissue were observed. Hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM) were used to evaluate the pathological morphology and the endoplasmic reticulum ultrastructure in the gastric tissue. The serum levels of pepsinogen Ⅰ (PGⅠ), pepsinogen Ⅱ (PGⅡ), gastrin-17 (G-17), and GP73 were determined by enzyme-linked immunosorbent assay (ELISA). The pepsinogen ratio (PGR, PGⅠ/PGⅡ) was calculated. The protein levels of GP73, PERK, phosphorylated (p)-PERK, glucose-regulated protein 78 (GRP78), ATF4, CCAAT enhancer-binding protein homologous protein (CHOP), cysteinyl aspartate-specific protease-12 (Caspase-12), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) were assessed by Western blot. The expression of GRP78 was detected by immunofluorescence (IF) assay, and the location of Bcl-2 and Bax by immunohistochemistry (IHC). ResultsCompared with the normal group, the model group showed pale gastric mucosa with flattened folds and reduced and loosely arranged gastric mucosal glands, declined serum levels of PGI, PGR, G-17, and GP73 (P<0.01). downregulated protein levels of GP73, p-PERK, ATF4, GRP78, CHOP, Caspase-12, and Bax in the gastric tissue, and upregulated protein level of Bcl-2 (P<0.01). Compared with the model group, the Morodan group and each Xianglian Huazhuo prescription group exhibited red gastric mucosa with increased folds, alleviated pathological damage, swelling endoplasmic reticulum, elevated serum levels of PGI, G-17, and GP73 (P<0.05, P<0.01), and upregulated protein levels of Caspase-12 and Bax and downregulated protein level of Bcl-2 in the gastric tissue (P<0.05, P<0.01). The Morodan group and the high-dose and medium-dose Xianglian Huazhuo prescription groups exhibited increased serum level of PGR (P<0.05, P<0.01) and upregulated protein levels of GP73, p-PERK, ATF4, GRP78, and CHOP in the gastric tissue (P<0.05, P<0.01). ConclusionXianglian Huazhuo prescription can activate the GP73/PERK/ATF4 signaling pathway and induce ERS-mediated apoptosis to alleviate the pathological damage of the gastric mucosa, thereby demonstrating a protective effect against CAG in mice.
2.Xianglian Huazhuo Prescription Regulates GP73/PERK/ATF4 Signaling Pathway to Influence Endoplasmic Reticulum Stress and Ameliorate Chronic Atrophic Gastritis
Pengli DU ; Yuxi GUO ; Yican WANG ; Ziqi JIN ; Xin KANG ; Xuemei JIA ; Weichao XU ; Yanru CAI ; Qian YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):19-28
ObjectiveTo explore the mechanism by which Xianglian Huazhuo prescription ameliorates chronic atrophic gastritis (CAG) through regulating the Golgi protein 73 (GP73)/protein kinase R-like endoplasmic reticulum kinase (PERK)/activating transcription factor 4 (ATF4) signaling pathway and modulating endoplasmic reticulum stress (ERS). MethodA mouse model of CAG was induced by multiple factors, including ranitidine, N-methyl-N′-nitro-N-nitrosoguanidine (MNNG), and irregular feeding. The CAG mice were randomized into five groups: model, Morodan (2.0 g·kg-1), and high-dose, medium-dose, and low-dose (7.6, 3.8, 1.9 g·kg-1, respectively) Xianglian Huazhuo prescription, with 10 mice in each group. At the same time, 10 mice in normal group were set up. The mice in the Morodan group and the high-dose, medium-dose, and low-dose groups of Xianglian Huazhuo prescription were administrated with corresponding agents by gavage, and those in the normal group and the model group were administrated with an equal volume of normal saline. All the mice were intervened once a day for 60 consecutive days. After the last administration, the overall morphological changes of the gastric tissue were observed. Hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM) were used to evaluate the pathological morphology and the endoplasmic reticulum ultrastructure in the gastric tissue. The serum levels of pepsinogen Ⅰ (PGⅠ), pepsinogen Ⅱ (PGⅡ), gastrin-17 (G-17), and GP73 were determined by enzyme-linked immunosorbent assay (ELISA). The pepsinogen ratio (PGR, PGⅠ/PGⅡ) was calculated. The protein levels of GP73, PERK, phosphorylated (p)-PERK, glucose-regulated protein 78 (GRP78), ATF4, CCAAT enhancer-binding protein homologous protein (CHOP), cysteinyl aspartate-specific protease-12 (Caspase-12), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) were assessed by Western blot. The expression of GRP78 was detected by immunofluorescence (IF) assay, and the location of Bcl-2 and Bax by immunohistochemistry (IHC). ResultsCompared with the normal group, the model group showed pale gastric mucosa with flattened folds and reduced and loosely arranged gastric mucosal glands, declined serum levels of PGI, PGR, G-17, and GP73 (P<0.01). downregulated protein levels of GP73, p-PERK, ATF4, GRP78, CHOP, Caspase-12, and Bax in the gastric tissue, and upregulated protein level of Bcl-2 (P<0.01). Compared with the model group, the Morodan group and each Xianglian Huazhuo prescription group exhibited red gastric mucosa with increased folds, alleviated pathological damage, swelling endoplasmic reticulum, elevated serum levels of PGI, G-17, and GP73 (P<0.05, P<0.01), and upregulated protein levels of Caspase-12 and Bax and downregulated protein level of Bcl-2 in the gastric tissue (P<0.05, P<0.01). The Morodan group and the high-dose and medium-dose Xianglian Huazhuo prescription groups exhibited increased serum level of PGR (P<0.05, P<0.01) and upregulated protein levels of GP73, p-PERK, ATF4, GRP78, and CHOP in the gastric tissue (P<0.05, P<0.01). ConclusionXianglian Huazhuo prescription can activate the GP73/PERK/ATF4 signaling pathway and induce ERS-mediated apoptosis to alleviate the pathological damage of the gastric mucosa, thereby demonstrating a protective effect against CAG in mice.
3.Safety and efficacy of secondary cytoreductive surgery in patients with platinum-sensitive recurrent ovarian cancer after first-line PARPi maintenance therapy
Yuxi ZHAO ; Hongwen YAO ; Jia ZENG ; Yangchun SUN ; Nan LI ; Guangwen YUAN ; Ning LI ; Lingying WU
Chinese Journal of Obstetrics and Gynecology 2025;60(8):600-607
Objective:To investigate the effectiveness and safety of secondary cytoreductive surgery (SCS) in patients with platinum-sensitive recurrent epithelial ovarian cancer who progressed after first-line maintenance therapy with poly adenosine diphosphate ribose polymerase inhibitor (PARPi).Methods:Clinical pathological data and prognostic information were retrospectively collected from 30 ovarian cancer patients who underwent SCS between January 2018 and June 2024. The Kaplan-Meier method was used to analyze the second progression-free survival (PFS2) time and 3-year overall survival (OS) rate.Results:(1) Primary treatment: the median age at diagnosis was 51.3 years. A total of 40% (12/30) patients underwent primary debulking surgery with an expectation of achieving no gross residual disease (R0), while 60% (18/30) received neoadjuvant chemotherapy and interval debulking surgery. Optimal cytoreduction was achieved in 93% (28/30) of patients. BRCA1/2 gene testing was performed in 29 patients (testing rate 97%, 29/30), identifying 11 BRCA-mutated (37%, 11/30) and 18 BRCA wild-type (60%, 18/30) patients. The median duration of PARPi maintenance therapy among the 30 patients was 11.9 months; patients with BRCA gene mutations had a median duration of 19.2 months, while those with BRCA wild-type had a median duration of 10.1 months. (2) Secondary surgery: pathologically confirmed recurrence patterns, single lesion in 9 patients (30%, 9/30), oligo-lesion (2 lesions) in 3 patients (10%, 3/30), and multi-lesion (≥3 lesions) in 18 patients (60%, 18/30). Among the 30 patients, optimal cytoreduction was achieved in 97% (29/30) of SCS patients, with suboptimal cytoreduction in 1 patient (3%, 1/30). Adjuvant chemotherapy included platinum+paclitaxel in 24 (80%, 24/30) patients and platinum+liposomal doxorubicin in 6 (20%, 6/30) patients. PARPi re-treatment was administered to 17 patients (57%, 17/30) after chemotherapy. (3) Efficacy and safety: as of the follow-up cutoff in June 2024, the median follow-up time was 28.0 months. A total of 19 (63%, 19/30) patients experienced the next recurrence. The median PFS2 time after SCS was 18.5 months. Recurrence occurred in 7 BRCA-mutated and 12 BRCA gene wild-type patients. Median PFS2 time was significantly longer in BRCA-mutated patients compared to BRCA wild-type patients (25.7 vs 14.1 months; P=0.028). Three deaths occurred during follow-up, resulting in a 3-year OS rate of 90%. Among the 30 patients, postoperative complications occurred in 4 patients (13%, 4/30). One patient developed a ureteral fistula on 7 days post-SCS requiring ureteral stenting, and one patient was transferred to the intensive care unit on 1 day post-SCS due to hypovolemic shock. No deaths occurred within 30 days after SCS. Conclusion:For platinum-sensitive recurrent ovarian cancer patients progressed after first-line PARPi maintenance therapy who are anticipated to achieve R0 resection, SCS represents a safe and effective second-line treatment option.
4.Clinical manifestations and disease severity of multi-respiratory infectious pathogens.
Mingyue JIANG ; Yuping DUAN ; Jia LI ; Mengmeng JIA ; Qing WANG ; Tingting LI ; Hua RAN ; Yuhua REN ; Jiang LONG ; Yunshao XU ; Yanlin CAO ; Yongming JIANG ; Boer QI ; Yuxi LIU ; Weizhong YANG ; Li QI ; Luzhao FENG
Chinese Medical Journal 2025;138(20):2675-2677
5.Application of Ferroptosis Regulation in Chronic Atrophic Gastritis Based on Spleen Deficiency and Turbid Toxin
Yuxi GUO ; Xuemei JIA ; Jie WANG ; Yanru CAI ; Pengli DU ; Yao DU ; Diangui LI ; Qian YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):279-285
Chronic atrophic gastritis (CAG), a common digestive system disease, has an unclear pathogenesis. Currently, it is mostly believed to be related to Helicobacter pylori (Hp) infection, immune factors, dietary factors, bile reflux, long-term use of antibiotics and anti-inflammatory drugs, and other factors. Ferroptosis is a regulated cell death mechanism that is iron-dependent and characterized by disruption of iron metabolism and accumulation of lipid peroxides. More and more studies have found that ferroptosis is closely related to the onset of CAG. Professor LI Diangui, a master of traditional Chinese medicine, first proposed the turbid toxin theory, which holds that spleen deficiency and turbid toxin is the main pathogenic mechanism of CAG. Abnormal iron metabolism regulation is a prerequisite for the accumulation of turbid toxin in CAG, and ferroptosis is in accordance with the pathogenic mechanism (spleen deficiency and turbid toxin) of CAG. This article explores the pathological mechanism of spleen deficiency and turbid toxin in CAG from the perspectives of iron metabolism, oxidative stress, and lipid peroxidation, providing theoretical support of traditional Chinese medicine for the modern research on CAG. It enriches the modern scientific connotation of the turbid toxicity theory and provides new ideas and breakthrough points for the clinical treatment of CAG.
6.Application of Ferroptosis Regulation in Chronic Atrophic Gastritis Based on Spleen Deficiency and Turbid Toxin
Yuxi GUO ; Xuemei JIA ; Jie WANG ; Yanru CAI ; Pengli DU ; Yao DU ; Diangui LI ; Qian YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):279-285
Chronic atrophic gastritis (CAG), a common digestive system disease, has an unclear pathogenesis. Currently, it is mostly believed to be related to Helicobacter pylori (Hp) infection, immune factors, dietary factors, bile reflux, long-term use of antibiotics and anti-inflammatory drugs, and other factors. Ferroptosis is a regulated cell death mechanism that is iron-dependent and characterized by disruption of iron metabolism and accumulation of lipid peroxides. More and more studies have found that ferroptosis is closely related to the onset of CAG. Professor LI Diangui, a master of traditional Chinese medicine, first proposed the turbid toxin theory, which holds that spleen deficiency and turbid toxin is the main pathogenic mechanism of CAG. Abnormal iron metabolism regulation is a prerequisite for the accumulation of turbid toxin in CAG, and ferroptosis is in accordance with the pathogenic mechanism (spleen deficiency and turbid toxin) of CAG. This article explores the pathological mechanism of spleen deficiency and turbid toxin in CAG from the perspectives of iron metabolism, oxidative stress, and lipid peroxidation, providing theoretical support of traditional Chinese medicine for the modern research on CAG. It enriches the modern scientific connotation of the turbid toxicity theory and provides new ideas and breakthrough points for the clinical treatment of CAG.
7.Safety and efficacy of secondary cytoreductive surgery in patients with platinum-sensitive recurrent ovarian cancer after first-line PARPi maintenance therapy
Yuxi ZHAO ; Hongwen YAO ; Jia ZENG ; Yangchun SUN ; Nan LI ; Guangwen YUAN ; Ning LI ; Lingying WU
Chinese Journal of Obstetrics and Gynecology 2025;60(8):600-607
Objective:To investigate the effectiveness and safety of secondary cytoreductive surgery (SCS) in patients with platinum-sensitive recurrent epithelial ovarian cancer who progressed after first-line maintenance therapy with poly adenosine diphosphate ribose polymerase inhibitor (PARPi).Methods:Clinical pathological data and prognostic information were retrospectively collected from 30 ovarian cancer patients who underwent SCS between January 2018 and June 2024. The Kaplan-Meier method was used to analyze the second progression-free survival (PFS2) time and 3-year overall survival (OS) rate.Results:(1) Primary treatment: the median age at diagnosis was 51.3 years. A total of 40% (12/30) patients underwent primary debulking surgery with an expectation of achieving no gross residual disease (R0), while 60% (18/30) received neoadjuvant chemotherapy and interval debulking surgery. Optimal cytoreduction was achieved in 93% (28/30) of patients. BRCA1/2 gene testing was performed in 29 patients (testing rate 97%, 29/30), identifying 11 BRCA-mutated (37%, 11/30) and 18 BRCA wild-type (60%, 18/30) patients. The median duration of PARPi maintenance therapy among the 30 patients was 11.9 months; patients with BRCA gene mutations had a median duration of 19.2 months, while those with BRCA wild-type had a median duration of 10.1 months. (2) Secondary surgery: pathologically confirmed recurrence patterns, single lesion in 9 patients (30%, 9/30), oligo-lesion (2 lesions) in 3 patients (10%, 3/30), and multi-lesion (≥3 lesions) in 18 patients (60%, 18/30). Among the 30 patients, optimal cytoreduction was achieved in 97% (29/30) of SCS patients, with suboptimal cytoreduction in 1 patient (3%, 1/30). Adjuvant chemotherapy included platinum+paclitaxel in 24 (80%, 24/30) patients and platinum+liposomal doxorubicin in 6 (20%, 6/30) patients. PARPi re-treatment was administered to 17 patients (57%, 17/30) after chemotherapy. (3) Efficacy and safety: as of the follow-up cutoff in June 2024, the median follow-up time was 28.0 months. A total of 19 (63%, 19/30) patients experienced the next recurrence. The median PFS2 time after SCS was 18.5 months. Recurrence occurred in 7 BRCA-mutated and 12 BRCA gene wild-type patients. Median PFS2 time was significantly longer in BRCA-mutated patients compared to BRCA wild-type patients (25.7 vs 14.1 months; P=0.028). Three deaths occurred during follow-up, resulting in a 3-year OS rate of 90%. Among the 30 patients, postoperative complications occurred in 4 patients (13%, 4/30). One patient developed a ureteral fistula on 7 days post-SCS requiring ureteral stenting, and one patient was transferred to the intensive care unit on 1 day post-SCS due to hypovolemic shock. No deaths occurred within 30 days after SCS. Conclusion:For platinum-sensitive recurrent ovarian cancer patients progressed after first-line PARPi maintenance therapy who are anticipated to achieve R0 resection, SCS represents a safe and effective second-line treatment option.
8.Reflections on the positioning and implementation pathways of adult vaccine prescriptions
Mengmeng JIA ; Yanlin CAO ; Yuxi LIU ; Li ZHANG ; Jixiang MA ; Luzhao FENG
Chinese Journal of Preventive Medicine 2024;58(10):1616-1619
The innovation of integrating medical treatment and prevention mechanisms is a key task deployed by the government, aiming to promote the construction of a Healthy China and address the prevalent "treatment over prevention" mindset in healthcare services and society. Vaccination is an effective strategy for preventing and controlling infectious diseases; however, adult vaccination rates in China remain low due to insufficient awareness and enthusiasm among the public and healthcare professionals. In recent years, various regions have begun to explore the model of physicians in medical institutions prescribing vaccines to improve vaccination rates. This article analyzes the positioning, current implementation status, and challenges of vaccine prescriptions, and proposes recommendations advocating policy formulation, improving service models and supporting measures, improving funding mechanisms, and strengthening publicity and education to promote the widespread implementation and effectiveness of vaccine prescriptions.
9.Efficacy of horizontal plate plus raft screws above the acetabulum in the treatment of acetabular fractures combined with dome impaction in the aged patients
Zhaojie LIU ; Jian JIA ; Haotian QI ; Yuxi SUN ; Gang LI ; Wei TIAN ; Hongchuan WANG ; Shucai BAI ; Pengfei LI
Chinese Journal of Trauma 2024;40(3):221-228
Objective:To compare the efficacy of the horizontal plate plus raft screws above the acetabulum and fixation with screws only for acetabular fractures combined with dome impaction in the aged patients.Methods:A retrospective cohort study was conducted to analyze the clinical data of 20 aged patients with acetabular fractures combined with dome impaction, who were admitted to Tianjin hospital between May 2013 and January 2023, including 5 males and 15 females, aged 61-84 years [(72.2±7.3)years]. According to Letournel and Judet classification, 13 patients had anterior column fracture, 5 anterior column fracture combined with posterior transverse fracture and 2 two-column fracture. All the patients underwent open reduction and internal fixation through an anterior approach. Of them, 11 patients were treated with the fixation with the horizonal plate plus raft screws above the acetabulum (plate plus raft screw group) and 9 with the screws only (screw only group). The operative time, intraoperative blood loss, and intraoperative fluoroscopy times were compared between the two groups. The quality of fracture reduction was evaluated with the Matta′s radiographic criteria at 3 days after surgery and the function of the hip joint was assessed with Merle D′Aubigné and Postel scoring system at 3 months after surgery and at the last follow-up as well as the excellent and good rate at te last follow-up. The occurrence of postoperative complications was observed.Results:All the patients were followed up for 6-18 months [(13.1±3.1)months]. There were no significant differences in the operative time, intraoperative blood loss or intraoperative fluoroscopy times between the two groups ( P>0.05). According to the Matta′s radiographic criteria at 3 days after surgery, patients with anatomical reduction and satisfactory reduction accounted 6 and 5 in the plate plus raft screw group, compared to 5 and 4 respectively in the screw only group ( P>0.05). The values of Merle D′Aubigné and Postel score at 3 months after surgery and at the last follow-up were (14.0±2.4)points and (15.8±2.2)points in the plate plus raft screw group, which were higher than those in the screw only group [(11.0±2.6)points and (13.0±3.1)points] ( P<0.01). The values of Merle D′Aubigné and Postel score at the last follow-up of both groups were further enhanced from those at 3 months after surgery ( P<0.01). At the last follow-up, 3 patients were rated excellent, 6 good, 1 fair and 1 poor in the plate plus raft screw group, with an excellent and good rate of 81.8%, while in the screw only group, 3 were rated good, 2 fair and 4 poor, with an excellent and good rate of 33.3% ( P<0.05). One patient in the plate plus raft screw group and 5 in the screw only group had displacement of the dome impaction fragment combined with traumatic arthritis after surgery ( P<0.05). Conclusion:For acetabular fractures combined with dome impaction in the aged patients, the horizontal plate plus raft screw above the acetabulum can effectively improve the function restoration of the hip joint and reduce the occurrence of the displacement of the dome impaction fragment and traumatic arthritis after surgery compared to the fixation with screws only.
10.Reflections on the positioning and implementation pathways of adult vaccine prescriptions
Mengmeng JIA ; Yanlin CAO ; Yuxi LIU ; Li ZHANG ; Jixiang MA ; Luzhao FENG
Chinese Journal of Preventive Medicine 2024;58(10):1616-1619
The innovation of integrating medical treatment and prevention mechanisms is a key task deployed by the government, aiming to promote the construction of a Healthy China and address the prevalent "treatment over prevention" mindset in healthcare services and society. Vaccination is an effective strategy for preventing and controlling infectious diseases; however, adult vaccination rates in China remain low due to insufficient awareness and enthusiasm among the public and healthcare professionals. In recent years, various regions have begun to explore the model of physicians in medical institutions prescribing vaccines to improve vaccination rates. This article analyzes the positioning, current implementation status, and challenges of vaccine prescriptions, and proposes recommendations advocating policy formulation, improving service models and supporting measures, improving funding mechanisms, and strengthening publicity and education to promote the widespread implementation and effectiveness of vaccine prescriptions.

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