1.Therapeutic Effects of Xiao Xumingtang Combined with Electroacupuncture on Cerebral Ischemia/Reperfusion Injury via NLRP3/GSDMD/Caspase-1 Pathway
Wei MAO ; Haiyang WU ; Ying WANG ; Haitao WANG ; Haisheng JI ; Junyu ZHANG ; Chenglong LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):39-47
ObjectiveTo comprehensively elucidate the potential mechanisms of Xiao Xumingtang (XXMT) combined with electroacupuncture (EA) collaboratively in alleviating cerebral ischemia/reperfusion (I/R) injury. MethodThe rat model of cerebral I/R injury was established using the modified suture-occluded method. Seven days after modeling, rats in the XXMT+EA groups were administered XXMT at low (15 g·kg-1), medium (30 g·kg-1), and high (60 g·kg-1) doses, alongside daily 20-min EA treatment (stimulating acupoints GV14 and GV20). Cerebral infarction and neuronal damage were evaluated using the Zea Longa test score, TTC staining, and TUNEL staining. Real-time fluorescence quantitative PCR and Western blot were used to detect the expression of NOD-like receptor hot protein domain related protein 3 (NLRP3), Gasdermin D (GSDMD), cysteinyl aspartate specific proteinase-1 (Caspase-1), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in the ischemic area of the cerebral cortex. ResultCompared with the sham group, the I/R group showed a significant increase in neurological deficit scores and infarct volume (P<0.01), along with a higher apoptosis rate of cortical neurons and elevated mRNA and protein expression levels of NLRP3, GSDMD, Caspase-1, IL-1β, and IL-18 (P<0.05). In contrast, the medium- and high-dose XXMT combined with EA treatment significantly reduced neurological deficit scores and infarct volume (P<0.01), and decreased the apoptosis rate of cortical neurons as well as the mRNA and protein expression levels of NLRP3, GSDMD, Caspase-1, IL-1β, and IL-18 (P<0.05). The improvement showed a dose-dependent relationship with XXMT. ConclusionThe combined use of XXMT and EA can exert neuroprotective effects by modulating the NLRP3/GSDMD/Caspase-1 signaling pathway, thereby reducing neurological deficits, minimizing brain infarct size, and improving cortical neuronal damage.
2.Role and mechanism of P311 in the differentiation of mouse skin fibroblasts into myofibroblasts
Xue HENG ; Buying LI ; Shijie GAO ; Changjin LU ; Xiaorong ZHANG ; Xiaohong HU ; Gaoxing LUO ; Haisheng LI
Chinese Journal of Burns 2024;40(9):849-856
Objective:To explore the role and mechanism of P311 in the differentiation of mouse skin fibroblasts (Fbs) into myofibroblasts.Methods:The study was an experimental research. Six 2-day-old male C57BL/6 mouse were used to extract skin Fbs by enzymatic hydrolysis method and routinely cultured. The 1 st to 3 rd passage cells were taken and divided into empty vector group transfected with empty adenovirus and P311 group transfected with P311 high expression adenovirus, and P311+myocardin-related transcription factor A (MRTF-A) small interfering RNA (siMRTF-A) group transfected with P311 high expression adenovirus and siMRTF-A according to the random number table. After 72 h of culture, the cell proliferation vitality of cells in 3 groups was detected by cell counting kit 8, the protein expressions of MRTF-A, α-smooth muscle actin (α-SMA), and serum response factor (SRF) in cells in 3 groups were detected by Western blotting, the collagen gel contraction assay was performed and the 72 h gel contraction rates in 3 groups were calculated. The sample numbers in the above experiments were all 3. The protein expressions of MRTF-A and SRF in cells, cytoplasm, and nucleus in cells in empty vector group and P311 group were detected by Western blotting, with sample number of 4. Results:After 72 h of culture, the cell proliferation vitality of cells in empty vector group, P311 group, and P311+siMRTF-A group was similar ( P>0.05). After 72 h of culture, compared with those in empty vector group, the protein expressions of MRTF-A, α-SMA, and SRF in cells in P311 group were significantly increased ( P<0.05), while the protein expressions of MRTF-A and SRF in cells in P311+siMRTF-A group were significantly decreased ( P<0.05). Compared with those in P311 group, the protein expressions of MRTF-A, SRF, and α-SMA in cells in P311+siMRTF-A group were significantly decreased ( P<0.05). The 72 h gel contraction rate showing cell contractility in P311 group was (84.8±6.2)%, which was significantly higher than (27.8±2.6)% in empty vector group and (24.7±3.2)% in P311+siMRTF-A group (with P values all <0.05). The 72 h gel contraction rates in empty vector group and P311+siMRTF-A group were similar ( P>0.05). After 72 hours of culture, the protein expressions of MRTF-A (with t values of 5.86 and 3.77, respectively, P<0.05) and SRF (with t values of 3.95 and 3.97, respectively, P<0.05) in cells and cytoplasm in P311 group were significantly higher than those in empty vector group, while the protein expressions of MRTF-A and SRF in the nucleus of cells were similar between the two groups ( P>0.05). Conclusions:P311 can promote the differentiation of fibroblasts into myofibroblasts through MRTF-A, and then participate in scar formation.
3.No administering prophylactic systemic antibiotics routinely during the shock phase after burn injury
Gaoxing LUO ; Haisheng LI ; Zhiqiang YUAN ; Yizhi PENG
Chinese Journal of Burns 2024;40(10):911-914
Infection is the most common complication following burn injury, while it is rare to induce immediately systemic infection after burn injury. Domestically, the burn patients especially the major burn patients are conventionally administered systemic antibiotics prophylactically during the shock phase after burn injury. However, the clinical evidences and all the international expert consensuses and guidelines on burn infections object strongly and clearly administration of systemic antibiotics prophylactically. The incidences of systemic infection and sepsis did not increase significantly after prohibiting prophylactical administration of systemic antibiotics routinely during the shock phase after burn injury based on the authors unit's clinical data of more than 100 major burn patients. Herein, we propose that the burn patients should not be routinely administered systemic antibiotics prophylactically during the burn shock phase.
4.Comparison of the efficacy between vonoprazan fumarate and rabeprazole combined with mucosal protectors for artificial ulcers after endoscopic submucosal dissection: a prospective randomized controlled study
Xin GAO ; Xuan LI ; Yun WANG ; Haisheng QIAN ; Guoxin ZHANG
Chinese Journal of Digestive Endoscopy 2024;41(5):366-371
Objective:To compare the efficacy between vonoprazan fumarate and rabeprazole for the treatment of artificial ulcers after endoscopic submucosal dissection (ESD).Methods:In this prospective randomized controlled study, patients who underwent ESD between December 2021 and August 2023 at Jiangsu Province Hospital were enrolled and randomly divided into two groups. Vonoprazan fumarate combined with rebamipide (vonoprazan group) or rabeprazole combined with rebamipide (rabeprazole group) were given respectively from the 4th day after ESD. After 8 weeks, the healing of the ulcers was compared.Results:Ninety-one patients were enrolled in the study, including 51 in the vonoprazan group and 40 in the rabeprazole group. The ulcer area reduction rate of the vonoprazan group was significantly higher than that of the rabeprazole group (92.86%±3.80% VS 90.04%±4.28%, t=3.281, P=0.001), but there was no significant difference in the healing rate [15.69% (8/51) VS 7.50% (3/40), χ2=1.414, P=0.234] or the adverse event occurrence ( P>0.05) between the two groups. Conclusion:Vonoprazan fumarate can achieve better ulcer treatment without increasing the risk of adverse events.
5.Analysis of effects and influencing factors of continuous renal replacement therapy in severe burn patients complicated with acute kidney injury
Xue HENG ; Changmin LI ; Wei LIU ; Ning LI ; Zhiqiang YUAN ; Yizhi PENG ; Haisheng LI ; Gaoxing LUO
Chinese Journal of Burns 2024;40(5):468-475
Objective:To preliminarily evaluate the effects and analyze the influencing factors of continuous renal replacement therapy (CRRT) in severe burn patients complicated with acute kidney injury (AKI).Methods:This study was a retrospective case series study. From January 2010 to December 2020, 79 severe burn patients complicated with AKI who received CRRT and met the inclusion criteria were admitted to the First Affiliated Hospital of Army Medical University (the Third Military Medical University). The general data (the same below) of all patients were collected, including gender, age, body mass index, burn area, burn index, cause of injury, whether combined with inhalation injury, acute physiology and chronic health status evaluation Ⅱ (APACHE Ⅱ) score and sepsis-related organ failure assessment (SOFA) score on admission, admission time after burn, and time of AKI after admission. The total efficacy of CRRT, including overall effective rate, complete effective rate, partial effective rate, ineffective rate, and deterioration rate, creatinine, urea, cystatin C, and fluid overload rate before and after treatment, in-hospital mortality, predictive mortality based on Baux scoring model, the most common cause of death, and length of hospital stay were recorded. According to the effect of CRRT, the patients were divided into effective group (42 patients) and ineffective group (37 patients). The general information of patients, the time to initiate CRRT after the occurrence of AKI, the duration of CRRT, etiology of AKI, AKI stage before CRRT initiation, CRRT mode, anticoagulant type, and in-hospital mortality were compared between the two groups of patients. The independent influencing factors for CRRT in severe burn patients complicated with AKI were screened. According to the etiology of AKI, the patients were divided into prerenal group (22 patients) and renal group (57 patients). The general information of patients, the time to initiate CRRT after the occurrence of AKI, the duration of CRRT, and total efficacy of CRRT (except for the most common cause of death) were compared between the two groups of patients.Results:Among the 79 patients, 73 cases were male and 6 cases were female, with age of (46±14) years, body mass index of (24.0±2.9) kg/m 2, total burn area of (69±26)% total body surface area (TBSA), full-thickness burn area of (44±25)%TBSA, and burn index of 57 (36, 76). There were 36 cases of flame burns, 19 cases of electrical burns, 16 cases of hydrothermal burns, 6 cases of explosive burns, and 2 cases of chemical burns. Thirty-nine patients were complicated with inhalation injury. The APACHE Ⅱ score was 16 (12, 18) and the SOFA score was 11 (5, 13) on admission. The patients were admitted to the hospital on 0 (0, 2) d after burn, and AKI occurred on 0 (0, 6) d after admission. The overall effective rate of CRRT was 53.16% (42/79), the complete effective rate was 30.38% (24/79), the partial effective rate was 22.78% (18/79), the ineffective rate was 31.65% (25/79), and the deterioration rate was 15.19% (12/79). The creatinine and urea of patients after treatment were significantly lower than those before treatment (with Z values of -3.26 and -2.54, respectively, P<0.05); there were no statistically significant differences in the cystatin C and fluid overload rate of patients before and after treatment ( P>0.05). The in-hospital mortality of patients was 17.72% (14/79), and the predictive mortality based on Baux scoring model was 75.10% (18.94%, 91.84%). The most common cause of death was multiple organ failure, and the length of hospital stay was 39.43 (11.52, 110.58) d. There were statistically significant differences in the full-thickness burn area, the duration of CRRT, and etiology of AKI of patients between effective group and ineffective group (with Z values of -1.99 and -2.90, respectively, χ2=5.58, P<0.05). There were no statistically significant differences in the other indicators ( P>0.05). The etiology of AKI and full-thickness burn area were the independent influencing factors for CRRT in severe burn patients complicated with AKI (with odds ratios of 4.21 and 1.03, respectively, 95% confidence intervals of 1.20-14.80 and 1.00-1.05, respectively, P<0.05). There were statistically significant differences in the cause of injury, overall effective rate of CRRT, total burn area, burn index, admission time after burn, time of AKI after admission, the time to initiate CRRT after the occurrence of AKI, and predictive mortality based on Baux score model of patients between prerenal group and renal group (with χ2 values of 12.59 and 5.58, respectively, Z values of 2.46, 2.43, -2.43, -4.03, -3.01, and -2.31, respectively, P<0.05). Before treatment, urea and cystatin C of patients in renal group were significantly higher than those in prerenal group (with Z values of -2.98 and -2.77, respectively, P<0.05), and the liquid overload rate was significantly lower than that in prerenal group ( Z=-2.99, P<0.05); after treatment, the cystatin C of patients in renal group was significantly higher than that in prerenal group ( Z=-2.08, P<0.05); there were no statistically significant differences in the other indicators ( P>0.05). Conclusions:CRRT can significantly improve renal function, avoid fluid overload, and alleviate renal injury in severe burn patients complicated with AKI. Prerenal AKI is the main independent influencing factor leading to ineffective CRRT.
6.Effect of bluetongue virusinfection on type Ⅰ interferon response in BHK-21 cells
Shimei LUO ; Yunyi CHEN ; Qisha LI ; Yanmei ZHOU ; Yifei WANG ; Xinyu LIAO ; Xuer-Ou HU ; Yuanjian WEI ; Mengqin LI ; Meng ZHU ; Xun ZHANG ; Beirui CHEN ; Xianping MA ; Jiarui XIE ; Meiling KOU ; Haisheng MIAO ; Fang LI ; Huashan YI
Chinese Journal of Veterinary Science 2024;44(8):1639-1644,1690
Bluetongue virus is an arbovirus that seriously harms ruminants such as sheep,this study aims to investigate the molecular mechanism of bluetongue virus infection and host cell interferon antiviral immune response.The study was conducted to characterize the mRNA expression of inter-feron pathway genes by real-time fluorescence quantitative PCR,as well as Western blot analysis of MDA5,TRAF3,RIG-Ⅰ,and TBK1 protein expression in BHK-21 cells induced by BTV with a multiplicity of infections(MOI)of 1 for 18,24,and 36 h.The results showed that the most pro-nounced changes in the expression of interferon signaling pathway genes were observed at 24 h of induction,the gene mRNA expression levels of the IFN-α,IFN-β,RIG-Ⅰ,TBK1,MDA5,VISA,and TRAF3 genes were upregulated.However,the mRNA expression levels of IKKε and TRAF6 genes were downregulated.At the protein level,MDA5 and TBK1 proteins were upregulated while RIG-1 and TRAF3 proteins were downregulated,which showed that BTV infection induces a typeⅠ interferon immune response in BHK-21 cells.This study lays the foundation for further exploring the antiviral immunity mechanism of IFN-Ⅰ signaling pathway regulatory genes in host cells infected with BTV infection.
7.A retrospective study on the efficacy of Roxadustat in peritoneal dialysis patients with erythropoietin hyporesponsiveness
Jie LIU ; Shuang LI ; Fan YANG ; Tianyu LI ; Rui LI ; Yousuf WAHEED ; Chen MENG ; Shulin LI ; Kun LIU ; Yanshan TONG ; Haisheng XU ; Chuankuo TIAN ; Xinglei ZHOU
The Korean Journal of Internal Medicine 2024;39(3):488-500
Background/Aims:
Roxadustat, an oral medication for treating renal anemia, is a hypoxia-inducible factor prolyl hydroxylase inhibitor used for regulating iron metabolism and promoting erythropoiesis. To investigate the efficacy and safety of roxadustat in patients undergoing peritoneal dialysis (PD) with erythropoietin hyporesponsiveness.
Methods:
Single-center, retrospective study, 81 PD patients (with erythropoietin hyporesponsiveness) were divided into the roxadustat group (n = 61) and erythropoiesis-stimulating agents (ESAs) group (n = 20). Hemoglobin (Hb), total cholesterol, intact parathyroid hormone (iPTH), brain natriuretic peptide (BNP), related indicators of cardiac function and high-sensitivity C-reactive protein (hs-CRP) were collected. Additionally, adverse events were also recorded. The follow-up period was 16 weeks.
Results:
The two groups exhibited similar baseline demographic and clinical characteristics. At baseline, the roxadustat group had a mean Hb level of 89.8 ± 18.9 g/L, while the ESAs group had a mean Hb level of 95.2 ± 16.0 g/L. By week 16, the Hb levels had increased to 118 ± 19.8 g/L (p < 0.05) in the roxadustat group and 101 ± 19.3 g/L (p > 0.05) in the ESAs group. The efficacy of roxadustat in improving anemia was not influenced by baseline levels of hs-CRP and iPTH. Cholesterol was decreased in the roxadustat group without statin use. An increase in left ventricular ejection fraction and stabilization of BNP were observed in the roxadustat group.
Conclusions
For PD patients with erythropoietin hyporesponsiveness, roxadustat can significantly improve renal anemia. The efficacy of roxadustat in improving renal anemia was not affected by baseline levels of hs-CRP0 and iPTH.
9.Chinese Medicine Regulates mTOR Signaling Pathway to Prevent and Treat Osteoporosis: A Review
Yize WU ; Xingyong LI ; Xiyan LYU ; Baohua YUAN ; Haisheng LIN ; Xiaotao WEI
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(23):253-263
Osteoporosis (OP), a common systemic skeletal disease in the elderly, is characterised by bone loss and bone microstructural degeneration. Its clinical manifestations include increased bone fragility and bone pain. Furthermore, OP increases the risk of fracture due to the high bone fragility, which leads to lifelong disability or death, imposing a heavy economic and psychological burden on the patients and their families. The pathogenesis of OP is extremely complex and associated with a variety of factors such as proliferation and differentiation of osteoblasts, impairment of osteoclast activity and function, and abnormalities in autophagy activation. Recent studies have found that mammalian target of rapamycin (mTOR) signaing pathway is involved in the regulation of bone homeostasis, which can promote bone formation and improve bone metabolism and bone microstructure by regulating osteoblast proliferation and differentiation and osteoclast function and activating cellular autophagy, thus playing a crucial role in the prevention and treatment of OP. The prevention and treatment of OP with Chinese medicine has a long history, clear efficacy, multiple targets of action, low adverse effects, and wide medicine sources. Therefore, this paper briefly describes the role of mTOR signaling pathway in the development of OP by reviewing the latest research reports and summarizes in detail the latest research results on the treatment of OP with Chinese medicine extracts and prescriptions via the mTOR signaling pathway. This review aims to provide a basis for the in-depth research on the relationship between mTOR signaling pathway and OP and the clinical application of traditional Chinese medicine in the prevention and treatment of OP.
10.Practice and exploration of online teaching in clinical medicine education in military teaching hospitals
Ting JIANG ; Biyuan LI ; Liqin ZOU ; Ping ZHAO ; Haisheng LI
Chinese Journal of Medical Education Research 2023;22(7):1017-1021
With the rapid development of information technology and the change in military education policy in the new era, online teaching has gradually become one of the main approaches to implement the clinical medical education in military teaching hospitals. In this study, the online teaching was performed mainly by pre-recorded teaching, supplemented by online live teaching. Massive open online courses (MOOCs) and the seminar-style teaching were advocated to be used in advanced disciplines. The quality of online teaching was guaranteed through infrastructure provision, teacher arrangement, teaching preparation, teaching interactivity, after-class test, teaching evaluation, supervision, and summary of teaching, which ultimately achieved a good effect. The results of the two-way questionnaires of 26 teachers and 129 students showed that 23.26% (30/129) of students and 65.38% (17/26) of teachers believed that students' learning ability was insufficient. 34.88% (45/129) of students and 23.08% (6/26) of teachers thought that the existing technology could not meet the requirements of online teaching. 55.04% (71/129) of students and 69.23% (18/26) of teachers held the view that the effect of online teaching was inferior to face-to-face teaching. 28.68% (37/129) of students and 57.69% (15/26) of faculty asked for the return of face-to-face education. Therefore, it is necessary to strengthen the construction of smart classroom platforms, establish a well-developed online teaching quality evaluation system, and integrate various innovative teaching modes with the online teaching. In these ways, it is expected to optimize the online teaching of clinical medicine and achieve the goal of online teaching.

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