1.Research Tackling Paradigm and Technological Layout Strategies Based on Erectile Dysfunction, A Clinical Dominant Disease of Traditional Chinese Medicine
Qi ZHAO ; Yun CHEN ; Baoxing LIU ; Xuejun SHANG ; Fei SUN ; Xiaozhi ZHAO ; Zhigang WU ; Chao SUN ; Peihai ZHANG ; Wanjun CHENG ; Xing ZHOU ; Zhan QIN ; Yufeng PAN ; Weiwei TAO ; Jianhuai CHEN ; Mei MO ; Xiaoxiao ZHANG ; Xing ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):291-299
To thoroughly implement the strategic deployment outlined in the Opinions of the Central Committee of the Communist Party of China and the State Council on Promoting the Inheritance and Innovative Development of Traditional Chinese Medicine regarding research on dominant diseases of traditional Chinese medicine and to uphold the development philosophy of equal emphasis on traditional Chinese medicine and western medicine,the China Association of Chinese Medicine has fully played a leading academic role by systematically organizing and conducting a series of academic youth salons on clinical dominant diseases of traditional Chinese medicine. On September 13,2024,the 36th Youth Salon on Clinical Dominant Diseases was successfully held in Nanjing,focusing on the advantages of traditional Chinese medicine and the integrative traditional Chinese medicine and western medicine in the diagnosis and treatment of erectile dysfunction (ED). The conference brought together leading experts from traditional Chinese medicine,western medicine,and interdisciplinary fields,facilitating in-depth multidisciplinary discussions that led to key consensus on optimizing traditional Chinese medicine treatment protocols for ED,researching and developing new drugs of traditional Chinese medicine,and advancing interdisciplinary development in traditional Chinese medicine. This salon systematically sorted out the clinical strengths and distinctive features of traditional Chinese medicine in the diagnosis and treatment of ED. Based on current research foundations and clinical needs,it identified key directions for future scientific layout and scientific research tackling: (1) Standardization of syndrome differentiation system of traditional Chinese medicine for ED. (2) Optimization and standardization of intervention methods of integrated traditional Chinese medicine and western medicine. (3) High-quality clinical research guided by evidence-based medicine. (4) In-depth analysis of the pharmacological mechanisms of traditional Chinese medicine in the treatment of ED. (5) Clinical translation and application promotion of new drugs of traditional Chinese medicine. (6) Interdisciplinary integration and innovation in traditional Chinese medicine. For each research direction,key focus areas,expected objectives,and clinical value were further refined,along with the establishment of a scientifically sound priority funding level evaluation system. Therefore,building on the series of salons on the ED-focused dominant diseases of traditional Chinese medicine,this paper provides standardized guidance for clinical practice of traditional Chinese medicine in ED management,effectively contributing to the high-quality development of traditional Chinese medicine. It serves as a valuable reference for national scientific and technological strategic layout, research and development decision-making in new drugs of traditional Chinese medicine,research topic planning,and clinical guideline formulation.
2.Surveillance of schistosomiasis in Jiangsu Province from 2012 to 2024
Wei LI ; Jianfeng ZHANG ; Liang SHI ; Tao WANG ; Yun FENG ; Lu LIU ; Kun YANG
Chinese Journal of Schistosomiasis Control 2026;38(1):8-13
Objective To evaluate the effectiveness of schistosomiasis surveillance in Jiangsu Province during the stage moving from transmission control to transmission interruption, and to analyze the current risk and challenges, so as to provide the evidence for achieving the target of schistosomiasis elimination. Methods Schistosomiasis surveillance data were collected from Jiangsu Province from 2012 to 2024, and the endemic areas, Schistosoma japonicum infections in humans and livestock, Oncomelania hupensis snail distribution and implementation of integrated interventions were descriptively analyzed. In addition, the trends in areas with snails, seroprevalence of human S. japonicum infections and numbers of advanced schistosomiasis cases were assessed using a Joinpoint regression model. Results The endemic areas of schistosomiasis continued to shrink in Jiangsu Province from 2012 to 2024, with the number of schistosomiasis-eliminated counties (cities, districts) increasing from 53 (75.71%) to 63 (96.92%), and interruption of schistosomiasis transmission was achieved across the province. A total of 4 600 300 person-times were tested for serum antibodies against S. japonicum, with 28 719 person-times positive detected; and 616 500 person-times were tested S. japonicum infections among local residents in Jiangsu Province from 2012 to 2024, with only 3 egg-positives detected, and no egg-positives found since 2017. A total of 187 600 herd-times were tested for schistosomiasis in livestock, and no S. japonicum infections were found. O. hupensis snail survey was performed covering 1 018 408.97 hm2, and a total of 35 556.35 hm2 was found with snail-infested habitats, including 174.40 hm2 of emerging snail-infested habitats. A total of 1 102 800 O. hupensis snails were identified for S. japonicum infections, and no infections were found. The areas of snail-infested habitats appeared a tendency towards a rise in Jiangsu Province from 2019 to 2023 (APC = 23.67%, P < 0.05), and the actual areas of snail-infested habitats appeared a tendency towards a decline from 2012 to 2015 (APC = −22.77%, P < 0.05), and towards a rise from 2015 to 2023 (APC = 9.76%, P < 0.01). The seroprevalence of anti-S. japonicum antibodies appeared a tendency towards a decline among residents in Jiangsu Province from 2017 to 2023 (APC = −14.92%, P < 0.01). In addition, the number of newly diagnosed advanced schistosomiasis cases appeared a tendency towards a decline from 2012 to 2024 (APC = −12.02%, P < 0.01), and the numbers of advanced schistosomiasis patients requiring treatment showed a tendency towards a decline from 2012 to 2021 (APC = −10.56%, P < 0.01) and from 2021 to 2023 (APC = −20.06%, P < 0.01). Conclusions Great progresses had been achieved in schistosomiasis control in Jiangsu Province following transmission control, and transmission interruption had been achieved; however, there are still snail-infested habitats. High-intensity surveillance and integrated control are required to be maintained to advance the achievement of the target of schistosomiasis elimination in Jiangsu Province.
3.Effect of Zhengan Xifengtang on Intestinal Mucosal Barrier in Spontaneously Hypertensive Rats via FXR-MLCK/p-MLC Pathway
Meilong SI ; Hua JIN ; Yu WANG ; Qiuju ZHANG ; Tao LIU ; Yun YONG ; Xuan BAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):1-10
ObjectiveTo investigate the repair effects of Zhengan Xifengtang on intestinal mucosal barrier in spontaneously hypertensive rats (SHRs) through the pathways of farnesoid X receptor (FXR)-myosin light chain kinase (MLCK)/phosphorylated myosin light chain (p-MLC) and its potential mechanism. MethodsForty 10-week-old male SHRs were randomly divided into model group, amlodipine besylate group (0.5 mg·kg-1·d-1), and high, middle and low dose groups of Zhengan Xifengtang (34.5, 17.25, 8.625 g·kg-1·d-1); eight age-matched male Wistar-Kyoto (WKY) rats of the same origin served as the normal control group. Drug intervention was carried out for 8 weeks, and the blood pressure of the rats was measured regularly. After the intervention, the rats were euthanized to collect tissue samples. Hematoxylin and eosin (HE) staining and Alcian blue-periodic acid-Schiff (AB-PAS) staining were used to evaluate the pathological morphology and the number of goblet cells in colonic mucosa. Enzyme-linked immunosorbent assay (ELISA) was employed to measure plasma lipopolysaccharide (LPS) and diamine oxidase (DAO) levels in each group of rats. Immunofluorescence (IF) assay was used to detect the relative fluorescence intensity of FXR and p-MLC in colonic tissue. Western blot was used to detect the zonula occludens-1 (ZO-1), Occludin, Claudin-1, junctional adhesion molecule-1 (JAM-1), mucin-2 (MUC2), FXR, MLCK, and p-MLC protein expression in colon tissue. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect mRNA expression levels of ZO-1, Occludin, Claudin-1, JAM-1, MUC2, FXR, MLCK, and MLC in colon tissue. ResultsCompared with the normal group, the blood pressure in the model group increased significantly (P<0.01), the colonic mucosal structure was seriously damaged, and the number of goblet cells decreased significantly. The contents of LPS and DAO increased significantly (P<0.01), the relative fluorescence intensity of FXR in colon decreased, while that of p-MLC increased (P<0.01). The protein and mRNA expressions of ZO-1, Claudin-1, JAM-1, Occludin, MUC2 and FXR decreased significantly (P<0.01), whereas the protein expression of MLCK and p-MLC increased significantly (P<0.01). Additionally, the mRNA expression of MLCK and MLC increased significantly (P<0.01). Compared with the model group, the Zhengan Xifengtang groups at various dosages and the amlodipine besylate group showed significantly reduced blood pressure (P<0.01). The damage of colonic mucosa structure was alleviated, the infiltration of inflammatory cells decreased, and the number of goblet cells increased. LPS and DAO levels were decreased (P<0.05, P<0.01). In the colon, the relative fluorescence intensity of FXR increased, while that of p-MLC decreased (P<0.05, P<0.01). The protein and mRNA expression levels of ZO-1, Claudin-1, JAM-1, Occludin, and FXR increased significantly (P<0.05, P<0.01), while the protein expression of MLCK and p-MLC decreased significantly (P<0.05, P<0.01). Furthermore, the mRNA expression of MLCK and MLC decreased significantly (P<0.05, P<0.01), and the protein expression of MUC2 increased significantly (P<0.05, P<0.01). The expression of MUC2 mRNA in each dose group of Zhengan Xifengtang increased significantly (P<0.05, P<0.01). ConclusionZhengan Xifengtang may regulate the FXR-MLCK/p-MLC signaling pathway and enhance the expression of tight junction protein, thereby reducing intestinal mucosal permeability, promoting mucosal barrier repair, decreasing LPS release into the blood, and ultimately lowering blood pressure.
4.Effect of Zhengan Xifengtang on Intestinal Mucosal Barrier in Spontaneously Hypertensive Rats via FXR-MLCK/p-MLC Pathway
Meilong SI ; Hua JIN ; Yu WANG ; Qiuju ZHANG ; Tao LIU ; Yun YONG ; Xuan BAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):1-10
ObjectiveTo investigate the repair effects of Zhengan Xifengtang on intestinal mucosal barrier in spontaneously hypertensive rats (SHRs) through the pathways of farnesoid X receptor (FXR)-myosin light chain kinase (MLCK)/phosphorylated myosin light chain (p-MLC) and its potential mechanism. MethodsForty 10-week-old male SHRs were randomly divided into model group, amlodipine besylate group (0.5 mg·kg-1·d-1), and high, middle and low dose groups of Zhengan Xifengtang (34.5, 17.25, 8.625 g·kg-1·d-1); eight age-matched male Wistar-Kyoto (WKY) rats of the same origin served as the normal control group. Drug intervention was carried out for 8 weeks, and the blood pressure of the rats was measured regularly. After the intervention, the rats were euthanized to collect tissue samples. Hematoxylin and eosin (HE) staining and Alcian blue-periodic acid-Schiff (AB-PAS) staining were used to evaluate the pathological morphology and the number of goblet cells in colonic mucosa. Enzyme-linked immunosorbent assay (ELISA) was employed to measure plasma lipopolysaccharide (LPS) and diamine oxidase (DAO) levels in each group of rats. Immunofluorescence (IF) assay was used to detect the relative fluorescence intensity of FXR and p-MLC in colonic tissue. Western blot was used to detect the zonula occludens-1 (ZO-1), Occludin, Claudin-1, junctional adhesion molecule-1 (JAM-1), mucin-2 (MUC2), FXR, MLCK, and p-MLC protein expression in colon tissue. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect mRNA expression levels of ZO-1, Occludin, Claudin-1, JAM-1, MUC2, FXR, MLCK, and MLC in colon tissue. ResultsCompared with the normal group, the blood pressure in the model group increased significantly (P<0.01), the colonic mucosal structure was seriously damaged, and the number of goblet cells decreased significantly. The contents of LPS and DAO increased significantly (P<0.01), the relative fluorescence intensity of FXR in colon decreased, while that of p-MLC increased (P<0.01). The protein and mRNA expressions of ZO-1, Claudin-1, JAM-1, Occludin, MUC2 and FXR decreased significantly (P<0.01), whereas the protein expression of MLCK and p-MLC increased significantly (P<0.01). Additionally, the mRNA expression of MLCK and MLC increased significantly (P<0.01). Compared with the model group, the Zhengan Xifengtang groups at various dosages and the amlodipine besylate group showed significantly reduced blood pressure (P<0.01). The damage of colonic mucosa structure was alleviated, the infiltration of inflammatory cells decreased, and the number of goblet cells increased. LPS and DAO levels were decreased (P<0.05, P<0.01). In the colon, the relative fluorescence intensity of FXR increased, while that of p-MLC decreased (P<0.05, P<0.01). The protein and mRNA expression levels of ZO-1, Claudin-1, JAM-1, Occludin, and FXR increased significantly (P<0.05, P<0.01), while the protein expression of MLCK and p-MLC decreased significantly (P<0.05, P<0.01). Furthermore, the mRNA expression of MLCK and MLC decreased significantly (P<0.05, P<0.01), and the protein expression of MUC2 increased significantly (P<0.05, P<0.01). The expression of MUC2 mRNA in each dose group of Zhengan Xifengtang increased significantly (P<0.05, P<0.01). ConclusionZhengan Xifengtang may regulate the FXR-MLCK/p-MLC signaling pathway and enhance the expression of tight junction protein, thereby reducing intestinal mucosal permeability, promoting mucosal barrier repair, decreasing LPS release into the blood, and ultimately lowering blood pressure.
5.Discriminating Tumor Deposits From Metastatic Lymph Nodes in Rectal Cancer: A Pilot Study Utilizing Dynamic Contrast-Enhanced MRI
Xue-han WU ; Yu-tao QUE ; Xin-yue YANG ; Zi-qiang WEN ; Yu-ru MA ; Zhi-wen ZHANG ; Quan-meng LIU ; Wen-jie FAN ; Li DING ; Yue-jiao LANG ; Yun-zhu WU ; Jian-peng YUAN ; Shen-ping YU ; Yi-yan LIU ; Yan CHEN
Korean Journal of Radiology 2025;26(5):400-410
Objective:
To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer.
Materials and Methods:
A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs.
Results:
All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027).
Conclusion
The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.
6.Effects and Efficacy of Wenyang Huayin Yangxin Prescription on the Traditional Chinese Medicine Syndromes of Patients With Chronic Heart Failure Combined With Diuretic Resistance
Jiali WU ; Dan XIAO ; Tao ZHAN ; Yi YUAN ; Yun ZHAN ; Hong LIU
Journal of Sichuan University (Medical Sciences) 2025;56(1):94-101
Objective To study the traditional Chinese medicine(TCM)syndromes of patients with chronic heart failure(CHF)combined with diuretic resistance by using the Wenyang Huayin Yangxin Prescription,and to observe its therapeutic efficacy.Methods A total of 68 CHF patients complicated with diuretic resistance and who had Yangqi deficiency and presenting blood stasis syndrome combined with Tanyin were randomly assigned to a control group and an observation group.The control group was given intravenous furosemide(≥ 80 mg/d)via infusion pump in addition to standard Western medical treatment,while the observation group was given intravenous furosemide(<80 mg/d)via infusion pump along with the Wenyang Huayin Yangxin Prescription(30 g Astragalus,15 g Poria,15 g Baizhu,15 g Chuanxiong,10 g Danfu tablet,10 g Cassia,10 g Alisma,and 10 g Zhimu).The quantitative index of diuretic resistance was used as the primary outcome measure.In addition,the differences between the two groups in TCM syndromes,cardiac function-related indicators,incidence of endpoint events,and readmission rate were compared.Results After 2 weeks of treatment,the filtration sodium excretion fraction(FENa)in the observation group was(0.18±0.04)%,while that of the control group was(0.16±0.03)%,showing a statistically significant difference(P=0.037).The 24-hour urine volume and urine Na+/K+ratio in the observation group increased significantly from baseline levels and were higher than those in the control group(P<0.05).The differences in the changes of 24-hour urine volume,urine sodium,FENa,and urine Na+/K+ratio between the two groups were statistically significant(P<0.05).The TCM syndrome scores decreased in both groups after 2 weeks of treatment,with the observation group showing a significantly greater reduction compared with the control group(P<0.001).The differences in the changes of TCM syndrome scores between the two groups were statistically significant(P<0.001).After 2 weeks of treatment,the observation group showed significant improvements in palpitations,shortness of breath,facial and limb edema,spontaneous sweating,chest tightness(pain),asthma,and oliguria compared with the baseline data(P<0.05),while the control group showed improvements only in facial and limb edema,asthma,and oliguria(P<0.05).Except for the asthma syndrome after 2 weeks of treatment,the observation group showed better outcomes in spontaneous sweating,chest tightness(pain),asthma,and oliguria at various time points after treatment compared with the control group(P<0.05).After 2 weeks of treatment,the observation group had significantly better cardiac output(CO)and stroke volume(SV)compared with those of the control group(P<0.05).The differences in the changes in N-terminal pro-brain natriuretic peptide(NT-proBNP),left ventricular ejection fraction(LVEF),SV,and CO between the two groups were statistically significant(P<0.05).After 24 weeks of follow-up,no significant differences in the incidence of end-point events or readmission rates between the two groups were observed.Conclusion The Wenyang Huayin Yangxin Prescription,combined with low-dose intravenous furosemide administered through an infusion pump,can improve the TCM syndromes of patients with Yangqi deficiency and blood stasis syndrome combined with Tanyin in addition to CHF complicated by diuretic resistance.This treatment improves the patients'heart function and diuretic resistance,reduces the intravenous dosage of diuretic,and enhances clinical efficacy.This approach should be more widely applied in clinical settings.
7.Exploring behavioral patterns and hippocampal neurogenesis in autism spectrum disorder mice
Xiao-Jie NIU ; Jiao LIU ; Xin-Wei ZHANG ; Ze-Tao WANG ; Ke-Qi YAN ; Qi-Yuan LIU ; Wan-Yun HAO ; Pei-Jun ZHANG
Acta Anatomica Sinica 2025;56(2):171-179
Objective To explore the behavioral patterns and hippocampal neurogenesis of CHD8+mice,and to provide behavioral and morphological basis for improving autism like behavior and neurogenesis.Methods Genotype of wild type(WT)and CHD8+/-mice was identified.Weight measurement was conducted on both male and female mice of the WT and CHD8+/-strains.Subsequently,a battery of behavioral tests was administered,which included three-chamber test,self-grooming test,nesting test,Y-maze spontaneous alternation test,food burial test,open-field test and light-dark transition test.Afterwards,the mice were administered 2%pentobarbital sodium(2 ml/kg)to induce anesthesia.Their brains were frozen with 4%paraformaldehyde,removed for photography and analysis to identify any alterations in brain size.Western blotting and immunofluorescent labeling were used to detect changes in the process of hippocampus neurogenesis.Results Western blotting analysis demonstrated a decrease in the amounts of chromodomain helicase DNA binding protein 8(CHD8)protein in both male and female mice with CHD8+genotype,as compared to WT mice.There were no notable disparities in body weight between male and female WT and CHD8+mice,as well as in brain size.The three-chamber social behavior test revealed that both male and female CHD8+/-mice had social deficiencies(P<0.05).During the open field test,there was no significant difference in the total distance moved by male and female WT and CHD8+/-mice.However,the amount of time spent in the central region was considerably lower in CHD8+/-mice compared to the WT mice(P<0.01).Furthermore,the light-dark transition test revealed that both male and female CHD8+/-mice spent considerably less time investigating the white box compared to the WT mice(P<0.05).Nevertheless,there were no notable alterations found in self-grooming,nesting,spontaneous alternation of Y-maze,and food burial experiments.In addition,Western blotting result demonstrated a significant drop in doublecortin(DCX)expression(P<0.001),and immunofluorescent staining revealed a notable reduction in the number of DCX+cells(P<0.01)in the hippocampus of CHD8+/-mice.Conclusion CHD8+/-mice exhibit social disorders and anxiety-like behaviors,with a decrease in the number of newly generated neurons in the hippocampus and neurogenesis disorders.
8.Discriminating Tumor Deposits From Metastatic Lymph Nodes in Rectal Cancer: A Pilot Study Utilizing Dynamic Contrast-Enhanced MRI
Xue-han WU ; Yu-tao QUE ; Xin-yue YANG ; Zi-qiang WEN ; Yu-ru MA ; Zhi-wen ZHANG ; Quan-meng LIU ; Wen-jie FAN ; Li DING ; Yue-jiao LANG ; Yun-zhu WU ; Jian-peng YUAN ; Shen-ping YU ; Yi-yan LIU ; Yan CHEN
Korean Journal of Radiology 2025;26(5):400-410
Objective:
To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer.
Materials and Methods:
A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs.
Results:
All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027).
Conclusion
The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.
9.6-Shogaol alleviates cerebral injury after cardiac arrest-cardiopulmonary resuscitation in rats by inhibiting death-associated protein kinase 1-mediated autophagy.
Ouyang RAO ; Shixin LI ; Ning ZHU ; Hangxiang ZHOU ; Jie HU ; Yun LI ; Junling TAO ; Yehong LI ; Ying LIU
Chinese Critical Care Medicine 2025;37(6):568-575
OBJECTIVE:
To observe the neuroprotective effect of 6-shogaol (6-SH) in global cerebral ischemia/reperfusion injury (CIRI) following cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) in rats.
METHODS:
Computer-aided molecular docking was used to determine whether 6-SH could spontaneously bind to death-associated protein kinase 1 (DAPK1). SPF-grade male SD rats were randomly divided into a sham group (n = 5), a CPR group (n = 7), and a CPR+6-SH group (n = 7). The CPR group and CPR+6-SH group were further divided into 12-, 24-, and 48-hour subgroups based on observation time points. A rat model of global CIRI after CA-CPR was established by asphyxiation. In the sham group, only tracheal and vascular intubation was performed without asphyxia and CPR induction. The CPR group was intraperitoneally injected with 1 mL of normal saline immediately after successful modeling. The CPR+6-SH group received an intraperitoneal injection of 20 mg/kg 6-SH (1 mL) immediately after successful modeling, followed by administration every 12 hours until the endpoint. Neurological Deficit Score (NDS) was recorded at each time point after modeling. After completion of observation at each time point, rats were anesthetized and sacrificed, and brain tissue specimens were collected. Histopathological changes of neurons were observed under light microscopy after hematoxylin-eosin (HE) staining. Ultrastructural changes of hippocampal neurons and autophagy were observed by transmission electron microscopy (TEM). Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect mRNA expression levels of DAPK1, vacuolar protein sorting 34 (VPS34), Beclin1, and microtubule-associated protein 1 light chain 3 (LC3) in brain tissues. Western blotting was used to detect protein expression levels of DAPK1, phosphorylated DAPK1 at serine 308 (p-DAPK1 ser308), VPS34, Beclin1, and LC3. Immunofluorescence was used to observe Beclin1 and LC3 expression in brain tissues under a fluorescence microscope.
RESULTS:
Molecular docking results indicated that 6-SH could spontaneously bind to DAPK1. Compared with the sham group, the NDS scores of the CPR group rats were significantly increased at all modeling time points; under light microscopy, disordered cell arrangement, widened intercellular spaces, and edema were observed in brain tissues, with pyknotic and necrotic nuclei in some areas; under TEM, mitochondria were markedly swollen with intact membranes, dissolved matrix, reduced or disappeared cristae, vacuolization, and increased autophagosomes. Compared with the CPR group, the NDS scores of the CPR+6-SH group rats were significantly decreased at all modeling time points; under light microscopy, local neuronal edema and widened perinuclear space were observed; under TEM, mitochondria were mostly mildly swollen with intact membranes, fewer autophagosomes, and alleviated injury. RT-qPCR results showed that compared with the sham group, mRNA expression levels of DAPK1, VPS34, Beclin1, and LC3 in brain tissues were significantly upregulated in all CPR subgroups, with the most pronounced changes at 24 hours. Compared with the CPR group, the CPR+6-SH group showed significantly lower mRNA expression of the above indicators at each time point [24 hours post-modeling (relative expression): DAPK1 mRNA: 3.41±0.68 vs. 4.48±0.62; VPS34 mRNA: 3.63±0.49 vs. 4.66±1.18; Beclin1 mRNA: 3.08±0.49 vs. 4.04±0.22; LC3 mRNA: 2.60±0.36 vs. 3.67±0.62; all P < 0.05]. Western blotting results showed that compared with the sham group, the protein expression levels of DAPK1, VPS34, Beclin1, and LC3 in all CPR subgroups were significantly increased, while the expression of p-DAPK1 ser308 was significantly decreased, with the most pronounced changes observed in the CPR 24-hour subgroup. Compared with the CPR group, the CPR+6-SH subgroups exhibited significantly reduced protein expression of DAPK1, VPS34, Beclin1, and LC3 [24-hour post-modeling: DAPK1/β-actin: 1.88±0.22 vs. 2.47±0.22; VPS34/β-actin: 2.55±0.06 vs. 3.46±0.05; Beclin1/β-actin: 2.12±0.03 vs. 2.87±0.03; LC3/β-actin: 2.03±0.24 vs. 3.17±0.23; all P < 0.05]. Conversely, the expression of p-DAPK1 ser308 was significantly upregulated in the CPR+6-SH group compared to the CPR group [24-hour post-modeling: p-DAPK1 ser308/β-actin: 0.40±0.02 vs. 0.20±0.07, P < 0.05]. Under the fluorescence microscope, fluorescence intensities of Beclin1 and LC3 in the CPR 24-hour group were significantly higher than those in the sham 24-hour group; compared with the CPR 24-hour group, the CPR+6-SH 24-hour group showed significantly reduced fluorescence intensities of Beclin1 and LC3.
CONCLUSION
6-SH inhibited the expression of DAPK1, alleviated excessive autophagy after global CIRI following CA-CPR in rats, and exerted neuroprotective effects. The mechanism may be related to phosphorylation at the DAPK1 ser308 site.
Animals
;
Rats, Sprague-Dawley
;
Male
;
Rats
;
Cardiopulmonary Resuscitation
;
Autophagy/drug effects*
;
Heart Arrest/therapy*
;
Death-Associated Protein Kinases/metabolism*
;
Reperfusion Injury/metabolism*
;
Disease Models, Animal
;
Neuroprotective Agents/pharmacology*
;
Brain Ischemia/metabolism*
10.Evidence-based guideline for diagnosis and early fixation of severe open tibiofibular fractures (version 2025)
Yongjun RUI ; Yongqing XU ; Qingtang ZHU ; Xin WANG ; Zhao XIE ; Shanlin CHEN ; Jingyi MI ; Xianyou ZHENG ; Juyu TANG ; Xiaoheng DING ; Aixi YU ; Tao SONG ; Jianxi HOU ; Jian QI ; Xinyu FAN ; Jun FEI ; Lin GUO ; Xingwen HAN ; Weixu LI ; Aiguo WANG ; Yun XIE ; Tao XING ; Meng LI ; Baoqing YU ; Yan ZHUANG ; Xiaoqing HE ; Tao SUN ; Pengcheng LI ; Jihui JU ; Hongxiang ZHOU ; Haidong REN ; Guangyue ZHAO ; Gang ZHAO ; Yongwei WU ; Jun LIU ; Yunhong MA ; Yapeng WANG
Chinese Journal of Trauma 2025;41(11):1021-1034
Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

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