Ischemic stroke (IS), a leading cause of morbidity and mortality worldwide, primarily results from blood clot formation in cerebral vessels, leading to vessel occlusion, reduced cerebral blood flow, and subsequent tissue ischemia. While thrombolytic therapies and mechanical thrombectomy remain cornerstone treatments for restoring blood flow, their clinical efficacy is significantly limited by the narrow therapeutic window, which underscores the critical need for novel, safe, and effective therapeutic strategies. In this review, we present an intensive analysis of four pathophysiological stages of IS progression and their intervention targets, and evaluate both established and emerging therapeutic strategies with the molecular mechanisms underpinning these methods, aiming to enhance the understanding of IS intervention. Additionally, we discuss current challenges in IS therapy, emphasizing the importance of timely, stage-specific approaches to optimize therapeutic outcomes. Finally, we highlight some promising research directions and innovations to advance IS field.

Objective:To analyze the causal relationship between intestinal flora and vitiligo by two-sample Mendelian randomization (MR) analysis based on "co-diseases of skin and gut" in TCM.Methods:Genome-wide association study (GWAS) data of intestinal flora samples and vitiligo samples were obtained from the databases of MiBioGen and IEU OpenGWAS Project, respectively. Intestinal flora was used as exposure factor, vitiligo as outcome, and single nucleotide polymorphism (SNP) associated with various intestinal floras was used as instrumental variable. After screening qualified instrumental variable in this study, inverse variance weighting (IVW) was used for MR analysis to investigate the potential causal relationship between intestinal flora and vitiligo, MR-Egger regression, weighted median estimator (WME), weighted mode (WM), and simple mode (SM) were used as supplementary methods for IVW. The Cochran's Q test, MR-Egger intercept test, MR-PRESSO and leave one-out analysis were used for sensitivity analysis.Results:Euryarchaeota (IVW method: OR<1, P<0.05) were the protective factors for the occurrence of vitiligo, and Clostridialesvadin-BB60group (IVW method: OR>1, P<0.05) and Subdoligranulum (IVW method: OR>1, P<0.05) were the risk factors for the occurrence of vitiligo. No heterogeneity effect was found by the Cochran's Q test ( P>0.05), no horizontal pleiotropy was found by the MR-Egger intercept test ( P>0.05), no outliers were found in the MR-PRESSO analysis ( P>0.05), and the results of leave-one-out analysis indicated that the causal effects of the 3 identified intestinal floras on vitiligo were not driven by any single SNP. Conclusions:There are causal effects between some intestinal floras and vitiligo, but the specific mechanisms still need to be further studied. The gut microbiota affects the onset and treatment of vitiligo. Using TCM to regulate the gut microbiota may have a good therapeutic effect on treating vitiligo, providing a direction for clinical diagnosis and treatment of vitiligo.

Objective:To evaluate the effect of pancreatic duct stenting in the treatment of severe acute pancreatitis (SAP).Methods:The clinical data of 68 patients with SAP admitted to the Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University from January, 2019 to July, 2020 were retrospectively analyzed, including 38 males and 30 females, aged (44.85±8.51) years old. The patients were divided into two groups according to the treatment modality: the conservative group ( n=41) which received the conservative management, and the stent group ( n=27) which underwent pancreatic duct stent implantation and conservative management. The basic information, parenteral nutrition support time, fasting days, and other clinical data of patients were collected. Serum amylase, white blood cell count, acute physiology and chronic health (APACHE) II score and CT score were compared between the two groups at admission and 48 hours after treatment. Results:The serum amylase, white blood cell count, APACHE II score and CT score of the two groups were significantly lower after treatment (all P<0.05). Compared with the conservative group, the APACHE II score [(5.52±2.15) vs. (8.76±2.50)] and CT score [(4.85±1.96) vs. (6.18±1.07)] of patients were lower in the stent group after treatment (both P<0.05). Pancreatic duct stents were successfully implanted in all 27 patients of the stent group. Intubation to the main pancreatic duct failed in one patient, while the accessory pancreatic duct was alternatively intubated through the accessory nipple. No severe complications such as iatrogenic pancreatitis, bleeding, and perforation occurred after endoscopic retrograde cholangiopancreatography. The incidence of postoperative local complications was lower [18.52%(5/27) vs. 41.46%(17/41)], the proportion of antibiotic use>3 types [29.63%(8/27) vs. 56.10%(23/41)] decreased, and the analgesic episodes decreased [2(1, 3) vs. 4(3, 6)] in the stent group. The antibiotic usage duration [8(3, 11) d vs. 13(10, 19) d], the parenteral nutrition time [7(4, 15)d vs. 15(8, 18)d], the fasting time [5(3, 11) d vs. 11(6, 13)d] and the hospital stay [10(5, 16) d vs. 15(13, 23)d] were all shortened (all P<0.05). Conclusion:Both conservative management and pancreatic duct stenting can alleviate the clinical symptoms of SAP, and pancreatic duct stenting could help reduce local complications, relieve symptoms, and shorten hospital stay.

Objective:To investigate the characteristics and clinical significance of distribution of bacteria and fungi in pancreatic fluid and bile in patients with acute biliary pancreatitis (ABP).Methods:The clinical data of patients with ABP who underwent endoscopic retrograde cholangiopancreatography (ERCP) and pancreatic duct stenting with simultaneous bacterial and fungal culture of bile and pancreatic fluid at the Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University from January 1, 2019, to June 30, 2021 were retrospectively analyzed. Of 202 patients, there were 102 males, and 100 females, aged (54±16) years old. Patients were divided into two groups by presence or absence of pancreatic infection: the pancreatic infection group ( n=20) and the non-pancreatic infection group ( n=182). Of the 76 patients with positive bile bacterial cultures, 60 patients with positive pancreatic fluid bacterial cultures were included in the positive pancreatic fluid culture group and 16 patients with negative pancreatic fluid cultures were included in the negative pancreatic fluid culture group. The clinical data including the type and distribution of bacteria cultured, complications, and co-infections of patients were compared. Factors associated with pancreatic infection were analyzed using logistic regression and the value of assessment of the associated factors was analyzed by plotting the receiver operating characteristic (ROC) curve. Results:Of 404 specimens (202 each of pancreatic fluid and bile) were sent for examination, 152 (37.6%) were positive. 174 strains were isolated from the 152 positive specimens, 96 (55.2%) gram-negative, 70 (40.2%) gram-positive and 8 (4.6%) fungal strains. Compared to the pancreatic fluid culture-negative group, patients in the pancreatic fluid culture positive group had a statistically significant ( P<0.05) increased risk of neutrophil to lymphocyte ratio, duration of fever, Balthazar CT score, complication rate, and development of pancreatic necrosis, pancreatic infection and systemic inflammatory response syndrome (SIRS). Compared to patients in the non-pancreatic infection group, patients in the pancreatic infection group had a statistically significant ( P<0.05) increase in duration of fever on admission, duration of fasting, and proportion of patients with combined SIRS, positive bile cultures, positive pancreatic fluid cultures, and diabetes mellitus. Logistic regression analysis showed that positive pancreatic fluid cultures ( OR=6.699, 95% CI: 1.159-38.725) and diabetes mellitus on admission ( OR=4.625, 95% CI: 1.304-16.394) were risk factors for late pancreatic infection ( P<0.05). The area under the ROC curve for the combination of both positive pancreatic fluid culture and diabetes mellitus in predicting late pancreatic infection in patients was 0.788, with a specificity of 59.30% and a sensitivity of 90.00%. Conclusions:Bacterial culture in pancreatic juice and bile of ABP patients showed mainly Gram-negative bacteria. Early culture of pancreatic juice and bile had positive significance in ABP evaluation, infection prediction and anti-infection treatment.

Objective:To evaluate the efficacy and safety of lactulose combined with polyethylene glycol for bowel preparation before colonoscopy in patients of different risks.Methods:A total of 208 patients undergoing colonoscopy were enrolled, including 108 high-risk and 100 low-risk patients. The high-risk patients were divided into group A (54 taking lactulose + polyethylene glycol) and group B (54 taking polyethylene glycol), and the low-risk patients were divided into group C (49 taking lactulose + polyethylene glycol) and group D (51 taking polyethylene glycol). The Boston bowel preparation score, cecal intubation time, withdrawal time, the detection rate of colonic polyps and adenoma, and the incidence of adverse reactions were observed.Results:Among the high-risk patients, the Boston bowel preparation score and adenoma detection rate in group A [(6.35±1.15) scores, 46.3%] were significantly higher than those in group B [(5.76±0.89) scores, 22.2%, both P<0.05], and the first defecation interval in group A was significantly shorter than that in group B [(1.20±0.85) h VS (3.29 ± 2.93) h, P<0.05]. There was no significant difference in adequate bowel preparation rate, polyp detection rate, frequency of defecation or incidence of adverse reactions between group A and B. In the low-risk patients, the first defecation interval in group C was significantly shorter than that in group D [(1.65 ± 1.35) h VS (3.42 ± 2.64) h, P<0.05], and the incidence of adverse reactions was significantly lower than that in group D (44.9% VS 64.7%, P<0.05). There was no significant difference in adequate bowel preparation rate, Boston bowel preparation score, adenoma detection rate, polyp detection rate or frequency of defecation between group C and D. Conclusion:For the high-risk patients, the effect of lactulose combined with polyethylene glycol for bowel cleansing is better than that of traditional polyethylene glycol in the improvement of the Boston bowel preparation score, adenoma detection rate, and the first defecation interval. For low-risk patients, lactulose combined with polyethylene glycol regimen has few advantages over traditional polyethylene glycol regimen.

OBJECTIVETo observe the effects of acupuncture at opposite acupoints on expression of hepatocyte growth factor (HGF) in rats with skeletal muscle contusion, and to explore the mechanism of acupuncture at opposite acupoints on skeletal muscle contusion.

METHODSFifty-four Sprague Dawley (SD) rats were randomly divided into a blank group (6 rats), a model group (24 rats) and an opposing needling group (24 rats). The model group and opposing needling group were further divided into 1-day subgroup, 3-day subgroup, 5-day subgroup and 7-day subgroup, 6 rats in each one. No intervention was given in the blank group, while the model of skeletal muscle contusion was established in the model group and opposing needling group by self-made contusion device. 24 hours after contusion, electroacupuncture (EA) was applied at "Zusanli" (ST 36) and the corresponding points ofpoints at health side for 15 min, once a day. The subgroups of opposing needling group were treated for 1 day, 3 days, 5 days and 7 days, respectively. No treatment was given in the model group. Samples were collected in the subgroups 1 day, 3 days, 5 days and 7 days after treatment. The morphological change of injured gastrocnemius muscle was observed by using microscope after HE staining. The positive cell rate of proliferating cell nuclear antigen (PCNA) was detected by immunohistochemistry. The expression levels of HGF protein and PCNA protein were observed by Western blot.

RESULTS① The results of HE staining showed that, 1 day after contusion, the inflammatory cells of gastrocnemius muscle in the opposing needling group were less than those in the model group; 3 days and 5 days after contusion, myoblasts and myotubes in the opposing needling group were more than those in the model group; 7 days after contusion, the neonatal muscle cells in the opposing needling group were more than those in the model group. ② The results of immunohistochemistry showed that, 1 day, 3 days and 5 days after contusion, the positive cell rate of PCNA in the opposing needling group was significantly higher than that in the model group (all<0.001); 7 days after contusion, the positive cell rate of PCNA in the opposing needling group was significantly less than that in the model group (<0.001). ③ The results of Western blot showed that, 1 day, 3 days and 5 days after contusion, the expression of HGF protein and PCNA protein in the opposing needling group was significantly higher than that in the model group (all<0.05); 7 days after contusion, the expression of HGF protein and PCNA protein in the opposing needling group was significantly lower than that in the model group (all<0.05).

CONCLUSIONAcupuncture at opposite acupoints could regulate the expression of HGF and promote the activation, proliferation, migration and differentiation of muscle satellite cells in rats with skeletal muscle contusion, which could speed up the process of skeletal muscle injury repair.

Objective To observe the effects of massage on inflammation,oxidative stress and autophagy during the repair of acute contusion of skeletal muscles so as to explore its biological mechanisms.Methods Forty-two adult Sprague-Dawley rats were randomly divided into a control group (n =6),a model group (n =18),and a treatment group (n =18).Acute contusion of the gastrocnemius muscles of the rats in the model and treatment groups was inflicted using a home-made impactor.Beginning forty-eight hours later,15 minutes of massage was administered daily for two weeks.After one,7 and 14 days of the massage treatment,the injured gastrocnemius was resected from 6 rats of both the model and treatment groups.Morphological changes were observed using haematoxylin and eosin (HE) staining.The serum content of tumor necrosis factor alpha (TNF-α),interleukin1β (IL-1 β),C reactive protein (CRP) and prostaglandin E2 (PGE2) were detected using enzyme-linked immunosorbent assay (ELISA).The serum content of superoxide (SOD) and malondialdehyde (MDA) were detected using spectrophotometry.The expression of microtubule-associated protein 1 light chain 3 (LC3),Bcl-2 homeodomain protein Beclin1 and ubiquitin binding protein P62 were detected using Western blotting.Results The HE staining showed more significant collapse and swelling of cells in the model group than in the control group at each time point.New muscle cells were observed at days 7 and 14 in the model group.At each time point,significantly better recovery was observed in the treatment group compared to the model group,with more new muscle cells and better cell morphology.According to the ELISA results,a significant increase in serum pro-inflammatory factors occurred in the model group compared to the control group and compared to the treatment group after one day and 7 days of treatment.The average serum content of SOD and MDA in the model group was significantly higher than in the control group,while the average serum content of SOD in the treatment group was significantly higher than in the model group and that of MDA was significantly lower.Western blotting showed a significant decrease in LC3 (Ⅱ/Ⅰ) and Beclin1,as well as a significant increase in P62 in the model group at each time point compared with the treatment group and the controls.Conclusion Inflammation and oxidative stress increase significantly in a skeletal muscle after injury,but autophagy decreases significantly.Massage can effectively reduce the inflammatory response and oxidative stress and promote autophagy,which leads to quicker repair of skeletal muscles.

Irrespective of physiological or pathological skeletal muscle atrophy, the endocrine and motor functions of skeletal muscle are impaired. The mechanism of acupuncture to prevent and treat skeletal muscle atrophy is not only related to classical protein synthesis and decomposition, but also involves apoptosis, autophagy, muscle satellite cell proliferation and differentiation, muscle fiber type conversion, neuromuscular junction conduction, and cell energy metabolism conversion.

Objective To explore the influence of lipoic acid injection on the oxidative stress state and local microcirculation of patients with diabetic foot.Methods A total of 74 patients with diabetic foot were randomly divided into two groups.Control group was treated with routine treatment for diabetic foot,while observation group was treated with lipoic acid injection on the basis of the control group.Oxidative stress state and local microcirculation indexes before and after the treatment were detected and compared.Results After treatment,oxidative stress state and local microcirculation indexes in both groups were significantly better than those before the treatment,and these indexes in the observation group were significantly better than the control group (P ＜ 0.05).Conclusion The lipoic acid injection can improve oxidative stress state and local microcirculation state of patients with diabetic foot.

Objective To explore the influence of lipoic acid injection on the oxidative stress state and local microcirculation of patients with diabetic foot.Methods A total of 74 patients with diabetic foot were randomly divided into two groups.Control group was treated with routine treatment for diabetic foot,while observation group was treated with lipoic acid injection on the basis of the control group.Oxidative stress state and local microcirculation indexes before and after the treatment were detected and compared.Results After treatment,oxidative stress state and local microcirculation indexes in both groups were significantly better than those before the treatment,and these indexes in the observation group were significantly better than the control group (P ＜ 0.05).Conclusion The lipoic acid injection can improve oxidative stress state and local microcirculation state of patients with diabetic foot.