1.Regulation of histidine metabolism by Lactobacillus Reuteri mediates the pathogenesis and treatment of ischemic stroke.
Kangrui HU ; Zhihao ZHOU ; Haofeng LI ; Jijun XIAO ; Yun SHEN ; Ke DING ; Tingting ZHANG ; Guangji WANG ; Haiping HAO ; Yan LIANG
Acta Pharmaceutica Sinica B 2025;15(1):239-255
Increasing evidence has underscored the significance of post-stroke alterations along gut-brain axis, while its role in pathogenesis and treatment of ischemic stroke (IS) remains largely unexplored. This study aimed to elucidate the therapeutic effects and action targets of Panax notoginseng saponins (PNS) on IS and explore a novel pathogenesis and treatment strategy of IS via profiling the microbial community and metabolic characteristics along gut-brain axis. Our findings revealed for the first time that the therapeutic effect of PNS on IS was microbiota-dependent. Ischemia/reperfusion (I/R) modeling significantly down-regulated Lactobacilli in rats, and PNS markedly recovered Lactobacilli, particularly Lactobacillus reuteri (L.Reu). Metabolomics showed a significant reduction in serum histidine (HIS) in clinical obsolete IS patients and rehabilitation period I/R rats. Meanwhile, the L.Reu colonization in I/R rats exhibited significant neuroprotective activity and greatly increased HIS in serum, gut microbiota, and brain. Moreover, exogenous HIS demonstrated indirect neuroprotective effects through metabolizing to histamine. Notably, vagus nerve severance in I/R rats was performed to investigate HIS's neuroprotective mechanism. The results innovatively revealed that PNS could promote HIS synthesis in gut by enhancing L.Reu proportion, thereby increasing intracerebral HIS through peripheral pathway. Consequently, our data provided novel insights into HIS metabolism mediated by L.Reu in the pathogenesis and treatment of IS.
2.Side-to-side anastomosis of superficial temporal artery and middle cerebral artery bypass using in-situ intravascular suture technique: a report of 10 cases
Zongyu XIAO ; Liang HE ; Ji WANG ; Yang LIU ; Yulun HUANG ; Zhimin WANG ; Haiping ZHU ; Likui SHEN
Chinese Journal of Microsurgery 2025;48(4):405-411
Objective:To investigate the feasibility and clinical efficacy of side-to-side anastomosis of superficial temporal artery (STA) and middle cerebral artery (MCA) bypass using in-situ intravascular suture technique.Methods:A retrospective analysis was conducted on the clinical data of 10 adult patients who were treated with side-to-side microvascular anastomosis of STA-MCA bypass to improve intracranial blood supply, between February 2024 and September 2024 in the Department of Neurosurgery of the Fourth Affiliated Hospital of Soochow University. Among the patients, 2 were of symptomatic MCA occlusion and 8 of Moyamoya disease. Diameter of STA and MCA, length of anastomosis and blocking time of MCA were recorded. Indocyanine green video angiography (ICG-VA) was performed to evaluate the immediate patency of the STA-MCA side-to-side anastomosis. Digital subtracted angiography (DSA) was performed at 1 week after the surgery to evaluate the patency of the STA-MCA bypass anastomosis, then follow-up DSA was performed at 1, 3 and 6 months after surgery to further evaluate the postoperative anastomotic patency. Neurological function was evaluated regularly with the modified Rankin Scale (mRS).Results:All of the 10 side-to-side STA-MCA bypass anastomoses were successfully performed using in-situ intravascular suture technique. The scalps of all patients healed well. The diameters of STA and MCA were 1.4-2.0 (1.76±0.27) mm and 0.8-1.4 (0.98±0.20) mm, respectively. The average length of the anastomoses was 3.5-5.0 (4.45±0.60) mm. The blocking time of MCA was 12.0-29.0 (21.50±6.62) min. A 100% vessel patency rate was achieved immediately after vessel anastomosis and at 1 month after surgery. DSA examinations were performed at 3 months after surgery on 6 patients and at 6 months after surgery on 1 patient, and all the anastomoses were found in full patency. All patients were included in the postoperative follow-up that lasted for 3 to 7 months. All patients recovered well without new neurological dysfunction. The mRS of 8 patients remained at 0 point before and after surgery. Two patients had improved postoperative mRS of 1 point from that of 2 points before surgery.Conclusion:STA-MCA side-to-side microvascular bypass anastomosis can be performed safely and efficiently using in-situ intravascular suture technique. It could efficiently reduce the incidence of perioperative complications. Meanwhile, it can self-regulate the blood flow and maximise the potential capability of STA.
3.Characteristics and influential factors for irAEs in patients with liver cancer caused by tislelizumab
Haiping LI ; Mengru SHEN ; Tao WEI ; Shengshen LI ; Cailu LEI ; Chun MO ; Liufeng LIAO
China Pharmacy 2025;36(24):3107-3112
OBJECTIVE To explore the characteristics and influencing factors of immune-related adverse events (irAEs) induced by tislelizumab in patients with liver cancer. METHODS A retrospective cohort of 203 liver cancer patients treated with tislelizumab in Guangxi Medical University Cancer Hospital from May 2022 to March 2024 was included. These patients were divided into an irAEs group (58 cases) and a non-irAEs group (145 cases). Clinical data were collected and compared between the two groups. A multivariate logistic regression model was employed to analyze factors influencing the occurrence of irAEs and establish a predictive model. The receiver operator characteristic (ROC) curve was plotted to evaluate the predictive value of the model for the occurrence of irAEs. The correlation between irAEs and overall survival (OS) as well as progression free survival (PFS) in patients was analyzed using the Kaplan-Meier method. RESULTS The irAEs induced by tislelizumab in liver cancer patients were predominantly grade 1-2 (89.71%), mainly manifesting as hematological toxicity (42.65%) and hepatotoxicity (20.59%), and mostly occurred within 1-12 cycles after tislelizumab treatment. Compared with liver cancer patients without underlying liver diseases, those with chronic hepatitis B had a higher incidence of irAEs. Statistically significant differences were observed between the irAEs and non-irAEs groups in terms of the number of patients with a China Liver Cancer Staging (CNLC) stage ≥Ⅱ, white blood cell count, neutrophil count, systemic immune-inflammation index (SII), and neutrophil-to-lymphocyte ratio (NLR) (P<0.05). Multivariate Logistic regression analysis revealed that CNLC stage ≥Ⅱ was an independent risk factor for the occurrence of irAEs (P=0.027). The ROC curve indicated that neutrophil count, white blood cell count, NLR, and SII all demonstrated certain predictive potential for the occurrence of irAEs (with area under the curve values of 0.614, 0.592,0.591, and 0.589, respectively). The Kaplan-Meier survival curve showed no statistically significant differences in PFS and OS between the irAEs and non-irAEs groups, among patients with different grades of irAEs, and among irAEs patients with different CNLC stages (P>0.05). CONCLUSION The irAEs induced by tislelizumab in liver cancer patients are relatively mild (grade 1-2),mainly manifesting as hematological toxicity and hepatotoxicity. Liver cancer patients with concurrent chronic hepatitis B are at a higher risk of developing irAEs. CNLC stage ≥Ⅱ is an independent risk factor for irAEs induced by tislelizumab. Neutrophil count, white blood cell count, NLR, and SII have certain predictive value for the occurrence of irAEs.
4.Performance evaluation of Vitek 2 AST-N335 card for testing susceptibility of Acinetobacter baumannii to cefoperazone/sul-bactam
Lingli GU ; Hongmei SHEN ; Linling HUANG ; Meirong XU ; Haiping LIU ; Peilong LIU ; Xiang LIU ; Shirong DAI
Chinese Journal of Clinical Laboratory Science 2025;43(10):794-797
Objective To evaluate the reliability of Vitek 2 AST-N335 card for determining the susceptibility of Acinetobacter bauman-nii(AB)to cefoperazone/sulbactam.Methods A total of 318 non-repeated clinical isolates of AB collected in 2023 were tested for antimicrobial susceptibility to cefoperazone/sulbactam using broth microdilution(BMD),the AST-N335 card,and the Kirby-Bauer(K-B)disk diffusion method.Using BMD as the reference method,the reliability of AST-N335 card was assessed,and the accuracy of K-B disk diffusion method as the confirmatory test was validated.Results Compared with BMD,the susceptibility testing of 318 AB strains to cefoperazone/sulbactam using the AST-N335 card showed categorical agreement(CA)of 87.8%(279/318),very major er-ror(VME)of 6.0%(19/318),major error(ME)of 0%(0/318),and minor error(mE)of 1.9%(6/318),which fall outside of the acceptable error range.In contrast,the K-B method achieved CA of 99.4%(316/318),VME of 0%,ME of 0.3%(1/318),and mE of 0.3%(1/318),all within acceptable limits.Of these,the errors with AST-N335 card occurred within the minimum inhibitory concentration(MIC)range of 8-32 μg/mL.Using BMD as the reference method,further analysis was performed on the 171 AB strains with AST-N335 card MIC values of 8-32 μg/mL for cefoperazone/sulbactam.It was revealed that at MIC of 32 μg/mL,the CA was 0%;at MIC of 16 μg/mL,CA was 5.3%(1/19)and VME rate was 84.2%(16/19),both of which substantially exceeded accepta-ble error ranges.At MIC of 8 μg/mL,the CA was 94.9%(131/138)and VME was 2.2%(3/138),both approaching the acceptable ranges.Conclusion The results obtained with Vitek 2 AST-N335 card in determining for cefoperazone/sulbactam are unreliable when the MIC values fall within the range of 8-32 μg/mL,which leads to an underestimation of the resistance rate to cefoperazone/sulbac-tam.This issue requires urgent attention in both laboratories and clinical practice.The K-B disk diffusion method could serve as a sup-plementary verification approach in routine laboratories.
5.Performance evaluation of Vitek 2 AST-N335 card for testing susceptibility of Acinetobacter baumannii to cefoperazone/sul-bactam
Lingli GU ; Hongmei SHEN ; Linling HUANG ; Meirong XU ; Haiping LIU ; Peilong LIU ; Xiang LIU ; Shirong DAI
Chinese Journal of Clinical Laboratory Science 2025;43(10):794-797
Objective To evaluate the reliability of Vitek 2 AST-N335 card for determining the susceptibility of Acinetobacter bauman-nii(AB)to cefoperazone/sulbactam.Methods A total of 318 non-repeated clinical isolates of AB collected in 2023 were tested for antimicrobial susceptibility to cefoperazone/sulbactam using broth microdilution(BMD),the AST-N335 card,and the Kirby-Bauer(K-B)disk diffusion method.Using BMD as the reference method,the reliability of AST-N335 card was assessed,and the accuracy of K-B disk diffusion method as the confirmatory test was validated.Results Compared with BMD,the susceptibility testing of 318 AB strains to cefoperazone/sulbactam using the AST-N335 card showed categorical agreement(CA)of 87.8%(279/318),very major er-ror(VME)of 6.0%(19/318),major error(ME)of 0%(0/318),and minor error(mE)of 1.9%(6/318),which fall outside of the acceptable error range.In contrast,the K-B method achieved CA of 99.4%(316/318),VME of 0%,ME of 0.3%(1/318),and mE of 0.3%(1/318),all within acceptable limits.Of these,the errors with AST-N335 card occurred within the minimum inhibitory concentration(MIC)range of 8-32 μg/mL.Using BMD as the reference method,further analysis was performed on the 171 AB strains with AST-N335 card MIC values of 8-32 μg/mL for cefoperazone/sulbactam.It was revealed that at MIC of 32 μg/mL,the CA was 0%;at MIC of 16 μg/mL,CA was 5.3%(1/19)and VME rate was 84.2%(16/19),both of which substantially exceeded accepta-ble error ranges.At MIC of 8 μg/mL,the CA was 94.9%(131/138)and VME was 2.2%(3/138),both approaching the acceptable ranges.Conclusion The results obtained with Vitek 2 AST-N335 card in determining for cefoperazone/sulbactam are unreliable when the MIC values fall within the range of 8-32 μg/mL,which leads to an underestimation of the resistance rate to cefoperazone/sulbac-tam.This issue requires urgent attention in both laboratories and clinical practice.The K-B disk diffusion method could serve as a sup-plementary verification approach in routine laboratories.
6.Side-to-side anastomosis of superficial temporal artery and middle cerebral artery bypass using in-situ intravascular suture technique: a report of 10 cases
Zongyu XIAO ; Liang HE ; Ji WANG ; Yang LIU ; Yulun HUANG ; Zhimin WANG ; Haiping ZHU ; Likui SHEN
Chinese Journal of Microsurgery 2025;48(4):405-411
Objective:To investigate the feasibility and clinical efficacy of side-to-side anastomosis of superficial temporal artery (STA) and middle cerebral artery (MCA) bypass using in-situ intravascular suture technique.Methods:A retrospective analysis was conducted on the clinical data of 10 adult patients who were treated with side-to-side microvascular anastomosis of STA-MCA bypass to improve intracranial blood supply, between February 2024 and September 2024 in the Department of Neurosurgery of the Fourth Affiliated Hospital of Soochow University. Among the patients, 2 were of symptomatic MCA occlusion and 8 of Moyamoya disease. Diameter of STA and MCA, length of anastomosis and blocking time of MCA were recorded. Indocyanine green video angiography (ICG-VA) was performed to evaluate the immediate patency of the STA-MCA side-to-side anastomosis. Digital subtracted angiography (DSA) was performed at 1 week after the surgery to evaluate the patency of the STA-MCA bypass anastomosis, then follow-up DSA was performed at 1, 3 and 6 months after surgery to further evaluate the postoperative anastomotic patency. Neurological function was evaluated regularly with the modified Rankin Scale (mRS).Results:All of the 10 side-to-side STA-MCA bypass anastomoses were successfully performed using in-situ intravascular suture technique. The scalps of all patients healed well. The diameters of STA and MCA were 1.4-2.0 (1.76±0.27) mm and 0.8-1.4 (0.98±0.20) mm, respectively. The average length of the anastomoses was 3.5-5.0 (4.45±0.60) mm. The blocking time of MCA was 12.0-29.0 (21.50±6.62) min. A 100% vessel patency rate was achieved immediately after vessel anastomosis and at 1 month after surgery. DSA examinations were performed at 3 months after surgery on 6 patients and at 6 months after surgery on 1 patient, and all the anastomoses were found in full patency. All patients were included in the postoperative follow-up that lasted for 3 to 7 months. All patients recovered well without new neurological dysfunction. The mRS of 8 patients remained at 0 point before and after surgery. Two patients had improved postoperative mRS of 1 point from that of 2 points before surgery.Conclusion:STA-MCA side-to-side microvascular bypass anastomosis can be performed safely and efficiently using in-situ intravascular suture technique. It could efficiently reduce the incidence of perioperative complications. Meanwhile, it can self-regulate the blood flow and maximise the potential capability of STA.
7.Comparison of the efficacy and safety between high-dose intravenous iron and oral iron in treating iron deficiency anemia: a multicenter, prospective, open-label, randomized controlled study
Qian ZHANG ; Hong WANG ; Yanming ZHANG ; Xiaoli LI ; Yaoyao SHEN ; Nan WEI ; Kai ZOU ; Wanxiu SU ; Haiping DAI ; Depei WU ; Limin LIU
Chinese Journal of Hematology 2024;45(12):1113-1118
Objective:This study aimed to compare the efficacy and safety between high-dose intravenous iron and oral iron in treating iron deficiency anemia (IDA) .Methods:This prospective randomized controlled study (1∶1) enrolled 338 patients with IDA at The First Affiliated Hospital of Soochow University, Suzhou Hongci Hematology Hospital, and Huai’an Second People’s Hospital from June 1, 2022, to January 19, 2024. Of all the patients, 169 received high-dose intravenous iron therapy and 169 received oral iron treatment for 12 weeks of observation. Focus on the hemoglobin (HGB) change from baseline to week 4, secondary focus was on the HGB and iron metabolism parameters (serum iron [SI], transferrin saturation [TSAT], total iron binding force [TIBC], serum ferritin [SF]), and changes in the fatigue score, efficacy, and treatment-related adverse effects were monitored throughout in the two treatment groups.Results:The HGB levels were improved in both treatments, but the HGB improved faster in the intravenous group compared with the oral group. HGB increased from (76.8±15.0) g/L to (118.0±13.3) g/L in the intravenous group and from (77.9±11.6) g/L to (104.3±15.0) g/L in the oral group after 4 weeks of treatment. The increase from baseline in the intravenous group (40.7±17.3) g/L was significantly higher than that in the oral group (27.2±17.5) g/L ( P<0.001). The intravenous group demonstrated a more significant early effect than the oral group in terms of iron metabolism parameter improvement. SI, TSAT, TBIC, and SF increased better from baseline at 4 weeks in the intravenous group than in the oral group ( P<0.001). Additionally, the intravenous group exhibited better fatigue scores for early improvement than the oral group ( P<0.001). The incidence of total adverse effects was similar in the intravenous group as compared to the oral group (3.5% [6/169] vs 5.9% [10/169], P=0.442) . Conclusion:High doses of intravenous iron quickly boost HGB early, causing rapid improvement in SI, TSAT, TBIC, SF, and patient fatigue scores. The patient was well tolerated.
8.Efficacy and safety of chimeric antigen receptor T-cell therapy followed by allogeneic hematopoietic stem cell transplantation in 21 patients with Ph-like acute lymphoblastic leukemia
Haiping DAI ; Hongjie SHEN ; Zheng LI ; Wei CUI ; Qingya CUI ; Mengyun LI ; Sifan CHEN ; Mingqing ZHU ; Depei WU ; Xiaowen TANG
Chinese Journal of Hematology 2024;45(1):35-40
Objective:To evaluate the efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with Ph-like acute lymphoblastic leukemia (Ph-ALL) .Methods:Patients with Ph-ALL who underwent CAR-T therapy followed by allo-HSCT from March 2018 to August 2023 at the First Affiliated Hospital of Soochow University were included, and their clinical data were retrospectively analyzed.Results:Of the 21 patients, 14 were male and 7 were female. The median age at the time of CAR-T therapy was 22 (6-50) years. Seven patients had ABL1-like rearrangements, and 14 had JAK-STAT rearrangements. Prior to CAR-T therapy, 12 patients experienced hematologic relapse; 7 were multiparameter flow cytometry minimal residual disease (MFC-MRD) -positive and 2 were MFC-MRD-negative. CAR-T cells were derived from patients’ autologous lymphocytes. Nine patients were treated with CD19 CAR-T cells, and 12 were treated with CD19/CD22 CAR-T cells. After assessment on day 28 after CAR-T therapy, 95.2% of the patients achieved complete remission, with an MRD-negative remission rate of 75%. Nineteen patients developed grade 0–2 cytokine release syndrome (CRS) and 2 patients suffered grade 3 CRS, all cases of which resolved after treatment. All patients underwent allo-HSCT after CAR-T therapy. The median time from CAR-T therapy to allo-HSCT was 63 (38-114) days. Five patients experienced relapse after CAR-T therapy, including four with hematologic relapse and one with molecular relapse. The 3-year overall survival (OS) rates in the ABL1 and JAK-STAT groups were (83.3±15.2) % and (66.6±17.2) %, respectively ( P=0.68) . The 3-year relapse-free survival (RFS) rates were (50.0±20.4) % and (55.6±15.4) % in the ABL1 and JAK-STAT groups, respectively. There was no significant difference in 3-year OS or RFS between the two groups. Conclusions:CAR-T therapy followed by allo-HSCT leads to rapid remission in most patients with Ph-ALL and prolongs leukemia-free survival.
9.The evaluation value of dynamic MRI imaging technology for LARS after anorectal preservation surgery in low rectal cancer
Cheng GU ; Xinyu SHEN ; Jinghua SUN ; Saike YAN ; Haiping WANG
Tianjin Medical Journal 2024;52(6):653-657
Objective To explore the value of dynamic MRI imaging in investigate the morphologic and dynamic factors of low anterior resection syndrome(LARS)after anal preservation surgery in patients with low rectal cancer.Methods Thirty-five patients who developed LARS after anal preservation surgery for low rectal cancer were prospectively collected.Subjects were underwent routine MRI and dynamic MRI of pelvis 1 week before and 3 months after surgery respectively.Routine MRI was used as the resting phase,and dynamic MRI was used to obtain the rapture phase and forceful phase.Parameters such as anal rectus angle(ARA),the length of the line connecting lower edge of pubic symphysis to the posterior wall attachment point of puborectal muscle(H-line),the vertical length from posterior wall attachment point of puborectal muscle to pubococcygeal line(M-line),thickness of puborectal muscle,and thickness of internal and external anal sphincter were measured at the three time phases.The differences between preoperative and postoperative,and moderate and severe LARS patients were compared by measuring relevant indicators.Results The preoperative and postoperative ARA,H-line length and M-line length of LARS patients were the smallest in the rapture phase,the largest in the forceful phase,and the middle in the resting phase.The postoperative thickness of puborectalis muscle and internal and external anal sphincter were the largest in the rapture phase,the smallest in the forceful phase,and the middle in the resting phase.There were significant differences between the three phases(P<0.05).There were no significant differences between the three phases of postoperative puborectalis muscle thickness and internal and external sphincter thickness(P>0.05).The postoperative ARA was greater than preoperative ARA in LARS patients,and the thickness of puborectalis muscle,the internal anal sphincter(resting phase and rapture phase),and the external anal sphincter were smaller than preoperative ARA,and the differences were statistically significant(P<0.05).The ARA in resting phase and rapture phase was greater in patients with severe LARS than that of patients with mild LARS,and the thickness of internal anal sphincter in resting phase was less in patients with severe LARS than that of patients with mild LARS(P<0.05).However,the differences between the other indicators were not statistically significant(P>0.05).Conclusion Dynamic MRI examination technology combines dynamic images with quantitative indicators can be used as an important evaluation basis for LARS patients.
10.Association of psychological stress with wives’ hypertension across over 10 million Chinese married female population aged 20-49 years
Zhenyan ZHAO ; Jiajing JIA ; Xinyi LYU ; Lihua ZHANG ; Yuanyuan WANG ; Yuan HE ; Zuoqi PENG ; Ya ZHANG ; Hongguang ZHANG ; Qiaomei WANG ; Haiping SHEN ; Yiping ZHANG ; Donghai YAN ; Xu MA ; Ying YANG
Chinese Medical Journal 2024;137(13):1583-1591
Background::Psychological stress has been reported to be a potential risk factor for hypertension among females, but it remains unclear whether spousal chronic stress levels alter the risk of hypertension among women. We examined the associations between stress within the family and hypertension among married women.Methods::Reproductive-aged women who were planning for pregnancy and their husbands were recruited from the National Free Pre-pregnancy Checkup Projects (NFPCP) across 31 provinces in China in 2016 and 2017. Perceived stress of wives or husbands was measured with a 5-point Likert-type scale, and assessed from three domains: work/life-related stress, economic stress, and overall stress. Multivariable-adjusted logistic regression models were used to assess the associations between stress status and the prevalence of hypertension.Results::Of 10,027,644 couples, 261,098 (2.60%) women had hypertension. The results showed that higher stress levels among themselves or their husbands were associated with a higher prevalence of hypertension in women ( Pfor trend <0.001). Compared with non-stressed participants, female participants with the highest stress themselves were at a greater risk of hypertension, with adjusted odds ratio (OR) of 1.31 (95% confidence interval [CI]: 1.25-1.37); and compared with participants whose husbands had no stress, those whose husbands had the highest stress level were at a higher risk of hypertension with adjusted OR of 1.24 (95% CI: 1.20-1.29). Moreover, compared with non-stressed status for both couples, only-wife-stressed, only-husband-stressed, and both-stressed couples were found to be significantly associated with increased risks of wives’ hypertension, with adjusted ORs of 1.28 (95% CI: 1.25-1.31), 1.19 (95% CI: 1.17-1.21), and 1.28 (95% CI: 1.26-1.31), respectively. Conclusion::Moderate to severe stress in both spouses might be associated with female hypertension prevalence, which highlights the importance of paying attention to the psychological stresses of couples within the family.

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