ObjectiveTo observe the effect of M1 bone marrow-derived macrophages （M1-BMDM） with Wnt5a knockdown on liver fibrosis and regeneration in a rat model of liver cirrhosis， and to investigate its gain-of-function effect compared with unmodified M1-BMDM. MethodsPrimary bone marrow-derived macrophages were isolated from rats and were polarized to M1 phenotype to construct M1-BMDM^Wnt5a-KD cells. A rat model of liver cirrhosis induced by CCl₄/2-AAF was established， and at the end of week 8， rats were randomly divided into model group， M1-BMDM group， M1-BMDM Wnt5a-knockdown empty vector group （M1-BMDM^KD-EV group）， and M1-BMDM Wnt5a-knockdown group （M1-BMDM^Wnt5a-KD group）， with 6 rats in each group. On the first day of week 9， the rats in each group were given a single injection of the corresponding cells via the caudal vein， along with an intraperitoneal injection of a CCR2 inhibitor. Six rats without any treatment were used as normal control group. Samples were collected at the end of week 12 to assess liver histopathology， serum liver function parameters， hepatic stellate cell activation， and the expression levels of mature hepatocyte markers. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the model group， all cell treatment groups had significant alleviation of liver inflammatory response and significant reductions in the activities of alanine aminotransferase and aspartate aminotransferase （AST） in serum （all P<0.01）， and the M1-BMDM^Wnt5a-KD group had a significantly lower serum level of AST than the M1-BMDM group （P<0.05）. The semi-quantitative analysis based on immunohistochemical staining showed that compared with the model group， all cell treatment groups had a significant reduction in the percentage of CD68-positive area （all P<0.05）， and compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had a significant reduction in the percentage of CD68-positive area and a significant increase in the percentage of CD163-positive area （both P<0.05）. Compared with the model group， all cell treatment groups had significant reductions in the mRNA expression levels of CD68 and tumor necrosis factor-α （all P<0.05） and the protein expression level of CD68 （all P<0.01）； compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significant increases in the protein and mRNA expression levels of CD163 （both P<0.05）， significant reductions in the protein and mRNA expression levels of CD68 （both P<0.05）， and a significant reduction in the protein expression level of tumor necrosis factor-α （P<0.01）. Sirius Red collagen staining and alpha-smooth muscle actin （α-SMA） immunohistochemical staining showed that compared with the model group， all cell treatment groups had significant alleviation of liver collagen deposition and α-SMA-positive area， with the most significant changes in the M1-BMDM^Wnt5a-KD group， and compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significantly smaller Sirius Red-positive area and α-SMA-positive area and a significantly lower content of hydroxyproline in liver tissue （all P<0.05）. Compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significant reductions in the protein and mRNA expression levels of α-SMA and the mRNA expression level of COL-I and TGF-β （all P<0.05）. Compared with the model group， all cell treatment groups had a significant increase in the protein expression level of HNF-4α in liver tissue （all P<0.05）， and the M1-BMDM^Wnt5a-KD group had significantly higher protein and mRNA expression levels of HNF-4α and hepatocyte specific antigen than the M1-BMDM^KD-EV group （both P<0.05）. The M1-BMDM^Wnt5a-KD group had a significantly higher serum level of albumin than the M1-BMDM^KD-EV group （P<0.01）. Immunofluorescence co-staining showed that compared with the model group， all cell treatment groups had a significant increase in the number of cells stained positive for HNF and HNF-4α and Ki67 （all P<0.01）， and the M1-BMDM^Wnt5a-KD group had a significantly higher number of such cells than the M1-BMDM^KD-EV group （P<0.05）. ConclusionInhibition of Wnt5a expression enhances the therapeutic effect of M1-BMDM on rats with liver cirrhosis induced by CCl₄/2-AAF， which provides new ideas for enhancing the anti-cirrhotic effect of M1-BMDM through genetic modification.

Objective To analyze the procurement data of lipid-lowering drugs in hospitals at different levels in Jiangsu Province from October 2019 to September 2023,to evaluate the impact of the volume-based procurement(VBP)policy,and to provide references for clinical rational drug use and healthcare policy optimization.Methods Based on procurement data from the Jiangsu Provincial Health Information Center,statistical analyses of procurement expenditures,defined daily doses(DDDs),and defined daily cost(DDC)were conducted.Mixed-effects models were applied to assess changes in procurement expenditures,DDDs,and DDC before and after VBP implementation.Results From 2019 to 2023,statins dominated the market in Jiangsu Province,with rosuvastatin recording the highest DDDs(748 million).Statins,traditional Chinese medicines,and cholesterol absorption inhibitors ranked highest in procurement expenditures.Tertiary hospitals accounted for the largest share of usage(47.6%)and expenditures(55.8%),while secondary hospitals had the lowest DDC(1.22 yuan)and tertiary hospitals the highest(1.89 yuan).Post-VBP,procurement expenditures and DDC decreased by 53.9%and 35.4%,respectively.Primary hospitals showed the largest expenditure reduction(61.6%),and secondary hospitals exhibited the greatest DDC decline(53.9%).DDDs increased significantly in primary care settings(e.g.,pitavastatin surged by 239.79%in secondary hospitals),while tertiary hospitals saw reduced usage of some drugs(e.g.,amlodipine/atorvastatin decreased by 7.34%).Mixed-effects models confirmed that VBP significantly reduced expenditures(OR=-1.07,P<0.01)and DDC(OR=-2.70,P<0.01)while indirectly lowering prices of non-VBP drugs.After covariate adjustment,expenditure reductions for rosuvastatin and atorvastatin narrowed,ezetimibe expenditures increased(OR=0.13,P<0.01),and pitavastatin usage declined(OR=-0.10,P<0.01).Changes in amlodipine/atorvastatin and ezetimibe lacked statistical significance due to short VBP implementation periods.Tertiary hospitals demonstrated the strictest policy adherence,with the largest expenditure and DDC reductions(P<0.01).Subgroup analysis revealed that the policy did not significantly affect clinical demand(DDDs)in hospitals at different levels,though it was considered to have triggered adjustments in medication structure.Conclusion Jiangsu's lipid-lowering drug structure aligns with guidelines(statin-based,moderate-intensity preference).VBP effectively reduced costs,with tertiary hospitals prioritizing originator-to-generic substitution and primary hospitals reflecting cost-control and demand variations.Confounding factors influenced policy evaluation.The study recommends continuous monitoring and policy optimization to enhance procurement efficiency,ensure rational clinical use,and sustain cost savings,providing insights for further healthcare reform.

Objective To analyze the procurement data of lipid-lowering drugs in hospitals at different levels in Jiangsu Province from October 2019 to September 2023,to evaluate the impact of the volume-based procurement(VBP)policy,and to provide references for clinical rational drug use and healthcare policy optimization.Methods Based on procurement data from the Jiangsu Provincial Health Information Center,statistical analyses of procurement expenditures,defined daily doses(DDDs),and defined daily cost(DDC)were conducted.Mixed-effects models were applied to assess changes in procurement expenditures,DDDs,and DDC before and after VBP implementation.Results From 2019 to 2023,statins dominated the market in Jiangsu Province,with rosuvastatin recording the highest DDDs(748 million).Statins,traditional Chinese medicines,and cholesterol absorption inhibitors ranked highest in procurement expenditures.Tertiary hospitals accounted for the largest share of usage(47.6%)and expenditures(55.8%),while secondary hospitals had the lowest DDC(1.22 yuan)and tertiary hospitals the highest(1.89 yuan).Post-VBP,procurement expenditures and DDC decreased by 53.9%and 35.4%,respectively.Primary hospitals showed the largest expenditure reduction(61.6%),and secondary hospitals exhibited the greatest DDC decline(53.9%).DDDs increased significantly in primary care settings(e.g.,pitavastatin surged by 239.79%in secondary hospitals),while tertiary hospitals saw reduced usage of some drugs(e.g.,amlodipine/atorvastatin decreased by 7.34%).Mixed-effects models confirmed that VBP significantly reduced expenditures(OR=-1.07,P<0.01)and DDC(OR=-2.70,P<0.01)while indirectly lowering prices of non-VBP drugs.After covariate adjustment,expenditure reductions for rosuvastatin and atorvastatin narrowed,ezetimibe expenditures increased(OR=0.13,P<0.01),and pitavastatin usage declined(OR=-0.10,P<0.01).Changes in amlodipine/atorvastatin and ezetimibe lacked statistical significance due to short VBP implementation periods.Tertiary hospitals demonstrated the strictest policy adherence,with the largest expenditure and DDC reductions(P<0.01).Subgroup analysis revealed that the policy did not significantly affect clinical demand(DDDs)in hospitals at different levels,though it was considered to have triggered adjustments in medication structure.Conclusion Jiangsu's lipid-lowering drug structure aligns with guidelines(statin-based,moderate-intensity preference).VBP effectively reduced costs,with tertiary hospitals prioritizing originator-to-generic substitution and primary hospitals reflecting cost-control and demand variations.Confounding factors influenced policy evaluation.The study recommends continuous monitoring and policy optimization to enhance procurement efficiency,ensure rational clinical use,and sustain cost savings,providing insights for further healthcare reform.

Objective:To evaluate the efficacy and safety of intrasaccular flow disruptor in wide-necked intracranial aneurysms.Methods:One hundred and seventeen patients with wide-necked intracranial aneurysms treated with intrasaccular flow disruptor were collected from Department of Neurointervention (First Affiliated Hospital of Zhengzhou University), Department of Neurosurgery (Beijing Tiantan Hospital, Capital Medical University), Department of Cerebrovascular Surgery, Neurosurgery Center (Zhujiang Hospital, Southern Medical University), and Department of Neurosurgery (First Affiliated Hospital of Harbin Medical University) from August 2022 to March 2024. Raymond-Roy Occlusion Classification (RROC) was employed to evaluate aneurysm embolization immediately after procedure; cranial CT or MRI within 48 hours of embolization were performed to identify any new intracranial hemorrhage, subarachnoid hemorrhage, or new symptomatic cerebral infarction related to the intracranial aneurysms. Modified Rankin Scale (mRS) was used to assess the neurological function at discharge. Imaging follow-up and outpatient follow-up were performed at 6 months after embolization to evaluate the aneurysm occlusion degree and complications.Results:A total of 117 intrasaccular flow disruptors were implanted in 117 patients, with a technical success rate of 100%; 115 patients (98.3%) enjoyed successful one-time release of their disruptors, and 2 patients (1.7%) required retrieval and redirection of the disruptors before second successful attempt. Flow disruptor plus stent was performed in 13 patients (11.1%). Immediately after procedure, RROC grading I was noted in 3 patients, grading II in 51 patients and grading III in 63 patients. Cranial CT or MRI within 48 hours of embolization indicated no new intracranial hemorrhage, subarachnoid hemorrhage, or symptomatic cerebral infarction related to the intracranial aneurysms. All patients had mRS score of 0 at discharge. Eighty-three patients completed a 6-month follow-up (RROC grading I in 41 patients, grading II in 33 patients and grading III in 9 patients), without ischemic or hemorrhagic adverse events.Conclusion:The results of this study preliminarily suggest that intrasaccular flow disruptor is effective and safe in wide-necked intracranial aneurysms.

Objective:To evaluate the efficacy and safety of Neuroform Atlas stent-assisted coil embolization in patients with middle cerebral artery bifurcation aneurysms.Methods:A retrospective analysis was performed; the clinical data of 46 patients with middle cerebral artery bifurcation aneurysms accepted Neuroform Atlas stent-assisted coil embolization in First Affiliated Hospital of Zhengzhou University, Beijing Tiantan Hospital Affiliated to Capital Medical University, First Affiliated Hospital of Harbin Medical University, Zhujiang Hospital of Southern Medical University and First Affiliated Hospital of Chongqing Medical University from January 2022 to March 2024 were collected. There were 28 ruptured aneurysms (60.87%) and 18 unruptured aneurysms (39.13%). Follow-up was performed for more than 3 months; Raymond-Roy grading was used to evaluate the aneurysm embolization immediately after embolization and during follow-up; perioperative hemorrhagic or ischemic complications were recorded; modified Rankin Scale (mRS) was used to evaluate the prognosis of the patients at discharge and during follow-up (mRS score≤2: good prognosis, and mRS score>2: poor prognosis).Results:Coil embolization was successful in all 46 patients. DSA immediately after embolization showed that 41 patients (89.13%) had completely occluded aneurysms (Raymond-Roy grading I), 2 patients (4.35%) had residual aneurysm neck (Raymond-Roy grading Ⅱ) and 3 patients (6.52%) had partially occluded aneurysms (Raymond-Roy grading Ⅲ). Perioperative complications occurred in 5 patients, including 2 with postoperative cerebral infarction, 1 with hydrocephalus, 1 with postoperative pneumonia leading to respiratory failure, and 1 with stent thrombosis during embolization. Both at discharge and 3 months after embolization, 43 patients (93.48%) had good prognosis and 3 patients (6.52%) had poor prognosis. No obvious ischemic complications (such as stent restenosis) or hemorrhagic complications (such as re-rupture of the aneurysms) were found in all patients. Thirty patients (65.22%) had imaging follow-up for 6-12 months: 26 (86.67%) had Raymond-Roy grading I, 3 (10.00%) had Raymond-Roy grading II, and 1 (3.33%) had Raymond-Roy grading III.Conclusion:Neuroform Atlas stent-assisted coil embolization has good short-term efficacy and high safety in middle cerebral artery bifurcation aneurysms, but long-term follow-up observation is still needed to verify its efficacy.

Objective: To investigate the status of tuberculin skin test (TST) results and the influencing factors among student close contacts with pulmonary tuberculosis, so as to provide the evidence for developing prevention and control strategies for pulmonary tuberculosis among students. Methods: The students aged 15 years and above who had close contact with pulmonary tuberculosis cases in Yuecheng District, Shaoxing City, Zhejiang Province, from October 2016 to December 2023 were recruited and investigated using questionnaires and TST to collect demographic information, contact history, and TST results. The influencing factors for TST positivity among student close contacts with pulmonary tuberculosis were analyzed using a multivariable logistic regression model. Results: A total of 5 507 student close contacts were investigated, including 2 982 males and 2 525 females, with a male-to-female ratio of 1.18∶1. The mean age was (19.10±1.71) years. Among them, 397 (7.21%) were technical secondary school students, 766 (13.91%) were senior high school students, 2 556 (46.41%) were junior college students, and 1 788 (32.47%) were college students or above. A total of 958 students tested positive for TST, with a positivity rate of 17.40%. The rates of general positivity, moderate positivity, and strong positivity were 10.53%, 4.98% and 1.89%, respectively. Multivariable logistic regression analysis showed that senior high school students (OR=1.473, 95%CI: 1.009-2.152) and junior college students (OR=1.467, 95%CI: 1.074-2.005), as well as those with an exposure-to-screening interval of ≥46 days (46-<61 days, OR=2.043, 95%CI: 1.478-2.826; ≥61 days, OR=1.291, 95%CI: 1.018-1.637) had a higher risk of TST positivity. Female student close contacts had a lower risk of TST positivity (OR=0.753, 95%CI: 0.649-0.873). Conclusion The TST positivity rate was relatively high, and gender, school type, and exposure-to-screening interval were influencing factors for TST positivity among student close contacts with pulmonary tuberculosis.

ObjectiveTo analyze the influencing factors for recurrence in successfully treated pulmonary tuberculosis patients with isoniazid-resistant and rifampicin-sensitive in Shaoxing City, Zhejiang Province. MethodsData on general demographic information, treatment information and drug susceptibility test results for pulmonary tuberculosis patients admitted to the designated tuberculosis medical institutions and registered in the tuberculosis information management system was collected in Shaoxing City from January 2011 to August 2024. A total of 428 patients with isoniazid resistance (including isoniazid single resistance and multiple resistance) but who were successfully treated were included in the study. Information for the recurrence after successful treatment of the patients was analyzed. The Cox proportional hazards models were used to analyze the influencing factors of recurrence in patients. ResultsAmong the 428 successfully treated patients included in the study, 31 cases (accounting for 7.24%) had recurrence by the end of the observation period, with a recurrence rate density of 1.31 per 100 person-years and a median recurrence time of 0.99 (0.08, 8.27) years. Among the relapsed population, 51.61% of the patients relapsed within one year after successful treatment. 77.42% of the patients relapsed within two years after successful treatment. Multivariate Cox regression analysis showed that when isoniazid resistance was discovered, the diagnosis classification of relapse (HR=4.115, 95%CI: 1.734‒9.767) and positive 0-month sequence smear (HR=4.457, 95%CI: 1.053‒18.866) were risk factors for recurrence after successful treatment in patients. ConclusionRegular follow-up should be strengthened for at least two years after the successful treatment of isoniazid-resistant pulmonary tuberculosis patients. Special attention should be paid to the treatment effect and regular re-examination and monitoring after the end of the treatment course of isoniazid-resistant pulmonary tuberculosis patients who have been re-treated and were sputum smear positive at baseline, so as to prevent recurrence and disease progression in high-risk populations.

Objective:To evaluate the efficacy and safety of intrasaccular flow disruptor in wide-necked intracranial aneurysms.Methods:One hundred and seventeen patients with wide-necked intracranial aneurysms treated with intrasaccular flow disruptor were collected from Department of Neurointervention (First Affiliated Hospital of Zhengzhou University), Department of Neurosurgery (Beijing Tiantan Hospital, Capital Medical University), Department of Cerebrovascular Surgery, Neurosurgery Center (Zhujiang Hospital, Southern Medical University), and Department of Neurosurgery (First Affiliated Hospital of Harbin Medical University) from August 2022 to March 2024. Raymond-Roy Occlusion Classification (RROC) was employed to evaluate aneurysm embolization immediately after procedure; cranial CT or MRI within 48 hours of embolization were performed to identify any new intracranial hemorrhage, subarachnoid hemorrhage, or new symptomatic cerebral infarction related to the intracranial aneurysms. Modified Rankin Scale (mRS) was used to assess the neurological function at discharge. Imaging follow-up and outpatient follow-up were performed at 6 months after embolization to evaluate the aneurysm occlusion degree and complications.Results:A total of 117 intrasaccular flow disruptors were implanted in 117 patients, with a technical success rate of 100%; 115 patients (98.3%) enjoyed successful one-time release of their disruptors, and 2 patients (1.7%) required retrieval and redirection of the disruptors before second successful attempt. Flow disruptor plus stent was performed in 13 patients (11.1%). Immediately after procedure, RROC grading I was noted in 3 patients, grading II in 51 patients and grading III in 63 patients. Cranial CT or MRI within 48 hours of embolization indicated no new intracranial hemorrhage, subarachnoid hemorrhage, or symptomatic cerebral infarction related to the intracranial aneurysms. All patients had mRS score of 0 at discharge. Eighty-three patients completed a 6-month follow-up (RROC grading I in 41 patients, grading II in 33 patients and grading III in 9 patients), without ischemic or hemorrhagic adverse events.Conclusion:The results of this study preliminarily suggest that intrasaccular flow disruptor is effective and safe in wide-necked intracranial aneurysms.

Objective:To evaluate the efficacy and safety of Neuroform Atlas stent-assisted coil embolization in patients with middle cerebral artery bifurcation aneurysms.Methods:A retrospective analysis was performed; the clinical data of 46 patients with middle cerebral artery bifurcation aneurysms accepted Neuroform Atlas stent-assisted coil embolization in First Affiliated Hospital of Zhengzhou University, Beijing Tiantan Hospital Affiliated to Capital Medical University, First Affiliated Hospital of Harbin Medical University, Zhujiang Hospital of Southern Medical University and First Affiliated Hospital of Chongqing Medical University from January 2022 to March 2024 were collected. There were 28 ruptured aneurysms (60.87%) and 18 unruptured aneurysms (39.13%). Follow-up was performed for more than 3 months; Raymond-Roy grading was used to evaluate the aneurysm embolization immediately after embolization and during follow-up; perioperative hemorrhagic or ischemic complications were recorded; modified Rankin Scale (mRS) was used to evaluate the prognosis of the patients at discharge and during follow-up (mRS score≤2: good prognosis, and mRS score>2: poor prognosis).Results:Coil embolization was successful in all 46 patients. DSA immediately after embolization showed that 41 patients (89.13%) had completely occluded aneurysms (Raymond-Roy grading I), 2 patients (4.35%) had residual aneurysm neck (Raymond-Roy grading Ⅱ) and 3 patients (6.52%) had partially occluded aneurysms (Raymond-Roy grading Ⅲ). Perioperative complications occurred in 5 patients, including 2 with postoperative cerebral infarction, 1 with hydrocephalus, 1 with postoperative pneumonia leading to respiratory failure, and 1 with stent thrombosis during embolization. Both at discharge and 3 months after embolization, 43 patients (93.48%) had good prognosis and 3 patients (6.52%) had poor prognosis. No obvious ischemic complications (such as stent restenosis) or hemorrhagic complications (such as re-rupture of the aneurysms) were found in all patients. Thirty patients (65.22%) had imaging follow-up for 6-12 months: 26 (86.67%) had Raymond-Roy grading I, 3 (10.00%) had Raymond-Roy grading II, and 1 (3.33%) had Raymond-Roy grading III.Conclusion:Neuroform Atlas stent-assisted coil embolization has good short-term efficacy and high safety in middle cerebral artery bifurcation aneurysms, but long-term follow-up observation is still needed to verify its efficacy.

ObjectiveTo investigate the effect of transplantation of bone marrow mesenchymal stem cells （BMSCs） co-cultured with bone marrow-derived M2 macrophages （M2-BMDMs）， named as BMSC^M2， on a rat model of liver cirrhosis induced by carbon tetrachloride （CCl₄）/2-acetaminofluorene （2-AAF）. MethodsRat BMDMs were isolated and polarized into M2 phenotype， and rat BMSCs were isolated and co-cultured with M2-BMDMs at the third generation to obtain BMSC^M2. The rats were given subcutaneous injection of CCl₄ for 6 weeks to establish a model of liver cirrhosis， and then they were randomly divided into model group （M group）， BMSC group， and BMSC^M2 group， with 6 rats in each group. A normal group （N group） with 6 rats was also established. Since week 7， the model rats were given 2-AAF by gavage in addition to the subcutaneous injection of CCl₄. Samples were collected at the end of week 10 to observe liver function， liver histopathology， and hydroxyproline （Hyp） content in liver tissue， as well as changes in the markers for hepatic stellate cells， hepatic progenitor cells， cholangiocytes， and hepatocytes. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the N group， the M group had significant increases in the activities of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in ALT and AST （P<0.01）， and the BMSC^M2 group had significantly better activities than the BMSC group （P<0.05）. Compared with the N group， the M group had significant increases in Hyp content and the mRNA and protein expression levels of alpha-smooth muscle actin （α-SMA） in the liver （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in Hyp content and the expression of α-SMA （P<0.05）， and the BMSC^M2 group had a significantly lower level of α-SMA than the BMSC group （P<0.01）. Compared with the N group， the M group had significant increases in the mRNA expression levels of the hepatic progenitor cell markers EpCam and Sox9 and the cholangiocyte markers CK7 and CK19 （P<0.01） and significant reductions in the expression levels of the hepatocyte markers HNF-4α and Alb （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in the mRNA expression levels of EpCam， Sox9， CK7， and CK19 （P<0.05） and significant increases in the mRNA expression levels of HNF-4α and Alb （P<0.05）， and compared with the BMSC group， the BMSC^M2 group had significant reductions in the mRNA expression levels of EpCam and CK19 （P<0.05） and significant increase in the expression level of HNF-4α （P<0.05）. ConclusionM2-BMDMs can enhance the therapeutic effect of BMSCs on CCl₄/2-AAF-induced liver cirrhosis in rats， which provides new ideas for further improving the therapeutic effect of BMSCs on liver cirrhosis.