Objective To investigate the histological and cellular bases for the improvement of portal hypertension(PH)by observing liver histopathological changes after treatment in patients with cirrhotic portal hypertension,and to provide a basis for clinical drug development.Methods A total of 322 patients with hepatitis B cirrhosis who completed 48 weeks of antiviral therapy or combined anti-fibrotic treatment in 20 hospitals across 12 provinces in China from September 2014 to October 2018 were enrolled,and the noninvasive diagnostic criteria for clinically significant portal hypertension(CSPH)from Baveno Ⅶ were used to assess the severity of PH;43 patients with a confirmed diagnosis of CSPH were identified based on liver stiffness measurement(LSM)≥25 kPa before treatment,and according to whether the severity of PH was reduced by≥2 grades after treatment,the patients were divided into PH improvement(n=19)group and PH non-improvement group(n=24).Related data were collected,including demographic data,laboratory tests.Liver fibrosis were assessed,including HE staining and reticular fiber staining;liver microvascular lesions were assessed,including obliterative portal venopathy(OPV),nodular regenerative hyperplasia(NRH),and incomplete septal fibrosis(ISF).Single immunohistochemical staining was performed for von Willebrand factor(vWF),and fibronectin;multiplex immunohistochemical staining was performed for fibrinogen,CD32b,CD31,alpha-smooth muscle actin(α-SMA).The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups,and the chi-square test was used for comparison of categorical data between two groups.Results After 48 weeks of treatment,43 patients had significant improvements in red blood cell count,alanine aminotransferase,aspartate aminotransferase,aspartate aminotransferase-to-platelet ratio index score,liver fibrosis grade,and PH grade(all P<0.05),among whom 19 patients showed a reduction in PH severity by≥2 grades(PH improvement group),while the remaining patients were enrolled as the PH non-improvement group.There was no significant difference in the outcome of liver fibrosis between the two groups(χ2=3.380,P=0.066).Microvascular lesion assessment showed that compared with the PH non-improvement group,the PH improvement group had significantly lower OPV severity,microvascular density(the expression level of vWF),and expression of fibronectin(all P<0.05),while there were no significant differences in NRH severity,ISF severity,and the expression level of fibrinogen between the two groups(all P>0.05).Cytological evaluation showed no significant differences in the expression levels of CD32b,CD31,and α-SMA between the two groups before and after treatment(all P>0.05),and comparison of the expression levels before and after treatment showed that the PH improvement group had a significant increase in the expression level of CD32b(t=-2.007,P=0.045)and a significant reduction in the expression level of α-SMA(t=2.628,P=0.013).Conclusion The pathological features of PH improvement are associated with liver fibrosis regression and the improvement in liver microvascular lesions,and at the cellular level,PH improvement is associated with the dedifferentiation of liver sinusoidal endothelial cells and the activated phenotype of hepatic stellate cells.

Objective:To explore the impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.

Objective To evaluate the value of tripartite motif-containing protein 21(TRIM21)mRNA expression in alveolar macrophages for the serverity and prognosis of patients with severe pneumonia complicated by acute respiratory distress syndrome(SP-ARDS).Methods A retrospective analysis was conducted on 42 SP-ARDS patients(SP-ARDS group)and 15 outpatient healthy controls(control group)admitted to the Department of Respiratory and Critical Care Medicine,Jinling Hospital Affilicated to Medical School of Nanjing University,from November 2023 to June 2024.Bronchoalveolar lavage fluid was collected,and alveolar macrophages were isolated.The expression levels of TRIM21 mRNA were quantified using qPCR.Differences in TRIM21 mRNA expression levels,clinical characteristics,and relevant laboratory test results were compared between the two groups.Correlations between TRIM21 mRNA expression and SP-ARDS severity,28-day mortality,inflammatory indicators,acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)scores,duration of mechanical ventilation,and ICU stay were analyzed using Pearson or Spearman correlation analysis.Logistic regression analysis was used to identify risk factors for 28-day mortality,and the predictive value of each factor was evaluated using receiver operating characteristic(ROC)curves.Results Compared with control group,the expression levels of TRIM21 mRNA,white blood cell counts,neutrophil-to-lymphocyte ratio(NLR),and C-reactive protein(CRP),and procalcitonin(PCT)levels increased(P<0.05),and hemoglobin levels decreased(P<0.05)in SP-ARDS group.No significant differences were observed in gender,age,smoking history,alcohol consumption,underlying disease history,and platelet count between the two groups(P>0.05).TRIM21 mRNA expression level in SP-ARDS patients was positively correlated with ARDS severity(P<0.05).Additionally,non-survivors within 28 days had a significantly higher expression level of TRIM21 mRNA compared to survivors(P<0.001).Correlation analysis indicated that the relative expression level of TRIM21 mRNA in SP-ARDS patients was positively correlated with CRP(r=0.309,P<0.05),NLR(r=0.422,P<0.01),PCT(r=0.561,P<0.001),APACHE Ⅱ score(r=0.615,P<0.001),and duration of mechanical ventilation(r=0.665,P<0.001).Logistic regression analysis revealed that elevated expression levels of TRIM21 mRNA(OR=2.886,P=0.043)and higher APACHE Ⅱ scores(OR=1.546,P=0.037)were independent risk factors for 28-day mortality in SP-ARDS patients.The areas under the ROC curves(AUCs)for predicting 28-day mortality using TRIM21 mRNA expression level and APACHE Ⅱ score were 0.889 and 0.874,respectively,with optimal cut-off values of 5.21 and 20.5 points,respectively.The combined AUC for prediction was 0.962.Conclusion Increased TRIM21 mRNA expression in alveolar macrophages of SP-ARDS patients is positively correlated with disease severity and may serve as a potential predictive marker for 28-day survival in SP-ARDS patients.

Objective To investigate the histological and cellular bases for the improvement of portal hypertension(PH)by observing liver histopathological changes after treatment in patients with cirrhotic portal hypertension,and to provide a basis for clinical drug development.Methods A total of 322 patients with hepatitis B cirrhosis who completed 48 weeks of antiviral therapy or combined anti-fibrotic treatment in 20 hospitals across 12 provinces in China from September 2014 to October 2018 were enrolled,and the noninvasive diagnostic criteria for clinically significant portal hypertension(CSPH)from Baveno Ⅶ were used to assess the severity of PH;43 patients with a confirmed diagnosis of CSPH were identified based on liver stiffness measurement(LSM)≥25 kPa before treatment,and according to whether the severity of PH was reduced by≥2 grades after treatment,the patients were divided into PH improvement(n=19)group and PH non-improvement group(n=24).Related data were collected,including demographic data,laboratory tests.Liver fibrosis were assessed,including HE staining and reticular fiber staining;liver microvascular lesions were assessed,including obliterative portal venopathy(OPV),nodular regenerative hyperplasia(NRH),and incomplete septal fibrosis(ISF).Single immunohistochemical staining was performed for von Willebrand factor(vWF),and fibronectin;multiplex immunohistochemical staining was performed for fibrinogen,CD32b,CD31,alpha-smooth muscle actin(α-SMA).The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups,and the chi-square test was used for comparison of categorical data between two groups.Results After 48 weeks of treatment,43 patients had significant improvements in red blood cell count,alanine aminotransferase,aspartate aminotransferase,aspartate aminotransferase-to-platelet ratio index score,liver fibrosis grade,and PH grade(all P<0.05),among whom 19 patients showed a reduction in PH severity by≥2 grades(PH improvement group),while the remaining patients were enrolled as the PH non-improvement group.There was no significant difference in the outcome of liver fibrosis between the two groups(χ2=3.380,P=0.066).Microvascular lesion assessment showed that compared with the PH non-improvement group,the PH improvement group had significantly lower OPV severity,microvascular density(the expression level of vWF),and expression of fibronectin(all P<0.05),while there were no significant differences in NRH severity,ISF severity,and the expression level of fibrinogen between the two groups(all P>0.05).Cytological evaluation showed no significant differences in the expression levels of CD32b,CD31,and α-SMA between the two groups before and after treatment(all P>0.05),and comparison of the expression levels before and after treatment showed that the PH improvement group had a significant increase in the expression level of CD32b(t=-2.007,P=0.045)and a significant reduction in the expression level of α-SMA(t=2.628,P=0.013).Conclusion The pathological features of PH improvement are associated with liver fibrosis regression and the improvement in liver microvascular lesions,and at the cellular level,PH improvement is associated with the dedifferentiation of liver sinusoidal endothelial cells and the activated phenotype of hepatic stellate cells.

Objective:To explore the impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.

Objective VATER/VACTERL-like association is associated with adverse pregnancy outcomes.Genetic evidence of this disorder is sporadic.In this study,we aimed to provide genetic insights to improve the diagnosis of VACTERL. Methods We have described a Chinese family in which four members were affected by renal defects or agenesis,anal atresia,and anovaginal fistula,which is consistent with the diagnosis of a VACTERL-like association.Pedigree and genetic analyses were conducted using genome and exome sequencing. Results Segregation analysis revealed the presence of a recessive X-linked microdeletion in two living affected individuals,harboring a 196-380 kb microdeletion on Xq27.1,which was identified by familial exome sequencing.Genome sequencing was performed on the affected male,confirming a-196 kb microdeletion in Xq27.1,which included a 28%loss of the CDR-1 gene.Four family members were included in the co-segregation analysis,and only VACTERL-like cases with microdeletions were reported in X27.1. Conclusion These results suggest that the 196-380 kb microdeletion in Xq27.1 could be a possible cause of the VATER/VACTERL-like association.However,further genetic and functional analyses are required to confirm or rule out genetic background as the definitive cause of the VACTERL association.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To compare the outcomes of transplant kidneys and patient survival between simultaneous pancreas-kidney transplantation(SPKT)recipients and deceased donor kidney transplant(DDKT)recipients in patients with type 2 diabetes mellitus(T2DM)complicated with end-stage renal disease(ESRD),and to analyze the risk factors affecting patient survival post-SPKT.Methods Clinical and prognostic data of patients who underwent kidney transplantation from January 27,2003,to January 1,2021,were retrieved from the United Network for Organ Sharing(UNOS)database.A total of 50 230 cases were selected based on inclusion criteria,with 48 669 cases in DDKT group and 1561 cases in SPKT group.Kaplan-Meier analysis was employed to compare transplant kidney and patient survival between the two groups,and propensity score matching(PSM)was utilized to balance confounding factors between the groups.Cox regression model was used to analyze independent risk factors affecting patient survival post-SPKT.Results Compared with DDKT group,recipients in SPKT group had a younger median age(P<0.001),a higher proportion of males(P<0.001),lower BMI(P<0.001),shorter dialysis and transplant waiting times(P<0.001),a higher percentage of private medical insurance(P<0.001),a lower proportion of previous transplants(P<0.001),a younger age at diabetes diagnosis(P<0.001),and a lower incidence of peripheral vascular disease(P=0.033).Compared with DDKT group,the donors in SPKT group had a younger median age(P<0.001),a higher proportion of males(P<0.001),lower BMI(P<0.001),and a lower prevalence of hypertension and diabetes history(P<0.001).In terms of transplant-related factors,the SPKT group had a shorter donor kidney cold ischemia time(P<0.001),a higher degree of HLA mismatch(P<0.001),and a lower Kidney Donor Profile Index(KDPI)(P<0.001)when compared with DDKT group.The SPKT group had lower serum creatinine levels at discharge(P<0.001),lower rates of postoperative delayed graft function(DGF)and acute rejection(AR)(P<0.001),but longer hospital stays(P<0.001)when compared with DDKT group.Kaplan-Meier survival analysis curves,both original and after propensity score matching(PSM),consistently showed significantly higher transplant kidney and patient survival rates in SPKT group compared with DDKT group(P<0.001).Cox regression model analysis indicated that recipient age,recipient race,donor age,and donor kidney cold ischemia time were independent risk factors influencing patient survival post-SPKT.Conclusions For ESRD patients with T2DM,SPKT offers improved long-term graft and patient survival rates compared with DDKT.Recipient age,recipient ethnicity,donor age,and cold ischemia time for the donor's kidney are independent risk factors affecting post-SPKT patient survival.

Objective:To carry out the policy diffusion analysis of centralized and volume-based drug procurement in China in recent years,and to provide reference for the formulation of centralized and volume-based drug procurement policy.Methods:Through the official websites of the central and provincial governments,the official websites of the Health Commission and the official websites of the Medical Security Bureau,the policy documents related to centralized and volume-based drug procurement from January 1,2009 to December 31,2023 were searched.Based on the policy diffusion theory,the reference network analysis method is used to analyze the intensity,breadth and speed of policy diffusion,and the sequential analysis method of policy keywords is used to analyze the direction of policy diffusion.Results:In the two stages of the development of centralized and volume-based drug procurement policy,the number of policies issued in the medical insurance management stage reached the peak;The top ten policies with the highest diffusion intensity and breadth are all central policies,and most of them are notices and opinions.In addition,the newly promulgated policies have a faster diffusion speed.In the direction of diffusion,top-down and parallel diffusion trends are obvious.Conclusion:The diffusion of centralized and volume-based drug procurement policy in China focuses on the central policy,and the diffusion speed is increasing year by year.It is suggested to strengthen the policy coordination between the central and local governments,establish a unified national information platform for centralized drug procurement,optimize the learning and competition mechanism between governments at all levels,and give play to the advantages of"policy experiment".

Objective: To analyze the difference of application methods and effects of local flap in small and medium-sized defects of different aesthetic subunits of nose, in order to provide reference for clinical work. Methods: A retrospective analysis was made on 59 patients with external nasal masses and scars who underwent surgical treatment in the Department of Aesthetic Plastic Surgery of the Affiliated Hospital of Qingdao University from July 1, 2021 to January 30, 2022, including 27 females and 32 males, aged 15 to 69 years. Using Likert scale, the repair methods and effects of local flap for nasal soft tissue defects were evaluated and summarized from three aspects of texture, flatness and scar concealment. GraphPad Prism 5.0 software was used for data statistics and analysis. Results: The use of skin flaps to repair small and medium-sized areas of the nose could achieve satisfactory results. For patients with different subunits, in terms of skin flatness and scar concealment degree in the operation area, patients' satisfaction with the dorsal and lateral nasal areas was higher than that of the alar and tip areas, respectively (F=6.40, P=0.001; F=10.57, P<0.001). For patients with different skin flap repair methods, the satisfaction of patients with Z-plasty and Dufourmentel skin flap was higher than that of other skin flap repair methods (F=4.38, P=0.002), and the satisfaction of patients with Dufourmentel skin flap was the highest in the degree of scar concealment (F=2.57, P=0.038). Conclusions: In the small and medium-sized defects of the nose, the use of multiple local flaps can achieve good cosmetic effects and functional recovery. The operator should select the appropriate flap repair method according to the characteristics of different aesthetic subunits of the nose.