ObjectiveTo investigate the efficacy of C-reactive protein （CRP） in predicting the progression to acute-on-chronic liver failure （ACLF） within 90 days after disease onset in patients with acute decompensation （AD） of cirrhosis， and to provide a reference for the early identification of high-risk populations in clinical practice. MethodsA retrospective study was conducted among 906 patients with liver cirrhosis who were hospitalized due to AD in Nanjing Second Hospital from January 1， 2015 to October 31， 2024， and demographic features， AD type， and laboratory markers were collected on admission. The primary endpoint was progression to ACLF within 90 days after admission， and according to the presence or absence of ACLF， the patients were divided into non-ACLF group with 676 patients and ACLF group with 230 patients. The independent-samples t test was used for comparison of normally distributed continuous data between groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The univariate and multivariate Cox proportional-hazards regression models were used to identify independent predictive factors for ACLF. The receiver operating characteristic （ROC） curve was used to assess the predictive performance of CRP and existing scoring systems （Model for End-Stage Liver Disease ［MELD］， Child-Turcotte-Pugh ［CTP］ score， and Chronic Liver Failure Consortium Acute Decompensation ［CLIF-C AD］ score）， and the restricted cubic spline analysis was used to investigate the nonlinear relationship between CRP and the risk of ACLF. Youden index was used to determine the optimal predictive cut-off value for CRP， and the Kaplan-Meier survival curve was plotted for risk stratification， while the log-rank test was used for survival analysis. ResultsAmong the 906 AD patients， the incidence rate of ACLF was 25.39% within 90 days. The incidence rate of ACLF within 90 days was 45.1% in the 264 patients with bacterial infection and 17.3% in the 642 patients without bacterial infection （χ²=74.791， P<0.001）. Among the 906 patients， 312 patients （34.44%） had acute-on-chronic pre-liver failure （pre-ACLF）， with a significantly higher proportion of patients who progressed to ACLF than those in the non-pre-ACLF group ［60.58% （189/312） vs 6.90% （41/594）， χ²=310.234， P<0.001］. Among the 230 patients with ACLF， there were 102 patients with stable ACLF （44.35%） and 128 patients with unstable ACLF （55.65%）， with a significant difference in CRP between the two groups of patients （U=5 234.500， P<0.001）. The restricted cubic spline analysis showed a significant nonlinear relationship between CRP and the risk of ACLF （P<0.001）. The optimal cut-off value of CRP was determined as 10.16 mg/L based on the Youden index， with a sensitivity of 70.4% and a specificity of 64.5%. The Kaplan-Meier curve analysis showed that the high-risk group with CRP≥10.16 mg/L had a significantly higher event-free survival rate of ACLF within 90 days compared with the low-risk group （P<0.001）. The multivariate Cox regression analysis showed that AD type-hepatic encephalopathy （hazard ratio ［HR］=4.199， 95% confidence interval ［CI］： 3.056 — 5.770， P<0.001）， AD type-bacterial infection （HR=1.826， 95%CI： 1.356 — 2.459， P<0.001）， CRP （≥10.16 mg/L） （HR=2.356， 95%CI： 1.825 — 3.047， P<0.001）， white blood cell count （HR=1.021， 95%CI： 1.002 — 1.041， P=0.035）， hemoglobin （HR=0.994， 95%CI： 0.989 — 0.999， P=0.025）， international normalized ratio （HR=1.657， 95%CI： 1.372 — 2.001， P<0.001）， total bilirubin （HR=1.003， 95%CI： 1.002 — 1.004， P<0.001）， albumin （HR=0.956， 95%CI： 0.926 — 0.986， P=0.004）， creatinine （HR=1.005， 95%CI： 1.004 — 1.006， P<0.001）， serum sodium （HR=0.976， 95%CI： 0.956 — 0.997， P=0.025）， and lactate dehydrogenase （HR=1.001， 95%CI： 1.001 — 1.002， P<0.001） were all independent predictive factors for progression to ACLF within 90 days. The ROC curve analysis showed that CRP alone had an area under the ROC curve （AUC） of 0.724 （95%CI： 0.685 — 0.763） in predicting ACLF， and CRP+MELD score had the best predictive performance （AUC=0.870， 95%CI： 0.843 — 0.898）， while CRP+CTP score and CRP+CLIF-C AD score had an AUC of 0.852 （95%CI： 0.823 — 0.881） and 0.845 （95%CI： 0.812 — 0.877）， respectively. There was a significant increase in model performance after integration （P<0.05）. ConclusionSerum CRP level on admission is an independent predictive factor for progression to ACLF within 90 days in patients with AD of cirrhosis， and a CRP level of ≥10.16 mg/L can be used as a simple threshold for identifying high-risk patients. Incorporating CRP into existing assessment systems may enhance the early identification of patients at a high risk for ACLF， which provides a reference for clinical intervention.

Plant-derived extracellular vesicles (PDEVs), describe a group of nanoparticles released by plants. These particles are characterized by a lipid bilayer structure containing various proteins, lipids, nucleic acids, and unique metabolites. Although the study on PDEVs is relatively new, having only been around for ten years, they have shown promising development prospects in both basic research and clinical transformation areas. Evidence suggests that PDEVs have excellent application prospects in regulating inflammation and treating tumors. Their distinctive, vesicle-mimicking architecture and stellar biocompatibility render them prime candidates for ferrying various anti-cancer agents, including RNA, proteins, and conventional chemotherapy drugs. Increasingly, studies have shown that PDEVs can be engineered as an innovative platform for combination cancer immunotherapy. Consequently, this paper provides an extensive summary of current developments in engineering methods and strategies for PDEVs in cancer treatment and combined cancer immune therapeutics. The essential characteristics of PDEVs, including the biogenesis process and components, as well as their anti-tumor activity and mechanism, are summarized. Finally, the in vivo safety of PDEVs as delivery vectors and the challenges of scale-up production and clinical transformation are discussed.

Objective To investigate the expression levels and clinical significance of type Ⅰ innate lymphoid cells(ILC1s),T-box transcription factor(T-bet),interleukin(IL)-12,IL-18 and interferon-gamma(IFN-γ)in peripheral blood of patients with primary immune thrombocytopenia(ITP).Methods Thirty-five ITP patients with their first episode were selected as the initial treatment group.Thirteen of these patients were followed up after receiving treatment.Additionally,20 healthy individuals underwent routine physical examinations during the same period were recruited as the control group.Peripheral blood samples were collected for analysis.The proportion of ILC1s was determined by flow cytometry.T-bet mRNA expression was measured using quantitative real-time PCR(qRT-PCR).Serum levels of IL-18,IL-12 and IFN-γ were quantified by enzyme-linked immunosorbent assay(ELISA).The differences in ILC1s proportion,T-bet mRNA expression and cytokine levels were compared between groups.Correlations between ILC1s proportion,T-bet mRNA,cytokine levels and platelet(PLT)counts were also analyzed.Results Compared with the control group,the initial treatment group exhibited significantly elevated levels of peripheral ILC1s,T-bet mRNA and serum IL-18,IL-12 and IFN-γ(P＜0.05).Among the 13 patients who were followed up,all these indices decreased significantly after treatment(P＜0.05).Correlation analysis revealed that the proportion of ILC1s in the initial treatment group was positively correlated with IL-12,IL-18,IFN-γ and T-bet mRNA levels(rs=0.666,0.647,0.677,and 0.750,respectively,P＜0.01),and negatively correlated with PLT count(rs=-0.637,P＜0.01).Conclusion Innate immunity may play a role in the pathogenesis and progression of ITP by regulating the expression levels of ILC1s,T-bet,IL-12,IL-18 and IFN-γ.

Porcine reproductive and respiratory syndrome virus(PRRSV)mainly causes sow abor-tion,stillbirth,mummified fetus and respiratory symptoms in piglets.Since first reported in China in 1996,the virus complexity has increased significantly in more than 20 years of genetic evolution,bringing huge economic losses to the pig industry.In recent years,with the emergence of various PRRSV recombinant virus strains,preventing and controlling this epidemic became increasingly difficult.The purpose of this article is to comprehensively review the genome structure and func-tion of PRRSV,RNA virus recombination mechanism,main types of recombination,and the epi-demic status and recombination for the dominant epidemic PRRSV strains,in order to provide clues for in-depth research on gene recombination of PRRSV,thus providing the theoretical sup-port for formulating scientific prevention and control strategies.

A case of Sifrim-Hitz-Weiss syndrome(Sifrim-Hitz-Weiss syndrome,SIHIWES)is presented.The patient was a 35-year-old male with cryptorchidism,growth retardation,skeletal malformations,muscular atrophy,a wide forehead,special facial features like square face,small low-set and cup-shaped ears since birth.Whole-exon sequencing identified a heterozygous mutation(NM_001273:c.3047A>G(chr12-6701125)(p.K1016R))in CHD4 gene.The clinical significance of this mutation is currently unknown,and has not been previously reported.In light of the patient's symptoms,the case was diagnosed as Sifrim-Hitz-Weiss syndrome.This case represents the first instance of Sifrim-Hitz-Weiss syndrome in an adult patient in China.

OBJECTIVE The emergence of evolving variants of Coronavirus disease 2019(COVID-19)has fostered the need for change of newer and adaptive treatments for these infections.During the COVID-19 pandemic and persists,traditional Chinese medicine(TCM)herbs exhibit significant bioactivity and therapeutic effect.This study is aimed to evaluate the efficacy of four TCM preparations on 28-day mortality risk of patients and changes of the laboratory indicators.METHODS The retrospective cohort study included patients with COVID-19 who were admitted to the Jiangsu Province Hospital of Chinese Medicine from December 15,2022 to January 15,2023,and those died within 48 hours of admission or cannot be tracked for outcomes were excluded.The pri-mary outcome was survival status in 28 days(death or survival)starting from the day of admission.The second outcomes were labora-tory indicators,including absolute lymphocyte count,lactate dehydrogenase,creatinine,and blood urea nitrogen.Binary logistic re-gressions were used to estimate the effect of TCM preparations on the primary and secondary outcomes in main analysis.Meanwhile,heterogeneity and robustness of results from main analysis were assessed by subgroup analyses and multiple sensitivity analyses.RESULTS 1 816 eligible patients were included in analysis dataset,including 573 patients received standard care(control group)and 1 243 patients received TCM preparations(hospital preparation group).The 28-day mortality rate of hospital preparation group was lower than that of control group(4.75%vs.14.83%),and the difference was statistically significant(χ2=54.666,P<0.001).The risk of 28-day mortality was 0.535 times lower in the hospital preparation group as compared with the control group(OR=0.46,95%CI:0.305-0.708,P<0.001)showed by multivariable binary logistic regressions.Subgroup analyses showed that taking TCM preparations reduced the 28-day mortality risk.Sensitivity analyses demonstrated that the results of the main analysis for primary outcomes were robust.For secondary outcomes,the risk of abnormal absolute lymphocyte counts at discharge in the hospital prepara-tion group decreased by 0.284 times(OR=0.703,95%CI:0.515-0.961,P=0.027).CONCLUSION Compared with standard of care,taking four hospital preparations including Kanggan Heji,Feining Heji,Qishen Gubiao Keli,and Qianghuo Qushi Qingwen Heji decreased risk of 28-day mortality among hospitalized COVID-19 patients.TCM therapy achieves adequate therapeutic effects in COVID-19.

Objective To investigate the expression levels and clinical significance of type Ⅰ innate lymphoid cells(ILC1s),T-box transcription factor(T-bet),interleukin(IL)-12,IL-18 and interferon-gamma(IFN-γ)in peripheral blood of patients with primary immune thrombocytopenia(ITP).Methods Thirty-five ITP patients with their first episode were selected as the initial treatment group.Thirteen of these patients were followed up after receiving treatment.Additionally,20 healthy individuals underwent routine physical examinations during the same period were recruited as the control group.Peripheral blood samples were collected for analysis.The proportion of ILC1s was determined by flow cytometry.T-bet mRNA expression was measured using quantitative real-time PCR(qRT-PCR).Serum levels of IL-18,IL-12 and IFN-γ were quantified by enzyme-linked immunosorbent assay(ELISA).The differences in ILC1s proportion,T-bet mRNA expression and cytokine levels were compared between groups.Correlations between ILC1s proportion,T-bet mRNA,cytokine levels and platelet(PLT)counts were also analyzed.Results Compared with the control group,the initial treatment group exhibited significantly elevated levels of peripheral ILC1s,T-bet mRNA and serum IL-18,IL-12 and IFN-γ(P＜0.05).Among the 13 patients who were followed up,all these indices decreased significantly after treatment(P＜0.05).Correlation analysis revealed that the proportion of ILC1s in the initial treatment group was positively correlated with IL-12,IL-18,IFN-γ and T-bet mRNA levels(rs=0.666,0.647,0.677,and 0.750,respectively,P＜0.01),and negatively correlated with PLT count(rs=-0.637,P＜0.01).Conclusion Innate immunity may play a role in the pathogenesis and progression of ITP by regulating the expression levels of ILC1s,T-bet,IL-12,IL-18 and IFN-γ.

OBJECTIVE The emergence of evolving variants of Coronavirus disease 2019(COVID-19)has fostered the need for change of newer and adaptive treatments for these infections.During the COVID-19 pandemic and persists,traditional Chinese medicine(TCM)herbs exhibit significant bioactivity and therapeutic effect.This study is aimed to evaluate the efficacy of four TCM preparations on 28-day mortality risk of patients and changes of the laboratory indicators.METHODS The retrospective cohort study included patients with COVID-19 who were admitted to the Jiangsu Province Hospital of Chinese Medicine from December 15,2022 to January 15,2023,and those died within 48 hours of admission or cannot be tracked for outcomes were excluded.The pri-mary outcome was survival status in 28 days(death or survival)starting from the day of admission.The second outcomes were labora-tory indicators,including absolute lymphocyte count,lactate dehydrogenase,creatinine,and blood urea nitrogen.Binary logistic re-gressions were used to estimate the effect of TCM preparations on the primary and secondary outcomes in main analysis.Meanwhile,heterogeneity and robustness of results from main analysis were assessed by subgroup analyses and multiple sensitivity analyses.RESULTS 1 816 eligible patients were included in analysis dataset,including 573 patients received standard care(control group)and 1 243 patients received TCM preparations(hospital preparation group).The 28-day mortality rate of hospital preparation group was lower than that of control group(4.75%vs.14.83%),and the difference was statistically significant(χ2=54.666,P<0.001).The risk of 28-day mortality was 0.535 times lower in the hospital preparation group as compared with the control group(OR=0.46,95%CI:0.305-0.708,P<0.001)showed by multivariable binary logistic regressions.Subgroup analyses showed that taking TCM preparations reduced the 28-day mortality risk.Sensitivity analyses demonstrated that the results of the main analysis for primary outcomes were robust.For secondary outcomes,the risk of abnormal absolute lymphocyte counts at discharge in the hospital prepara-tion group decreased by 0.284 times(OR=0.703,95%CI:0.515-0.961,P=0.027).CONCLUSION Compared with standard of care,taking four hospital preparations including Kanggan Heji,Feining Heji,Qishen Gubiao Keli,and Qianghuo Qushi Qingwen Heji decreased risk of 28-day mortality among hospitalized COVID-19 patients.TCM therapy achieves adequate therapeutic effects in COVID-19.

Porcine reproductive and respiratory syndrome virus(PRRSV)mainly causes sow abor-tion,stillbirth,mummified fetus and respiratory symptoms in piglets.Since first reported in China in 1996,the virus complexity has increased significantly in more than 20 years of genetic evolution,bringing huge economic losses to the pig industry.In recent years,with the emergence of various PRRSV recombinant virus strains,preventing and controlling this epidemic became increasingly difficult.The purpose of this article is to comprehensively review the genome structure and func-tion of PRRSV,RNA virus recombination mechanism,main types of recombination,and the epi-demic status and recombination for the dominant epidemic PRRSV strains,in order to provide clues for in-depth research on gene recombination of PRRSV,thus providing the theoretical sup-port for formulating scientific prevention and control strategies.

A case of Sifrim-Hitz-Weiss syndrome(Sifrim-Hitz-Weiss syndrome,SIHIWES)is presented.The patient was a 35-year-old male with cryptorchidism,growth retardation,skeletal malformations,muscular atrophy,a wide forehead,special facial features like square face,small low-set and cup-shaped ears since birth.Whole-exon sequencing identified a heterozygous mutation(NM_001273:c.3047A>G(chr12-6701125)(p.K1016R))in CHD4 gene.The clinical significance of this mutation is currently unknown,and has not been previously reported.In light of the patient's symptoms,the case was diagnosed as Sifrim-Hitz-Weiss syndrome.This case represents the first instance of Sifrim-Hitz-Weiss syndrome in an adult patient in China.