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Objective To observe the clinical efficacy of compound Wufengcao liquid combined with negative pressure wound therapy with instillation(NPWTi)for the treatment of stage Ⅲ-Ⅳ pressure injury(PI),and to preliminarily explore its action mechanism.Methods(1)Clinical research:from January 2019 to October 2022,60 PI patients who were admitted to the Scrofula Department and Wound Care Clinic at Nanjing Municipal Hospital of Traditional Chinese and Western Medicine were randomly divided into normal saline NPWTi group and compound Wufengcao liquid NPWTi group,with 30 cases in each group.Both groups underwent NPWTi under the premise of systemic basic treatment,before treatment,after removing the negative pressure device in the 1st,2nd and 3rd weeks of treatment,the pressure ulcer scale for healing(PUSH)score,the wound bacterial culture detection rate and the wound healing time were counted,and the vascular endothelial growth factor(VEGF)content of wound tissue was detected by ELISA method.(2)Animal experiments:24 SD rats were randomly divided into blank group,model group,normal saline NPWTi group and compound Wufengcao liquid NPWTi group,6 rats in each group.PI rat model was established by local tissue ischemia/reperfusion injury method,and the negative pressure device was removed at the end of each day of treatment.Before treatment and 3,7 and 10 days after treatment,the wound morphology of each group of rats was observed,the wound histopathology was observed by HE staining,the CD34 positive cells rate of wound tissue was detected by immunohistochemistry,and the expressions of p38 mitogen-activated protein kinase(p38 MAPK),nuclear factor-κB p65(NF-κB p65),inducible nitric oxide synthase(iNOS),tumor necrosis factor-α(TNF-α),arginase-1(Arg-1)and transforming growth factor-β(TGF-β)in rat blood and wound tissue were detected by ELISA and RT-qPCR.Results(1)Clinical research:Both groups could effectively reduce the PUSH score and the wound bacterial culture detection rate,shorten the wound healing time,and promote the expression of VEGF in wound tissue,the compound Wufengcao liquid NPWTi group was better than the normal saline NPWTi group(P<0.05).(2)Animal experiments:Compared with blank group,the rats in the model group showed obvious wound inflammatory response and tissue damage,and the CD34 positive cells rate,blood and wound tissue p38 MAPK,NF-κB p65,iNOS and TNF-α levels were significantly increased,Arg-1 and TGF-β level was significantly reduced(P<0.05);Compared with model group,after 7 days of treatment,the normal saline NPWTi group and the compound Wufengcao liquid NPWTi group significantly decreased the wound morphology score,the histopathological morphology was significantly improved,the CD34 positive cells rate was significantly increased(P<0.05),the levels of blood and wound tissue p38 MAPK,NF-κB p65,iNOS,and TNF-α were significantly reduced,and the levels of Arg-1 and TGF-β were significantly increased(P<0.05),and the compound Wufengcao liquid NPWTi group was better than that of the normal saline NPWTi group(P<0.05).Conclusion Compound Wufengcao liquid combined with NPWTi can effectively promote the healing of PI wounds,and its mechanism of action may be by inhibiting the activation and expression of p38 MAPK/NF-κB signaling pathway,thereby regulating the polarization balance of M1/M2 macrophages.

Background and purpose:According to current consensus,adverse high-risk pathological features are only associated with adjuvant therapy for stage Ⅱ colorectal cancer(CRC).As important prognostic factors,we further explored the possibility of identifying patients with potential recurrence and poor prognosis based on these incorporating high-risk pathological features.Methods:This is a cohort study.A retrospective analysis was conducted on clinical data of CRC patients who underwent surgical treatment at the Second Department of Colorectal Surgery,Fudan University Affiliated Shanghai Cancer Center from 2008 to 2018.This study was approved by the Ethics Committee of the Fudan University Shanghai Cancer Center(approval No.:050432-4-2108*),and the study complies with the Declaration of Helsinki.A total of 9875 patients were enrolled,including 5859 males and 4016 females,aged[M(IQR)]60(16)years(range:16 to 94).Median follow-up time was 1779.0 days[95%CI:1750.1-1807.9].We used the Kaplan-Meier method to plot survival curves for different groups.Cox multivariate analysis was used to identify independent risk factors for 5-year overall survival(OS),disease-free survival(DFS)and recurrence-free survival(RFS).Finally,a column chart model was constructed to evaluate and stratify patient prognosis.The Strengthening the Reporting of Observational Studies in Epidemiology(STROBE)checklist was followed for this cohort study.Results:According to the number of incorporating high-risk pathological features,patients were divided into five groups:Hr_0 group(0 incorporating high-risk pathological feature),Hr_1 group(1 incorporating high-risk pathological feature),Hr_2 group(2 incorporating high-risk pathological features),Hr_3 group(3 incorporating high-risk pathological features),and Hr_4 group(4 or more incorporating high-risk pathological features).The Kaplan-Meier survival curve results indicated significant differences in OS,DFS and RFS among different groups(all P<0.001).Subgroup analysis was conducted on stage Ⅱ colorectal cancer,and the survival curves of OS,DFS and RFS in different Hr groups overlapped with each other.Compared to the overall population,the survival differences in different groups were significantly reduced,indicating that stage Ⅱ colon cancer patients with incorporating high-risk pathological features may benefit from adjuvant chemotherapy.The independent prognostic factors for RFS included age,pT stage,pN stage and Hr group.The survival curves of OS,DFS and RFS indicated that the prognosis of Hr_4 group was significantly worse than that of stage Ⅲc patients;5.2%and 14.1%of stage Ⅰ and Ⅱ patients had two or more incorporating high-risk pathological features(Hr group≥2),respectively.Finally,a column chart model was constructed by incorporating the independent prognostic risk factors for CRC mentioned above.The calibration curve showed a good consistency between the actual observations and the predictions made by the nomogram,and the decision curve analysis(DCA)indicated that the model constructed in this study had good efficacy in stratifying recurrence.Conclusion:The number of incorporating high-risk pathological features is an independent prognostic factor for RFS in patients with stage Ⅰ-ⅢCRC.Combining it as a multiclass variable with age,pT and pN stage has good prognostic stratification and recurrence stratification efficacy,which is expected to guide clinical treatment.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Demyelination of the central nervous system often occurs in neurodegenerative diseases， such as multiple sclerosis （MS）. The myelin sheath， a layer of myelin membrane wrapping the axon， plays a role in the rapid conduction and metabolic coupling of impulses for neurons. The exposure of the axon will lead to axonal degeneratio， and further neuronal degeneration， which is the main cause of dysfunction and even disability in patients with demyelinating neurodegenerative diseases. In addition to the demyelination of mature myelin sheath， remyelination disorder is also one of the major reasons leading to the development of the diseases. The myelin sheath is composed of oligodendrocytes （OLs） derived from oligodendrocyte progenitor cells （OPCs） which are differentiated from neural stem cells （NSCs）. The process of myelin regeneration， i.e.， remyelination， is the differentiation of NSCs into OLs. Recent studies have shown that this process is regulated by a variety of genes. MicroRNAs， as important regulators of neurodegenerative diseases， form a complex regulatory network in the process of myelin regeneration. This review summarizes the main molecular pathways of myelin regeneration and microRNAs involved in this process and classifies the mechanisms and targets. This review is expected to provide a theoretical reference for the future research on the treatment of demyelinating diseases by targeting the regulation of microRNAs.

BACKGROUND:silencing information regulatory 1(SIRT1)regulates the function of related proteins in chondrocytes in a deacetylated manner and participates in chondrocyte proliferation and differentiation,thereby promoting cartilage defect repair. OBJECTIVE:To screen for signaling pathways with unclear action status after SIRT1 gene knockdown in chondrocytes,as well as diseases or functions that produce changes using high-throughput technology. METHODS:ATDC5 chondrocytes from mice in logarithmic growth phase were divided into two groups:the cells were transfected with SIRT1 gene knockdown negative control lentivirus in control group and SIRT1 gene knockdown lentivirus in experimental group.GeneChip? Mouse Genome 430 2.0 Array was used to detect the mRNA expression at 72 hours after transfection.Applied bioinformatics technology was also used to screen for unclear activation or inhibition signaling pathways and their related factors.Moreover,enrichment of disease or function modules was analyzed. RESULTS AND CONCLUSION:After knocking down the SIRT1 gene,there were 245 signaling pathways with unclear activation or inhibition status in the mouse ATDC5 chondrocytes.According to the ranking of-Log(P-value),we reported the factors in the top 20 signaling pathways with unclear activation or inhibition status,including IGFBP4,TGFBR1,CTGF,COL4A5,LHX2,IL1RL1,and KLF6.According to the ranking of-Log(P-value),there were significant changes in 14 disease or function modules,including cellular growth and proliferation,organism survival,cell death and survival.According to the number of differentially expressed genes,there were significant changes in three disease or function modules,including organismal injury and abnormalities,cancer,and cell death and survival.According to the comprehensive ranking of-Log(P-value)and the number of differentially expressed genes,the disease or function module related to intrinsic immune response was significantly activated.

Objective To observe the value of apparent diffusion coefficient(ADC)for evaluating short-term efficacy of TACE for treating colorectal cancer liver metastases(CRLM).Methods Data of 60 liver metastases in 28 CRLM patients who underwent TACE were retrospectively analyzed.Based on MRI after the first TACE,according to the response evaluation criteria of solid tumors,the liver metastases were divided into response group(n=38)and non-response group(n=22).ADC parameters obtained with diffusion weighted imaging(DWI)before and after TACE,including ADC before TACE(ADCpre),after the first TACE(ADCpost1)and after the second TACE(ADCpost2)were compared between groups,while ADC change value(ΔADC)and the percentage of ΔADC were calculated.The maximum diameter of the target foci were measured,and the correlation between ΔADCpost1 and the change of the maximum diameter of target foci were analyzed.Receiver operating characteristic curve was drawn,the area under the curve(AUC)was calculated to observe the efficacy of ΔADCpost1 for evaluating short-term efficacy of TACE for CRLM.Results No significant difference of ADCpre was found between groups(P=0.484).After the first TACE,ADCpost1,ΔADCpost1 and percentage of ΔADCpost1 in response group were all higher than those in non-response group(all P＜0.05).After the second TACE,no significant difference of ADCpost2,ΔADCpost2 nor percentage of ΔADCpost2 was found between groups(all P＞0.05).The maximum diameter change of the target foci after the first TACE was(-0.48±0.93)cm,which was negatively correlated with ΔADCpost1(rs=-0.347,P=0.007).AUC of ΔADCpost1 for evaluating short-term efficacy of TACE for CRLM was 0.717.Conclusion ADC had good efficacy for evaluating short-term efficacy of TACE for treating CRLM.

ObjectiveThis study explores the efficacy and pharmacological mechanism of Wujiwan in rats with inflammatory bowel disease （IBD） from the perspectives of the peroxisome proliferator-activated receptor γ （PPARγ） signaling pathway and T-cell immunity， providing reference for the treatment of IBD with traditional Chinese medicine. MethodThe study involved administering 2，4，6-trinitrobenzenesulfonic acid （TNBS） enemas to 35 rats to induce acute IBD. After 24 hours， the animals were divided into the following groups： normal group， model group， Wujiwan treatment group， and positive drug control group. Each group received gastric gavage for 8 consecutive days before the rats were dissected to compare the disease activity index （DAI） of the rat colon tissue， the colon mucosal damage index （CMDI）， and the spleen index. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin-1β （IL-1β）， interleukin-10 （IL-10）， and tumor necrosis factor-α （TNF-α） in the serum. Quantitative real-time polymerase chain reaction （Real-time PCR） was used to determine the mRNA expression levels of T-bet （T-box expressed in T cells） and Gata3 （Gata-binding protein-3） in the colon tissue. Western blot analysis was conducted to detect the protein expression levels of PPARγ， T-bet， and nuclear factor-κB p65 （NF-κB p65） in the rat colon. ResultThe rat model of IBD was successfully established. Compared with the model group， the Wujiwan treatment group showed reduced DAI， CMDI， and spleen index， decreased content of TNF-α in the serum（P<0.01）， significantly increased content of IL-10（P<0.01）， and elevated mRNA content of T-bet and Gata3（P<0.05） in the colon tissue. The expression of PPARγ protein was augmented（P<0.05）， and the expression of T-bet and NF-κB p65 protein was decreased（P<0.05，P<0.01）. ConclusionWujiwan activates or upregulates PPARγ expression in IBD rats to inhibit the generation of pro-inflammatory factors， participates in the inflammatory immune process， and alleviates inflammatory reactions. Its mechanism may involve regulating the NF-κB pathway through PPARγ， enhancing Th2 cell transcription expression， and reducing Th1 cell transcription.

Traditional Chinese medicine （TCM） has a long history of application in China and has consistently played a vital role in treating diseases and saving lives. TCM prescriptions （compounds） constitute the primary form of clinical TCM treatment and significantly differ from western medicine （chemicals） due to the diverse composition and chemical constituents of TCM （compounds）. Nevertheless， the potential multi-component， multi-target， and multi-pathway action characteristics of TCM prescriptions also demonstrate their possible （complementary） therapeutic advantages when compared with single-component chemical drugs. Therefore， driven by the development of modern science and technology and the demands of the modernization and internationalization of TCM， modern theories regarding the complexity of TCM prescription effects have been continuously proposed： Different from the abstract language of traditional prescription theory， the modern TCM prescription theory is more inclined to illustrate the connotation of prescription compatibility concretely and vividly from an experimental and scientific perspective. In this paper， new theories on the complexity of TCM prescriptions proposed in recent years are summarized to provide research references and ideas for the greater role of TCM prescriptions and a better scientific understanding.

Objective To explore whether 5/6 nephrectomy can establish a rat model of chronic renal failure-in-duced sarcopenia.Methods The rats were randomly divided into control group,sham operation group and 5/6 ne-phrectomy model group.Chronic renal failure and sarcopenia were further verified.Results Compared with the sham group:① In the model group,the qualitative analysis of urinary protein,serum creatinine,blood urea nitrogen and serum uric acid levels were increased(P＜0.05);② In the model group,the degree of renal fibrosis and the rate of apoptosis were high(P＜0.05);③ In the model group,the muscle strength and function declined(P＜0.05);④ In the model group,the degree of muscle fibrosis was obvious(P＜0.05).Conclusion Through the 5/6 nephrectomy method,an animal model of chronic renal failure-induced sarcopenia can be established,which provides an experimental basis for further prevention and treatment of this disease.