Objective To elucidate the molecular mechanisms underlying the effects of Kanggan Mixture(KGM)on key targets in rats with acute lung injury,network pharmacology and in vivo micro-CT experiments were employed.Methods Network pharmacology was utilized to forecast the target genes and principal pathways involved in the intervention of KGM in acute lung injury(ALI).Lipopolysaccharide(LPS)-induced ALI rat models were utilized,and micro-computed tomography(micro-CT)was employed to evaluate the extent of lung injury in vivo.Experiments were conducted to verify the intervention mechanism of KGM on ALI rats.Results The findings revealed that 190 chemical constituents were identified from KGM,and 579 potential targets and 204 pathways associated with KGM's impact on ALI were predicted.The principal components of KGM,such as quercetin,luteolin,kaempferol,betulin,and lupenone,exhibit anti-viral,anti-inflammatory,and immunomodulatory properties by targeting TP53,AKT1,SRC,EP300,and STAT3,and modulating the FoxO signaling pathway,TNF signaling pathway,PI3K-Akt signaling pathway,and MAPK signaling pathway,demonstrating an influence on acute lung injury.Micro-CT results suggest that KGM can improve lung texture enhancement and lung injury in ALI rats,with an increase in end-expiratory lung volume(inspiratory phase-expiratory phase).The HE and W/D ratio results indicate that KGM can improve lung tissue injury and reduce the lung tissue wet/dry weight ratio(P<0.01).Blood cell analysis results show that the anti-inflammatory agent can decrease the WBC(white blood cell count)and N%(neutrophil percentage)in ALI rats'blood(P<0.01),and increase lymphocytes(P<0.05).Real-time quantitative PCR,WES,and immunohistochemistry results suggest that KGM can decrease the mRNA expression,protein distribution,and protein expression levels of TP53,AKT1,SRC,EP300,and STAT3 in lung tissue of ALI rats(P<0.05).Conclusion KGM has a certain intervention effect on acute lung injury,mainly achieved through the core targets STAT3,EP300,SRC,AKT1,and TP53.

Objective To explore the function of electroacupuncture(EA)on body mass,fasting blood glucose,heat pain threshold,and transient receptor potential vanilloid 4(TRPV4)in the dorsal root ganglia(DRG)of rats with diabetic neuropathic pain(DNP).Methods A DNP rat model was formed by intraperitoneally injecting the animals with STZ.From days 15 to 21,bilateral Zusanli and Kunlun points of the DNP rat model were treated with electroacupuncture once daily for 30 min.We then measured their body mass,fasting blood glucose,and heat pain threshold.The co-expression of TRPV4 and NeuN in the rat L4～L6 DRG was detected by immunofluorescence.The effects of the TRPV4 agonist GSK1016790A on body mass,fasting blood glucose,and the heat pain threshold of DNP rats treated with electroacupuncture were detected.Results After the 7th day,body mass was significantly decreased(P<0.01)and fasting glucose was significantly increased(P<0.01)in the model group compared with the normal group.After the 21st day,compared with the model group,heat pain threshold of the model+electroacupuncture group was significantly higher(P<0.01);the results of co-expression of TRPV4 and NeuN immunofluorescence on rat L4～L6 DRG showed that:the expression of positive cells in the model group was significantly higher(P<0.01)than that in the normal group,the co-expression of TRPV4 and NeuN positive cells in L4～L6 DRG of rats in the model+electroacupuncture group was significantly lower(P<0.01)than that in the model group.The TRPV4 agonist GSK1016790A can reverse the downregulation of thermal pain threshold induced by electroacupuncture in DNP rats(P<0.01).Conclusion Electroacupuncture alleviated the DNP induced by STZ,and its mechanism may involve the inhibition of TRPV4 protein expression in the DRG.

AIM:To investigate the efficacy and safety of TACE combined with lenvatinib and PD-1 inhitibors for hepatocellular carcinoma(HCC)with portal vein tumor thrombus(PVTT).METHO DS:HCC patients with PVTT who received TACE combined with lenvatinib and PD-1 inhitibors as first-line ther-apy in clinical practice were included in this study retrospectively.Therapeutic outcomes of this regi-men were calculated based on the target lesions evaluated using mRECIST criteria.Additionally,all the subjects were followed up regularly to obtain the prognostic outcomes.Safety profile observed during the combination therapy was collected and documented specifically.Log-rank test was used for exploratory analysis between prognosis and base-line characteristics,and Cox regression analysis was adopted for multivariate analysis.RESULTS:A total of 67 HCC patients with PVTT who received TACE combined with lenvatinib and PD-1 inhitibors were included in this study ultimately,4 patients achieved complete response,30 patients were par-tial response,25 patients were stable disease,5 pa-tients were disease progression and 3 patients were not available for the response outcomes.Therefore,the objective response rate(ORR)of this regimen was 50.7％and disease control rate(DCR)was 88.1％.Prognostic data suggested that the me-dian progression free survival(PFS)of the 67 HCC patients with PVTT was 9.3 months(95％CI:5.85-12.75),and the median overall survival(OS)was 24.4 months(95％CI:19.11-29.69).Safety profile highlighted that a total of 65 patients experienced adverse reactions regardless of grade when re-ceived TACE combined with lenvatinib and PD-1 in-hitibors(97.0％),among whom,a total of 34 pa-tients were deemed as grade ≥3 adverse reactions(50.7％).The most common adverse reactions were hypertension,fatigue,abnormal liver function,nau-sea and vomiting and diarrhea.CONCLUSION:TACE combined with lenvatinib and PD-1 inhitibors as first-line therapy for HCC with PVTT demonstrated encouraging efficacy and acceptable safety profile.

The risk of post-transfusion hepatitis(PTH)primarily stems from blood transfusion containing HBV-infected blood that is HBsAg-negative,specifically during the serological window period(WP)and occult HBV infection(OBI).OBI is a low viral replication form of HBV,making it a challenge in hepatitis B virus infection prevention and control,and a significant transmission source of post-transfusion hepatitis.Although nucleic acid testing(NAT)can reduce the occurrence of post-transfusion hepatitis to some extent,some OBI-infected individuals exist among blood donors,representing a potential risk of HBV transmission through blood.This article primarily summarizes an overview of OBI's concept,serological characteristics,genomic features,pathogenesis mechanisms,epidemiological characteristics,and advances in detection strategies,to provide theoretical basis for the collection,quality control and safe use of blood products for the OBI population.

Natural products (NPs) have historically been a fundamental source for drug discovery. Yet the complex nature of NPs presents substantial challenges in pinpointing bioactive constituents, and corresponding targets. In the present study, an innovative natural product virtual screening-interaction-phenotype (NP-VIP) strategy that integrates virtual screening, chemical proteomics, and metabolomics to identify and validate the bioactive targets of NPs. This approach reduces false positive results and enhances the efficiency of target identification. Salvia miltiorrhiza (SM), a herb with recognized therapeutic potential against ischemic stroke (IS), was used to illustrate the workflow. Utilizing virtual screening, chemical proteomics, and metabolomics, potential therapeutic targets for SM in the IS treatment were identified, totaling 29, 100, and 78, respectively. Further analysis via the NP-VIP strategy highlighted five high-confidence targets, including poly [ADP-ribose] polymerase 1 (PARP1), signal transducer and activator of transcription 3 (STAT3), amyloid precursor protein (APP), glutamate-ammonia ligase (GLUL), and glutamate decarboxylase 67 (GAD67). These targets were subsequently validated and found to play critical roles in the neuroprotective effects of SM. The study not only underscores the importance of SM in treating IS but also sets a precedent for NP research, proposing a comprehensive approach that could be adapted for broader pharmacological explorations.

Natural products(NPs)have historically been a fundamental source for drug discovery.Yet the complex nature of NPs presents substantial challenges in pinpointing bioactive constituents,and corresponding targets.In the present study,an innovative natural product virtual screening-interaction-phenotype(NP-VIP)strategy that integrates virtual screening,chemical proteomics,and metabolomics to identify and validate the bioactive targets of NPs.This approach reduces false positive results and enhances the ef-ficiency of target identification.Salvia miltiorrhiza(SM),a herb with recognized therapeutic potential against ischemic stroke(IS),was used to illustrate the workflow.Utilizing virtual screening,chemical proteomics,and metabolomics,potential therapeutic targets for SM in the IS treatment were identified,totaling 29,100,and 78,respectively.Further analysis via the NP-VIP strategy highlighted five high-confidence targets,including poly[ADP-ribose]polymerase 1(PARP1),signal transducer and activator of transcription 3(STAT3),amyloid precursor protein(APP),glutamate-ammonia ligase(GLUL),and glutamate decarboxylase 67(GAD67).These targets were subsequently validated and found to play critical roles in the neuroprotective effects of SM.The study not only underscores the importance of SM in treating IS but also sets a precedent for NP research,proposing a comprehensive approach that could be adapted for broader pharmacological explorations.

Objective To investigate the relationship between triple motif protein(TRIM)3,TRIM44 and clinicopathological parameters and prognosis in human papillomavirus(HPV)positive cervical cancer tissues.Methods The cancer tissues and adjacent normal cervical tissues(≥2 cm from the resection margin of the cancer)of 158 patients with HPV positive cervical cancer admitted to the hospital from February 2019 to Feb-ruary 2021 were selected,and the cancer tissues of 100 patients with HPV negative cervical cancer admitted to the hospital during the same period were selected.The positive expression rates of TRIM3 and TRIM44 in cancer tissues of HPV positive cervical cancer patients and their adjacent normal cervical tissues,and cancer tissues of HPV negative cervical cancer patients were detected and compared by immunohistochemistry.The relationship between the positive expression rate of TRIM3 and TRIM44 and the clinicopathological parame-ters of HPV positive cervical cancer patients was analyzed.The 3-year cumulative survival rate of patients with negative/positive TRIM3 expression and negative/positive TRIM44 expression were analyzed by Kaplan-Meier survival curve.The influencing factors of the prognosis of HPV positive cervical cancer patients were analyzed by COX regression model.Results Compared with adjacent normal cervical tissues and HPV nega-tive cervical cancer tissues,the positive expression rate of TRIM3 in HPV positive cervical cancer tissues was significantly decreased(P＜0.05),and the patients expression rate of TRIM44 was significantly increased(P＜0.05).Compared with the patients with FIGO stage Ⅰ A-Ⅰ B and no lymph node metastasis,the pa-tients with FIGO stage Ⅱ A and lymph node metastasis,the positive rate of TRIM3 expression decreased sig-nificantly(P＜0.05),while the positive rate of TRIM44 expression increased significantly(P＜0.05).A total of 3 patients were lost during the 3-year follow-up among 158 HPV positive cervical cancer patients,and 155 patients were finally followed up.Kplan-Meier survival curve showed that,the 3-year cumulative survival rate in TRIM3 negative expression group was significantly lower than that in TRIM3 positive expression group(P＜0.05).The 3-year cumulative survival rate in TRIM44 positive expression group was significantly lower than that in TRIM44 negative expression group(P＜0.05).COX regression analysis showed that lymph node metastasis,FIGO stage,negative expression of TRIM3 and positive expression of TRIM44 were risk factors for the prognosis of HPV positive cervical cancer patients(P＜0.05).Conclusion The expression of TRIM3 is low and the expression of TRIM44 is high in HPV positive cervical cancer tissues,which is relate to lymph node metastasis,FIGO stage and decrease 3-year cumulative survival rate.

Objective:To explore the mechanism of Shiwei Chaihu Shugan Powder in the treatment of breast hyperplasia using network pharmacology; To verify the mechanism of Shiwei Chaihu Shugan Powder in the treatment of breast hyperplasia through animal experiments.Methods:The active components and potential targets of Shiwei Chaihu Shugan Powder were searched in TCMSP and Uniprot databases. Breast hyperplasia genes were searched in GeneCards and OMIM databases. The intersection targets were obtained by online tool Venny, and the "drug-component-target" network was constructed by Cytoscape 3.8.2 software. The protein interaction (PPI) network was constructed using the String platform, and GO function and KEGG pathway enrichment analysis were performed using the DAVID annotation database. Molecular docking was performed using PDB, PubChem database, PyMOL 2.1 and AutoDockvina 1.2.5 software to predict the biological mechanism of Shiwei Chaihu Shugan Powder in the treatment of breast hyperplasia. Rats were divided into blank group, model group, tamoxifen group and Shiwei Chaihu Shugan Powder low-, medium- and high-dosage groups according to the random number table method, with 6 rats in each group. Except for the blank group, the other groups were prepared with the modified estrogen-progesterone-induced rat mammary hyperplasia model. Shiwei Chaihu Shugan Powder low-, medium- and high-dosage groups were intragastrically administered with Shiwei Chaihu Shugan Powder solution at 7.425 g/kg, 14.850 g/kg, and 29.700 g/kg respectively, while the tamoxifen group was intragastrically administered with 2.1 mg/kg tamoxifen. The blank group and the model group were intragastrically administered with the same volume of drinking water, once a day, for consecutive 28 d. The thickness of the mammary gland was measured by small animal ultrasound. The height and width of the nipples were measured by vernier calipers. The levels of serum E2 and P were detected by ELISA. The morphology of mammary tissue was observed by HE staining. The expressions of ERα, ERβ, SRC-1 and CBP/p300 proteins were detected by Western blot.Results:A total of 92 active components and 274 disease-drug intersection targets were screened out. GO functional enrichment analysis showed that Shiwei Chaihu Shugan Powder was closely related to positive regulation of gene expression, positive regulation of RNA polymerase Ⅱ promoter transcription, signal transduction, negative regulation of apoptosis process, response to heterogeneous stimulation, and regulation of hormone levels. KEGG enrichment analysis showed that the core targets might be related to NF-κB signaling pathway, MAPK signaling pathway, AGE-RAGE signaling pathway, PI3K/Akt signaling pathway, and regulating hormone levels. Molecular docking results showed that the core components had a good binding energy with the core target and a stable conformation. Compared with the model group, the thickness of the mammary gland in the tamoxifen group and Shiwei Chaihu Shugan Powder low-, medium- and high-dosage groups decreased ( P<0.01), the serum P level increased ( P<0.05), the expressions of ERα, SRC-1, and CBP/p300 proteins decreased ( P<0.01), and the expression of ERβ protein increased ( P<0.01); the height of the nipples in the Shiwei Chaihu Shugan Powder medium- and high-dosage groups and the tamoxifen group decreased ( P<0.01), and the serum E2 level increased ( P<0.05). Conclusion:Shiwei Chaihu Shugan Powder may play a role in the treatment of breast hyperplasia by regulating the levels of estrogen and related proteins.

Objective:To explore the clinicopathologic features of early-onset pancreatic cancer (EOPC) and its correlation with dyslipidemia and prognostic analysis.Methods:This is a retrospective cohort study. Clinical and pathological data of 455 patients with pancreatic cancer who underwent radical surgery from January 2013 to September 2020 in the Department of Pancreatic Surgery, Qilu Hospital, Shandong University were retrospectively collected. According to the onset age≤50 years, the patients were divided into EOPC group(67 cases) and later-onset pancreatic cancer (LOPC) group(388 cases). There were 48 males and 19 females in the EOPC group, aged (44.4±5.7) years(range: 28.0 to 50.0 years); and 230 males and 158 females in the LOPC group, aged (63.0±7.2)years (range: 51.0 to 86.0 years). EOPC was divided into two groups according to the blood lipid status: dyslipidemia (50 cases) and normal (17 cases). General information, blood lipid data, clinicopathological parameters and follow-up information were collected. χ2 test, Mann-Whitney U test and Logistic regression analysis were used to evaluate the difference or correlation between groups, and Cox regression analysis and Kaplan-Meier survival curve were used to analyze the impact of EOPC and dyslipidemia on the prognosis. Propensity score matching was used to match two groups of patients in a 1∶1 ratio using nearest neighbor matching, with a caliper set at 0.05. Results:Compared with LOPC group, EOPC group with a higher proportion of patients with body mass index ≥24 kg/m 2 (55.8%(24/43) vs. 38.7%(113/292), χ2=4.542 ,P=0.033), dyslipidemia(74.6%(50/67) vs. 57.7%(224/388), χ2=6.808, P=0.009), pancreatic head cancer (73.1% (49/67) vs. 60.0%(231/385), χ2=4.176, P=0.041) and a lower proportion of patients with type 2 diabetes (9.0%(6/67) vs. 24.2%(94/388), χ2=7.771, P=0.005) and hypertension (9.0%(6/67) vs. 33.0%(128/388), χ2=15.885, P<0.01). Compared the proportion of dyslipidemia in the two groups,there was a higher proportion of high density lipoprotein cholesterol(HDL-C) abnormality in the EOPC group (65.7%(44/67) vs. 42.8%(166/388), χ2=12.044, P<0.01), whereas there was no significant difference in other lipid indices. Kaplan-Meier survival curve analysis of dyslipidemia did not have a significant effect on the prognosis of EOPC patients ( P=0.430). The results of further Logistic regression analysis showed that gender( OR=6.445 (95% CI: 1.692 to 24.548), P=0.006) and tumor location ( OR=5.352 (95% CI: 1.374 to 20.846), P=0.016) were independent related factors with serum lipid level in patients with EOPC. Conclusions:Compared with LOPC, EOPC is more likely to be combined with obesity and HDL-C abnormalities, and the proportion of pancreatic head cancer is also higher, but there is no significant difference in prognosis between the two groups. In the EOPC patients, serum lipid level is associated with gender and tumor site, but has no effect on survival.