Objective:To explore the mechanism of miR-30e-5p inhibiting the invasion and migration of hepatoma cells by targeting phosphoinositide-3-kinase catalytic delta polypeptide(PIK3CD)-mediated phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of the rapamycin(mTOR)signaling pathway.Methods:HepG2 cells were divided into control group,miR-30e-5p mimics group,PIK3CD knockdown group,negative control group,and miR-30e-5p mimics+PIK3CD overexpression group by transfecting the corresponding plasmids,the expression of miR-30e-5p,PIK3CD and PI3K/AKT/mTOR signaling pathway was detected by qRT-PCR and Western blot;the proliferation rate of Hep G2 cells in each group was detected by CCK-8 method;cell migration and invasion were measured by cell scratch test and Transwell test;the expression of matrix metalloproteinase(MMP)2,MMP9,E-cadherin,N-cadherin,Vimentin in Hep G2 cells of each group were detected by Western blot.The targeting regulation of miR-30e-5p on PIK3CD in Hep G2 cells was detected by double luciferase report assay.Results:Compared with the control group,the proliferation rate,migration rate,invasion number,the expression of N-cadherin,MMP2 and MMP9 proteins,the expression of PIK3CD protein and mRNA,p-P13K/PI3K,p-AKT/AKT,and p-mTOR/mTOR in the miR-30e-5p mimics group and PIK3CD knockdown group were lower(P＜0.05),the expression of E-cadherin protein was higher(P＜0.05).Overexpression of PIK3CD attenuates the inhibitory effects of miR-30e-5p mimics on proliferation,migration and invasion of hepatocellular carcinoma cells and elevates the expression of PI3K/AKT/mTOR pathway-related proteins;miR-30e-5p targets down-regulation of PIK3CD expression.Conclusion:Up-regulation of miR-30e-5p can prevent PI3K/AKT/mTOR signal activation by decreasing the expression of PIK3CD,thereby inhibiting the proliferation,migration and invasion of hepatocellular carcinoma cells.

Improving the prognosis of patients with colorectal cancer (CRC) holds important clinical and social significance. Immunotherapy is an emerging therapy approach for cancers, which mainly include immune checkpoint inhibitors (ICI), immune vaccine and adoptive cell therapy. ICI have achieved good clinical translation in treatment of metastatic CRC with deficient DNA mismatch repair/high microsatellite instability (dMMR/MSI-H) status. The application of some ICI, such as PD-1 inhibitors pembrolizumab and nivolumab, in this type patients have been approved by the FDA. In addition,numerous positive results are acquired in clinical trials of neoadjuvant therapy for resectable dMMR/MSI-H CRC. These results greatly bolstered the exploration enthusiasm of CRC immunotherapy. However, the proficient DNA mismatch repair/microsatellite stability (pMMR/MSS) CRC, which accounting for the vast majority in related patients, hardly benefit from ICI therapy. Various combination strategies, mainly including ICI combined with traditional chemotherapy, radiotherapy, or targeted therapy, have been attempted to alter the “cold tumors” microenvironment characteristics of pMMR/MSS CRC in clinical trials, whereas no breakthrough results were reached. Theoretically, tumor vaccines are ideal choice to break down the barrier of insufficient immune infiltration in solid tumors. However, the outcomes of related clinical trials in CRC patents are not satisfactory, and partially due to the weak specificity of the applied tumor-associated antigens. Clinical studies of adoptive cell therapy in CRC are also actively underway. The favorable efficacy of tumor-infiltrating lymphocyte, cytokine-induced killer (CIK) and dendritic cell-CIK in CRC have been confirmed, while the CAR-T and TCR-T therapies need more exploration based on screening more suitable antigens and optimizing engineering design. In this review, we made a summary based on the mainline of clinical studies related to diverse immunotherapies, so as to clarify the progress of CRC immunotherapy and provide bases for exploration of better treatment options.

Objective To explore the expression of junctophilin 2(JP2)and fibroblast growth factor 23(FGF23)in a rabbit model of atrial fibrillation mediated-cardiomyopathy(AMC).Methods Rabbit models of atrial fibrillation(AF)were developed through rapid atrial stimulation and then divided into three groups:control group(pacemak-ers implanted without pacing,n=6),AF group(pacing with ejection fraction decrease＜10％,n=5),and AMC group(pacing with ejection fraction decrease≥10％,n=6).Echocardiography was performed to detect left ventric-ular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD)and left ventricular ejection fraction(LVEF).JP2 and FGF23 were detected by ELISA method.Western blot and RT-qPCR were conducted to detect protein and mRNA expression of JP2 and FGF23.Results Left atrial diameter,right atrial diameter and right ventricular diameter increased and LVEF decreased in the AMC group as compared with the control group.AMC group had lower LVEF and larger aorta and right ventricle diameter.Compared with the control group,the ex-pression of FGF23(P＜0.001)and JP2(P＜0.01)in left atrial cardiomyocytes was significantly increased in the AF group,while the expression of JP2 was decreased in the AMC group(P＜0.001).AMC group had lower expression of JP2 and FGF23 compared with AF group.Compared to the control group,plasma concentration of JP2 and FGF23 increased in the AF group and FGF23 plasma concentration increased in the AMC group.Plasma concentration of FGF23 and JP2 was lower in AMC group than that in AF group.Conclusions FGF23 expression increased and JP2 expression decreased as found in the rabbit AMC model.

Objective:To evaluate the effect of statins combined with PCSK9 inhibitors on coronary artery atherosclerotic plaque, as well as to verify the lipid-lowering effect of the combined therapy.Methods:A computerized search of PubMed, Embase, Web of Science, Cochrane Library, Wanfang, and CNKI databases was conducted to retrieve published literature from inception to December 20, 2022. The English search terms utilized included "PCSK9 inhibitors," "Alirocumab," "Evolocumab," "plaque," "IVUS," and "OCT." The corresponding Chinese search terms were "PCSK9 inhibitors," "plateau," "intravascular ultrasound," and "optical coherence tomography." The literature that examined the effect of statins alone or in combination with PCSK9 inhibitors on coronary atherosclerotic plaques using intravascular ultrasound or optical coherence tomography was identified. The collected data were subsequently processed using Review Manager (Revman) version 5.4.Results:In the final analysis, nine studies involving 1912 patients were included. The analysis results revealed that compared with statins alone, statins combined with PCSK9 inhibitors significantly reduced the percentage of atherosclerotic volume ( MD: -2.08 mm 3, 95% CI: -2.94 to -1.23 mm 3, P < 0.001), accelerated the regression of atherosclerotic volume ( MD: -1.13 mm 3, 95% CI: -1.49 to -0.77 mm 3, P < 0.001), slightly, but not significantly, reduced the overall atherosclerotic volume ( MD: -6.42 mm 3, 95% CI: -14.34-1.51 mm 3, P = 0.110). Nevertheless, the combined therapy contributed to a significant reduction in atherosclerotic volume ( MD: -5.16 mm 3, 95% CI: -7.09 to -3.23 mm 3, P < 0.001) and significantly increased the fiber cap thickness of thin cap plaques ( MD: 8.46 μm, 95% CI: 5.13-11.79 μm, P < 0.001). Additionally, this combined therapy significantly lowered blood lipid levels. Conclusion:The combination of statins and PCSK9 inhibitors can significantly improve the characteristics and phenotype of atherosclerotic plaques and significantly reduce blood lipid levels. For patients with high cardiovascular risk, it is recommended to initiate treatment with statins combined with PCSK9 inhibitors as soon as possible and maintain it for a long time to ensure more benefits.

Objective To investigate the effectiveness and safety of endoscopic mucosal resection with precutting(EMR-P)for the treatment of rectal neuroendocrine neoplasm(RNEN)smaller than 1 cm in diameter.Methods Clinical data of 177 patients with RNEN smaller than 1 cm in diameter from December 2016 to December 2021 were retrospectively analyzed.According to different treatment protocols,177 patients with RNEN were divided into endoscopic mucosal resection(EMR)group(n = 46),EMR-P group(n = 40)and endoscopic submucosal dissection(ESD)group(n = 91).The en bloc resection rate,complete resection rate,operation time,postoperative hospitalization time and incidence of operative complications among the three groups were compared.Results The complete resection rate in the EMR-P group(95.0%)and ESD group(97.8%)were significantly higher than that in the EMR group(87.0%)(P<0.05);The operation time in the EMR-P group(9.86±2.23)min was longer than that in the EMR group(4.12±0.88)min,EMR-P group and EMR group were shorter than that in the ESD group(19.55±3.67)min,the difference was statistically significant(P<0.05);Postoperative hospitalization time in the EMR group was(2.45±0.29)d and EMR-P group was(2.43±0.23)d,which were shorter than that in the ESD group(3.30±0.32)d,and the difference was statistically significant(P<0.05).There were no significant difference in the rates of en bloc resection and operative complications among the three groups(P>0.05).Conclusion EMR-P for the treatment of RNEN<1 cm in diameter has the advantages,such as simple operation,short operation time and hospitalization time,high histological complete resection rate and low complication rate,which is worthy of clinical application.

We aimed to identify the infectious source of a case of melioidosis,to provide evidence for the prevention and control of melioidosis in Shanxi Province,China.The patient developed repeated fever,fatigue,diarrhea,and other symptoms after being caught in the rain while traveling in Hainan Province.The blood culture was positive,and the bacterial strain was i-dentified as Burkholderia thayensis and sent to the provincial Center for Disease Control and Prevention for further evaluation.MALDI-TOF MS and biochemical identification were used to identify the strain,whole genome sequencing was performed after nucleic acid extraction,MLST type and drug-resistance genes were analyzed,and a phylogenetic tree was constructed.The iso-lated strain was identified as Burkholderia pseudomallei by MALDI-TOF MS and biochemistry,and the MLST type was 366.The whole gene sequencing analysis indicated a close evolutionary relationship with the three isolates in Hainan Province,with high homology.This case of melioidosis was indeed imported from Hainan Province,according to molecular tracing analysis and epidemiological investigation,thus suggesting that medical institutions and disease control departments should strengthen understanding of melioidosis,and improve the diagnosis and treatment ability.

Objective To systematically evaluate the value of optical coherence tomography angiogra-phy (OCTA) for detecting the vessel density (VD) changes after open-angle glaucoma (OAG) surgery.Meth-ods The studies on OCTA for detecting the VD changes after OAG surgery were searched in the CNKI,WanFang,VIP,SinoMed,PubMed,Embase and Web of Science databases from the database establishment to May 2024.Literature screening,data extraction and risk of bias assessment of included studies were conducted independently by two reviewers.Descriptive analysis was adopoted for the systematic evaluation,the meta a-nalysis was conducted by using the R software and mean difference (MD) and its 95％CI were calculated.Re-sults A total of 13 studies were included,involving 472 patients with 500 tested eyes.The results of meta-a-nalysis showed that compared with pre-surgery,VD around the optic nerve head (ONH) and in nasal superi-or,temporal inferior,temporal superior,superior temporal and superior nasal regions at postoperative 6 months were significantly decreased.VD in the perimacular,perimacular superior hemisphere,permacular su-perior hemisphere,perimacular superior and permacular superior regions at postoperative 6 months were sig-nificantly increased.Conclusion OCTA could effectively detect the postoperative VD changes in the patients with OAG and predict postoperative visual function changes in glaucoma,and could serve as an effective test means for assessing the clinical treatment effect of the patients with OAG.

Objective Recombinase-aided polymerase chain reaction(RAP)is a sensitive,single-tube,two-stage nucleic acid amplification method.This study aimed to develop an assay that can be used for the early diagnosis of three types of bacteremia caused by Staphylococcus aureus(SA),Pseudomonas aeruginosa(PA),and Acinetobacter baumannii(AB)in the bloodstream based on recombinant human mannan-binding lectin protein(M1 protein)-conjugated magnetic bead(M1 bead)enrichment of pathogens combined with RAP. Methods Recombinant plasmids were used to evaluate the assay sensitivity.Common blood influenza bacteria were used for the specific detection.Simulated and clinical plasma samples were enriched with M1 beads and then subjected to multiple recombinase-aided PCR(M-RAP)and quantitative PCR(qPCR)assays.Kappa analysis was used to evaluate the consistency between the two assays. Results The M-RAP method had sensitivity rates of 1,10,and 1 copies/μL for the detection of SA,PA,and AB plasmids,respectively,without cross-reaction to other bacterial species.The M-RAP assay obtained results for<10 CFU/mL pathogens in the blood within 4 h,with higher sensitivity than qPCR.M-RAP and qPCR for SA,PA,and AB yielded Kappa values of 0.839,0.815,and 0.856,respectively(P<0.05). Conclusion An M-RAP assay for SA,PA,and AB in blood samples utilizing M1 bead enrichment has been developed and can be potentially used for the early detection of bacteremia.

Objective:To investigate the postoperative renal function and oncologic outcomes of cystic renal cell carcinoma with partial nephrectomy,and to compared the single-center data on surgical out-comes with the Surveillance,Epidemiology,and End Results(SEER)database.Methods:This was a retrospective study that included the patients with cystic renal cell carcinoma who underwent partial ne-phrectomy in the Department of Urology,Peking University Third Hospital(PUTH)from 2010 to 2023.The clinical data and depicting baseline characteristics were collected.Renal dynamic imaging and the Chinese Coefficients for Chronic Kidney Disease Epidemiology Collaboration(C-CKD-EPI)formulae were used to calculate the estimated glomerular filtration rate(eGFR).The renal function curves over time were then plotted,and the patients were followed-up to record their survival status.Cases of cystic renal cell carcinoma in the SEER database between 2000 and 2020 were included,propensity score matching(PSM)was performed to balance the differences between SEER cohort and PUTH cohort,and the cancer-specific survival(CSS)curves for both groups were plotted and statistical differences were calcu-lated by the Kaplan-Meier method.Results:A total of 38 and 385 patients were included in the PUTH cohort and SEER cohort,respectively,and 31 and 72 patients were screened in each cohort after PSM.Of the baseline characteristics,only tumor size(P=0.042)was found to differ statistically between the two groups.There was no statistically significant difference between the two cohorts in terms of CSS after PSM(P=0.556).The median follow-up time in the SEER cohort was 112.5(65,152)months and a 10-year survival rate of 97.2％,while the PUTH cohort had a median follow-up of 57.0(20,1 172)months and a 10-year survival rate of 100.0％.There was no statistically significant difference between eGFR determined by preoperative renal dynamic imaging and the results of the C-CKD-EPI formulae based on creatinine estimation(P=0.073).There was a statistically significant difference in eGFR among the preoperative,short-term postoperative,and long-term postoperative(P＜0.001),which was characterized by the presence of a decline in renal function in the short-term postoperative period and the recovery of renal function in the long-term period.Conclusion:Partial nephrectomy for cystic renal cell carcinoma is safe and feasible with favorable renal function and oncologic outcomes.

Objective To investigate the clinical efficacy of Xuanfei Yipi Formula,a prescription derived from modified Jianpi Pill recorded in Yi Fang Ji Jie(A Collection of Prescriptions with Expositions),in treating senile sarcopenia with spleen-stomach weakness type,and to observe its effect on chronic low-grade inflammation of the patients.Methods Seventy cases of senile sarcopenia patients of spleen-stomach weakness type were randomly divided into an observation group and a control group,with 35 cases in each group.The control group was given exercise and nutritional guidance,while the observation group was treated with Xuanfei Yipi Formula orally on the basis of the control group,and the intervention time of both groups was eight weeks.The changes of traditional Chinese medicine(TCM)syndrome scores,appendicular skeletal muscle mass index(ASMI),grip strength,6-meter walking pace,and the serum levels of C-reactive protein(CRP),interleukin 6(IL-6),tumor necrosis factor α(TNF-α)in the two groups before and after treatment were observed.After treatment,the clinical efficacy and safety of the patients in the two groups were evaluated.Results(1)After eight weeks of treatment,the total effective rate in the observation group was 94.29%(33/35),and that in the control group was 77.14%(27/35),the intergroup comparison(by chi-square test)showed that the efficacy of the observation group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the TCM syndrome scores in the two groups were significantly lower than those before treatment(P＜0.05),and the decrease of TCM syndrome score in the observation group was more obviously than that in the control group(P＜0.01).(3)After eight weeks of treatment,the ASMI,grip strength and 6-meter walking pace in the two groups were significantly higher than those before treatment,and the increase of ASMI and grip strength in the observation group was more obviously than that in the control group(P＜0.05).(4)After eight weeks of treatment,the levels of serum CRP,IL-6,and TNF-α in the two groups were decreased significantly compared with those before treatment(P＜0.05),and the decrease of serum CRP level in the observation group was more obviously than that in the control group(P＜0.05).(5)During the treatment,no obvious adverse reactions occurred in both groups,and the safety indexes of liver and kidney functions of the patients were all within the normal range.Conclusion Xuanfei Yipi Formula can improve the clinical symptoms of senile sarcopenia patients,and its mechanism is probably related with the regulation of chronic low-grade inflammation.