Objective To study the effect of microRNA-192(miR-192)on the proliferation,migration and invasion ability of colorectal cancer(CC)cell lines.Methods Group A(SW1116 CC transfected with physio-logical saline),group B(SW1116 CC transfected with miR-192 mimics)and group C(SW1116 CC transfected with miR-192 inhibitor)were set up,respectively.Cell proliferation was detected by MTT assay,cell apoptosis was detected by flow cytometry,cell migration ability was detected by scratch assay,and cell invasion ability was detected by Transwell assay.Real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)was used to detect the mRNA expression levels of miR-192 and WNT family member 2B(WNT2B)in each group.Results The survival rate and monoclonal number of SW1116 CC cells in group B were(57.32± 6.19)％and(284.59±15.08),which were lower than(76.21±8.23)％and(601.47±23.16)in group A and(89.52±10.62)％and(2 150.68±34.79)in group C,while the apoptosis rate in group B was(20.52± 2.52)％,which was higher than(13.78±1.62)％in group A and(11.62±1.41)％in group C.The survival rate and number of monoclonal formation of SW1116 CC cells in group C were higher than those in group A,while the apoptosis rate was lower than that in group A(all P＜0.05).The scratch width of SW1116 CC cells in group B was(785.10±46.18)mm,which was higher than(601.32±33.21)mm in group A and(326.99± 17.48)mm in group C,while the scratch width in group C was lower than that in group A.The number of per-forating cells in group B was(624.67±19.05),which was lower than(875.23±27.30)in group A and(1 204.17±34.59)in group C,and the number of perforating cells in group C was higher than that in group A(all P＜0.05).The relative expression level of miR-192 mRNA in SW1116 CC cells in group B was(3.01± 0.26),which was higher than(1.87±0.20)in group A and(0.97±0.23)in group C,and the relative expres-sion level of miR-192 mRNA in group C was lower than that in group A.The expression level of WNT2B mR-NA in group B was(2.16±0.26),which was lower than(4.11±0.50)in group A and(6.08±0.72)in group C,and the expression level of WNT2B mRNA in group C was higher than that in group A(all P＜0.05).Con-clusion miR-192 could inhibit the malignant evolution of CC,and one of its main mechanisms may be related to the regulation of WNT2B expression.

Objective To investigate the immediate brain effect of acupuncture at Fengchi using amplitude of low-frequency fluctuation(ALFF)and functional connectivity by the resting-state functional magnetic resonance imaging(rs-fMRI)in patients with posterior circulation ischemia vertigo(PCIV).Methods Twenty patients with PCIV were enrolled.The dizziness handicap inventory(DHI)was used to evaluate the severity of vertigo.The patients were randomly divided into acupuncture group and sham acupoint acupuncture group.Rs-fMRI scan was performed before and after acupuncture.MATLAB-based DPABI 6.1 software was used to analyze rs-fMRI data.Correlation analysis was used between the altered ALFF values and DHI scores.The regions of altered ALFF were taken as seeds to analyze functional connectivity.Results Compared with the sham acupoint acupuncture group,the increased ALFF values were mainly located on the left precuneus,left superior frontal gyrus and left caudate nucleus after acupuncture in the acupuncture group;the decreased ALFF values were mainly located on the left cerebellum and right inferior occipital gyrus.The ALFF value of the left superior frontal gyrus was negatively correlated with the DHI score(P=0.04).The increased functional connectivity was mainly found between left precuneus and the right middle frontal gyrus,the right superior frontal gyrus,the decreased functional connectivity was mainly found between left precuneus and the bilateral paracentral lobule and right cerebellum.Conclusion The ALFF value and functional connectivity are different before and after acupuncture,indicating that the vestibular network,visual and motor brain regions functional activities are changed after needling at Fengchi,which may be the brain functional basis of Fengchi for vertigo in PCIV.

ObjectiveTo explore the effectiveness and safety of Yiqi Huoxue Formula （益气活血方， YHF） in the adjuvant treatment of chronic pulmonary heart disease （CPHD） and heart failure （HF）with qi deficiency and blood stasis pattern. MethodsOne hundred and twenty patients with CPHD and HF with qi deficiency and blood stasis pattern were allocated randomly into treatment group and control group， with 60 case in each group. The control group was given conventional basic western medicine， while the treatment group was given oral administration of YHF granules in addition， one dose per day. The treatment course for both groups was 8 weeks. The TCM symptom scores， Minnesota Life Quality Scale （MLHF-Q） scores， echocardiographic indicators including right ventricular end-diastolic diameter （RVEDD）， left ventricular end-diastolic diameter （LVEDD）， left atrial end-diastolic diameter （LAEDD） and pulmonary artery mean pressure （PAMP）， six-minute walking distance （6MWD）， and plasma N-terminal pro-B-type natriuretic peptide （NT-ProBNP） level were compared between the groups. The effectiveness regarding cardiac function and TCM syndromes were compared between the two groups after treatment， and the occurrence of adverse events was observed. ResultsWith two drop-outs both in the treatment group and control group， and 58 cases in each group were included in the outcome analysis. The total effective rate regarding cardiac function and TCM syndromes in the treatment group were 91.38% （53/58） and 96.55% （56/58）， respectively， significantly higher than the corresponding 70.69% （41/58） and 48.27% （28/58） in the control group （P＜0.05）. After treatment， the TCM symptom scores and RVEDD level were significantly reduced in the treatment group， and MLHF-Q score， plasma NT-ProBNP level and PAMP level decreased significantly， while 6MWD increased in both groups （P＜0.01）. Compared to those in the control group， the TCM symptom scores， MLHF-Q score， plasma NT-ProBNP level and PAMP level significantly decreased， while 6MWD increased in the treatment group （P＜0.01）. There were no obvious abnormalities in the blood， urine， stool routine and liver and kidney function indicators in both groups. One adverse reaction each occurred in both groups， and there was no statistically significant difference in the incidence rates（P＞0.05）. ConclusionYHF combined with conventional western medicine can significantly improve the clinical efficacy， improve the clinical symptoms and cardiac function， increase the quality of life and exercise tolerance， and is relatively safe.

ObjectiveTo investigate the effects of maltol aluminum exposure on miR-193a-3p, demethylase AlkB homolog 5 (ALKBH5), phosphatase and tensin homolog deleted on chromosome ten (PTEN) and protein kinase B (AKT), and whether miR-193a-3p is involved in aluminum-induced cognitive impairment by regulating ALKBH5/PTEN/AKT signaling pathway. Methods Specific pathogen-free male SD rats were randomly divided into control group and low-, medium- and high- dose groups according to their body weight, with eight rats in each group. Rats in the low-, medium-, and high- dose groups were intraperitoneally injected with maltol aluminum solution at concentrations of 10.00, 20.00, and 40.00 μmol/kg body weight, respectively, while the rats in control group were given an equal volume of 0.9% sodium chloride solution. Rats were injected for five days every week for three months. After injection, the novel object recognized test was used to assess the learning and memory ability of the rats. The relative expression of miR-193a-3p and B-cell lymphocytoma-2 (Bcl-2), Bcl-2 associated X protein (Bax) and cysteine aspartate protease-3 (Caspase-3) mRNA in rat hippocampus was detected using the real-time quantitative polymerase chain reaction. The relative protein expression of ALKBH5, PTEN, and AKT2 in the rat hippocampus was detected using Western blot. Results The discrimination index and the preference index of the new object recognition test of the rats in high-dose group were lower than those in control group and low-dose group (all P<0.05). The relative expression of miR-193a-3p and Bcl-2 mRNA in the hippocampus of the rats in high-dose group was lower than those in control group and low-dose group (all P<0.05). The relative mRNA expression of Bax in the high-dose group was higher than those in the control group and low-dose group (both P<0.05). The relative mRNA expression of Caspase-3 of the rats in the high-dose group was higher than that in the other three groups (both P<0.05). The relative protein expression of ALKBH5 in the hippocampus of the rats in the high-dose group was lower than that in the control group (P<0.05). The relative expression of PTEN protein was higher than those in the control group and low-dose group (both P<0.05). The relative protein expression of AKT2 was lower than those in the control group and low-dose group (both P<0.05). Conclusion Sub-chronic aluminum exposure can inhibit the expression of miR-193a-3p in the hippocampus of rats, which may disrupt the ALKBH5/PTEN/AKT pathway and affect normal neuronal homeostasis and cellular function. This pathway may play an important role in aluminum-induced cognitive impairment.

Objective To evaluate the intraoperative identification of ectopic parathyroid tissue in the central neck region using autofluorescence point-spectral analysis(AFPSA)combined with immune colloidal gold technique(ICGT),for guiding total parathyroidectomy(TPTX)or clean parathyroidectomy(CPTX)in the management of secondary hyperparathyroidism(SHPT).Methods Retrospectively collected and compared the clinical data of 64 patients with SHPT from October 2019 to June 2023.In the observation group,TPTX was performed as the initial procedure in 36 cases,followed by sampling of suspicious targets using AFPSA in the central neck area and subsequent detection through ICGT.CPTX was then conducted if a positive result was obtained.On the other hand,the control group consisted of 28 cases where only TPTX was performed without any additional tests during surgery.The surgical data,parathyroid hormone(PTH)levels,blood calcium levels,blood phosphorus levels,alkaline phosphatase(ALP)levels,regression of clinical symptoms,changes in parathyroid function and occurrence of hypocalcemia were compared between these two groups.Results In the observation group,there were 9 cases of AFPSA-ICGT positivity,including 2 left-sided cases,4 right-sided cases,and 3 thymic cases;among these posi-tive cases,there were a total of 10 locations with mildly hyperplastic or nonhyperplastic microscopic parathyroid tissue.The difference in the number of total parathyroid glands removed(including ectopic)between the two groups was statistically significant(P<0.05).At both 3 and 6 months postoperatively,ALP levels in the observation group were significantly lower than those in the control group(P<0.01 and P<0.001 respectively);at 6 months postoperatively,differences in PTH and blood phosphorus levels between the two groups were also statistically significant(P<0.05 and P<0.001 respectively).Joint bone pain and skin itching recurred in some patients within the control group at six months after surgery(P<0.05),whereas recurrence of SHPT was less frequent within the observation group compared to controls(P<0.05);however,no statistically significant differences were observed regarding postoperative hypoparathyroidism or hyperparathyroidism as well as hypocalcemia between either groups.Conclusion The AFPSA-ICGT intraoperative test can be utilized to guide surgery for SHPT,enabling accurate and efficient identification as well as safe targeting of parathyroid tissues that may not exhibit obvious hyperplasia in the central cervical region.

Objective:To investigate the efficacy of programmed death receptor-1(PD-1)/ programmed death-ligand 1 (PD-L1) inhibitors in the treatment of recurrent or metastatic cervical cancer and its effect on serum levels of squamous cell carcinoma antigen (SCC-Ag), carcinoembryonic antigen (CEA), and carbohydrate antigen 125 (CA125) in patients.Methods:This study was a retrospective study. Ninety patients with cervical cancer treated at Lishui Municipal Central Hospital between January 2019 and December 2022 were randomly divided into two groups. Forty-five patients in the control group received routine radiotherapy and chemotherapy, while forty-five patients in the observation group received PD-1/PD-L1 inhibitors in addition to the treatment provided to the control group. The effectiveness and safety were compared between the two groups.Results:The effectiveness in the observation group was superior to that in the control group ( P < 0.05). After treatment, the levels of serum tumor markers, including SCC-Ag, CA125, CEA, and human epididymal protein 4, were significantly lower in the observation group compared with the control group ( t = 5.44, 6.20, 14.74, 4.06, all P < 0.001). After treatment, the levels of interferon-γ, interleukin-2, and interleukin-6 in the observation group were significantly lower compared with the control group ( t = 6.24, 8.95, 8.38, all P < 0.001). After treatment, the levels of CD 3+, CD 4+, and CD 4+/CD 8+ in the observation group were significantly higher compared with those in the control group ( t = 8.82, 6.53, 5.27, all P < 0.001). After treatment, the Functional Assessment of Cancer Therapy-Cervix score in the observation group was significantly higher than that in the control group ( t = 4.35, 4.35, 5.17, 5.24, all P < 0.001). The incidence of various adverse reactions in the observation group was significantly lower than that in the control group ( χ2 = 3.85, 3.87, 5.08, 4.44, all P < 0.05). The cumulative survival rate in the observation group was significantly higher than that in the control group [60.00% (27/45) vs. 40.00% (18/45), P < 0.05]. The median survival time in the observation group was significantly longer than that in the control group (365 days vs. 222 days, P < 0.05). Conclusion:PD-1/PD-L1 inhibitors are effective in the treatment of recurrent or metastatic cervical cancer. They can reduce the serum levels of SCC-Ag, CEA, and CA125, prolong the survival time of patients, and improve their quality of life.

Objective To study the correlation between expression levels of serum microRNA(miRNA)-21 and miRNA-27b and the prognosis in colorectal cancer patients.Methods A total of 60 colorectal cancer pa-tients who were treated in the hospital from January to May 2021 were selected as the observation group.An-other 60 healthy volunteers who underwent the physical examination in the hospital during the same period were selected as the control group.The expression levels of serum miRNA-21 and miRNA-27b in the two groups,the expression levels of serum miRNA-21 and miRNA-27b levels in patients with different pathologi-cal features were detected and compared,and the survival prognosis of patients with different expression levels of serum miRNA-21 and miRNA-27b were compared.Results The expression levels of serum miRNA-21 and miRNA-27b in the observation group were significantly higher than those in the control group(P＜0.05).The expression levels of serum miRNA-21 and miRNA-27b were lower in patients with TNM stage Ⅲ-Ⅳand with lymph node metastasis than those in stage Ⅰ-Ⅱ and without lymph node metastasis respectively(P＜0.05).With follow-up of 2 years,the mean survival time in the miRNA-21 high expression group was(15.36±2.32)months,and the mean survival time in the low miRNA-21 expression group was(21.54±2.46)months.The mean survival time in the miRNA-27b high expression group was(16.11±3.20)months,and the mean survival time in the miRNA-27b low expression group was mean(21.37±2.55)months.The 1 and 2-year survival rates in the miRNA-21 high expression group and miRNA-27b high expression group were significantly lower than those in the miRNA-21 low expression group and miRNA-27b low expression group,respectively(P＜0.05).Serum miRNA-21 and miRNA-27b levels were negatively correlated with the survival prognosis of patients(P＜0.05).Conclusion Serum miRNA-21 and miRNA-27b are highly expressed in pa-tients with colorectal cancer,and the expression levels of both are negatively correlated with the prognosis of patients,and they could be used for clinical monitoring of patients'condition and prognosis status,which de-serves attention.

Objective To explore the incidence and risk factors of antibiot-associated diarrhea(AAD)in patients with sepsis.Methods A total of 126 patients with sepsis admitted to Department of Critical Care Medicine,Jinhua Hospital Affiliated to Zhejiang University School of Medicine from July 2021 to July 2023 were selected as the subjects.They were divided into AAD group and non AAD group based on whether AAD occurred.Compare the clinical data and antibiotic use between two groups of patients,and use Logistic regression analysis to identify the risk factors for AAD in sepsis patients.Results There were 72 cases of respiratory system infections,18 cases of urinary system infections,15 cases of bloodstream infections,12 cases of chest and abdominal infections,and 9 cases of other infections in 126 patients with sepsis;32 cases(25.4%)developed AAD.Logistic multiple regression analysis showed that age≥60 years,lactic acid(Lac)level,albumin(ALB)level,use of carbapenems and enzyme inhibitors,combination of antibiotics,using hormones,and length of hospital stay were risk factors for AAD in sepsis patients(95%CI were 0.847-0.983,0.074-0.527,1.147-2.034,0.624-1.687,2.132-5.220,0.439-0.882,0.411-0.853,0.478-0.848,P<0.05).Conclusion Sepsis patients of department of critical care medicine have a high risk of developing AAD.Age≥60 years old,Lac level,ALB level,use of carbapenems and enzyme inhibitors,combination of antibiotics therapy,using hormones,and length of hospital stay are risk factors for AAD in sepsis patients.

Objective To investigate the protective effect and mechanism of apigenin on the liver of hyperlipidemic mice based on metabolomics methods.Methods C57BL/6 mice were randomly divided into four groups including blank,model,fenofibrate(26.0 mg·kg-1),and apigenin(12.5 mg·kg-1)groups,with six mice in each group.Each group was treated with corresponding drug by gavage once a day for five days.On the third day of administration,the mouse model of acute hyperlipidemia was induced by a single intramuscular injection of Triton WR-1339(5 mL·kg-1)at a concentration of 0.12 g·mL-1.Biochemical indexes such as TC and TG in mice serum were measured by using a fully automatic microplate reader.HE staining was used to observe pathological changes in liver tissue.UPLC-Q-TOF-MS/MS technology was applied to analyze liver tissue samples.Differential metabolites were screened by using multivariate statistical analysis methods such as PCA,PLS-DA,and OPLS-DA.Then we ran the mass spectrometry information of these metabolites through online databases including HMDB,METLIN and KEGG,as well as combined with relevant literature to obtain the potential differential metabolites.The identified potential differential compounds were imported into the MetaboAnalyst platform for metabolic pathway analysis.Results Compared with the blank group,TC and TG levels in mice serum of model group increased obviously(P＜0.01).Irregular arrangement of liver cells,fat vacuoles and infiltration of inflammatory cells were found.Compared with the model group,TC and TG levels in mice serum of apigenin group decreased(P＞0.05).Fatty lesions in liver tissue were significantly improved,and fat vacuoles and inflammatory cell infiltration were significantly reduced.A total of 35 differential metabolites were screened.Twenty-six differential metabolites showed callback trend after apigenin treatment.Eight metabolic pathways were obviously affected,among which pantothenate and CoA biosynthesis,as well as arachidonic acid metabolism are two main metabolic pathways(P＜0.05).Conclusion Apigenin exhibits a certain protective effect on liver of hyperlipidemic mice,and its mechanism may be related to regulating liver inflammatory response and lipid metabolism-related pathways.

It is discovered that activated caspase-3 tends to induce apoptosis in gasdermin E (GSDME)-deficient cells, but pyroptosis in GSDME-sufficient cells. The high GSDME expression and apoptosis resistance of pancreatic ductal adenocarcinoma (PDAC) cells shed light on another attractive strategy for PDAC treatment by promoting pyroptosis. Here we report a hGLuc-hGSDME-PCA system for high-throughput screening of potential GSDME activators against PDAC. This screening system neatly quantifies the oligomerization of GSDME-N to characterize whether pyroptosis occurs under the stimulation of chemotherapy drugs. Based on this system, ponatinib and perifosine are screened out from the FDA-approved anti-cancer drug library containing 106 compounds. Concretely, they exhibit the most potent luminescent activity and cause drastic pyroptosis in PDAC cells. Further, we demonstrate that perifosine suppresses pancreatic cancer by promoting pyroptosis via caspase-3/GSDME pathway both in vitro and in vivo. Collectively, this study reveals the great significance of hGLuc-hGSDME-PCA in identifying compounds triggering GSDME-dependent pyroptosis and developing promising therapeutic agents for PDAC.