[摘 要] 目的：探讨KH型剪切调节蛋白（KHSRP）靶向调控JAK1/STAT3信号轴对食管胃结合部腺癌（AEG）细胞增殖、迁移和侵袭及移植瘤生长与肺转移的影响。方法：收集2017年1月至2018年12月间在淮河医院确诊的64例AEG组织和癌旁组织标本及临床资料，采用免疫组化法观察AEG组织和癌旁组织中KHSRP的表达水平。qPCR法检测AEG细胞OE-19、TE-7、BIC-1、FLO-1、SK-GT-4、BE-3与正常食管上皮细胞Het-1A中KHSRP的表达差异。通过慢病毒载体对KHSRP进行敲减和过表达处理，分别转染OE-19与TE-7细胞、FLO-1与SK-GT-4细胞，实验分为sh-NC组、sh-KHSRP组和Vector组、KHSRP过表达组（KHSRP组）。采用qPCR法检测敲减或过表达效率，CCK-8法、Transwell小室法分别检测敲减或过表达KHSRP对AEG细胞增殖、迁移和侵袭的影响。构建小鼠异种移植瘤和肺转移模型，观察KHSRP对移植瘤体内生长和转移的作用。WB法验证KHSRP靶向JAK/STAT信号通路。细胞拯救实验验证KHSRP是否通过调节JAK1/STAT3信号通路促进AEG细胞的恶性进程。结果：与癌旁组织相比，AEG组织中KHSRP表达水平显著增高（P < 0.05或P < 0.01）。细胞功能实验分析显示，KHSRP过表达在体外均显著促进AEG细胞增殖、迁移和侵袭（P < 0.05或P < 0.01）。动物实验结果显示，KHSRP在裸鼠体内具有促进AEG细胞移植瘤生长与肺转移的作用（P < 0.05或P < 0.01）。在敲减KHSRP后，JAK/STAT信号通路中JAK1、STAT3磷酸化水平均明显降低，过表达KHSRP后情况则均反之（P < 0.05或P < 0.01）。细胞拯救实验显示，KHSRP可以逆转敲减JAK1/STAT3对细胞增殖、迁移和侵袭的抑制作用（P < 0.05或P < 0.01）。结论：KHSRP通过激活JAK1/STAT3信号通路调控AEG细胞转移的恶性进程，KHSRP有望成为AEG临床治疗的潜在靶点。

ObjectiveTo investigate the protective effect of Rehmanniae Radix iridoid glycosides （RIG） on the kidney tissue of streptozotocin （STZ）-induced diabetic mice and explore the underlying mechanism. MethodsTwelve of 72 male C57BL/6J mice were randomly selected as the normal group， and the remaining 60 mice were fed with a high-fat diet for six weeks combined with injection of 60 mg·kg^-1 STZ for 4 days to model type 2 diabetes mellitus. The successfully modeled mice were randomized into model， metformin （250 mg·kg^-1）， catalpol （100 mg·kg^-1）， low-dose RIG （RIG-L， 200 mg·kg^-1） and high-dose RIG （RIG-H， 400 mg·kg^-1） groups （n=11）. Mice in each group were administrated with corresponding drugs， while those in the normal group and model group were administrated with the same dose of distilled water by gavage once a day. After 8 weeks of intervention， an oral glucose tolerance test （OGTT） was performed， and the area under the curve （AUC） was calculated. After mice were sacrificed， both kidneys were collected. The body weight， kidney weight， and fasting blood glucose （FBG） were measured. Biochemical assays were performed to measure the serum levels of triglycerides （TG）， total cholesterol （TC）， serum creatinine （SCr）， and blood urea nitrogen （BUN）. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the serum level of fasting insulin （FINS）， and the insulin sensitivity index （ISI） and homeostatic model assessment for insulin resistance （HOMA-IR） were calculated. The pathological changes in kidneys of mice were observed by hematoxylin-eosin staining and Masson staining. The immunohistochemical method （IHC） was employed to assess the expression of interleukin-1 （IL-1）， interleukin-6 （IL-6）， tumor necrosis factor-α（TNF-α）， transforming growth factor-β₁ （TGF-β₁）， and collagen-3 （ColⅢ） in the kidney tissue. The protein levels of TGF-β₁， cell signal transduction molecule 3 （Smad3）， matrix metalloproteinase-9 （MMP-9）， and ColⅢ in kidneys of mice were determined by Western blot. ResultsCompared with the normal group， the model group showcased decreased body weight and ISI （P<0.01）， increased kidney weight， FBG， AUC， FINS， HOMA-IR， TC， TG， SCr， and BUN （P<0.01）， glomerular hypertrophy， capsular space narrowing， and collagen deposition in the kidney， up-regulated protein levels of IL-1， IL-6， TNF-α， TGF-β₁， ColⅢ， and Smad3 （P<0.01）， and down-regulated protein level of MMP-9 （P<0.01） in the kidney tissue. Compared with the model group， the treatment groups had no significant difference in the body weight and decreased kidney weight （P<0.05， P<0.01）. The FBG level declined in the RIG-H group after treatment for 4-8 weeks and in the metformin， catalpol， and RIG-L groups after treatment for 6-8 weeks （P<0.01）. The AUC in the RIG-L， RIG-H， and metformin groups decreased （P<0.05， P<0.01）. The levels of TC， SCr， and BUN in the serum of mice in each treatment group became lowered （P<0.05， P<0.01）. The level of TG declined in the RIG-L， RIG-H， and metformin groups （P<0.05， P<0.01）. The serum level of FINS declined in the catalpol， RIG-L， and metformin groups （P<0.01）. Compared with the model group， the treatment groups showed decreased HOMA-IR （P<0.01）， increased ISI （P<0.01）， alleviated pathological changes in the kidney tissue， and down-regulated expression of IL-1 and TGF-β₁. In addition， the protein levels of IL-6， TNF-α， and ColⅢ in the RIG-H and metformin groups and IL-6 and TNF-α in the RIG-L group were down-regulated （P<0.05， P<0.01）， and the protein levels of IL-6， TNF-α， and ColⅢ in the catalpol group and ColⅢ in the RIG-L group showed a decreasing trend without statistical difference. The protein levels of TGF-β₁， Smad3， and ColⅢ in the RIG-H and metformin groups were down-regulated （P<0.01）. Compared with that in the model group， the protein level of MMP-9 was up-regulated in each treatment group （P<0.01）. ConclusionRIG can improve the renal structure and function of diabetic mice by regulating the TGF-β₁/Smads signaling pathway.

AIM: To observe the effect of fudosteine on induced sputum cell components and lung function in patients with stable neutrophil-dominated COPD. METHODS: From October 2019 to October 2022, 53 patients with stable COPD were selected and divided into fudosteine group and placebo group. The placebo group was treated with routine treatment, and the fudosteine group was treated with fudosteine on the basis of routine treatment. The two groups were treated for 6 months. The clinical symptoms [Saint George's Respiratory Questionnaire (SGRQ), COPD Assessment Test (CAT) and Modified British Medical Research Council Dyspnea scale (MMRC), Breathlessness, Cough, and Sputum Scale (BCSS)], lung function index, induced sputum cytology analysis and other related examination results were recorded in detail before and after treatment. RESULTS: (1) Compared with the baseline, the forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and the ratio of FEV1 to FVC (FEV1/FVC) of the two groups were improved after treatment, and the differences were statistically significant (P<0.05). However, after treatment, there was no significant difference in pulmonary function between the two groups except for the percentage of carbon monoxide diffusion in the predicted value (DLCO%pre) (DLCO%pre in the fudosteine group was higher than that in the placebo group). (2) After treatment, the total number of induced sputum cells and neutrophil counts in the fudosteine group were lower than those in the placebo group. Compared with the number of cells in each component at baseline, the total number of induced sputum cells and neutrophil count in the fudosteine group were significantly lower (P< 0.05). CONCLUSION: Fudosteine treatment in patients with stable neutrophil-dominated COPD can improve lung function, reduce the total number of induced sputum cells and the total number of neutrophils, thereby improving airway inflammation.

Objective To investigate the clinical effect of transhepatic arterial chemoembolization(TACE)combined with tyrosine kinase inhibitors(TKIs)and programmed death receptors-1(PD-1)inhibitors(TACE+TKIs+PD-1 antibody)in the treatment of moderate advanced unresectable hepatocellular carcinoma(HCC).Methods The clinical data of 65 patients with moderate advanced unresectable hepatocellular carcinoma admitted to the Affiliated Hospital of North Sichuan Medical College from January 2020 to January 2022 were analyzed retrospectively.65 patients were treated with TACE+TKIs+PD-1 antibody.The observation indexes were tumor response,objective response rate(ORR),disease control rate(DCR),total survival time,progression free survival time,conversion operation rate and adverse drug reaction.Results The ORR of 65 p-atients with hepatocellular carcinoma was 49.2％(32/65),and the DCR was 89.2％(58/65).Among them,there were 2 patients with complete remission(CR),30 patients with partial remission(PR),26 patients with stable disease(SD),and 7 patients with progression disease(PD).Among 65 patients with hepatocellular carcinoma,18 patients were transformed into resectable hepatocell-ular carcinoma and underwent RO surgery.The conversion rate was 27.6％(18/65).65 patients were followed up for 3 to 22.4 months,The median follow-up time was 16.5 months.The median overall survival time and median disease progression free survival time of 65 patients were 14.5 months(95％CI:12.3～16.6 months)and 8.8 months(95％CI:6.9～10.6 months),respectively.After treatment,65 patients all had post embolism syndrome(abdominal pain,fever,nausea,vomiting and other symptoms),and some patients had transient abnormal liver function.Adverse drug reactions below grade 3 recovered within a few days.Some patients were associated with multiple adverse drug reactions.1 patient(1.5％)stopped using TACE because of stubborn vomiting,and 5 patients(7.6％)stopped using Lenvatinib because of severe liver function damage during treatment,2 patients(3％)stopped using Camrelizumab because of severe reactive capillary hyperplasia,one patient(1.5％)stopped using Tislelizumab because of severe hypothyroidism,one patient(1.5％)stopped the treatment of Lenvatinib and Sintilimab due to severe gastrointestinal bleeding.The adverse drug reactions of grade 3～4 occurred in other patients were alleviated after drug reduction,symptomatic treatment and hormone treatment.Conclusion TACE+TKIs+PD-1 antibody can obtain reliable clinical efficacy and anti-tumor activity in the treatment of moderate advanced unresectable hepatocellular carcinoma.

AIM:To observe the effect of fudostei-ne on induced sputum cell components and lung function in patients with stable neutrophil-dominat-ed COPD.METHODS:From October 2019 to Octo-ber 2022,53 patients with stable COPD were select-ed and divided into fudosteine group and placebo group.The placebo group was treated with routine treatment,and the fudosteine group was treated with fudosteine on the basis of routine treatment.The two groups were treated for 6 months.The clinical symptoms[Saint George's Respiratory Questionnaire(SGRQ),COPD Assessment Test(CAT)and Modified British Medical Research Council Dys-pnea scale(MMRC),Breathlessness,Cough,and Sputum Scale(BCSS)],lung function index,induced sputum cytology analysis and other related exami-nation results were recorded in detail before and after treatment.RESULTS:(1)Compared with the baseline,the forced expiratory volume in one sec-ond(FEV1),forced vital capacity(FVC),and the ra-tio of FEV1 to FVC(FEV1/FVC)of the two groups were improved after treatment,and the differenc-es were statistically significant(P＜0.05).However,after treatment,there was no significant difference in pulmonary function between the two groups ex-cept for the percentage of carbon monoxide diffu-sion in the predicted value(DLCO％pre)(DLCO％pre in the fudosteine group was higher than that in the placebo group).(2)After treatment,the total num-ber of induced sputum cells and neutrophil counts in the fudosteine group were lower than those in the placebo group.Compared with the number of cells in each component at baseline,the total num-ber of induced sputum cells and neutrophil count in the fudosteine group were significantly lower(P＜0.05).CONCLUSION:Fudosteine treatment in pa-tients with stable neutrophil-dominated COPD can improve lung function,reduce the total number of induced sputum cells and the total number of neu-trophils,thereby improving airway inflammation.

Objective:To investigate the clinical efficacy of single-incision plus one-port three dimensional (3D) laparoscopic pancreaticoduodenectomy (SILPD+1).Methods:The retrospective cohort study was conducted. The clinicopathological data of 40 patients who underwent 3D laparos-copic pancreaticoduodenectomy in Affiliated Hospital of North Sichuan Medical College from January to October 2023 were collected. There were 24 males and 16 females, aged (63±10)years. Of the 40 patients, 18 cases undergoing SILPD+1 were divided into the SILPD+1 group, and 22 cases under-going conventional five-trocar 3D laparoscopic pancreaticoduodenectomy (CLPD) were divided into the CLPD group. Observation indicators: (1) surgical situations; (2) postoperative situations and complications. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the Mann-Whitney rank sum test. Results:(1) Surgical situa-tions. Seventeen patients of the SILPD+1 group completed surgery successfully, and the rest of one patient with an inflammatory mass of the pancreatic head was converted to open surgery due to unclear boundary with mesenteric blood vessels and severe adhesion of surrounding tissues. All patients of the CLPD group completed surgery successfully, without conversion to open surgery. There was no significant difference in conversion to open surgery between the two groups ( P>0.05), and there was no significant difference in the volume of intraoperative blood loss, intraoperative blood transfusion or operation time ( P>0.05). (2) Postoperative situations and complications. There was no significant difference in tumor diameter, the number of lymph node dissected, the number of positive lymph node, R 0 resection, tumor type, time to postoperative first flatus, time to postopera-tive first intake liquid food, tome to first out-of-bed activity, time to postoperative drainage tube removal, duration of postoperative hospital stay, postoperative bleeding, pancreatic fistula, chylous leakage, delayed gastric emptying, abdominal fluid collection, incision infection, classification of com-plications between the two groups ( P>0.05). Postoperative pain score of the SILPD+1 group and the CLPD group was 5.0(4.5,6.0) and 6.5(6.0,7.0), respectively, showing a significant difference ( Z=-3.61, P<0.05). Both groups of patients had no occurrence of biliary fistula or abdominal infection after surgery, and there was no readmission within 30 days after surgery or no death within 90 days after surgery. Conclusions:Compared with CLPD, SILPD+1 is safe and feasible, with less postoperative pain. While ensuring oncological outcomes, SILPD+1 does not increase surgical time, postoperative hospital stay, or incidence of postoperative complications.

ObjectiveSerum metabolomics of acute lung injury（ALI） in rats was conducted using ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） to explore the similarities and differences in the mechanism of Qingqiao（harvested when the fruits of Forsythiae Fructus were initially ripe and still green in color） and Laoqiao（harvested when the fruits of Forsythiae Fructus were ripe） in the treatment of ALI. MethodA total of 24 SD male rats were acclimatized and fed for 1 week， 6 of them were randomly selected for the blank group and 18 for the experimental group. The ALI model was induced in the experimental group by tracheal intubation with lipopolysaccharide（LPS）. After successfully constructing the ALI model， these rats was randomly divided into model group， Qingqiao group and Laoqiao group， with 6 rats in each group. The Qingqiao and Laoqiao groups were administered orally once a day at a dose of 1.5 g·kg^-1， while the blank and model groups received an equivalent volume of saline for 3 consecutive days. The pathological conditions of rat lung tissues were comprehensively assessed by hematoxylin-eosin（HE） staining， wet-to-dry mass ratio（W/D） of lung tissues， and protein concentration in rat bronchoalveolar lavage fluid（BALF）. The levels of interleukin（IL）-6， IL-1β and tumor necrosis factor（TNF）-α in BALF were quantified using enzyme-linked immunosorbent assay（ELISA）. UPLC-Q-TOF-MS was used to identify and analyze the chemical compositions of Qingqiao and Laoqiao， and serum metabolomics of rats in each group was analyzed， combined with multivariate statistical analysis with variable importance in the projection（VIP） value>1， P<0.05 from t-test， and fold change（FC）≥1.5 or FC≤0.5 to screen the differential metabolites Qingqiao and Laoqiao for the treatment of ALI. The Kyoto Encyclopedia of Genes and Genomes（KEGG） database was used in combination with MetaboAnalyst for the metabolic pathway analysis of the screened differential metabolites. ResultCompared with the blank group， rats in the model group exhibited enlarged alveolar lumen， ruptured alveoli， interstitial hemorrhage， bronchial exudation of a large number of neutrophils and erythrocytes， and a significant increase in the protein concentration in the BALF and the W/D value of the lung tissues（P<0.01）. In contrast， compared with the model group， rats in the Qingqiao group and the Laoqiao group showed reduced bronchial hemorrhage in the lungs， and the protein concentration in the BALF and the W/D value of the lung tissues were significantly decreased（P<0.01）， the lung injury was significantly alleviated， but more obvious in the Qingqiao group. Compared with the blank group， the expression levels of IL-6， IL-1β and TNF-α in the BALF of the model group were significantly higher（P<0.01）. Additionally， compared with the model group， the expression levels of IL-6， IL-1β and TNF-α in the Qingqiao and Laoqiao groups were significantly lower（P<0.01）. The chemical composition analysis of Qingqiao and Laoqiao revealed that 63 components were detected in Qingqiao and 55 components were detected in Laoqiao， with 47 common components， 16 components unique to Qingqiao and 8 components unique to Laoqiao. Characterizing the differences in serum metabolomics in rats， 19 and 12 metabolites were called back by Qingqiao and Laoqiao， respectively. The metabolic pathway enrichment analysis showed that Qingqiao exerted its therapeutic effects by affecting 6 key metabolic pathways， including linoleic acid metabolism， phenylalanine metabolism， phenylalanine， tyrosine and tryptophan biosynthesis， glycerophospholipid metabolism， α-linolenic acid metabolism， and arachidonic acid metabolism， and Laoqiao exerted therapeutic effects by affecting 6 key metabolic pathways， including linoleic acid metabolism， arachidonic acid metabolism， sphingolipid metabolism， phenylalanine metabolism， ascorbate and aldarate metabolism， and glycerophospholipid metabolism. ConclusionQingqiao and Laoqiao have therapeutic effects on ALI， and Qingqiao is more effective. Both of them can play a therapeutic role in ALI by regulating amino acid metabolism and lipid metabolism， but the metabolic pathways affected by them are different.

AIM:To observe the effect of fudostei-ne on induced sputum cell components and lung function in patients with stable neutrophil-dominat-ed COPD.METHODS:From October 2019 to Octo-ber 2022,53 patients with stable COPD were select-ed and divided into fudosteine group and placebo group.The placebo group was treated with routine treatment,and the fudosteine group was treated with fudosteine on the basis of routine treatment.The two groups were treated for 6 months.The clinical symptoms[Saint George's Respiratory Questionnaire(SGRQ),COPD Assessment Test(CAT)and Modified British Medical Research Council Dys-pnea scale(MMRC),Breathlessness,Cough,and Sputum Scale(BCSS)],lung function index,induced sputum cytology analysis and other related exami-nation results were recorded in detail before and after treatment.RESULTS:(1)Compared with the baseline,the forced expiratory volume in one sec-ond(FEV1),forced vital capacity(FVC),and the ra-tio of FEV1 to FVC(FEV1/FVC)of the two groups were improved after treatment,and the differenc-es were statistically significant(P＜0.05).However,after treatment,there was no significant difference in pulmonary function between the two groups ex-cept for the percentage of carbon monoxide diffu-sion in the predicted value(DLCO％pre)(DLCO％pre in the fudosteine group was higher than that in the placebo group).(2)After treatment,the total num-ber of induced sputum cells and neutrophil counts in the fudosteine group were lower than those in the placebo group.Compared with the number of cells in each component at baseline,the total num-ber of induced sputum cells and neutrophil count in the fudosteine group were significantly lower(P＜0.05).CONCLUSION:Fudosteine treatment in pa-tients with stable neutrophil-dominated COPD can improve lung function,reduce the total number of induced sputum cells and the total number of neu-trophils,thereby improving airway inflammation.

AIM:To observe the effect of fudostei-ne on induced sputum cell components and lung function in patients with stable neutrophil-dominat-ed COPD.METHODS:From October 2019 to Octo-ber 2022,53 patients with stable COPD were select-ed and divided into fudosteine group and placebo group.The placebo group was treated with routine treatment,and the fudosteine group was treated with fudosteine on the basis of routine treatment.The two groups were treated for 6 months.The clinical symptoms[Saint George's Respiratory Questionnaire(SGRQ),COPD Assessment Test(CAT)and Modified British Medical Research Council Dys-pnea scale(MMRC),Breathlessness,Cough,and Sputum Scale(BCSS)],lung function index,induced sputum cytology analysis and other related exami-nation results were recorded in detail before and after treatment.RESULTS:(1)Compared with the baseline,the forced expiratory volume in one sec-ond(FEV1),forced vital capacity(FVC),and the ra-tio of FEV1 to FVC(FEV1/FVC)of the two groups were improved after treatment,and the differenc-es were statistically significant(P＜0.05).However,after treatment,there was no significant difference in pulmonary function between the two groups ex-cept for the percentage of carbon monoxide diffu-sion in the predicted value(DLCO％pre)(DLCO％pre in the fudosteine group was higher than that in the placebo group).(2)After treatment,the total num-ber of induced sputum cells and neutrophil counts in the fudosteine group were lower than those in the placebo group.Compared with the number of cells in each component at baseline,the total num-ber of induced sputum cells and neutrophil count in the fudosteine group were significantly lower(P＜0.05).CONCLUSION:Fudosteine treatment in pa-tients with stable neutrophil-dominated COPD can improve lung function,reduce the total number of induced sputum cells and the total number of neu-trophils,thereby improving airway inflammation.

AIM:To observe the effect of fudostei-ne on induced sputum cell components and lung function in patients with stable neutrophil-dominat-ed COPD.METHODS:From October 2019 to Octo-ber 2022,53 patients with stable COPD were select-ed and divided into fudosteine group and placebo group.The placebo group was treated with routine treatment,and the fudosteine group was treated with fudosteine on the basis of routine treatment.The two groups were treated for 6 months.The clinical symptoms[Saint George's Respiratory Questionnaire(SGRQ),COPD Assessment Test(CAT)and Modified British Medical Research Council Dys-pnea scale(MMRC),Breathlessness,Cough,and Sputum Scale(BCSS)],lung function index,induced sputum cytology analysis and other related exami-nation results were recorded in detail before and after treatment.RESULTS:(1)Compared with the baseline,the forced expiratory volume in one sec-ond(FEV1),forced vital capacity(FVC),and the ra-tio of FEV1 to FVC(FEV1/FVC)of the two groups were improved after treatment,and the differenc-es were statistically significant(P＜0.05).However,after treatment,there was no significant difference in pulmonary function between the two groups ex-cept for the percentage of carbon monoxide diffu-sion in the predicted value(DLCO％pre)(DLCO％pre in the fudosteine group was higher than that in the placebo group).(2)After treatment,the total num-ber of induced sputum cells and neutrophil counts in the fudosteine group were lower than those in the placebo group.Compared with the number of cells in each component at baseline,the total num-ber of induced sputum cells and neutrophil count in the fudosteine group were significantly lower(P＜0.05).CONCLUSION:Fudosteine treatment in pa-tients with stable neutrophil-dominated COPD can improve lung function,reduce the total number of induced sputum cells and the total number of neu-trophils,thereby improving airway inflammation.