[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.

ObjectiveTo evaluate the clinical effectiveness and safety of Bairui Granules （百蕊颗粒） in the treatment of acute pharyngitis with wind-heat syndrome. MethodsA multicenter， double-blind， double-simulation， randomised controlled trial was conducted， in which 162 patients with acute pharyngitis and wind-heat syndrome from 7 centers were recruited， and each center was divided into trial group and control group on the ratio of 2∶1. In the trial group， 108 cases were orally administered with Bairui Granules plus Reyanning Granules （热炎宁颗粒） simulant， and in the control group， 54 cases were orally administered with Reyanning Granules plus Bairui Granules simulant for 5 days， with a follow-up visit on the 6th day. Full analysis set （FAS） analysis and per protocol set （PPS） were used for analysis， respectively. The primary efficacy index was the disappearance rate of sore throat after 5-day treatment； the secondary efficacy indexes were the disappearance rate of sore throat after 3-day treatment， as well as the visual analogue score （VAS） of sore throat before treatment， every day during the treatment， and follow-up on day 6， and the traditional Chinese medicine （TCM） syndrome score was performed before treatment and at the follow-up on day 6. The effectiveness on TCM syndrome was evaluated at the follow-up on day 6， and the changes of vital signs， blood routine， urine routine， liver functions， kidney function， the adverse events before and after the treatment were recorded， and safety analysis set （SS） was analysed. Results162 patients entered the FAS and SS analyses， and 158 cases （105 cases in the trial group and 53 cases in the control group） entered the PPS analysis. FAS analysis showed that the disappearance rate of sore throat after 5-day treatment was 80.56% （87/108） in the trial group and 64.81% （35/54） in the control group， and the difference between groups was statistically significant （χ² = 5.10， P = 0.0239）. PPS analysis showed that the disappearance rate of sore throat after 5-day treatment was 80.00% （84/105） in the trial group and 64.15% （34/53） in the control group， and the difference between groups was statistically significant （χ² =4.85， P = 0.0277）. FAS and SS analyses both showed that the difference in disappearance rate of sore throat between groups on 3-day treatment was not statistically significant （P＞0.05）. Compared with those before treatment， the VAS scores of sore throat were lower in both groups during treatment on day 2， 3， 4， 5， and follow-up on day 6 （P＜0.01）， but the difference between groups at each time point was not statistically significant （P＞0.05）. TCM syndrome scores of both groups at the follow-up were lower than that before treatment， and those of the trial group were lower than those of the control group （P＜0.01）. The cure rate and effective rate of TCM syndrome of the trial group were significantly higher than those of the control group （P＜0.01）. There was no significant difference in blood routine， urine routine， liver function， kidney function between groups before and after treatment （P＞0.05）， and no serious adverse events occured in both groups. ConclusionBairui Granules showed clinical effectiveness in the treatment of acute pharyngitis of wind-heat syndrome， and it could significantly improve the clinical symptoms， accelerate the disappearance time of sore throat with good safety.

ObjectiveTo observe the clinical efficacy and safety of Chinese herbal enema combined with fumigation as adjunctive therapy for non-dialysis chronic kidney disease （CKD） patients of stage 3-5 with spleen-kidney yang deficiency and turbid toxin blood stasis pattern. MethodsA total of 120 non-dialysis CKD，patients of stage 3-5 with spleen-kidney yang deficiency and turbid toxin blood stasis pattern were randomly divided into treatment group and control group， with 60 cases in each group. The control group received conventional western medical treatment， while the treatment group additionally received Chinese herbal enema combined with fumigation， with enema and fumigation performed alternately， once every other day， three times a week. The treatment course for both groups was 4 weeks. The levels of serum creatinine （Scr）， estimated glomerular filtration rate （eGFR）， and the total score of traditional Chinese medicine symptoms were compared before and after treatment in both groups. The efficacy of traditional Chinese medicine symptoms and clinical efficacy were compared between the two groups after treatment. Adverse reactions in both groups were observed during the treatment period. ResultsThe total score of traditional Chinese medicine symptoms was significantly reduced after treatment in both groups （P＜0.01）. Compared to the control group after treatment， the treatment group showed significant decreases in Scr and the total score of traditional Chinese medicine symptoms， and a significant increase in eGFR （P＜0.05）. The total effective rate of traditional Chinese medicine symptoms in the treatment group （96.67%） was higher than that in the control group （46.67%， P＜0.01）， as well as the total effective rate of clinical efficacy in the treatment group （75.00%） versus that in the control group （28.33%， P＜0.01）. During the treatment period， the vital signs of patients in both groups remained stable， and there were no significant abnormalities in blood routine， urine routine， stool routine， liver function indicators， and electrocardiogram after treatment. ConclusionChinese herbal enema combined with fumigation as adjunctive therapy can significantly alleviate clinical symptoms， improve renal function， and demonstrate good safety for non-dialysis CKD patients of stage 3-5 with spleen-kidney yang deficiency and turbid toxin blood stasis pattern.

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.

Biliary tract carcinoma （BTC） is a type of gastrointestinal tumor with a low incidence rate and a strong invasive ability， mainly including intrahepatic cholangiocarcinoma （ICC）， extrahepatic cholangiocarcinoma （ECC）， and gallbladder carcinoma （GC）， often accompanied by local progression or distant metastasis. Surgery is often the preferred treatment method for patients with local resectable tumor； however， there is still a high risk of recurrence after radical surgery. Therefore， multiple treatment modalities are often required for BTC patients， including surgical resection， systemic treatment （such as targeted therapy， chemotherapy， and immunotherapy）， and/or a combination of local treatment methods. With the development of the field of BTC， it is critical for surgical oncologists to understand and master the latest surgical strategies and the best patient selection and management systems. In view of the complexity of treatment and the continuous development of diagnosis and treatment techniques， Annals of Surgical Oncology， an authoritative American journal of cancer surgery， recently published the practical diagnosis and treatment guidelines for hepatobiliary tumors， including hepatocellular carcinoma （HCC）， ICC， ECC， and GC， aiming to provide more evidence-based evidence for the clinical management and decision-making of patients with hepatobiliary tumors. Due to the limitations of length and different emphases， this article mainly introduces the recommendations for the evaluation points and clinical treatment of ECC and GC in the guidelines， so as to provide a reference for clinical practice.

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.

Objective:To investigate the diagnostic efficacy of targeted biopsy combined with regional systematic biopsy in prostate cancer(PCa)in patients with prostate imaging reporting and data system v2.1(PI-RADS v2.1)4-5.Methods:From January 2023 to October 2023,patients who underwent prostate biopsy for the first time with total prostate specific antigen(tPSA)≤20 ng/mL and had a multi-parametric magnetic resonance imaging(mpMRI)PI-RADS of 4-5 in Peking University First Hospital were prospectively collected.All the patients underwent transrectal ultrasound-guided cognitive fusion tar-geted biopsy(3 cores)followed by systematic biopsy(12 cores).Various hypothetical biopsy schemes were defined based on different biopsy sites.The detection effectiveness of targeted biopsy combined with regional systematic biopsy and other biopsy schemes for prostate cancer were compared using Cochran's Q and McNemar tests.Results:A total of 255 patients were enrolled,of whom 204(80.0％)were de-tected with prostate adenocarcinoma and 187(73.3％)were clinically significant with prostate cancer(csPCa).The detection rate of PCa with targeted biopsy was significantly lower than that of targeted biopsy combined with 12-core system biopsy(77.3％vs.80.0％,P=0.016),and 71.4％(5/7)of the missed patients was csPCa.There was no significant difference in the detection rate between targeted biopsy combined with 4-core regional system biopsy and 12-core system biopsy(P＞0.999),and 1 case of csPCa and clinically insignificant prostate cancer(cisPCa)were missed.There was no significant difference in the detection rate of PCa between targeted combined regional system biopsy and targeted combined lateral or traditional 6-core system biopsy and the number of cores were reduced.Missed diag-nosis of targeted biopsy was correlated with the maximum diameter of the lesion(OR=0.086,95％CI:0.013-0.562,P=0.010).For the patients with PI-RADS 5,only 1 case of PCa was missed in 122 cases by targeted biopsy alone.For patients with PI-RADS 4,6 PCa cases were missed among the 133 patients with targeted biopsy alone,and 1 case of csPCa and cisPCa were missed by targeted biopsy com-bined with regional system biopsy.The statistics of positive core counts for different biopsy schemes indi-cated that targeted combined regional systematic biopsy had a higher proportion of positive cores second only to targeted biopsy alone.Conclusion:Targeted biopsy combined with regional systematic biopsy has high diagnostic efficacy in patients with PI-RADS 4-5 and can be considered as one of the improved schemes for combined biopsy.Targeted biopsy alone is also a feasible option for patients for patients with a PI-RADS score of 5.

OBJECTIVE To compare the efficacy and safety of lacosamide （LCM） and carbamazepine （CAR） as monotherapy in the treatment of adult patients with newly diagnosed epilepsy. METHODS By methods of retrospective analysis， 84 adult patients with newly diagnosed epilepsy， were admitted to the Department of Neurology， Huaihe Hospital of Henan University during Sept. 2020-Jun. 2022， were divided into the control group （40 cases， receiving CAR treatment） and the observation group （44 cases， receiving LCM treatment） according to different medication regimens. Total response rate， epilepsy seizure frequency， blood lipid levels， and the occurrence of adverse events （AEs） of patients were compared between the 2 groups. RESULTS In the first month after treatment， there was no statistically significant difference in the total response rate between the observation group （63.64%） and the control group （55.00%， P＞0.05）； the frequency of epilepsy seizure in both groups was significantly reduced compared to before treatment （P＜0.05）， but there was no statistically significant difference between 2 groups （P＞0.05）. In the third month after treatment， the total response rate of the observation group （90.91%） was significantly higher than control group （67.50%， P＜0.05）； the frequencies of epilepsy seizure in both groups were significantly reduced compared to before treatment， and the observation group was significantly lower than the control group （P＜0.05）. In the third month after treatment， the levels of total cholesterol （TC）， triglyceride （TG） and low-density lipoprotein cholestrol （LDL-C） in the control group and the level of LDL-C in the observation group were significantly higher than before treatment， and the levels of TC， TG and LDL-C in the observation group were significantly lower than those in the control group （P＜0.05）. There was no statistically significant difference in the incidence of AEs between the observation group （15.91%） and the control group （17.50%， P＞0.05）. CONCLUSIONS Both LCM and CAR have certain effects in the treatment of newly diagnosed epilepsy in adults， which can reduce the frequency of epilepsy seizure in patients and have comparable safety. Meanwhile， LCM has better long-term efficacy than CAR in treating newly diagnosed epilepsy in adults， and its impact on the patient’s blood lipid is smaller than CAR.

【Objective】 To investigate the efficacy and safety of 450 nm blue laser with 6 o’clock positioning in the treatment of middle lobe hyperplasia of prostate, in order to promote the clinical application of this surgery. 【Methods】 Clinical data of 20 patients with middle lobe hyperplasia of prostate treated with 450 nm blue laser with 6 o’clock positioning during Mar.and Aug.2023 were retrospectively analyzed.The operation time, postoperative bladder irrigation time, catheter indwelling time, hospital stay, and complications were recorded.The maximum urinary flow rate (Qmax), post-void residual volume (PVR), quality of life scale (QoL), international prostate symptom score (IPSS) before surgery and 1 month after surgery were compared. 【Results】 The operation time was (26.80±7.22) min, and bladder irrigation time was (20.50±1.79) h.The catheter was removed on the next day after surgery and all patients were discharged 2 days after operation.Compared to preoperative, one month after surgery, the Qmax [(7.40±1.05) mL/s vs.(19.60±1.76) mL/s] was significantly higher, PVR [(73.50±12.26) mL vs.(9.25±4.94) mL], QoL [(4.55±1.19) vs.(1.95±0.95)], and IPSS [(26.55±1.88) vs.(10.05±1.36)] were significantly lower, the differences being statistically significant (P<0.05).No complications occurred during operation and 1-month follow-up. 【Conclusion】 The 450 nm blue laser with 6 o’clock positioning is a new, safe and effective surgical treatment of middle lobe hyperplasia of prostate, which is worthy of clinical promotion and application.