Approximately 60% of colorectal cancer (CRC) patients exhibit TP53 mutations, which are strongly associated with tumor progression, chemotherapy resistance, and an unfavorable prognosis. However, targeting p53 has historically been challenging, and currently, there are no approved p53-based therapeutics for clinical use worldwide. In this study, we discovered that ubiquitin carboxyl terminal hydrolase L3 (UCHL3) plays a crucial role in high-level glycolysis, enhanced stem-like properties, and 5-fluorouracil (5-FU) chemoresistance in TP53-mutant CRC by exerting its deubiquitinating enzyme activity to stabilize α-enolase (ENO1) protein. Notably, we identified a newly Food and Drug Administration (FDA)-approved drug, pacritinib, that potently suppresses UCHL3 expression by blocking the janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway in TP53-mutant CRC. Furthermore, Pacritinib was demonstrated to effectively inhibit glycolysis and improve the sensitivity to 5-FU chemotherapy in TP53-mutant CRC. Our findings suggest that targeting the JAK2-STAT3-UCHL3-ENO1 axis is a promising strategy to suppress glycolysis and enhance the efficacy of 5-FU chemotherapy in TP53-mutant CRC. Pacritinib shows potential for clinical application in the treatment of TP53-mutant CRC.

The pathogenesis of male infertility is intricate and complex,and now,Western medicine is primarily based on empirical drug treatment.Male infertility is one of the advantageous diseases of traditional Chinese medicine,and traditional Chinese medicine has obvious effect in improving male reproductive function,which is one of the important means of clinical treatment of this disease.Based on the classical ancient books and modern research,and based on the traditional tonifying kidney method,we have innovatively put forward the concept of treating male infertility with the principle of"deficiency of kidney essence as the root,tonifying kidney and benefiting essence as the method,and regulating yin and yang mildly as the rule",which has achieved good clinical efficacy.At the same time,combined with the long-term clinical practice of our team,we have proposed five major diagnosis and treatment strategies for male infertility,i.e.,combining disease identification with syndrome identification,combining macroscopic with microscopic approaches,combining holistic with localized treatments,combining traditional Chinese medicine with surgery,and combining treatment of the disease and treatment of the person.In addition,we have summarized some of the current problems in the treatment of male infertility with traditional Chinese medicine and put forward corresponding suggestions,with a view to promoting the development and application of traditional Chinese medicine in the treatment of male infertility.

Objective To investigate the effect of nicotine on coagulation in intestinal ischemia-reperfusion injury rats.Methods 32 male Sprague-dawley rats,weighing 250-300g,were randomly divided into 4 groups(n=8):sham operation group(S),intestinal ischemia-reperfusion(IR)group,nicotine(NIC)group,α7 nicotinic acetylcholine receptor(α7nAchR)antagonist group α-bungarotoxin(α-BGT)group.Intestinal IR was induced by clamping superior mesenteric artery for 45min and 120min of reperfusion.In group NIC nicotine 400μg/kg was injected intraperitoneally at 30min before superior mesenteric artery occlusion.In group α-BGT 1μg/kg was injected intraperitoneally at 15min before superior mesenteric artery occlusion.Plasma tumor necrosis factor-α(TNF-α),tissue factor(TF),antithrombin(AT),tissue plasminogen activator(tPA),fiber plasminogen activator inhibitor-1(PAI-1),D-dimer levels and platelet count(PLT)were measured after 120min reperfusion.Chiu's count was used to assess the changes in intestinal mucosal pathlolgical morphology.Results Compared with group S and group NIC,the plasma TNF-α,TF,tPA,PAI-1 and D-dimer levels were significantly increased,and plasma AT level and platelet count were significantly decreased,in group IR and group α-BGT(P<0.05),Chiu's scores were significantly increased(P<0.05).Conclusion Nicotine can inhibit the excessive activation of coagulation function in intestinal ischemia-reperfusion injury rats.Its mechanism may be related to activation of cholinergic antiinflammatory pathway,reducing the release of pro-inflammatory cytokines thereby reducing endothelial cell injury.

Objective:To investigate the clinical value of ultrasound-guided thoracic paravertebral block (TPVB) combined with bronchial blocker (BB) placement in thoracoscopic surgery.Methods:A randomized controlled study was conducted involving 60 patients scheduled for thoracoscopic surgery at The First Affiliated Hospital of Xiamen University from November to December 2023. These patients were classified as American Society of Anesthesiologists (ASA) I-II. They were divided into an observation group (BB placement) and a control group (double-lumen bronchial blocker placement) using the random number table method, with 30 patients in each group. Preoperatively, TPVB was performed under ultrasound guidance. After the induction of general anesthesia, a single-lumen tracheal tube was inserted, followed by the placement of a BB in the observation group, while a corresponding type of double-lumen bronchial tube was inserted in the control group. A fiberoptic bronchoscope was used for positioning and fixation in both groups, and anesthesia was maintained with intravenous anesthesia. The following parameters were assessed in each group: positioning time for intubation; number of cases with tube displacement; number of cases of postoperative pharyngeal pain; hemodynamic parameters [mean arterial pressure (MAP) and heart rate (HR)] before and after intubation; and blood gas analysis [partial pressure of oxygen (PaO 2) and carbon dioxide (PaCO 2)]. Additionally, the surgical field exposure score and the dosages of propofol and remifentanil administered during surgery were recorded. Levels of inflammatory markers [interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF) -α, and TNF-β] and Visual Analog Scale scores for pain at rest and during cough, recorded at 2, 4, 8, 10, 12, and 24 hours postoperatively were compared between the two groups. Results:The total amounts of propofol [(569.7 ± 29.2) mg] and remifentanil [(289.3 ± 46.3) μg] in the observation group were significantly lower than those in the control group [(612.6 ± 28.7) mg, (361.7 ± 40.6) μg, t = 5.74, 6.44, both P = 0.001]. The recovery time in the observation group [(31.8 ± 11.4) minutes] was significantly shorter than that in the control group [(37.5 ± 10.1) minutes, t = 2.10, P = 0.040]. There was no significant difference in positioning time for intubation between observation and control groups [(67 ± 13) seconds vs. (80 ± 36) seconds, t = 1.86, P = 0.068). There was no significant difference in percentage of cases who underwent tube displacement after intubation between observation and control group [23.3% (7/30) vs. 16.7% (5/30), χ2 = 0.58, P = 0.445]. The incidence of postoperative pharyngeal pain in the observation group was significantly lower than that in the control group [10.0% (3/30) vs. 33.3% (10/30), χ2 = 5.02, P = 0.025). There were no statistically significant differences between the two groups in terms of number of cases with tube displacement, hemodynamic parameters, blood gas analysis, inflammatory markers, surgical field exposure, and postoperative Visual Analog Scale scores between the two groups (all P > 0.05). Conclusion:Ultrasound-guided TPVB combined with BB placement during thoracoscopic surgery can reduce airway injury compared with the use of a double-lumen bronchial tube. It provides adequate sedation and analgesia during the procedure, facilitates rapid awakening, promotes early recovery of spontaneous breathing, and has fewer adverse reactions, making it worthy of clinical promotion.

Oligoasthenozoospermia is the main cause of male infertility， with complex and diverse causes. Currently， there are still some unclear causes of oligoasthenozoospermia in clinical practice， known as idiopathic oligoasthenozoospermia. With the development of high-throughput sequencing technology， it has been found that intestinal microbiota disorder may be an important promoting factor for the onset of oligoasthenozoospermia. Traditional Chinese medicine believes that "deficiency of kidney essence" is the core pathogenesis of oligoasthenozoospermia. In clinical practice， the method of tonifying the kidney and strengthening the essence has a significant therapeutic effect on oligoasthenozoospermia， but its mechanism of action has not been fully elucidated. Based on the basic theories of traditional Chinese medicine and molecular biology research， it has been found that there is a similarity between "kidney essence" and intestinal microbiota. During the onset of oligoasthenozoospermia， the disorder of intestinal microbiota has similarities with the pathogenesis of "deficiency of kidney essence" in traditional Chinese medicine. Moreover， traditional Chinese medicine for tonifying the kidney and strengthening the essence can regulate the disorder of intestinal microbiota， which may be one of the effective mechanisms for the treatment of oligoasthenozoospermia with the Bushen Yijing method. Based on this， this article explored the mechanism of Bushen Yijing method of traditional Chinese medicine in treating oligoasthenozoospermia from the perspective of intestinal microbiota， so as to provide new ideas for the treatment of oligoasthenozoospermia with traditional Chinese medicine.

The pathogenesis of varicocele infertility is complex, and currently, there is no specific drug for clinical treatment, traditional Chinese medicine (TCM) has certain advantages in improving clinical symptoms of patients and improving sperm quality. Based on the theory of deficiency and stasis in TCM and modern related research, we believe that static blood blocking collaterals is the initiating factor of this disease, and kidney essence deficiency is the immanent trend of this disease. The pathogenesis and treatment method of this disease are studied on the basis of "soil theory". Guilu Tongqu Decoction is a formula developed by our team based on "soil theory" for the treatment of varicocele infertility. It is a modified version of the classic formula Zuogui Pill , which has the effects of tonifying the kidney, nourishing essence, and promoting blood circulation for removing blood stasis. Its clinical efficacy is good. At the same time, based on our team's extensive clinical practice, we propose three treatment strategies for varicocele infertility, namely, the combination of systemic and local treatment, the combination of radial and symptomatic treatment, and the combination of TCM and surgical procedures. These methods can effectively improve the overall therapeutic effect and provide a reference for the treatment of varicocele infertility with TCM.

In recent years，with the change in lifestyle and social environment and the increase in pressure in both life and work，male fertility has decreased significantly in China，and the incidence of male infertility has increased year by year，which has brought great challenges to andrologists. Traditional Chinese medicine （TCM） has a definite curative effect in the treatment of male infertility and is widely applied in clinical practice. In order to clarify the role of TCM in different types and each stage of male infertility，the China Association of Chinese Medicine （CACM） invited outstanding young andrologists in the clinic of TCM and western medicine to discuss topics such as idiopathic oligospermia and teratospermia，abnormal semen liquefaction，varicocele，immune infertility，improving success ratio of assisted reproductive technology，and ameliorating depression or anxiety. They conducted in-depth discussions on the advantages，characteristics，disadvantages，diseases responding specifically，and advantageous aspects of TCM treatment. The causes of male infertility and related links of treatment were summarized. Due to the unclear etiology and complex pathogenesis of male infertility，western medicine cannot achieve a good curative effect，while TCM，taking the holistic view as the core，specializes in improving functional diseases and can correspond to multiple targets and factors，with comprehensive treatments such as internal treatment and external treatment. This study summarized the advantageous diseases and advantageous stages of TCM treatment alone and integrated TCM and western medicine treatment and put forward suggestions for the treatment of the diseases by TCM and western medicine in order to promote the therapeutic effects and advantages of TCM among andrologists，increase mutual learning and communication between TCM and western physicians，provide patients with excellent and personalized treatment plans in clinical practice，and improve the curative effect of male infertility and fertility of males in China.

Experimental research on male infertility is critical to the study of the pathogenesis of male infertility and the evaluation of drug therapy. This paper reviewed animal experiments on male infertility in recent years. The experimental models of male infertility mainly include oligoasthenozoospermia （OA），teratozoospermia，azoospermia， and varicocele animal models. The OA animal models are mostly induced by glycosides of Tripterygium wilfordii （GTW）， adenine，hydrocortisone， and radiation，which are mainly chemical means. The animal models of azoospermia were usually constructed by intraperitoneal injection of bissulfonyl alkylating agent busulfan and immersion of scrotum in 43 ℃ water. There are few studies on animal models of teratozoospermia，and the induction methods by GTW and methyl methanesulfonate（MMS） are common. The animal models of varicocele-caused infertility are usually induced by operation. The ligation of the middle division of the left renal vein between the lateral inferior vena cava and the medial spermatic vein has a significant influence on testicular morphology and epididymal sperm quality. Animal experimental studies have shown that classic prescriptions for tonifying the kidney and promoting spermatogenesis represented by Wuzi Yanzongwan and clinical empirical prescriptions by modern research have played a significant role in the treatment of male infertility. The mechanism of tonifying the kidney in the treatment of male infertility mainly focuses on inhibiting spermatogenic cell apoptosis. The kidney-tonifying method can regulate the apoptosis of spermatogenic cells，which provides a new treatment idea and a reliable scientific basis for traditional Chinese medicine in the field of male reproduction.

Objective To investigate the expression levels of microRNA(miR)-191,miR-23a,and miR-145 in plasma of patients with prostate cancer and their correlation with prognosis.Methods Sixty prostate cancer patients admitted to Zhumadian Central Hospital from December 2019 to December 2021 were selected as the observation group,and 60 healthy subjects who underwent physical examinations during the same period were selected as the control group.The expression levels of miR-191,miR-23a and miR-145 in plasma of subjects in the two groups were measured by real-time fluorescence quantita-tive polymerase chain reaction.The patients in the observation group were divided into poor prognosis group(n=11)and good prognosis group(n=49)according to their prognosis.The expression levels of miR-191,miR-23a,and miR-145 in plasma of prostate cancer patients were compared before and after treatment.The general data of patients was compared between the poor prognosis group and the good prognosis group.The receiver operator characteristic curve was drawed to analyse the predictive value of plasma miR-191,miR-23a,and miR-145 levels on prognosis.Results The relative expression levels of miR-191 and miR-23 a in plasma of patients in the observation group were significantly higher than those in the control group,while the relative expression level of miR-145 was significantly lower than that in the control group(P＜0.05).The relative expression levels of miR-191 and miR-23a of patients in the observation after treatment were significantly lower than those before treat-ment,while the relative expression level of miR-145 was significantly higher than that before treatment(P＜0.05).There was no significant difference in age,body mass index,smoking history,alcohol consumption history,and prostate volume of patients between the poor prognosis group and the good prognosis group(P＞0.05);there was significant differences in TNM staging,Gleason score,serum prostate specific antigen level and relative expressions of miR-191,miR-23a,miR-145 in plasma of patients between the two groups(P＜0.05).Plasma miR-191,miR-23a and miR-145 levels were influence factor for prognosis in patients with prostate cancer(P＜0.05).There was predictive value of plasma miR-191,miR-23a and miR-145 for prognosis of prestate cancer patients;the combined predictive value of plasma miR-191,miR-23a and miR-145 for the prognosis of prostate cancer patients was significantly higher than that of plasma miR-191,miR-23a and miR-145 alone for the prognosis of prostate cancer patients(P＜0.05).Conclusion The expression of miR-191 and miR-23a in plasma increases and the expression of miR-145 in plasma decreases in patients with prostate cancer.The combined detection of plasma miR-191,miR-23a and miR-145 has higher predictive value for the prognosis of prostate cancer.

Objective:To explore the risk factors and preventive strategies of pancreatitis after percutaneous transhepatic biliary drainage (PTBD) in patients with pancreatic cancer and obstructive jaundice.Methods:A total of 241 patients were retrospectively analyzed from May 2001 to October 2014 in Tianjin Medical University Cancer Institute and Hospital. The possibly correlated 9 factors were analyzed, including gender, age, hemoglobin level, total bilirubin level, degree of pancreatic duct dilatation, degree of pancreatic atrophy, degree of biliary stenosis, the pancreatic duct visualization, and drainage mode.Results:Univariate analysis suggested that pancreatic duct dilatation, pancreatic atrophy, visualized pancreatic duct and drainage mode were associated with the incidence of pancreatitis after PTBD ( P<0.05). Logistic regression analysis showed that visualization of pancreatic duct ( OR=6.33) was a risk factor for pancreatitis, while pancreatic duct dilatation ( OR=0.14), pancreatic atrophy ( OR=0.12) and external drainage ( OR=0.11) were protective factors for pancreatitis. Conclusion:In pateints with pancreatic cancer and obstructive jaundice, pancreatic duct dilatation and pancreatic atrophy predict low risk of pancreatitis after PTBD,while intraoperative pancreatic duct visualization and internal or external drainage may increase the incidence of postoperative pancreatitis.