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.

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.

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.

To explore the effects of KIAA0196 gene on cardiac development and the establishment of zebrafish strain.
 Methods: Peripheral blood and gDNA from patients were extracted. Copy number variation analysis and target sequencing were conducted to screen candidate genes. The KIAA0196 knockout zebrafish was generated by CRISPR/Cas9 to detect whether KIAA0196 deficiency could affect cardiac development. Finally, the wild-type and mutant zebrafish were anatomized and histologically stained to observe the phenotype of heart defects.
 Results: The KIAA0196 knockout zebrafish strain was successfully constructed using CRISPR/Cas9 technology. After 60 hours fertilization, microscopic examination of KIAA0196 knockout zebrafish (heterozygote + homozygote) showed pericardial effusion, cardiac compression and severely curly tail. Compared with wild-type zebrafish, the hearts of mutant KIAA0196 zebrafish had cardiac defects including smaller atrium and larger ventricle, and the myocardial cells were looser.
 Conclusion: KIAA0196 gene plays an important regulatory role in the development of heart. It might be a candidate gene for congenital heart disease.
Animals ; DNA Copy Number Variations ; Heart ; Heart Defects, Congenital ; genetics ; Humans ; Myocytes, Cardiac ; Phenotype ; Proteins ; Zebrafish ; genetics ; Zebrafish Proteins ; genetics

Objective To investigate the clinical effect of anterior controllable antedisplacement and fusion (ACAF) for the treatment of ossification of the posterior longitudinal ligament (OPLL) of the cervical spine.Methods The data of 45 cases with cervical posterior longitudinal ligament ossification treated by ACAF from March 2017 to October 2017 were retrospectively analyzed,including 25 males and 20 females,age 45-68 years,average 57.5 years.There were 18 cases involving C3 vertebral body,30 cases involving C4 vertebral body,40 cases involving C5 vertebral body,34 cases involving C6 vertebral body,and 7 cases involving C7 vertebral body.The function of the neural function was evaluated by the Japanese Orthopaedic Association (JOA) scoring system at preoperation and latest follow-up.The curvature of the cervical spine was measured on the lateral X-ray film of the cervical spine,the maximum occupying ratio of the spinal canal was measured on the cross section of the CT scan,and compression of the cervical spinal cord was evaluated by the cervical MRI.Results Patients were followed up for 3 to 6 months (average,3.9 months).The improvement of neurological function was obtained in all the patients.The JOA score improvement rate at the latest follow-up was 71.3％±9.6％.The cervical lordosis was improved from preoperative 4.5°±3.8° to 10.3°±4.8° at the latest follow-up.The canal stenosis ratio was decreased from preoperative 54.3％±8.2％ to 12.5％±5.3％ at the latest follow-up.MRI showed that the cervical spinal cord was adequately decompressed in situ.No specific complications were identified that were associated with this technique.Conclusion The present study elaborates the surgical tips and demonstrates the satisfactory outcome of ACAF for the treatment of OPLL.This novel technique has the potential to serve as an alternative surgical technique for the treatment of cervical OPLL.

OBJECTIVETo evaluate the clinical therapeutic effects and safety on moderate and severe persistent allergic rhinitis treated with acupoint application therapy of the different intensity during the dog days.

METHODSOne hundred and sixty patients of moderate and severe persistent allergic rhinitis were randomized into a No.1 treatment group, a No.2 treatment group, a No.3 treatment group and a placebo group, 40 cases in each one. The same acupoints were used in the four groups, named Dazhui (GV 14), Dingchuan (EX-B1), Feishu (BL 13), Pishu (BL 20), Mingmen (GV 4), Gaohuang (BL 43), Shenshu (BL 23) and Qihai (CV 6). In the three treatment groups, the fine powder of the ingredients (,,,) of compoundformula was used. In the No.1 treatment group, the herbal paste (ginger-prepared paste) was prepared with ginger juice and the above herbal powder. In the No.2 and No.3 treatment groups, the herbal paste (honey-prepared paste) was prepared with honey with the above herbal powder. In the placebo group, the pseudo-herbal paste of the same appearance was prepared with millet powder and distilled water. The acupoint application was given for 2 h in the No.1 and No.2 groups and was for 6 h in the No.3 treatment group and the placebo group. The acupoint application therapy was given once every week during the dogdays, continuously for 5 weeks. The total nasal symptom score (TNSS), the score of the rhinoconjunctivitis quality of life questionnaire (RQLQ) and the count of blood eosinophils (EOS) were observed in the patients of the 4 groups before and after treatment. The clinical therapeutic effects were compared among the 4 groups. The incidences of the skin adverse reactions were observed in each treatment group.

RESULTSAfter treatment, the scores of TNSS and RQLQ were all reduced as compared with those before treatment in the three treatment groups (<0.05,<0.01), in which, the improvements in the No.3 treatment group were better than those in the No.1 treatment group and the No.2 treatment group (both<0.05). After treatment, the count of EOS was all reduced as compared with that before treatment in the three treatment groups (all<0.05). The differences were not significant statistically among the three treatment groups (all>0.05). The total effective rate was 85.0% (34/40) in the No.3 treatment group, better than 76.3% (29/38) in the No.1 treatment group, 71.8% (28/39) in the No.2 treatment group and 5.0% (2/40) in the placebo group (<0.05,<0.01). The incidences of the skin adverse reaction in the No.3 treatment group and the No.2 treatment group were lower than those in the No.1 treatment group (both<0.01).

CONCLUSIONThe acupoint application of the different intensity relieves the symptoms and improves the living quality in the patients of moderate and severe persistent allergic rhinitis. The stimulation of the ginger-prepared herbal paste is strong and induces skin blisters after 2 h herbal application. The stimulation of the honey-prepared herbal paste is moderate and does not induce blisters. The 6 h stimulation of the honey-prepared herbal paste is mild and the therapeutic effect is optimal.

Objective To establish a study cohort of chronic hepatitis B (CHB) in Qidong and evaluate its baseline characteristics. Methods CHB outpatients of the Third People's Hospital of Qidong were invited to participate in baseline survey from January 1, 2016, including questionnaire survey, liver function detection, serum detection of HBV infection and upper abdomen ultrasound detection. Anticipated sample size was at least one thousand. Baseline data were inputted by EpiData 3.1 software and then cleaned and analyzed by SAS 9.3 software. Results As of 18 July, 2016, a total of 1006 participants had been enrolled into the current study, including 615 males with an average age of (44.26±9.97) years and 391 females with an average age of (46.66±11.17) years. The difference in family history of liver disease was not significant between males and females (P>0.05), while the differences in other key information, such as age, education level, tobacco consumption, alcohol drinking, tea consumption, and antiviral intervention, were significant between males and females (P<0.05). Among the key clinical parameters, such as ALT, HBeAg, HBsAg, HBV DNA, albumin, and width of splenic vein and portal vein, only the abnormal rates of ALT and total bilirubin levels were higher in males than in females, the difference was significant (P<0.05). Conclusion Outpatient department-based CHB cohort was established successfully in Qidong, and sub-cohort could be divided according to the differences on baseline characteristics.

Objective:To evaluate the clinical efficacy of paclitaxel combined with epirubicin neoadjuvant chemotherapy in the treatment of triple negative breast cancer and the effect on the Ki-67,p53,P-glycoprotein (P-gp) and glutathione transferase (GST-π).Methods:84 patients with triple-negative breast cancer admitted in our hospital from June 2010 to June 2012 were selected and divided into the observation group and the control group according to the order of admission.The control group was treated with epirubicin,and cyclophosphamide.The observation group was given paclitaxel neoadjuvant chemotherapy combined with epirubicin.The clinical efficacy,expressions of Ki-67,p53,P-gp and GST-π were compared between the two groups.Results:After treatment,the total remission rate of observation group was significantly higher than that of the control group [76.19％(32/42) vs 45.24％(19/42)] (P ＜0.05).Before chemotherapy,the positive expression rates of Ki-67,p53,P-gp and GST-π in the two groups showed no statistical difference(P＞0.05).After chemotherapy,the positive expression rates of Ki-67,p53,P-gp and GST-π in the observation group were significantly lower than those of the control group (P＜0.05),but the positive expression rates of Ki-67,p53,P-gp and GST-π in the control group had no significant difference compared with those before chemotherapy (P＞0.05).The positive expression rates of Ki-67,p53,P-gp and GST-π in the observation group were significantly lower than those of the control group (P ＜0.05).There was no significant difference in the incidence of adverse reaction rate between the observation group and the control group (P＞ 0.05).Conclusion:Paclitaxel combined with Epirubicin neoadjuvant chemotherapy could effectively reduce the expression of Ki-67,p53,P-gp and GST-π in triple-negative breast cancer with exact clinical efficacy.

BACKGROUND:Anular repair after discectomy in intervertebral disc degeneration obtains good clinical outcomes and reduces the recurrent rate, but there is little report on the effective suturing method and reliable instrument. OBJECTIVE: To investigate the clinical effectiveness of annulus repair after discectomy under Mast Quadrant system for lumbar disc herniation. METHODS: Fifty patients with lumbar disc herniation admitted in the Hubei Provincial Hospital of TCM from August 2013 to August 2015 were selected, followed by divided into experimental and control groups (n=25 per group), and then received annulus repair after discectomy and simple discectomy, respectively. The length of incision, operation time and intraoperative blood loss were compared between two groups, and the Oswestry disability index and visual analogue scale scores for lumbago and lower limb pain before and after surgery were detected, as well as the incidence of complications and recurrence were recorded. RESULTS AND CONCLUSION:All patients in the experimental group completed the follow-up, while only 23 in the control group finished the follow-up. There were no significant differences in the baseline data between two groups (P > 0.05). The postoperative Oswestry disability index and visual analogue scale scores in both two groups were significantly lower than those before surgery (P < 0.05). There was a significant difference in the visual analog scale score at 1 month postoperatively between two groups (P < 0.05), while the scores at other time points showed insignificant difference between two groups (P > 0.05). There were two cases of recurrence in the control group, one of which received secondary treatment, and the recurrent rate was 9%. In the experimental group, there was only one case of recurrence receiving no treatment, and the recurrent rate was 4%. There were no cerebrospinal fluid leakage, infection, never root injury or other serious complications in both two groups. These results indicate that annulus repair after discectomy is minimally invasive, achieves the reconstruction of disc, and reduces the recurrence rate, which is available for lumbar disc herniation.