The treatment of castration-resistant prostate cancer (CRPC) faces major challenges characterized by acquired resistance to androgen deprivation therapy (ADT) and consequent aggressive tumor progression. In this context, ubiquitination and deubiquitination modifications, as key protein post-translational modifications, play a crucial role in prostate tumourigenesis and progression. In recent years, the regulation of ubiquitination and deubiquitination in CRPC by the androgen receptor signalling pathway and the tumour microenvironment has received extensive attention, and these dynamic regulatory processes have become important molecular events driving CRPC progression by affecting the proliferation, metastasis, and immune escape ability of tumour cells. Therefore, in-depth analysis of the mechanisms of ubiquitination and deubiquitination in CRPC will help develop new therapeutic targets and provide more therapeutic options for patients.

The treatment of castration-resistant prostate cancer (CRPC) faces major challenges characterized by acquired resistance to androgen deprivation therapy (ADT) and consequent aggressive tumor progression. In this context, ubiquitination and deubiquitination modifications, as key protein post-translational modifications, play a crucial role in prostate tumourigenesis and progression. In recent years, the regulation of ubiquitination and deubiquitination in CRPC by the androgen receptor signalling pathway and the tumour microenvironment has received extensive attention, and these dynamic regulatory processes have become important molecular events driving CRPC progression by affecting the proliferation, metastasis, and immune escape ability of tumour cells. Therefore, in-depth analysis of the mechanisms of ubiquitination and deubiquitination in CRPC will help develop new therapeutic targets and provide more therapeutic options for patients.

Objective:To investigate molecules involved in the occurrence of pruritus in patients with mycosis fungoides (MF) .Methods:Totally, 522 patients with MF were enrolled from Peking University First Hospital from October 2009 to August 2021, and the incidence of pruritus was calculated. The patients were grouped according to whether they suffered from pruritus or not. RNA sequencing data on biopsied skin lesions of 49 patients were analyzed to identify differentially expressed genes between patients with pruritus and those without; enzyme-linked immunosorbent assay and immunohistochemical techniques were performed to determine the protein expression of CC chemokine ligand 17 (CCL17) in serum samples from 88 MF patients, and in tissue samples from 81 MF patients, respectively; flow cytometry was conducted to detect markers for T lymphocyte activation and differentiation in peripheral blood samples from 46 MF patients to identify peripheral blood lymphocyte subsets associated with pruritus. Statistical analysis was carried out by using chi-square test, Mann-Whitney U test, and Spearman correlation analysis. Results:Among the 522 patients with MF, 305 were males and 217 were females; 347 were diagnosed with early-stage MF, and 175 with advanced MF. The incidence of pruritus was 67.2% (351/522) in the patients with MF, and significantly higher in the patients with advanced MF (81.7%, 143/175) than in those with early-stage MF (59.9%, 208/347; χ2 = 25.03, P < 0.001) . RNA sequencing showed that CCL17 mRNA expression was significantly higher in the MF patients with pruritus than in those without (fold change = 10.09, P < 0.001) . The serum CCL17 concentration was significantly elevated in the patients with pruritus (1 017.05[377.12, 4 831.80] pg/ml) compared with those without (361.66 [180.47, 500.08] pg/ml; Z = -4.57, P < 0.001) , and correlated with pruritus scores ( r = 0.57, P = 0.010) . In both early and advanced stages of MF, the serum CCL17 concentration was significantly higher in the patients with pruritus than in those without ( Z = -3.68, P < 0.001; Z = -2.54, P = 0.011, respectively) . Immunohistochemical staining revealed that there was no significant difference in the relative quantification value of CCL17 between the patients with pruritus and those without ( Z = -1.84, P = 0.066) . The percentage of CD3 +CD4 +CD26 -CCR4 + malignant T cells significantly increased in the MF patients with pruritus than in those without ( Z = -2.03, P = 0.043) , and was positively correlated with serum CCL17 concentrations ( r = 0.49, P < 0.001) . Conclusions:Both CCL17 mRNA expression in lesional tissues and serum CCL17 concentrations increased in MF patients with pruritus, and CCL17 was associated with the occurrence of pruritus. CCL17 may be involved in the occurrence of pruritus through the recruitment of CD3 +CD4 +CD26 -CCR4 + malignant T cells.

Objective: : Dermoid cysts are uncommon in spinal cord tumors, and the phenomenon of their spontaneous rupture into the syrinx cavity is quite rare. We aimed to analyze the imaging characteristics and etiologies, and propose some surgical strategies, for this uncommon phenomenon. Methods: : We retrospectively reviewed 14 cases with spinal dermoid cysts that ruptured into the cervical and thoracic syrinx cavity. There were six male and eight female cases, aged 21 to 46 years, who had lipid droplets in the syrinx cavity from C1 to L3. The dermoid cysts were always located at the conus. Based on patients’ complaints, clinical manifestations, and imaging results, we adopted tumor excision and/or syrinx cavity aspiration in one stage or multiple stages. Results: : Three patients had only a syrinx cavity aspiration surgery due to a history of dermoid cyst excision. Eight patients had dermoid cyst resection and syrinx cavity aspiration in one stage. One patient was operated upon in two stages due to the development of new symptoms at nine months follow-up. Two patients underwent only tumor resection since they did not show similar symptoms or signs caused by the cervicothoracic syrinx. The axial magnetic resonance imaging indicated that the lipid droplets were always not at the center but were eccentric. The clinical effect was satisfactory during the follow-up period in this group. Conclusion : The lipid droplets filled the spinal syrinx cavity, not entirely confined to the central canal. Based on the chief complaints and associated signs, we adopted different surgical strategies and had satisfactory clinical results.

Objective:To study the outcomes of coronavirus disease 2019 (COVID-19) patients with history of thoracotomy.Methods:A retrospective analysis of clinical diagnosis, treatment data and outcomes of 10 COVID-19 patients with history of thoracotomy were studied in Tongji Hospital of Wuhan.Results:10 COVID-19 patients with history of thoracotomy were severe or critical cases. The clinical manifestations of all patients were mainly represented in respiratory system, and these patients were all confirmed by chest CT and virus nucleic acid detection. After admission, all patients were given oxygen therapy, antiviral therapy (abidol and Lianhuaqingwen), and antibiotic therapy (Moxifloxacin and / or Cefoperazone Sodium and Sulbactam Sodium). Finally, 3 patients died of respiratory failure and 7 patients were cured and discharged smoothly.Conclusion:COVID-19 patients with a history of thoracotomy are easy to develop progression, and the use of antibiotics might be more active. At present, there is no specific treatment, and the combination of multiple methods may be effective.

Vaccination is the most effective way to prevent influenza and severe outcoming caused by influenza viruses.Health care workers(HCW) are exposed to patients with influenza and they are at high risk of occupationally acquired influenza and of causing nosocomial infection among patients,increasing the incidence rate,the risk of severe and death of patients.Improving the influenza immunization in HCW can not only reduce the prevalence of themselves and keep a weel-oiled of health care facilities during the influenza seasons,but also reduce the risk of severe and death among patients and increase the influenza vaccine uptake in whole population.At present,the influenza immunization coverage of HCW is low.The obstacles and myths of influenza vaccine are barriers for vaccine uptake among HCW.The various strategies are critical in order to improve the influenza coverage rates of HCW.

Objective To explore the correlation between fasting blood glucose (FBG) and hepatocarcinogenesis.Methods The retrospective cohort study was conducted.The data of 94 264 participants who participated health examination at the Kailuan General Hospital of North China University of Science and Technology,Kailuan Linxi Hospital,Kailuan Zhaogezhuang Hospital,Kailuan Tangjiazhuang Hospital,Kailuan Fan'gezhuang Hospital,Kailuan Jinggezhuang Hospital,Kailuan Lyujiatuo Hospital,Kailuan Linnancang Hospital,Kailuan Qianjiaying Hospital,Kailuan Majiagou Hospital and Kailuan Branch Hospital from July 2006 to December 2015 were collected.There were 75 134 males and 19 130 females,aged (51:±:12)years,with a range of 18-98 years.All the subjects were allocated into 3 groups according to tertiles of FBG,including 31 083 with FBG ＜ 4.82 mmol/L in the T1 group,31 594 with 4.82 mmol/L≤ FBG ＜5.49 mmol/L in the T2 group and 31 587 with FBG ≥5.49 mmol/L in the T3 group.All participants received the same-order health examinations by the fixed team of doctors in 2006,2008,2010,2012 and 2014 at the same place.Epidemiological investigation,anthropometric parameters and biochemical indicators were collected.Observation indicators:(1) comparisons of clinical characteristics among the 3 groups;(2) follow-up and incidence of liver cancer;(3) situations of non-liver cancer death;(4) risk factors analysis affecting new-onset liver cancer;(5) comparisons of the prognostic value of FBG on liver cancer model;(6) effects of FBG on new-onset liver cancer using competing risk model.Follow-up using physical examination was performed to detect new-onset liver cancer and survival up to December 31,2015.The start time of follow-up was the first health examination in 2016 and the terminal event was new-onset liver cancer,loss of follow-up and death.Measurement data with normal distribution were expressed as Mean±SD,and comparisons among groups were analyzed using the one-way ANOVA.Measurement data with skewed distribution were described as M (range),and comparisons among groups were analyzed using the Kruskal-Wallis rank sum test.Count data were described as absolute number and percentage,and comparisons among groups were analyzed using the chi-square test.The cumulative incidence and mortality of new-onset liver cancer were calculated and incidence curve was drawn by the Kaplan-Meier method,and comparisons of incidences among groups were done by the Log-rank test.The incidence of liver cancer in patients with different levels of FBG was calculated by person-year incidence (incidence density).The hazard ratio (HR) and 95％ confidence interval (CI) of different levels of FBG (classification variable and continuous variable) on new-onset liver cancer were estimated by the COX proportional hazards regression models.Restrictive cubic spline regression was used to calculate the dose-response relation between the continuous FBG and the risks of new-onset liver cancer.The fitting degree of FBG on new-onset liver cancer model was calculated by the likelihood ratio test and akaike information criterion (AIC).The predictive power of different models was calculated using the C-statistics.The net effects of FBG on incidence of liver cancer were analyzed using cause-specific hazard function (CS) and sub-distribution hazard function (SD).Results (1) Comparisons of clinical characteristics among the 3 groups:gender (male),age,systolic pressure,diastolic pressure,waistline,body mass index (BMI),total cholesterol (TC),alanine aminotransferase (ALT),triglyceride (TG),cases with drinking,smoking,physical exercise,positive HBsAg and fatty liver were 23 567,(51±13)years,(128±21)mmHg (1 mmHg=0.133 kPa),(82±12)mmHg,(86± 10) cm,(24±3) kg/m2,(4.8± 1.2) mmol/L,17.12 U/L (range,12.21-24.01 U/L),1.18 mmol/L (range,0.82-1.75 mmol/L),5 080,9 423,4 779,724,7 591 in the T1 group,24 870,(50±12)years,(129±:20)mmHg,(83±12)mmHg,(86±10)cm,(25±3)kg/m2,(4.9±l.1) mmol/L,18.31 U/L (range,13.01-24.31 U/L),1.23 mmol/L (range,0.88-1.83 mmol/L),5 448,9 397,4 570,619,9 009 in the T2 group and 26 697,(53±11)years,(135±22)mmHg,(86±12)mmHg,(89±10)cm,(26±3)kg/m2,(5.1± 1.2) mmol/L,19.00 U/L (range,13.79-26.61 U/L),1.44 mmol/L (range,1.00-2.21 mmol/L),6 354,10 292,5 369,608,13 397 in the T3 group,showing statistically significant differences among groups (x2 =761.68,F=417.84,1 010.71,747.64,702.73,1 075.06,703.83,x2=447.44,2 109.38,165.97,66.69,78.90,15.50,2 576.95,P＜0.05).(2) Follow-up and incidence of liver cancer:all 94 264 participants were followed up for 817 475 person-year,with a total person-year incidence of 3.71/10 000 person-year,1.13/10 000 person-year in the female participants and 4.37/10 000 person-year in the male participants.The incidence density of liver cancer was 2.84/10 000 person-year,3.64/10 000 person-year,4.64/10 000 person-year in the T1,T2,T3 groups,respectively.The cumulative incidence was 2.76‰,3.90‰,4.90‰ in the T1,T2,T3 groups,respectively,showing statistically significant differences among groups (x2=11.95,P ＜ 0.05),showing no statistically significant difference between T1 and T2 groups (x2 =2.73,P＞0.05),showing statistically significant differences between T1 and T3 groups,between T2 and T3 groups (x2=11.56,4.10,P＜0.05).(3) Situations of non-liver cancer death:during the follow-up,6 880 of 94 264 participants had of non-liver cancer related death,with a non-liver cancer death intensity of 84.16/10 000 person-year.The non-liver cancer death intensity was 79.19/10 000 person-year,68.17/10 000 person-year,105.32/10 000 person-year in the T1,T2,T3 groups.The accumulative mortality was 78.90‰,67.80‰,104.40‰ in the T1,T2,T3 groups,respectively,showing a statistically significant difference among groups (x2 =1 231.46,P ＜ 0.05),showing statistically significant differences between T1 and T2 groups,between T1 and T3 groups (x2 =5.29,4.36,P＜0.05),showing no statistically significant difference between T2 and T3 groups (x2 =0.09,P＞ 0.05).(4) Risk factors analysis affecting new-onset liver cancer.Results of COX proportional hazards regression model analysis showed that continuous FBG was a related factor affecting new-onset liver cancer after adjustment of gender,age,BMI,ALT,drinking,smoking,physical exercise,positive HBsAg,fatty liver,liver cirrhosis,malignant tumor in immediate family (HR =1.06,95％ CI:1.01-1.12,P＜0.05).After ln transformation of FBG,ln FBG was a related factor affecting new-onset liver cancer (HR=1.81,95％ CI:1.21-2.70,P＜0.05).Results of restrictive cubic spline regression showed that continous FBG and ln FBG were nonlinear correlated with incidence of liver cancer (RCS_ S1_x2 =7.21,4.36,P＜0.05).After adding FBG as classification variable in the COX model,risk of new-onset liver cancer in the T2 and T3 groups was increased compared with the T1 group (HR=1.45,1.67,95％ CI:1.07-1.95,1.25-2.22,P ＜ 0.05).(5) Comparisons of the prognostic value of FBG on liver cancer model:multivariate model was constructed after adding risk factors of gender,age,BMI,ALT,drinking,smoking,physical exercise,positive HBsAg,fatty liver,liver cirrhosis,malignant tumor in immediate family,and C-value,-2Log L and AIC were 0.79,6 313.30 and 6 345.30 for the multivariate model.Then FBG variable was added into the multivariate model,and the C-value,-2Log L and AIC of the multivariate model + FBG model were 0.80,6 300.48 and 6 336.48,respectively,showing statistically significant differences compared with the T1 group (x2 =12.82,P＜0.05).(6) Effects of FBG on new-onset liver cancer using competing risk model.Results of competing risk model showed that the risk of new-onset liver cancer in the T2 group was not affected compared with the T 1 group (HR =1.42,95％CI:0.98-1.97,P＞0.05) and risk of new-onset liver cancer in the T3 group was increased compared with the T1 group with the SD model (HR=1.63,95％ CI:1.16-2.26,P＜0.05),after adjustment of gender,age,BMI,ALT,drinking,smoking,physical exercise,positive HBsAg,fatty liver,liver cirrhosis,malignant tumor in immediate family.In the CS model,the risk of new-onset liver cancer in the T2 group was not affected compared with the T1 group (HR=1.43,95％ CI:0.99-1.97,P＞0.05) and risk of new-onset liver cancer in the T3 group was increased compared with the T1 group (HR=1.65,95％ CI:1.18-2.23,P＜ 0.05).Conclusions The elevated FBG is an independent risk factor for the incidence of liver cancer.After considering the competitive risk of death,the risk effect of high-level FBG on the liver cancer still exists.

Objective    To summarize the individualized selection of surgical treatment strategies and the key points of perioperative management for patients with heart valve disease complicated with severe chronic heart failure. Methods    The clinical characteristics of 5 male patients with valvular heart disease complicated with severe chronic heart failure (CHF) were analyzed retrospectively from June 2017 to October 2018 in Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, with an average age of 60.21 years. Results    Five patients were given angiotensin receptor and neprilysin inhibitor (ARNI)-based anti-heart failure treatment after admission. The operation mode of these patients was decided to be valve replacement under cardiopulmonary bypass after individualized evaluation of patients’ improving symptoms. Three patients were treated with intra-aortic balloon pump (IABP) and continuous renal replacement therapy (CRRT) early after operation to assist patients in improving cardiac function. Five patients recovered oral anti-heart failure after awakening. All patients were discharged smoothly 2 weeks after operation. Conclusion    Individualized evaluation is needed for the choice of operation timing and mode, standardized preoperative treatment for heart failure, shortening the aortic blocking time during cardiopulmonary bypass, and early application of left ventricular adjuvant drugs or instruments are all important measures to help patients recover smoothly.

Objective To express UL148 RNA of human cytomegalovirus (HCMV) clinical strains in vitro and to study its functions. Methods Urine of a newborn with HCMV infection was inocula-ted into human embryo lung cells. HCMV clinical strain was isolated and identified by multiplex PCR. UL148 gene was amplified and cloned into pGEM-T-Easy plasmid after double enzyme digestion. A recombi-nant plasmid was constructed and located at the downstream of the T7 promoter. The recombinant plasmid was identified by electrophoresis of the recombinant plasmid,PCR product and double enzyme product. Se-quencing analysis was used for final confirmation. UL148 was transcribed into RNA by 32P labeling. Post-translational modification sites were analyzed by bioinformatics method based on UL148 sequence characteris-tics. Results The clinical strain of HCMV was obtained in vitro. Electrophoresis and sequencing analysis confirmed the successful construction of the recombinant plasmid. UL148 RNA was transcribed in vitro by T7RNA polymerase. Post-translational modification sites showed that UL148 gene contained one cell adhe-sion sequence, one legume lectins beta-chain signature, two N-myristoylation sites, one casein kinase Ⅱphosphorylation site,seven protein kinase C phosphorylation sitse, one cAMP/cGMP-dependent protein ki-nase phosphorylation site, two N-glycosylation sites and one transmembrane region. Conclusion UL148 gene might encode a viral adhesion molecule involving in the signal transduction in host cells.

Objective To summarize the characteristics and management of pregnancy complicated with aortic dissection, and to explore the reasonable diagnosis and treatment plan. Methods The clinical data of 10 patients of pregnancy complicated with aortic dissection in Wuhan Tongji Hospital from January 2011 to June 2017 were collected. Their age was 25.2 (21-29) years. Results In the 10 patients, the majority (8 patients) were primipara, and most of them were in the late stages of pregnancy (5 patients) and puerperal (4 patients). Among them, 1 patient had gestational hypertension, and the blood pressure of the left and right upper extremities was significantly abnormal (initial blood pressure: left upper limb blood pressure: 90/60 mm Hg, right upper limb blood pressure: 150/90 mm Hg). The major clinical manifestations were severe chest and back pain which happened suddenly, with D-dimmer and C-creative protein increased which may be associated with inflammatory reaction. All patients were diagnosed by thoracoabdominal aortic CTA, including 5 patients of Stanford type A dissection and 5 patients of Stanford type B dissection. In the 10 patients, 1 patient refused surgery and eventually died of aortic rupture with the death of fetus before birth. And the remaining 9 patients underwent surgical treatment, 3 patients of endovascular graft exclusion for thoracic aortic stent graft, 2 patients underwent Bentall operation, 1 patient with Bentall + total aortic arch replacement + vascular thoracic aortic stent graft, 1 patient with Bentall operation combined with endovascular graft exclusion for thoracic aortic stent graft, 1 patient with Bentall + coronary artery bypass grafting, 1 patient of thoracoabdominal aortic vascular replacement. Among them, 1 patient underwent endovascular graft exclusion for thoracic aortic stent graft died of severe postoperative infection, and the remaining 8 patients were discharged from hospital. Nine patients were single birth, among them 5 newborn patients had severe asphyxia, 4 patients had mild asphyxia. Finally, 3 neonates died of severe complications, and the remaining 6 survived. Conclusion The ratio of pregnancy with Stanford type A aortic dissection is far higher than in the general population, the possibility of fetal intrauterine asphyxia is larger, but through active and effective surgical and perioperative treatment, we can effectively save the life of mother and fetus.