The dysregulation of cyclin-dependent kinase 12 (CDK12), which may result from genomic alterations or modulation by upstream effectors, is implicated in cancer oncogenesis and progression. CDK12 overexpression or activation is sufficient to induce tumor initiation, recurrence, and therapeutic resistance. However, CDK12 may also exert tumor-suppressive functions in a context-dependent manner. Therefore, caution is warranted when targeting CDK12 in future clinical trials. A comprehensive elucidation of the dual roles and underlying mechanisms of CDK12 in carcinogenesis is urgently needed to advance precision oncology. This review provides an overview of the current understanding of the dysregulation and biological roles of CDK12 in cancer. Subsequently, we systematically summarize the functions and mechanisms of the oncogenic and tumor-suppressive roles of CDK12 in different contexts. Finally, we discuss the potential of CDK12 as a novel therapeutic target and its implications in clinical oncology, offering insights into future directions for innovative cancer treatment strategies.

Objectives:To evaluate the learning curve of transcatheter aortic valve replacement(TAVR)in a single center by single operator using Venus A valve. Methods:A total of 150 patients with severe aortic stenosis who underwent TAVR using Venus A valve in Fujian Provincial Hospital from July 2018 to May 2022 were selected.According to the time order of TAVR,the 1st-50th patients were included in group A,the 51st-100th patients were included in group B and the 101st-150th patients were included in group C.The basic clinical data,perioperative parameters and postoperative follow-up data of the three groups were analyzed. Results:All high-risk patients with severe aortic stenosis had an average STS score(7.9±1.5)and were treated with Venus A valve.The total operation time of group A,group B and group C was(226.2±86.3)min,(115.2±47.1)min,(108.2±38.1)min;the peripheral path operation time was(45±10)min,(20±7)min,(18±6)min;the valve release time was(13.0±2.3)min,(5.0±2.1)min,(3.0±1.7)min;the X-ray fluoroscopy time was(24±8)min,(11±5)min,(10±3)min;the radiation dose was(1 266±227)mGy,(532±132)mGy,(519±108)mGy;and the total incidence of perioperative adverse events was 46%,18%,16%,respectively.The differences were statistically significant(all P<0.05).The total incidence of adverse events during follow-up within 6 months for patients in group A,group B,and group C were 6%,2%,and 0%(P>0.05).With the increase of TAVR cases,the correlation curve of each time node of TAVR and radiation dose tended to be stable after the 50th-60th cases. Conclusions:With the increase of procedural experience,the total operation time,operative time nodes,radiation dose and perioperative adverse events of TAVR with Venus A valve decreases gradually,and the operator usually needs 50-60 cases to cross the TAVR learning curve.

Objectives:To investigate the effect of body mass index(BMI)on perioperative and long-term prognosis of patients with severe aortic stenosis(AS)after transcatheter aortic valve replacement(TAVR). Methods:This retrospective study imcluded 180 patients with severe AS who received TAVR in Fujian Provincial Hospital from January 2019 to January 2022.According to the BMI,patients were divided into four groups:low weight group(BMI<18.5 kg/m2,n=23),normal weight group(18.5 kg/m2≤BMI<24.0 kg/m2,n=65),overweight group(24.0 kg/m2≤BMI<28.0 kg/m2,n=57),obesity group(BMI≥28.0 kg/m2,n=35).The general clinical characteristics,imaging parameters,perioperative indexes,all-cause death and the incidence of other adverse cardiac events during(18.0±6.8)months follow-up were compared among different groups.Risk factors for the perioperative complications and long-term outcomes of TAVR were evaluated. Results:The prevalence of hypertension and diabetes,left ventricular end-diastolic diameter,ventricular septal thickness and left ventricular posterior wall thickness were significantly higher in the obese group than in normal weight group(all P<0.05).The level of prealbumin in low weight group was lower than in normal weight group(P<0.05).The total perioperative complications in low weight group were higher than in normal weight group(60.9%vs.12.3%,P=0.042).During(18.0±6.8)months follow-up,the incidence of all-cause death in the low weight group was significantly higher than that in normal weight group,overweight group and obese group(17.4%vs.4.6%vs.3.5%vs.5.7%,P=0.003).Kaplan-Meier survival analysis evidenced higher mortality rate in low weight group at 18 months after TAVR(log-rank P<0.01).Multivariate Cox regression analysis showed that the risk of long-term adverse cardiovascular events was significantly higher in low weight group than in normal weight group(HR=7.633,95%CI:1.012-57.564,P=0.049). Conclusions:Low weight patients with severe AS have a higher incidence of perioperative complications and a poor long-term prognosis.Such patients should appropriately strengthen their nutritional intake and adjust their body weight to normal levels before performing TAVR.

Objective:To improve the prognosis stratification, especially early mortality(EM), of elderly patients with newly diagnosed multiple myeloma(NDMM).Methods:In this retrospective study, univariate and multivariate Cox regression analysis were conducted to identify the independent prognostic factors associated with overall survival(OS)and the chi-square test and multivariate Logistic analysis were used to identify the prognostic factors associated with EM in 223 elderly patients(age≥65 years)with NDMM from three centers in the country.Results:Increased NT-pro-BNP(≥300 pg/ml), ECOG-PS≥2 and stage Ⅲ R-ISS were identified as three independent adverse prognostic factors of OS.The rates of EM3, EM6, EM12 and EM24 were 12.1%, 20.1%, 32.2% and 60%, respectively.The most common cause for EM6(particularly EM3)was disease-related complications resulting from ineligibility for treatment due to poor physical performance, severe organ dysfunction or treatment discontinuation due to treatment intolerance, while the most common cause for EM12(particularly EM24)was disease progression or relapse mainly as a result of inadequate treatment.R-ISS staging failed to predict EM, while decreased eGFR, ECOG-PS≥2, and increased NT-pro-BNP were able to estimate the risk of EM, with increased NT-pro-BNP as a common independent factor for EM12( P=0.03)and EM24( P=0.015). Conclusions:R-ISS staging, which primarily reflects MM biology, cannot predict EM.However, factors such as NT-pro-BNP, eGFR and ECOG-PS associated with frailty and impairment of organ functions can be used to estimate the risk of EM, among which NT-pro-BNP may be the most important independent factor for EM.Therefore, incorporation of these frailty-related biomarkers into R-ISS staging may be able to more precisely estimate the prognosis and particularly early death of elderly patients with NDMM.

Objective: In this study, we used HepG2 human hepatocellular carcinoma cells to study the effects of Compound Xishu Granule (CXG) on cell proliferation, apoptosis, and the cell cycle in vitro. We also used a xenograft tumor model to study the anti-tumor effects of CXG and related mechanisms in vivo.Methods: The effect of CXG on cell viability was measured using Cell Counting Kit-8 and a colony for-mation assay. The effect of CXG on apoptosis and the cell cycle was analyzed using flow cytometry. The in vivo anti-tumor effect of CXG was assessed by measuring the volume change in xenograft tumors after drug administration. The CXG anti-tumor mechanism was studied using western blotting assay to detect cell cycle and apoptotic associated proteins. Results: CXG suppressed HepG2 cell proliferation in a time-and dose-dependent manner in vitro. Colony formation experiments showed that CXG administration for 24 h significantly reduced HepG2 cell for-mations (P<.01). Flow cytometric analysis showed that CXG treatment for 48 h promoted apoptosis and blocked HepG2 cells in the G2/M phase. Western blotting results showed that Bax was significantly up-regulated and Bcl-2 was down-regulated in graft tumor tissues and HepG2 cells after CXG administra-tion, which increased the Bax/Bcl-2 ratio. PLK1, CDC25C, CDK1, and Cyclin B1 expression were up-regulated. CXG had a good inhibitory effect on graft tumor growth in vivo. Conclusion: CXG has good anti-tumor effects in vitro and in vivo. In vitro, CXG promoted HepG2 cell apoptosis and induced G2/M phase arrest. In vivo, CXG significantly inhibited graft tumor growth. The CXG mechanism in treating hepatocellular carcinoma may be that CXG can induce abnormal apoptotic and cell cycle associated protein expression, leading to mitotic catastrophe and apoptosis.

Modular scientific research teaching is an open teaching mode for undergraduates in medical colleges and universities. Under the premise of students' own choice, the lab-based training was performed for 15 teaching weeks, with three modular scientific research courses. Meanwhile, with the help of a series of scientific research lectures, literature reports, and discussions of experimental results, the teachers guided the students to carry out modular scientific research training and taught related theoretical knowledge during experimental teaching. The modular scientific research teaching for undergraduates in medical colleges and universities helps to enhance their knowledge of life science and basic medical knowledge, cultivate basic experimental abilities, and make them fully prepared for clinical research or postgraduate study.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of adult lymphoma and is a group of invasive and heterogeneous diseases. Although rituximab in combination with CHOP regimen (R-CHOP) for DLBCL is better, one third of patients have relapsed/refractory conditions. DLBCL is divided into many subtypes due to its high heterogeneity. Different histological types have different response to treatment. High-risk DLBCL has little effect on R-CHOP treatment. How to further improve the first-line cure rate of high-risk DLBCL has become an important challenge in the field of lymphoma treatment. Currently in the era of precision medicine, in recent years, many new targeted drugs, such as immunosuppressive agents, mammalian target of rapamycin (mTOR) receptor inhibitors and Bruton tyrosine kinase (BTK) inhibitors, have been developed for DLBCL-related pathways and molecular targets, provide more new possibilities for the treatment of DLBCL.

Objective: To explore the application value of thyroid alar cartilage(TAC) in the laryngotracheal reconstruction of subglotticstenosis in the paediatric population. Methods: Twelve patients(7 males,5 females; range from 2.3 to 12.0 years) with subglotticstenosis who had undergone laryngotracheal reconstruction procedures at our hospital fromSeptember 2016 to July 2018 were analyzed retrospectively.The degree of stenosis was classified according to Myer-Cotton classification system:grade Ⅱ(n=4),grade Ⅲ(n=6) and grade Ⅳ(n=2). The stenosis planes were subglotticbut did not exceed the 3rd tracheal cartilage ring. Results: Of all 12 patients, 11 were decannulated and 1 failed. All patients with grade Ⅱ and Ⅲ patients were decannulated at one procedure. There were no severe complications such as tube dislogement,asphyxia and unhealed wound. Conclusions The TAC for widening laryngotracheal lumen is relatively simple and reliable for laryngotracheal reconstruction in the pediatric population with subglottic stenosis. This would′t cause any structural damage to the laryngeal cavity.

Objective To investigate the density seasonal fluctuation and insecticide resistance of Anopheles sinensis in the Taibai Lake area and to provide a scientific basis for formulation of Anopheles sinensis control strategy.Methods The surveillance was carried out from June to October in 2013-2016.The adult mosquito density was monitored using human bait trapping method.WHO bioassay method was used to measure the sensibility of mosquitoes to insecticides.Results In 2013-2016,totally 2 318 Anopheles sinensis were captured,the Anopheles sinensis peaked in late July till early August,which were 67-127,317-386,77-89,107-139,respectively.Anopheles sinensis showed high resistance to dichlorodiphenyltrichloroethane,malathion,and initial resistance to propoxur and deltamethrin (mortality ratio:38.10％,41.82％,86.11％,83.02％).Conclusions The Taibai Lake area has a diverse Anopheles sinensis population,its seasonal fluctuations and insecticide resistance monitoring can provide effective guidance for malaria control.In order to prevent the development of resistance to the insecticides,integrated management measures should be adopted in the future.

Objective     To discuss the key points of anesthesia for patients undergoing transcatheter aortic valve implantation (TAVI) surgery. Methods     We retrospectively collected and analyzed the data of 70 patients who underwent TAVI in the Department of Cardiovascular Surgery, West China Hospital from March 2014 to October 2015. There were 39 males and 31 females with an average age of 73.7±4.5 years. The perioperative preparation and anesthesia points of TAVI were summarized. Results     All of the 70 included patients were aged and at high risk severe comorbidities such as ischemic heart disease and stroke. The aortic stenosis and regurgitation occurred in 39 and 31 patients respectively. No patients died during the surgery. The total success rate was 95.7%. Conclusion     TAVI is a complex procedure for high risk patients and need more attention during anesthesia. The successful conduction of the procedure requires the whole team to prepare carefully and cooperate closely.