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.

BackgroundMajor depressive disorder （MDD）， a prevalent mental disorder， is characterized by persistent depressed mood， impaired concentration， loss of interest in daily activities， decreased appetite， and sleep disturbances. Randomized controlled trials （RCTs） indicate potential benefits of Bifidobacterium supplementation for MDD， but the evidence base remains insufficient to draw definitive conclusions. ObjectiveTo explore the causal association between Bifidobacterium and MDD through a Mendelian randomization （MR） approach， with the hope of providing genetic evidence to elucidate the etiological mechanisms and risk factors underlying MDD. MethodsSummary-level data from genome-wide association studies （GWAS） was conducted， specifying Bifidobacterium as the exposure variable and MDD as the outcome variable， to rigorously investigate the causal association between Bifidobacterium and MDD. Multiple complementary analytical approaches were employed， including inverse-variance weighted， weighted median estimator， MR-Egger regression， weighted mode and simple mode， to derive robust causal estimates. Furthermore， to ensure the robustness and validity of the findings， a series of comprehensive sensitivity analysis were systematically performed， encompassing MR-Egger regression test， MR-PRESSO test and leave-one-out analysis. ResultsInverse-variance weighted revealed a causal link from Bifidobacterium to MDD （OR=1.018， 95% CI： 1.001–1.035， P=0.035）， whereas no evidence of reverse causality was observed （OR=0.603， 95% CI： 0.116–3.130， P=0.547）. ConclusionBifidobacterium is a risk factor for MDD， and its presence may increase the risk of MDD onset.

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 over-expression 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 pre-cision 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.

ObjectiveTo evaluate the methodological and reporting quality of clinical practice guidelines for Chinese patent medicine （CPM） with internationally recognized tools the appraisal of guidelines for research and evaluation （AGEREE） Ⅱ and reporting items for practice guidelines in healthcare （RIGHT）， thereby providing refe-rence for the clinical application and future development of CPM guidelines. MethodsDatabases including CNKI， VIP， Wanfang and Sinomed were searched for CPM guidelines， as well as medlive.cn， websites of China Association of Chinese Medicine and Chinese Medical Association， and reference lists of the included papers. The quality of the guidelines was evaluated using the AGREE Ⅱand RIGHT tools， and consistency tests were performed using Interclass Correlation Coefficient， and descriptive analysis and chi-square test were used to analyze the reporting rate for each domain and the average score for each item. ResultsFinally， 140 CPM guidelines were included， of which 51 were disease-oriented and 89 were drug-oriented， all of which were issued by China. For 51 disease-oriented CPM guidelines， the highest average score of all six AGREE Ⅱ domains was 73.32% for clarity， and the lowest was 26.80% for application； for 89 drug-oriented CPM guidelines， the highest average score was 55.62% for scope and purpose， and the lowest was 31.32% for rigour of development. In terms of the seven domains of the RIGHT checklist， the highest reporting rate was 68.26% for background， and lowest was 27.45% for other areas regarding the disease-oriented CPM guidelines； the highest reporting rate was 61.31% for background， and the lowest was 4.49% for other areas regarding drug-oriented CPM guidelines. The average reporting rate was higher for disease-oriented than drug-oriented CPM guidelines in three domains of AGREE Ⅱ （rigour of development， clarity of presentation， editorial independence）， as well as four domains of RIGHT checklist （basic information， evidence， funding and declaration and management of interests， and other areas）. ConclusionThe overall methodology and reporting quality of the current CPM guidelines still need to be improved. It is recommended that future guideline development teams should strictly refer to the AGREE Ⅱ and RIGHT checklist， and take into account of the characteristics of CPM guidelines and relevant methodo-logical suggestions in the development and reporting of CPM guidelines， thereby guiding the clinical use of CPM in a better way.

Objective:To investigate the efficacy of 125I seed implantation combined with programmed cell death 1 (PD-1) monoclonal antibody in the treatment of patients with stage Ⅳ non-small cell lung cancer. Methods:A retrospective analysis was performed on 106 patients with stage Ⅳ non-small cell lung cancer treated in Department of Radiology of the Sixth Medical Center of PLA General Hospital from February 2017 to January 2020. All patients were divided into the combination group, radiotherapy group and immunotherapy group according to treatment methods. Besides conventional chemotherapy in all three groups, 125I seed implantation combined with PD-1 monoclonal antibody therapy was given in the combination group, 125I seed implantation therapy was delivered in the radiotherapy, and PD-1 monoclonal antibody therapy was supplemented in the immunotherapy group, respectively. Differences in the general data, maximum tumor diameter, efficacy, progression-free survival (PFS) and safety among the three groups were analyzed. One-way ANOVA was used for comparison between groups, paired sample t-test was used for comparison before and after treatment. Kaplan-Meier method was used to calculate the survival rate, and log-rank test was used to compare the survival curve. Results:After treatment, the maximum tumor diameter in the three groups was decreased, and the data in the combination group was smaller than those in the radiotherapy and immunotherapy groups ( F=4.67, P=0.011). The objective response rate (ORR), disease control rate (DCR) and PFS rate in the combination group were higher than those in the radiotherapy and immunotherapy groups ( χ2=18.93, P<0.001; χ2=11.11, P=0.004; χ2=6.67, P=0.036), and the ORR in the immunoradiotherapy group was higher than that in the radiotherapy group ( χ2=4.23, P=0.040). There was no significant difference in the occurrence of adverse reactions among the three groups ( χ2=1.60, P=0.449). Conclusion:125I seed implantation combined with PD-1 monoclonal antibody may yield high efficacy in patients with stage Ⅳ non-small cell lung cancer, which can alleviate clinical symptoms and improve long-term survival rate with good safety.

Objective Hypothyroidism(HypoPT) is one of the most common complications of thyroid reoperation,and hypocalcemia caused by HypoPT is a difficult problem in clinical practice.This study aims to investigate the risk factors for hypoealcemia after reoperation of thyroid cancer.Methods Data of 106 patients who underwent reoperation for thyroid cancer from 2013 to 2018 were retrospectively analyzed.According to the parathyroid area involved in the reoperation,the reoperation was graded:low-risk group,intermediate-risk group and high-risk group.Parathyroid hormone(PTH) and total calcium(Ca) levels were monitored at 12 to 24 hours after surgery.The follow-up period was at least 6 months.The PTH cut-off values of postoperative hypocalcemia were analyzed by ROC curve.The chi-square test and logistic regression analysis were used to analyze the risk factors of postoperative hypocalcemia.Results The incidence of transient HypoPT after reoperation was 35％,and the permanent HypoPT was 1.9％.The grade of reoperation was positively correlated with postoperative HypoPT.The ROC curve showed that the PTH cut-off values of postoperative hypocalcemia was 15 pg/ml and area under curve(AUC) was 0.636(95％ CI:0.530-0.742,P＜0.017).Univariate and multivariate analysis showed that reoperation grade and postoperative PTH＜15 pg/ml were independent risk factors for postoperative hypocalcemia.Conclusion The grade of reoperation and postoperative PTH value ＜15 pg/ml can predict postoperative hypocalcemia.

The technical operation criteria and clinical application guidelines for pediatric nuclear medicine include information related to the preparations,precautions,responsibilities of nuclear personnel,dosage of radiopharmaceutical,history-taking,imaging protocol,as well as indication and safety,focusing primarily on the usual pediatric nuclear medicine examinations.The purpose of the criteria and guidelines is to offer nuclear medicine physicians a framework that could prove practical and helpful in daily clinical practice.

Increasing evidence suggests that cancer stem cells (CSCs) are responsible for tumor initiation and maintenance. Additionally, it is becoming apparent that cyclooxygenase (COX) signaling is associated with canine mammary tumor development. The goals of the present study were to investigate COX-2 expression patterns and their effect on CSC-mediated tumor initiation in primary canine mammary tissues and tumorsphere models using immunohistochemistry. Patterns of COX-2, CD44, octamer-binding transcription factor (Oct)-3/4, and epidermal growth factor receptor (EGFR) expression were examined in malignant mammary tumor (MMT) samples and analyzed in terms of clinicopathological characteristics. COX-2 and Oct-3/4 expression was higher in MMTs compared to other histological samples with heterogeneous patterns. In MMTs, COX-2 expression correlated with tumor malignancy features. Significant associations between COX-2, CD44, and EGFR were observed in low-differentiated MMTs. Comparative analysis showed that the levels of COX-2, CD44, and Oct-3/4 expression varied significantly among TSs of three histological grades. Enhanced COX-2 staining was consistently observed in TSs. Similar levels of staining intensity were found for CD44 and Oct-3/4, but EGFR expression was weak. Our findings indicate the potential role of COX-2 in CSC-mediated tumor initiation, and suggest that COX-2 inhibition may help treat canine mammary tumors by targeting CSCs.
Animals ; Antigens, CD44/genetics/metabolism ; Biomarkers, Tumor/genetics/metabolism ; Cell Transformation, Neoplastic/*genetics/metabolism ; Cyclooxygenase 2/*genetics/metabolism ; Dog Diseases/*genetics/metabolism ; Dogs ; Female ; Immunohistochemistry/veterinary ; Mammary Neoplasms, Animal/*genetics/metabolism ; Mammary Neoplasms, Experimental/*genetics/metabolism ; Neoplastic Stem Cells/*metabolism ; Octamer Transcription Factor-3/genetics/metabolism ; Receptor, Epidermal Growth Factor/genetics/metabolism ; Retrospective Studies

BACKGROUND:Chitosan hydrogel has good biocompatibility, biodegradability and antibacterial property, which can promote tissue healing and induce bone formation. As a scaffold carrying growth factors, it can ensure the efficient and slow release of exogenous growth factors.
OBJECTIVE: To observe the effect of injectable nano/chitosan/bone morphogenetic protein-2 composite to promote periodontal tissue regeneration in rats.
METHODS:Fifty-four Wistar rats were randomized into three groups, and then chronic periodontitis model of the second molar was established. After modeling, injectable nano/chitosan/bone morphogenetic protein-2 composite was implanted into the periodontal tissue of the second molar in the experimental group; injectable nano/chitosan hydrogel was implanted in the control grouop; and nothing was implanted in the blank group. At 3, 6, 9 weeks after surgery, gingival bleeding index, probing depth, and tooth mobility were detected. X-ray and histopathological observations were carried out.
RESULTS AND CONCLUSION:At 9 weeks after surgery, the probing depth and tooth mobility were both lower in the experimental group than the other two groups (P < 0.05). In the experimental group, the alveolar bone height was restored at the root bifurcations, bone trabeculae were arranged densely and evenly, the newly formed periodontal ligament and alveolar bone tissues were dense and equaly distributed in the bone defect area at 9 weeks after surgery, indicating a better restoration effect than the control and blank groups. These findings suggest that the injectable nano/chitosan/bone morphogenetic protein-2 composite has an anti-inflammatory role and can guide periodontal tissue regeneration.

Objective:To investigate the effects of Nano-chitosan rhBMP-2 Gel(NCS/BMP-2 Gel)on the repair of mandibular de-fect.Methods:NCS/BMP-2 Gel and NCS Gel were prepared and respectively injected into the subcutaneous space on both sides of dorsum of 9 rats.3 rats were respectively sacrificed 10,20 and 30 d after injection.The subcutaneous nodules were histologicaly ex-amined.Mandibular defect was made in 54 SD rats and the rats were divided randomly and into 3 groups(n=18):NCS/BMP-2 Gel was implanted into the defects in group 1,NCS Gel in group 2,no injection in group 3.Animals were sacrificed 3,6 and 9 weeks after transplantation.X-ray examination,pathologic observation were conducted.Results:Subcutaneous nodules were found in both sides of the rat dorsum.The residual mandibular defect area in study group 1 was apparently smaller than that in group 2 and 3(P<0.05). More new bone formation was observed in the gel injected area in group 1 than in group 2 and 3.Conclusion:Nano-CS/BMP-2 Gel is biocompatible and can accelerate the healing of mandibular defect.