Objective To investigatethe relationship between gastroesophageal reflux disease (GERD) symptoms and clinicopathological characteristics, p53 expression, and survival of Chinese patients with esophageal adenocarcinoma. Methods A total of 3882 patients with esophageal adenocarcinoma, 970 matched patients with esophageal squamous cell carcinoma, and 970 matched patients with gastric cardia adenocarcinoma were included to compare the incidence of GERD symptoms. Patients with esophageal adenocarcinoma were divided into two groups according to the presence and absence of GERD symptoms. The differences in clinicopathological characteristics and p53 expression between the two groups were compared by chi-square test, and the differences in survival between the two groups were compared by landmark analysis. Results The incidence of GERD symptoms increased successively in esophageal squamous cell carcinoma, esophageal adenocarcinoma, and gastric cardia adenocarcinoma. In patients with esophageal adenocarcinoma, the proportions of male, less than 65 years old, lower thoracic tumors, tumors without squamous cell carcinoma, poorly differentiation, early tumors (stage 0-I), and p53-positive tumors in the group with GERD symptoms were higher than those in the group without GERD symptoms; moreover, the long-term survival (≥15 years) was better. Conclusion GERD symptom is an important clinical sign of esophageal adenocarcinoma. It is closely related to specific clinicopathological characteristics, p53 overexpression, and good long-term prognosis.

BACKGROUND: Severe stroke has high rates of mortality and morbidity. This study aimed to investigate the clinical course, causes of worsening, and outcomes of severe ischemic stroke. METHODS: This prospective, multicenter cohort study enrolled adult patients admitted ≤30 days after ischemic stroke from nine hospitals in China between September 2017 and December 2019. Severe stroke was defined as a score of ≥15 on the National Institutes of Health Stroke Scale (NIHSS). Clinical worsening was defined as an increase of 4 in the NIHSS score from baseline. Unfavorable functional outcome was defined as a modified Rankin scale score ≥3 at 3 months and 1 year after stroke onset, respectively. We performed Logistic regression to explore baseline features and reperfusion therapies associated with clinical worsening and functional outcomes. RESULTS: Among 4201 patients enrolled, 854 patients (20.33%) had severe stroke on admission. Of 3347 patients without severe stroke on admission, 142 (4.24%) patients developed severe stroke in hospital. Of 854 patients with severe stroke on admission, 33.95% (290/854) experienced clinical worsening (median time from stroke onset: 43 h, Q1-Q3: 20-88 h), with brain edema (54.83% [159/290]) as the leading cause; 24.59% (210/854) of these patients died by 30 days, and 81.47% (677/831) and 78.44% (633/807) had unfavorable functional outcomes at 3 months and 1 year respectively. Reperfusion reduced the risk of worsening (adjusted odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.12-0.49, P  <0.01), 30-day death (adjusted OR: 0.22, 95% CI: 0.11-0.41, P  <0.01), and unfavorable functional outcomes at 3 months (adjusted OR: 0.24, 95% CI: 0.08-0.68, P <0.01) and 1 year (adjusted OR: 0.17, 95% CI: 0.06-0.50, P  <0.01). CONCLUSIONS: Approximately one-fifth of patients with ischemic stroke had severe neurological deficits on admission. Clinical worsening mainly occurred in the first 3 to 4 days after stroke onset, with brain edema as the leading cause of worsening. Reperfusion reduced the risk of clinical worsening and improved functional outcomes. REGISTRATION ClinicalTrials.gov , NCT03222024.
Humans ; Male ; Female ; Prospective Studies ; Ischemic Stroke/mortality* ; Aged ; Middle Aged ; Aged, 80 and over ; Stroke ; Brain Ischemia

OBJECTIVE: To compare the effects of double-channel core decompression (CD) combined with medullary cavity irrigation with those of simple CD on progression of collapse and clinical outcomes in non-traumatic osteonecrosis of the femoral head (ONFH). METHODS: A retrospective analysis was conducted on the clinical data of 19 patients (30 hips) with non-traumatic ONFH who underwent double-channel CD combined with medullary cavity irrigation and admitted between January 2024 and October 2024 (CD+irrigation group). According to a 1: 2 ratio, 54 patients (60 hips) who underwent simple CD and were matched in terms of age, gender, and body mass index (BMI) were included as the control (CD group). There was no significant difference in baseline data such as age, gender, BMI, affected side, ONFH type, preoperative Association Research Circulation Osseous (ARCO) stage, bone marrow edema stage, visual analogue scale (VAS) score for pain, and Harris score between the two groups ( P>0.05). The postoperative discharge time and occurrence of complications were recorded for both groups. The VAS scores before operation and at discharge after operation were compared, and the differences between pre- and post-operation (change values) were calculated for intergroup comparison. The Harris scores before operation and at discharge and 3 months after operation were also compared. During follow-up, X-ray film, CT, and MRI were performed for reexamination. The ARCO stage and bone marrow edema stage were evaluated at 3 months after operation and compared with those before operation to determine whether there was radiological progression or relief. RESULTS: All incisions in both groups healed by first intention after operation, with no infection, femoral neck fracture, or other operation-related complications. All patients were followed up, and the follow-up time of the CD+irrigation group was (146.8±27.7) days, and that of the CD group was (164.3±48.2) days; there was no significant difference between the two groups ( t=1.840, P=0.069). There was no significant difference in the length of hospital stay between the two groups ( P>0.05). At discharge after operation, the VAS score of the CD+irrigation group was significantly lower than that of the CD group ( P<0.05), and the change value was significantly higher than that of the CD group ( P<0.05). The Harris scores at discharge and 3 months after operation in the CD+irrigation group were significantly higher than those in the CD group ( P<0.05). The Harris score gradually increased with time, and the differences between different time points were significant ( P<0.05). Radiological reexamination showed that there was no significant difference in the ARCO stage and the incidence of radiological progression between the two groups at 3 months after operation ( P>0.05); however, the bone marrow edema stage and the degree of bone marrow edema relief in the CD+irrigation group were better than those in the CD group, with significant differences ( P<0.05). CONCLUSION Double-channel CD combined with medullary cavity irrigation can significantly alleviate hip joint pain and improve joint function in patients with non-traumatic ONFH, reduce the degree of bone marrow edema in the femoral head, and delay the progression of ONFH.
Humans ; Femur Head Necrosis/therapy* ; Retrospective Studies ; Male ; Female ; Decompression, Surgical/methods* ; Therapeutic Irrigation/methods* ; Adult ; Treatment Outcome ; Middle Aged ; Femur Head/surgery*

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 investigate the predictive factors of stroke associated-pneumonia (SAP) in patients with acute stroke, develop nomogram and neural network prediction models and verify their predictive performance.Methods:Patients with acute stroke admitted to the First Affiliated Hospital of Kunming Medical University and Zhenxiong County People's Hospital were included retrospectively. Multivariate logistic regression analysis was used to determine the independent predictive factors of SAP, and develop nomogram and neural network prediction models. Receiver operating characteristic curve (ROC) curves were used to validate and compare the predictive performances. Results:A total of 450 patients with acute stroke were enrolled, including 286 males (63.6%), aged 64.28±13.24 years; 344 patientss (76.4%) had ischemic stroke and 106 (23.6%) had hemorrhagic stroke; 128 patients (28.4%) experienced SAP. According to the random number method, they were divided into a modeling cohort ( n=300) and a validation cohort ( n=150). Multivariate logistic regression analysis in the modeling cohort showed that a higher baseline National Institutes of Health Stroke Scale (NIHSS) score, gastric tube placement, use of proton pump inhibitors, heart failure, and higher neutrophil/lymphocyte ratio (NLR) were the independent predictive factors of SAP. ROC curve analysis showed that the area under the ROC curve of the nomogram model for predicting SAP in the modeling cohort and validation cohort was 0.841 (95% confidence interval [ CI] 0.795-0.880) and 0.863 (95% CI 0.798-0.914), respectively. The sensitivity for predicting SAP were 75.00% and 70.45%, respectively, and the specificity was 81.94% and 92.45%, respectively. The area under the ROC curve of the neural network model for predicting SAP in the modeling cohort and validation cohort was 0.847 (95% CI 0.802-0.866) and 0.862 (95% CI 0.796-0.913), respectively. The sensitivity for predicting SAP were 76.19% and 72.73%, and the specificity was 79.17% and 89.62%, respectively. Conclusions:Higher NIHSS score, gastric tube placement, use of proton pump inhibitors, heart failure, and higher NLR are the independent risk factors for SAP in patients with acute stroke. The nomogram and neural network prediction model developed using the above risk factors have higher predictive value for SAP.

Objective To investigate the impacts of miR-141-3p on the proliferation,migration and epithelial-mesen-chymal transformation of glioma cells by regulating lysophosphatidic acid receptor 3(LPAR3).Methods RT-qPCR was used to detect the level of miR-141-3p and LPAR3 in glioma tissues and cells.Dual luciferase was used to de-tect the targeting relationship between miR-141-3p and LPAR3.The cells were divided into control group,miR-NC group,miR-141-3p mimics group,miR-141-3p mimics+pcDNA3.1 group,and miR-141-3p mimics+pcDNA-LPAR3 group,and then transfected with corresponding plasmids.RT-qPCR was used to detect the level of miR-141-3p and LPAR3 in cells.EdU method was used to detect cell proliferation.The scratch healing experiment was used to detect cell migration.Western blot was used to detect the expression of proteins related to cell proliferation,migration,and epithelial-mesenchymal transformation.Xenograft tumor model in nude mice was used to observe tumor formation.RT-qPCR was used to detect the level of miR-141-3p in tumor tissue.In addition,Western blot was performed to detect the expression of LPAR3,PCNA,and MMP-2.Results miR-141-3p was downregulated,whereas LPAR3 mRNA was upregulated in glioma tissues and U251,T98G,and CHG-5 cell lines(P＜0.05).There was a targeted binding site between miR-141-3p and LPAR3.miR-141-3p mimics significantly increased the ex-pression of miR-141-3p and E-cadherin,but decreased LPAR3 mRNA level,EdU-positive rate,scratch wound healing rate,and the expression of PCNA,cyclin D1,MMP-2,MMP-9,N-cadherin,and vimentin(P＜0.05).pcDNA-LPAR3 reversed effect on expression of these factors(P＜0.05).Tumor transplantation experiments in nude mice showed that miR-141-3p mimics reduced tumor volume,tumor weight,LPAR3,PCNA,and MMP-2 expres-sion,and increased the level of miR-141-3p(P＜0.05).Conclusions miR-141-3p can inhibit proliferation,mi-gration,and epithelial-mesenchymal transformation of glioma cells by down-regulating LPAR3.

AIM: To investigate the effect of different lens combinations on visual acuity, visual quality and patient satisfaction by comparing mixed implantation of Tecnis Symfony ZXR00(ZXR00)and Tecnis ZMB00(ZMB00)lenses, bilateral implantation of ZMB00 lenses, and bilateral implantation of ZXR00 lenses.METHODS:This retrospective case-control study included 117 patients with cataracts(234 eyes)who underwent phacoemulsification combined with intraocular lens(IOLs)implantation from August 2020 to December 2021. The 3 groups included 36 patients(72 eyes)who underwent bilateral implantation of ZXR00(RR group), 37 patients(74 eyes)who underwent bilateral implantation of ZMB00(MM group), and 44 patients(88 eyes)who underwent implantation with a combination of ZXR00 and ZMB00(MR group). The uncorrected distance visual acuity(UDVA, 5 m), uncorrected intermediate visual acuity(UIVA, 80 cm), uncorrected near visual acuity(UNVA, 40 cm), corrected distance visual acuity(CDVA), defocus curve, stereopsis and VF-14 and QoV visual quality scale of the patients in the three groups were assessed at 3-month follow-up.RESULTS:Bilateral UNVA in the MM and MR group were significantly better than that in the RR group(P<0.05). Bilateral UIVA was the best in the RR group. There were no significant differences in bilateral UDVA, CDVA and stereopsis among the groups(P>0.05). Values for near-stereoscopic acuity at 40 cm were 107.27±80.53, 105.67±83.79, and 108.69±97.66(20-400)arcsec in the MR, MM, and RR groups, respectively(P>0.05). Satisfaction rates exceeded 90% in all groups.CONCLUSION:All groups achieved good distance, intermediate, and near visual acuity and near-stereoscopic vision postoperatively. Mixed implantation with ZXR00 and ZMB00 lenses achieved excellent full-range vision and resulted in high satisfaction. These results may aid in developing individualized clinical treatment plans.

Rapid and living guidelines are those developed in response to public health emergencies in a short period of time using a scientific and standardized approach. Subsequently， they provide timely and credible recommendations for decision makers through regular and frequent updates of clinical evidence and recommendations. In this paper， we introduced the definition of rapid and living guideline as well as analyzed the basic characteristics of eight rapid and living guidelines in the field of traditional Chinese medicine （TCM） published till 2023 June， summarizing three core methodological issues in relation to how to rapidly develop guidelines， how to formulate recommendations when there is lack of evidence， and how to ensure the timeliness of guidelines. Based on the analysis of current rapid and living guidelines， it is implicated that there is necessity to carry out rapid and living guideline in the field of TCM， and the methodology of rapid integration of multivariate evidence in the field of TCM needs to be further explored； furthermore， it is necessary to further explore the obstacles of implementation of guidelines and promote timely updating， all of which provide certain theoretical references for relevant guideline developers and researchers.

The irrational use of Chinese patent medicines （CPM） is becoming more and more prominent， which makes the demand for clinical practice guidelines of CPM gradually increase. In order to make domestic scholars understand the latest developments and existing problems of the CPM guidelines， and promote its development， this paper introduced the concept of CPM guidelines， summarized the characteristics of the two development modes， namely “taking CPM as the key” and “taking disease/syndrome as the key”， and analyzed the current methodological status of developing and reporting CPM guidelines. Based on the existed problems， three suggestions have been put forward to optimize the quality of CPM guidelines， which were clarifying the target users and scope of CPM guidelines， establishing an open and transparent mechanism of the personnel involvement and process steps， and formulating implementable and operable recommendations for the use of CPM.

This paper summarized the key points and methods in terms of the establishment of the guideline working group and the management of conflict of interests， trying to provide reference for the development of clinical practice guidelines for Chinese patent medicine （CPM）. The establishment of the working group is the first important step for developing CPM guidelines. Considering the characteristics of the clinical practice guidelines for CPM， this study suggests that the three key elements of ‘multidisciplinarity’， ‘clinical relevance’ and ‘geographical representativeness’ should be put focus on when forming the working group. The guideline advisory committee， clinical expert group， evidence systematic evaluation group， secretary group and the external review group should be established. All group members should clarify the conflict of interest， and the process and management method of the conflict of interest should be clearly reported.