BACKGROUND:Myocardial hypertrophy often leads to severe cardiovascular diseases and is difficult to diagnose due to its early stages being hard to detect.Circulating inflammatory proteins have been found to be significantly associated with cardiovascular diseases,yet the specific mechanisms linking them to myocardial hypertrophy remain unclear.OBJECTIVE:To investigate the relationship between circulating proteins and myocardial hypertrophy using multiple Mendelian randomization approaches.METHODS:Utilizing data from 91 circulating inflammatory proteins in the GWAS Catalog database and the latest myocardial hypertrophy data from the R11 FinnGen database,we employed bidirectional two-sample Mendelian randomization,multivariate Mendelian randomization,and Genome-Wide Association Studies co-localization to investigate the causal relationship between circulating inflammatory proteins and myocardial hypertrophy.The accuracy of the results was verified through sensitivity tests including MR-PRESSO,Cochran's Q test,MR-Egger intercept assessment,leave-one-out analysis,and funnel plot analysis.RESULTS AND CONCLUSION:In the results of two-sample Mendelian randomization,the primary method used for evaluation was the Inverse Variance Weighting(IVW)approach.It was found that the level of T-cell surface glycoprotein CD6 isoform(IVW:P=0.046,OR=0.74,95％Cl:0.66-1.00),level of slit chemokine(IVW:P=2.1×10-2,OR=0.74,95％CI:0.556-0.95),level of Delta and Notch-like epidermal growth factor-related receptor(IVW:P=3.7×10-4,OR=0.66,95％CI:0.49-0.87),level of interleukin-2(IVW:P=3.8×103,OR=0.667,95％CI:0.50-0.88),and sulfotransferase 1A1(IVW:P=1.42×102,OR=0.80,95％CI:0.67-0.96)had a unidirectional causal effect on cardiac hypertrophy.(2)Among the findings in multivariate Mendelian randomization,the levels of the CD6 isoform of T-cell surface glycoprotein(IVW:P=1.39×102,OR=0.81,95％CI:0.69-0.96)and the levels of Delta and Notch-like epidermal growth factor-related receptor(IVW:P=3.7×10-2,OR=0.73,95％CI:0.55-0.98)were positive,indicating that the results remained significant after excluding the effects of other circulating inflammatory proteins that had an impact on myocardial hypertrophy.(3)In colocalization,T-cell surface glycoprotein CD6 isoform levels had H3+H4=0.96,with the most significant single nucleotide polymorphism being rs59570070,suggesting an intrinsic link between T-cell surface glycoprotein CD6 isoform levels and myocardial hypertrophy.(4)Sensitivity results showed no abnormalities,indicating no heterogeneity or pleiotropic effects influencing the results.(5)These results verified that T cell surface glycoprotein CD6 isoforms,Slit chemokine,Delta and Notch-like epidermal growth factor-related receptors,interleukin-2,and sulfotransferase 1A1 had a unidirectional causal effect on myocardial hypertrophy.T cell surface glycoprotein CD6 isoforms and Delta and Notch-like epidermal growth factor-related receptors had the deepest impact,suggesting that there may be related pathways between T cell surface glycoprotein CD6 isoforms and myocardial hypertrophy.Mendelian randomization studies require large amounts of clinical data and therefore often use European samples from international databases for analysis.Since this analytical method has significant advantages in causal inference,precision medicine,and cross-population validation,its research results still hold great significance for the medical development in China.As Mendelian randomization research deepens,it also promotes the collection and analysis of clinical data in China to some extent.In the future,we can further analyze key protein mechanisms,combine multiomics and clinical validation,develop an inflammatory marker monitoring system and novel anti-inflammatory therapies,thereby promoting the prevention and control of cardiovascular diseases and the development of personalized medicine.

BACKGROUND:Myocardial hypertrophy often leads to severe cardiovascular diseases and is difficult to diagnose due to its early stages being hard to detect.Circulating inflammatory proteins have been found to be significantly associated with cardiovascular diseases,yet the specific mechanisms linking them to myocardial hypertrophy remain unclear.OBJECTIVE:To investigate the relationship between circulating proteins and myocardial hypertrophy using multiple Mendelian randomization approaches.METHODS:Utilizing data from 91 circulating inflammatory proteins in the GWAS Catalog database and the latest myocardial hypertrophy data from the R11 FinnGen database,we employed bidirectional two-sample Mendelian randomization,multivariate Mendelian randomization,and Genome-Wide Association Studies co-localization to investigate the causal relationship between circulating inflammatory proteins and myocardial hypertrophy.The accuracy of the results was verified through sensitivity tests including MR-PRESSO,Cochran's Q test,MR-Egger intercept assessment,leave-one-out analysis,and funnel plot analysis.RESULTS AND CONCLUSION:In the results of two-sample Mendelian randomization,the primary method used for evaluation was the Inverse Variance Weighting(IVW)approach.It was found that the level of T-cell surface glycoprotein CD6 isoform(IVW:P=0.046,OR=0.74,95％Cl:0.66-1.00),level of slit chemokine(IVW:P=2.1×10-2,OR=0.74,95％CI:0.556-0.95),level of Delta and Notch-like epidermal growth factor-related receptor(IVW:P=3.7×10-4,OR=0.66,95％CI:0.49-0.87),level of interleukin-2(IVW:P=3.8×103,OR=0.667,95％CI:0.50-0.88),and sulfotransferase 1A1(IVW:P=1.42×102,OR=0.80,95％CI:0.67-0.96)had a unidirectional causal effect on cardiac hypertrophy.(2)Among the findings in multivariate Mendelian randomization,the levels of the CD6 isoform of T-cell surface glycoprotein(IVW:P=1.39×102,OR=0.81,95％CI:0.69-0.96)and the levels of Delta and Notch-like epidermal growth factor-related receptor(IVW:P=3.7×10-2,OR=0.73,95％CI:0.55-0.98)were positive,indicating that the results remained significant after excluding the effects of other circulating inflammatory proteins that had an impact on myocardial hypertrophy.(3)In colocalization,T-cell surface glycoprotein CD6 isoform levels had H3+H4=0.96,with the most significant single nucleotide polymorphism being rs59570070,suggesting an intrinsic link between T-cell surface glycoprotein CD6 isoform levels and myocardial hypertrophy.(4)Sensitivity results showed no abnormalities,indicating no heterogeneity or pleiotropic effects influencing the results.(5)These results verified that T cell surface glycoprotein CD6 isoforms,Slit chemokine,Delta and Notch-like epidermal growth factor-related receptors,interleukin-2,and sulfotransferase 1A1 had a unidirectional causal effect on myocardial hypertrophy.T cell surface glycoprotein CD6 isoforms and Delta and Notch-like epidermal growth factor-related receptors had the deepest impact,suggesting that there may be related pathways between T cell surface glycoprotein CD6 isoforms and myocardial hypertrophy.Mendelian randomization studies require large amounts of clinical data and therefore often use European samples from international databases for analysis.Since this analytical method has significant advantages in causal inference,precision medicine,and cross-population validation,its research results still hold great significance for the medical development in China.As Mendelian randomization research deepens,it also promotes the collection and analysis of clinical data in China to some extent.In the future,we can further analyze key protein mechanisms,combine multiomics and clinical validation,develop an inflammatory marker monitoring system and novel anti-inflammatory therapies,thereby promoting the prevention and control of cardiovascular diseases and the development of personalized medicine.

Objective:To construct and verify a risk prediction model for pulmonary infection in patients with aneurysmal subarachnoid hemorrhage (aSAH) after craniotomy and clipping, providing theoretical basis and practical guidance for improving the quality of postoperative care.Methods:Using the convenience sampling method, a retrospective selection was made of 397 patients with aSAH after craniotomy and clipping who were hospitalized in the Department of Neurosurgery of Shanxi Bethune Hospital (Shanxi Academy of Medical Sciences) from January 2019 to December 2023 as the modeling group. They were randomly divided into the training set and the test set at a ratio of 7:3, with 278 cases in the training set and 119 cases in the test set. Patients were divided into the infection group and the non-infection group based on whether they developed pulmonary infection. Univariate analysis was used to model the risk factors of pulmonary infection after aSAH craniotomy and clamping in the group, and Lasso regression was used to construct a predictive model. A total of 119 patients with aSAH admitted to the neurosurgery department of the same hospital from January to April 2024 were selected for the external validation of the model. The predictive effect of the model was evaluated through the receiver operating characteristic (ROC) curve.Results:In the modeling group, there were 216 male patients and 181 female patients. The incidence of pulmonary infection was 38.54% (153/397). Finally, five influencing factors, namely stroke, Hunt-Hess classification, mechanical ventilation, indwelling nasogastric tube and the timing of initiating enteral nutrition, were included to construct a predictive model. The areas under the ROC curves of the nomogram prediction models of this model in the training set, test set, and external validation group were 0.859(95% CI 0.791-0.928), 0.843(95% CI 0.796-0.890), and 0.800(95% CI 0.711-0.889), respectively. The calibration curve shows that the model's prediction fits well with the actual situation and has a high degree of calibration. Decision curve analysis indicates that this model has high clinical application value under different risk thresholds. Conclusions:The risk prediction model for pulmonary infection in patients after craniotomy and clipping with aSAH has good discrimination and calibration, which can provide reference for medical staff to identify high-risk patients at an early stage and take preventive intervention measures.

Objective:To construct and verify a risk prediction model for pulmonary infection in patients with aneurysmal subarachnoid hemorrhage (aSAH) after craniotomy and clipping, providing theoretical basis and practical guidance for improving the quality of postoperative care.Methods:Using the convenience sampling method, a retrospective selection was made of 397 patients with aSAH after craniotomy and clipping who were hospitalized in the Department of Neurosurgery of Shanxi Bethune Hospital (Shanxi Academy of Medical Sciences) from January 2019 to December 2023 as the modeling group. They were randomly divided into the training set and the test set at a ratio of 7:3, with 278 cases in the training set and 119 cases in the test set. Patients were divided into the infection group and the non-infection group based on whether they developed pulmonary infection. Univariate analysis was used to model the risk factors of pulmonary infection after aSAH craniotomy and clamping in the group, and Lasso regression was used to construct a predictive model. A total of 119 patients with aSAH admitted to the neurosurgery department of the same hospital from January to April 2024 were selected for the external validation of the model. The predictive effect of the model was evaluated through the receiver operating characteristic (ROC) curve.Results:In the modeling group, there were 216 male patients and 181 female patients. The incidence of pulmonary infection was 38.54% (153/397). Finally, five influencing factors, namely stroke, Hunt-Hess classification, mechanical ventilation, indwelling nasogastric tube and the timing of initiating enteral nutrition, were included to construct a predictive model. The areas under the ROC curves of the nomogram prediction models of this model in the training set, test set, and external validation group were 0.859(95% CI 0.791-0.928), 0.843(95% CI 0.796-0.890), and 0.800(95% CI 0.711-0.889), respectively. The calibration curve shows that the model's prediction fits well with the actual situation and has a high degree of calibration. Decision curve analysis indicates that this model has high clinical application value under different risk thresholds. Conclusions:The risk prediction model for pulmonary infection in patients after craniotomy and clipping with aSAH has good discrimination and calibration, which can provide reference for medical staff to identify high-risk patients at an early stage and take preventive intervention measures.

B-cell lymphomas account for 70％-80％of non-Hodgkin lymphomas(NHL)and exhibit significant heterogeneity in genetic profiles,phenotypic characteristics,and clinical manifestations,posing substantial challenges for clinical management.The B-cell receptor(BCR)is a transmembrane receptor on the surface of B cells that plays a central regulatory role in B-cell development,activation,and adaptive immune responses.As a core mechanism driving malignant transformation in various B-cell malignancies,aberrant activation of the BCR signaling pathway,plays a pivotal role in B lymphoma pathogenesis.Dysregulated BCR signaling not only promotes tumor cell proliferation,survival,and anti-apoptotic capacity but also accelerates malignant progression.Consequently,researchers are vigorously exploring therapeutic strategies targeting BCR and its downstream pathways,including inhibitors of Bruton's tyrosine kinase(BTK)and PI3K,as well as direct BCR-targeted approaches.The central role of BCR signaling in lymphoma pathogenesis and treatment underscores its potential as a critical focus for future therapeutic development,offering new directions and hope for improved clinical outcomes.

B-cell lymphomas account for 70％-80％of non-Hodgkin lymphomas(NHL)and exhibit significant heterogeneity in genetic profiles,phenotypic characteristics,and clinical manifestations,posing substantial challenges for clinical management.The B-cell receptor(BCR)is a transmembrane receptor on the surface of B cells that plays a central regulatory role in B-cell development,activation,and adaptive immune responses.As a core mechanism driving malignant transformation in various B-cell malignancies,aberrant activation of the BCR signaling pathway,plays a pivotal role in B lymphoma pathogenesis.Dysregulated BCR signaling not only promotes tumor cell proliferation,survival,and anti-apoptotic capacity but also accelerates malignant progression.Consequently,researchers are vigorously exploring therapeutic strategies targeting BCR and its downstream pathways,including inhibitors of Bruton's tyrosine kinase(BTK)and PI3K,as well as direct BCR-targeted approaches.The central role of BCR signaling in lymphoma pathogenesis and treatment underscores its potential as a critical focus for future therapeutic development,offering new directions and hope for improved clinical outcomes.

Objective To analyze the nonlinear relationship between hypothermic machine perfusion (HMP) parameters and delayed graft function (DGF) and optimize the construction of a predictive model for DGF. Methods The data of 923 recipients who underwent kidney transplantation from deceased donors were retrospectively analyzed. According to the occurrence of DGF, the recipients were divided into DGF group (n=823) and non-DGF group (n=100). Donor data, HMP parameters and recipient data were analyzed for both groups. The nonlinear relationship between HMP parameters and the occurrence of DGF was explored based on restricted cubic splines (RCS). Over-sampling, under-sampling and balanced sampling were used to address the imbalance in the proportion of DGF to construct logistic regression predictive models. The area under the curve (AUC) of each model was compared in the validation set, and a nomogram model was constructed. Results Donor BMI, cold ischemia time of the donor kidney, and HMP parameters (initial and final pressures, resistance, and perfusion time) were significantly different between the DGF and non-DGF groups (all P<0.05). The RCS analysis revealed a threshold-like nonlinear relationship between HMP parameters and the risk of DGF. Among the models constructed using different sampling methods, the balanced sampling model had the highest AUC. Using this model, a nomogram was constructed to stratify recipients based on risk scores. Recipients in the high-risk group had higher serum creatinine levels at 1, 6, and 12 months after kidney transplantation compared to those in the low-risk group (all P<0.05). Conclusions There is a nonlinear relationship between HMP parameters and the risk of DGF, and the threshold is helpful for organ quality assessment and monitoring of graft function after transplantation. The predictive model for DGF constructed on the base of balanced sampling algorithms helps perioperative decision-making and postoperative graft function monitoring of kidney transplantation.

OBJECTIVE To provide reference for the rational use of antiemetic drugs in tumor chemotherapy patients. METHODS The data of tumor patients who were given antiemetic drugs were collected from 9 departments of our hospital with hospital information system from Oct. 1st to Nov. 30th in 2022， such as oncology department， radiotherapy department， gynecology department， and gastroenterology department. The application of chemotherapy drugs and the use of antiemetic drugs were analyzed statistically， and the irrational use of antiemetic drugs was analyzed. RESULTS A total of 520 patients were included， involving 248 （47.69%） using chemotherapy drugs with a moderate emetogenic risk level and 135 （25.96%） with a high emetogenic risk level. A total of 461 cases （73.06%） of 5-hydroxytryptamine 3-receptor antagonists were used， including palonosetron in 333 cases， ondansetron in 106 cases， tropisetron in 15 cases and granisetron in 7 cases， and only 148 cases of patients were prioritized for the use of nationally procured medicines and national essential medicines （32.10%）. Neurokinin-1 receptor antagonists were used in 170 cases （26.94%）， including fosaprepitant in 112 cases and aprepitant in 58 cases. The use of antiemetic drugs was unreasonable in 162 patients （31.15%）； among the types of irrational drugs， the antiemetic regimen was unreasonable in the largest number of cases （22.40%）， followed by the irrational pharmacoeconomics （19.13%）. CONCLUSIONS The emetogenic risk levels of chemotherapy drugs used for tumor patients in our hospital are primarily moderate to high， and there is irrational use of antiemetic regimen and pharmacoeconomics. Clinicians， nurses， pharmacists and hospital departments should collaborate as multiple teams to strengthen full supervision of the standardization of antiemetic drugs， reasonably select antiemetic drugs based on emetogenicity rating， and improve the compliance of doctors with the guidelines to ensure the safety， effectiveness， and cost-effective of patient medication.

Objective:To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT).Methods:This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups.Results:Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P>0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P<0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P<0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion:Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.

Objective To study the relationship between detachment and puncture site and chest wall thickness after preoperative positioning of peripheral lung nodules by CT-guided Hookwire puncture.Methods From July 2017 to December 2021,190 patients in our hospital underwent thoracoscopic surgery for peripheral lung nodules.All patients underwent preoperative CT-guided HOOKWIRE puncture mapping,recording the puncture site,whether the needle had fallen off,chest wall thickness,and the interval between the end of the puncture and the start of the surgery,logistic regression analysis,and receiver operating characteristic(ROC)curve analysis to explore the risk factors affecting needle fall off.Results Clinical data were collected for 190 patients,including 119 males and 71 females,age 22 to 78(58.1±10.2)years.There were 31 cases of shedding,with a shedding rate of 16.3％.Among them,31 cases were detached in the medial aspect of the subscapular horn line,15 cases were detached,with detachment rate being 48.4％;67 cases were detached in the medial axillary line,10 cases were detached,with detachment rate being 14.9％;65 cases were detached in the medial axillary line of the midclavicular line,5 cases were detached,with detachment rate being 7.6％;27 cases were detached in the medial axillary line,1 case was detached,with detachment rate being 3.7％;the detachment rate was highest in the subscapular horn line,with statistical significance(P＜0.05)compared with other locations;the tissue thickness of the thoracic wall was(49.38±6.28)mm,but the tissue thickness of the thoracic wall was(36.36±7.77)mm,with statistical significance(P＜0.05).The interval between puncture and operation was 73 to 98 min,with an average one of(81.99±4.48)min.Conclusions The detachment of the positioning needle is related to the thickness of the chest wall,and the proportion of detachment is significantly higher in the chest back,especially in the subscapular angle,before surgical treatment of peripheral lung nodules.In cases of peripheral pulmonary nodules with surface projections medial to the inferior scapular horn line,other methods of localization should be preferably considered.