Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objective:To conduct a systematic review of risk prediction models for enteral feeding intolerance in ICU patients.Methods:Relevant literature was searched in China National Knowledge Infrastructure, Wanfang Data, China Biology Medicine disc, VIP, PubMed, Web of Science, Cochrane Library, Embase, CINAHL, and Scopus, with search limits from the establishment of the databases up to July 24, 2024. Two researchers independently screened the literature and extracted data, using Prediction model Risk Of Bias ASsessment Tool to evaluate the quality of the included studies.Results:A total of 12 studies were included, which included 20 prediction models. The area under the receiver operating characteristic curve or C-index for these models ranged from 0.70 to 0.94. The overall bias risk of the 12 studies was high, with three studies having good applicability. The bias risk primarily stemmed from issues such as measurement of prediction factors, variable handling, sample size, outcome definition, and model performance evaluation.Conclusions:Existing risk prediction models for enteral feeding intolerance in ICU patients exhibit a high risk of bias. Further validation, optimization, or development of new models is required in the future.

Objective:To explore the diagnostic value of serum soluble semaphorin 4D (sSema4D) and soluble CD40 ligand (sCD40L) in left ventricular hypertrophy (LVH) in patients with primary hypertension (EH).Methods:Eighty-four patients with EH combined with LVH admitted to Qingdao Hospital of Shandong First Medical University from December 2022 to December 2023 were prospectively selected as the study group, and 84 patients with EH and without LVH admitted to Qingdao Hospital of Shandong First Medical University during the same period were regarded as the control group. Enzyme linked immunosorbent assay was applied to detect the levels of sSema4D and sCD40L. Employing Pearson correlation coefficient, the study assessed the association between concentrations of sSema4D and sCD40L in serum and various echocardiographic measurements. A multivariate Logistic regression model was engaged to probe into the contributing factors for the development of LVH. ROC curve was plotted to analyze the diagnostic value of serum sSema4D and sCD40L for EH combined with LVH.Results:Serum sSema4D and sCD40L levels were significantly higher in the study group than in the control group: (8.56 ± 2.19) μg/L vs. (5.12 ± 1.43) μg/L, (4.02 ± 1.03) μg/L vs. (3.22 ± 0.98) μg/L, and the differences were statistically significant ( P<0.05). The duration of hypertension, LVEDD, IVSTD, LVPWT, and LVMI were significantly higher in the study group than in the control group: (7.33 ± 1.53) years vs. (4.26 ± 1.35) years, (50.28 ± 3.33) mm vs. (44.45 ± 3.76) mm, (11.64 ± 3.21) mm vs. (9.53 ± 2.89) mm, (12.45 ± 1.52) mm vs. (9.13 ± 0.98) mm, (126.11 ± 15.28) g/m 2 vs. (81.15 ± 11.31) g/m 2, and the differences were statistically significant ( P<0.05). According to Pearson correlation analysis, it was known that both serum sSema4D and sCD40L were positively correlated with LVEDD, IVSTD, LVPWT and LVMI ( r = 0.425 and 0.533, 0.612 and 0.436, 0.513 and 0.628, 0.589 and 0.618; P<0.05). Multivariate Logistic regression analysis showed that hypertension duration, LVEDD, IVSTD, LVPWT, LVMI, sSema4D, sCD40L were risk factors for LVH in EH patients ( P<0.05). According to the ROC curve, the AUC for diagnosing EH combined with LVH with serum sSema4D was 0.848, the AUC for diagnosing EH combined with LVH with serum sCD40L was 0.725, and the AUC for diagnosing EH combined with LVH with serum sCD40L was 0.888, the combination of sCD40L and sCD40L was superior to their respective individual diagnoses ( Z = 2.651 and 2.526, P<0.05). Conclusions:The serum levels of sSema4D and sCD40L in patients with EH combined with LVH are obviously elevated, which are influencing factors for the occurrence of EH combined with LVH. Combined testing of the two has high diagnostic value for EH combined with LVH.

Objective:To systematically evaluate studies validating the performance of the Global Leadership Initiative on Malnutrition (GLIM) in diagnosing malnutrition.Methods:Seven Chinese and English databases including Embase, Web of Science (WOS), PubMed, CINAHL, Cochrane Library, SinoMed, CNKI, Wanfang Data, and VIP Database were searched for articles on the validation of GLIM criteria published between September 2018 and September 2024. Two researchers independently performed literature screening and data extraction. The concurrent and predictive validity of the criteria was analyzed.Results:A total of 136 papers were included for analysis. The GLIM criteria for diagnosing malnutrition had a sensitivity of 77%, a specificity of 87%, and an area under the curve (AUC) of 0.90. Malnutrition diagnosed by the GLIM criteria predicted prolonged hospital and intensive care unit (ICU) stays, increased readmission and complication rates (both overall and infectious), reduced survivals (median, overall, and disease-free), and increased in-hospital and follow-up mortalities. Both moderate and severe malnutrition predicted decreased overall survival. However, only three studies analyzed the impact of nutritional therapy on the clinical outcomes of malnourished patients.Conclusions:The GLIM criteria accurately differentiate malnutrition and are a valid predictive tool of clinical outcomes. However, the validity criteria in these validation studies were questionable, along with high methodological heterogeneity. Furthermore, there is a lack of studies validating the role of nutritional therapy in improving the clinical outcomes of malnourished patients.

Objective:To systematically evaluate studies validating the performance of the Global Leadership Initiative on Malnutrition (GLIM) in diagnosing malnutrition.Methods:Seven Chinese and English databases including Embase, Web of Science (WOS), PubMed, CINAHL, Cochrane Library, SinoMed, CNKI, Wanfang Data, and VIP Database were searched for articles on the validation of GLIM criteria published between September 2018 and September 2024. Two researchers independently performed literature screening and data extraction. The concurrent and predictive validity of the criteria was analyzed.Results:A total of 136 papers were included for analysis. The GLIM criteria for diagnosing malnutrition had a sensitivity of 77%, a specificity of 87%, and an area under the curve (AUC) of 0.90. Malnutrition diagnosed by the GLIM criteria predicted prolonged hospital and intensive care unit (ICU) stays, increased readmission and complication rates (both overall and infectious), reduced survivals (median, overall, and disease-free), and increased in-hospital and follow-up mortalities. Both moderate and severe malnutrition predicted decreased overall survival. However, only three studies analyzed the impact of nutritional therapy on the clinical outcomes of malnourished patients.Conclusions:The GLIM criteria accurately differentiate malnutrition and are a valid predictive tool of clinical outcomes. However, the validity criteria in these validation studies were questionable, along with high methodological heterogeneity. Furthermore, there is a lack of studies validating the role of nutritional therapy in improving the clinical outcomes of malnourished patients.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objective:To explore the diagnostic value of serum soluble semaphorin 4D (sSema4D) and soluble CD40 ligand (sCD40L) in left ventricular hypertrophy (LVH) in patients with primary hypertension (EH).Methods:Eighty-four patients with EH combined with LVH admitted to Qingdao Hospital of Shandong First Medical University from December 2022 to December 2023 were prospectively selected as the study group, and 84 patients with EH and without LVH admitted to Qingdao Hospital of Shandong First Medical University during the same period were regarded as the control group. Enzyme linked immunosorbent assay was applied to detect the levels of sSema4D and sCD40L. Employing Pearson correlation coefficient, the study assessed the association between concentrations of sSema4D and sCD40L in serum and various echocardiographic measurements. A multivariate Logistic regression model was engaged to probe into the contributing factors for the development of LVH. ROC curve was plotted to analyze the diagnostic value of serum sSema4D and sCD40L for EH combined with LVH.Results:Serum sSema4D and sCD40L levels were significantly higher in the study group than in the control group: (8.56 ± 2.19) μg/L vs. (5.12 ± 1.43) μg/L, (4.02 ± 1.03) μg/L vs. (3.22 ± 0.98) μg/L, and the differences were statistically significant ( P<0.05). The duration of hypertension, LVEDD, IVSTD, LVPWT, and LVMI were significantly higher in the study group than in the control group: (7.33 ± 1.53) years vs. (4.26 ± 1.35) years, (50.28 ± 3.33) mm vs. (44.45 ± 3.76) mm, (11.64 ± 3.21) mm vs. (9.53 ± 2.89) mm, (12.45 ± 1.52) mm vs. (9.13 ± 0.98) mm, (126.11 ± 15.28) g/m 2 vs. (81.15 ± 11.31) g/m 2, and the differences were statistically significant ( P<0.05). According to Pearson correlation analysis, it was known that both serum sSema4D and sCD40L were positively correlated with LVEDD, IVSTD, LVPWT and LVMI ( r = 0.425 and 0.533, 0.612 and 0.436, 0.513 and 0.628, 0.589 and 0.618; P<0.05). Multivariate Logistic regression analysis showed that hypertension duration, LVEDD, IVSTD, LVPWT, LVMI, sSema4D, sCD40L were risk factors for LVH in EH patients ( P<0.05). According to the ROC curve, the AUC for diagnosing EH combined with LVH with serum sSema4D was 0.848, the AUC for diagnosing EH combined with LVH with serum sCD40L was 0.725, and the AUC for diagnosing EH combined with LVH with serum sCD40L was 0.888, the combination of sCD40L and sCD40L was superior to their respective individual diagnoses ( Z = 2.651 and 2.526, P<0.05). Conclusions:The serum levels of sSema4D and sCD40L in patients with EH combined with LVH are obviously elevated, which are influencing factors for the occurrence of EH combined with LVH. Combined testing of the two has high diagnostic value for EH combined with LVH.

Objective:To conduct a systematic review of risk prediction models for enteral feeding intolerance in ICU patients.Methods:Relevant literature was searched in China National Knowledge Infrastructure, Wanfang Data, China Biology Medicine disc, VIP, PubMed, Web of Science, Cochrane Library, Embase, CINAHL, and Scopus, with search limits from the establishment of the databases up to July 24, 2024. Two researchers independently screened the literature and extracted data, using Prediction model Risk Of Bias ASsessment Tool to evaluate the quality of the included studies.Results:A total of 12 studies were included, which included 20 prediction models. The area under the receiver operating characteristic curve or C-index for these models ranged from 0.70 to 0.94. The overall bias risk of the 12 studies was high, with three studies having good applicability. The bias risk primarily stemmed from issues such as measurement of prediction factors, variable handling, sample size, outcome definition, and model performance evaluation.Conclusions:Existing risk prediction models for enteral feeding intolerance in ICU patients exhibit a high risk of bias. Further validation, optimization, or development of new models is required in the future.

Objective To determine the therapeutic effect of fasciotomy+hypertonic saline flushing for crush syndrome(CS)in rats.Methods SD rats(weighing 250±20 g)were randomly divided into normal control group(NC group,n=10)and CS group(n=14).Rat CS model was established by compressing the buttocks and both hindlimbs with a weight of 7.5 kg for 4 h,and the presence of hematuria or anuria was defined as success of modeling.In 6 h after modeling,the fluid exuded from the compressed tissues was collected,and the contents of potassium ions(K+),calcium ions(Ca2+),myoglobin(Mb),and lactic acid(Lac)in the exudate of each group were detected.Another 63 male SD rats(weighing 250±20 g)were randomly and equally divided into blank control group(NC group),CS group,CS+fasciotomy group(CSO group),and CS+fasciotomy+difference doses of NaCl solution irrigation groups(0.9％,3.0％,5.0％and 7.0％NaCl,respectively).At 6 h after modeling,the renal blood flow was measured,the contents of K+,Ca2+,Mb,Lac,AST,ALT,Cr,and urea in the plasma of each group were detected,and the compressed tissues and kidney tissues were observed for pathological changes.Results Detection of exudates showed the contents of K+,Mb,and Lac were significantly higher,while that of Ca2+content was obviously decreased in the CS group than the NC group(P＜0.01).Plasma detection indicated that simple fasciotomy had no therapeutic effect,while it combined with NaCl solution flushing decreased the contents of K+,Mb,Lac,AST,ALT,urea and Cr,and increased the Ca2+content in the blood of the CS group(P＜0.05).Laser speckle contrast imaging revealed that simple fasciotomy could not increase renal blood flow,while the combination of fasciotomy and NaCl solution flushing notably increased the renal blood flow in the CS rats(P＜0.05).In addition,the combination treatment reduced the pathological damage in the kidneys induced by CS,but fasciotomy alone had no such effect(P＜0.5).Conclusion Fasciotomy combined with hypertonic NaCl solution(3％)flushing can significantly reduce the damage caused by CS in rats.

Objective:To investigate the status of medical care seeking delay and diagnosis delay of pulmonary tuberculosis (PTB) patients in Tongzhou District and Changping District of Beijing, analyze the related factors and put forward suggestions for early detection and scientific management of PTB patients.Methods:A retrospective epidemiological survey was conducted to collect the incidence data of PTB registered in Tongzhou and Changping from January 1 to December 31, 2021 by using the Chinese Tuberculosis Information Management System, and telephone interview were used for information supplement. Multivariate logistic regression model and decision tree model were used to analyze the influencing factors of medical care seeking delay and diagnosis delay of PTB patients.Results:In 2021, the medical care seeking delay time M( Q1, Q3) in the PTB patients in Tongzhou and Changping was 11 (5, 26) days, with a delay rate of 41.71%. Results from multivariate logistic regression model analysis revealed that factors influencing the medical care seeking delay included regular health check-up ( OR=0.033, 95% CI: 0.008-0.147), coughing for less than 2 weeks or showing any symptom of PTB before medical care seeking ( OR=0.378, 95% CI: 0.215-0.665), showing other symptoms before medical care seeking( OR=2.791, 95% CI: 1.710-4.555), no work or school in medical care seeking ( OR=2.990, 95% CI: 1.419-6.298). The diagnosis delay time M( Q1, Q3) in the PTB patients was 8 (0, 18) days, with a delay rate of 35.20%. Multivariate logistic regression model analysis revealed that the factors influencing the diagnosis delay of PTB included being diagnosed at a specialized tuberculosis hospital ( OR=0.426, 95% CI: 0.236-0.767) or a tuberculosis prevention and control institution ( OR=1.843, 95% CI: 1.061-3.202) and being traced as a source of infection ( OR=2.632, 95% CI: 1.062-6.521). The overall performance of the multivariate logistic regression model was comparable to that of the decision tree model, with the decision tree model exhibiting higher sensitivity but lower specificity. Conclusions:The medical care seeking delay rate and diagnosis delay rate of tuberculosis in Tongzhou and Changping were at low levels in 2021. However, it is still necessary to strengthen the health education and active screening, improve the public awareness of PTB prevention and control, and further improve the level of medical services and medical access to reduce the medical care seeking delay and diagnosis delay of PTB patients.