Various therapeuti modailities have been engineered for lung cancer treatment, but their clinic application is severely impeded by the poor therapy efficiency and immunosuppressive microenvironment. Herein, we fabricated a library of small molecule redox-labile nanoparticles (NPs) (i.e., diPTX-2C NPs, diPTX-2S NPs, and diPTX-2Se NPs) by the self-assembly of dimer paclitaxel (PTX) prodrug, and then utilized these NPs with the traditional Chinese medicine (TCM) Qi-Yu-San-Long-Fang (Q) for effective chemoimmunotherapy on Lewis lung carcinoma (LLC)-bearing mice models. Under the high concentration of glutathione (GSH) and H₂O₂, diPTX-2Se NPs could specifically release PTX in cancer cells and exert a higher selectivity and toxicity than normal cells. In LLC tumor-bearing mice, oral administration of Q not only effectively downregulated programmed death ligand-1 (PD-L1) expression, but also remodeled the immunosuppressive tumor immune microenvironment via the increase of CD4⁺ T and CD8⁺ T cell proportion and the repolarization of M2 into M1 macrophages in tumor tissues, collectively achieving superior synergistic treatment outcomes in combination with intravenous PTX prodrug NPs. Besides, we found that the combination regimen also demonstrated excellent chemoimmunotherapeutic performances on low-dose small established tumor and high-dose large established tumor models. This study may shed light on the potent utilization of Chinese and Western-integrative strategy for efficient tumor chemoimmunotherapy.

Objective:To investigate the incidence of postoperative infection and its risk factors in patients with oral squamous cell carcinoma (OSCC), so that to provide a clinical basis for the prevention and management of postoperative infection in these patients.Methods:Ninety-seven patients pathologically diagnosed with OSCC who underwent surgical treatment in the Department of Oral and Craniomaxillofacial Oncology, Shanghai Ninth People′s Hospital, Shanghai Jiaotong University School of Medicine between December 2020 and March 2022 were included. This study was a clinical retrospective cohort study. The clinical characteristics and preoperative laboratory indicators of the included patients were collected. Based on the presence or absence of infection, the patients were divided into infection group and non-infection group. Chi-square test and independent samples t test were used for statistical methods. Binary logistic regression analysis was used to identify influencing factors for postoperative infection, and interaction terms were introduced to assess effect modification between variables. Results:Among the 97 patients, 46(47.42%) developed postoperative infections, of which 44(95.65%) were pulmonary infections. The proportion of hypertension in the infection group was 43.48%(20/46), which was higher than 23.53%(12/51) in the non-infection group, and the difference was statistically significant ( χ2=4.35, P=0.037). The preoperative glycosylated hemoglobin level in the infection group was 6.26%±0.85%, which was higher than that in the non-infection group (5.77%±0.57%), and the difference was statistically significant ( t=-2.81, P=0.007). Binary logistic regression analysis showed that male (odds ratio ( OR)=0.598, 95% confidence interval ( CI) 0.519 to 0.689, P<0.001), absence of diabetes ( OR=0.416, 95% CI 0.340 to 0.509, P<0.001), and absence of hypertension ( OR=0.647, 95% CI 0.569 to 0.735, P<0.001) were protective factors against postoperative infection. Age>60 years ( OR=1.159, 95% CI 1.031 to 1.304, P=0.014) and alcohol consumption ( OR=1.262, 95% CI 1.024 to 1.555, P=0.029) were risk factors for postoperative infection. Effect modification analysis found that males without diabetes ( OR=0.027, 95% CI 0.001 to 0.687, P=0.029) and the absence of both diabetes and hypertension ( OR=0.378, 95% CI 0.163 to 0.880, P=0.024) were also protective factors against postoperative infection. Conclusions:Risk factors for postoperative infection in OSCC include elder age, alcohol consumption, hypertension, and poor preoperative glycemic control. Therefore, clinical practice should enhance preoperative assessment, promote lifestyle modifications, optimize perioperative blood pressure management, implement glycemic control, and provide perioperative alcohol cessation interventions to reduce the risk of postoperative infection.

Objective:To investigate lipid metabolism gene mutations and pathogenicity of hypertriglyceridemia acute pancreatitis (HTG-AP) patients.Methods:Clinical data of 495 HTG-AP patients admitted from June 2018 to June 2020 in the center for severe acute pancreatitis of Eastern Theater General Hospital were retrospectively analyzed. Whole-exome sequencing and mutation verification were performed by next-generation sequencing technology and Sanger sequencing. The pathogenicity of gene mutation was analyzed by population mutation ratio, pathogenicity prediction software, conservation scoring software, protein structure prediction, and in vitro experiments. Results:The mutation ratio of lipid metabolism-related genes, namely LPL, APOA5, LMF1, GPIHBP1, and APOC2, were 14.81%, 55.78%, 43.61%, 1.62%, and 0.61%, respectively. Among them, 44 heterozygous mutations in LPL gene were detected including 36 missense mutations, 5 nonsense mutations and 3 frameshift mutations, which were all rarely carried in single patient. Six HTG-AP patients carried the LPL gene heterozygous mutation c.835C>G (p.Leu279Val). The mean level of serum triglyceride at the onset of HTG-AP was 27.4 mmol/L. All of them had a history of recurrent HTG-AP, and most of them had severe acute pancreatitis. The serum LPL concentration and activity were lower than the normal level. The pathogenicity analysis results suggested that the LPL p.Leu279Val was a rare, highly possible pathogenic and highly conserved gene mutation. The in vitro results showed that the LPL p.Leu279Val could significantly reduce the synthesis and secretion ability of LPL as well as its enzymatic activity. Conclusions:The mutation ratio of lipid metabolism-related genes, including LPL, APOA5, LMF1, GPIHBP1, and APOC2, are relatively high in the HTG-AP patients. The LPL p.Leu279Val is a rare and highly possible pathogenic gene mutation, which may lead to recurrent episodes of HTG-AP.

Objective:The high-quality clinical studies published in the field of hypertriglyceridemia associated acute pancreatitis (HTG-AP) were summarized to analyze the incidence and trends of HTG-AP in China.Methods:Clinical studies related to acute pancreatitis in PubMed, Medline, Cochrane Library and Web of Science from January 1, 2000 to November 12, 2021 were searched and screened. Keywords included China, acute pancreatitis, and clinical study. According to the inclusion and exclusion criteria, related literature were accurately selected and evaluated before extracting data. Meta-analysis was performed using R4.2 and RevMan5.3 software. The effect sizes of annual average percentage change (AAPC) for acute pancreatitis in different regions were merged and forest plot was drawn. Patients were divided into severe acute pancreatitis (SAP) group, moderately severe acute pancreatitis (MSAP) group and mild acute pancreatitis (MAP) group, and forest plot was drawn to analyze the AAPC of HTG-AP. Regression curve for time-dependent changes in the percentage of AP with different etiological factors was constructed.Results:Totally, 67 articles (33 randomized clinical trials, 34 retrospective cohort study) and 30 421 patients were included. The meta-analysis showed that the proportion of HTG-AP among AP patients was increasing over the past 20 years, with an AAPC of 0.52% (95% CI 0.34-1.39). In subgroup analyses, the proportion of HTG-AP in SAP and MSAP group both increased significantly, with the AAPC of 0.74% (95% CI 0.23-1.24) and 3.12% (95% CI 1.62-4.63), respectively. Furthermore, the proportion of HTG-AP among AP patients has shown an upward trend over the past 20 years with faster speed. The proportion of biliary pancreatitis among AP patients has also shown an upward trend, with the rate of increase gradually slowed. The proportion of alcohol-associated pancreatitis among AP patients has remained stable. Conclusions:Since 2000, the incidence proportion of HTG-AP has significantly increased in China with the rate of increase gradually quicker.

Objective:To investigate the impact of plasmapheresis therapy on the clinical efficacy in predicted severe hypertriglyceridemia-associated acute pancreatitis (HTG-AP) patients.Methods:The clinical data of 500 HTG-AP patients admitted to 36 medical centers across China in the Chinese Acute Pancreatitis Clinical Trials Group-PERFORM database from November 2020 to June 2023 were retrospectively analyzed. Besides the inclusion and exclusion criteria from PERFORM study, patients who had acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score ≥8 or CRP>150 mg/L on admission were included in the final analyses ( n=189). Patients were categorized into the plasmapheresis group ( n=51) and the routine treatment group ( n=138) according to the triglyceride-lowering therapies they received. General data, laboratory findings, AP severity, and clinical outcomes were recorded. Results:Patients undergoing plasmapheresis had higher initial triglyceride levels, APACHEⅡ score, SOFA score, and more organ failure than those receiving routine medical treatment. Results of multivariable logistic regression models showed that the plasmapheresis group, as compared to the routine treatment group, was neither associated with decreased risk of persistent organ failure within 14 days [54.9% (28/51) vs 37.7% (52/138), OR=0.89, 95% CI 0.36-2.21, P=0.810], nor with reduced incidence of organ failure on day 7 [17.7% (9/51) vs 15.9% (22/138), OR=0.60, 95% CI 0.19-1.88, P=0.378]. There was no significant difference on the dynamic changes of serum triglyceride within the first three days of admission ( P=0.108). Conclusions:Early plasmapheresis is not associated with reduced incidence of persistent organ failure in predicted severe HTG-AP patients.

Objective:To investigate lipid metabolism gene mutations and pathogenicity of hypertriglyceridemia acute pancreatitis (HTG-AP) patients.Methods:Clinical data of 495 HTG-AP patients admitted from June 2018 to June 2020 in the center for severe acute pancreatitis of Eastern Theater General Hospital were retrospectively analyzed. Whole-exome sequencing and mutation verification were performed by next-generation sequencing technology and Sanger sequencing. The pathogenicity of gene mutation was analyzed by population mutation ratio, pathogenicity prediction software, conservation scoring software, protein structure prediction, and in vitro experiments. Results:The mutation ratio of lipid metabolism-related genes, namely LPL, APOA5, LMF1, GPIHBP1, and APOC2, were 14.81%, 55.78%, 43.61%, 1.62%, and 0.61%, respectively. Among them, 44 heterozygous mutations in LPL gene were detected including 36 missense mutations, 5 nonsense mutations and 3 frameshift mutations, which were all rarely carried in single patient. Six HTG-AP patients carried the LPL gene heterozygous mutation c.835C>G (p.Leu279Val). The mean level of serum triglyceride at the onset of HTG-AP was 27.4 mmol/L. All of them had a history of recurrent HTG-AP, and most of them had severe acute pancreatitis. The serum LPL concentration and activity were lower than the normal level. The pathogenicity analysis results suggested that the LPL p.Leu279Val was a rare, highly possible pathogenic and highly conserved gene mutation. The in vitro results showed that the LPL p.Leu279Val could significantly reduce the synthesis and secretion ability of LPL as well as its enzymatic activity. Conclusions:The mutation ratio of lipid metabolism-related genes, including LPL, APOA5, LMF1, GPIHBP1, and APOC2, are relatively high in the HTG-AP patients. The LPL p.Leu279Val is a rare and highly possible pathogenic gene mutation, which may lead to recurrent episodes of HTG-AP.

Objective:The high-quality clinical studies published in the field of hypertriglyceridemia associated acute pancreatitis (HTG-AP) were summarized to analyze the incidence and trends of HTG-AP in China.Methods:Clinical studies related to acute pancreatitis in PubMed, Medline, Cochrane Library and Web of Science from January 1, 2000 to November 12, 2021 were searched and screened. Keywords included China, acute pancreatitis, and clinical study. According to the inclusion and exclusion criteria, related literature were accurately selected and evaluated before extracting data. Meta-analysis was performed using R4.2 and RevMan5.3 software. The effect sizes of annual average percentage change (AAPC) for acute pancreatitis in different regions were merged and forest plot was drawn. Patients were divided into severe acute pancreatitis (SAP) group, moderately severe acute pancreatitis (MSAP) group and mild acute pancreatitis (MAP) group, and forest plot was drawn to analyze the AAPC of HTG-AP. Regression curve for time-dependent changes in the percentage of AP with different etiological factors was constructed.Results:Totally, 67 articles (33 randomized clinical trials, 34 retrospective cohort study) and 30 421 patients were included. The meta-analysis showed that the proportion of HTG-AP among AP patients was increasing over the past 20 years, with an AAPC of 0.52% (95% CI 0.34-1.39). In subgroup analyses, the proportion of HTG-AP in SAP and MSAP group both increased significantly, with the AAPC of 0.74% (95% CI 0.23-1.24) and 3.12% (95% CI 1.62-4.63), respectively. Furthermore, the proportion of HTG-AP among AP patients has shown an upward trend over the past 20 years with faster speed. The proportion of biliary pancreatitis among AP patients has also shown an upward trend, with the rate of increase gradually slowed. The proportion of alcohol-associated pancreatitis among AP patients has remained stable. Conclusions:Since 2000, the incidence proportion of HTG-AP has significantly increased in China with the rate of increase gradually quicker.

Objective:To investigate the impact of plasmapheresis therapy on the clinical efficacy in predicted severe hypertriglyceridemia-associated acute pancreatitis (HTG-AP) patients.Methods:The clinical data of 500 HTG-AP patients admitted to 36 medical centers across China in the Chinese Acute Pancreatitis Clinical Trials Group-PERFORM database from November 2020 to June 2023 were retrospectively analyzed. Besides the inclusion and exclusion criteria from PERFORM study, patients who had acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score ≥8 or CRP>150 mg/L on admission were included in the final analyses ( n=189). Patients were categorized into the plasmapheresis group ( n=51) and the routine treatment group ( n=138) according to the triglyceride-lowering therapies they received. General data, laboratory findings, AP severity, and clinical outcomes were recorded. Results:Patients undergoing plasmapheresis had higher initial triglyceride levels, APACHEⅡ score, SOFA score, and more organ failure than those receiving routine medical treatment. Results of multivariable logistic regression models showed that the plasmapheresis group, as compared to the routine treatment group, was neither associated with decreased risk of persistent organ failure within 14 days [54.9% (28/51) vs 37.7% (52/138), OR=0.89, 95% CI 0.36-2.21, P=0.810], nor with reduced incidence of organ failure on day 7 [17.7% (9/51) vs 15.9% (22/138), OR=0.60, 95% CI 0.19-1.88, P=0.378]. There was no significant difference on the dynamic changes of serum triglyceride within the first three days of admission ( P=0.108). Conclusions:Early plasmapheresis is not associated with reduced incidence of persistent organ failure in predicted severe HTG-AP patients.

Objective:To investigate the incidence of postoperative infection and its risk factors in patients with oral squamous cell carcinoma (OSCC), so that to provide a clinical basis for the prevention and management of postoperative infection in these patients.Methods:Ninety-seven patients pathologically diagnosed with OSCC who underwent surgical treatment in the Department of Oral and Craniomaxillofacial Oncology, Shanghai Ninth People′s Hospital, Shanghai Jiaotong University School of Medicine between December 2020 and March 2022 were included. This study was a clinical retrospective cohort study. The clinical characteristics and preoperative laboratory indicators of the included patients were collected. Based on the presence or absence of infection, the patients were divided into infection group and non-infection group. Chi-square test and independent samples t test were used for statistical methods. Binary logistic regression analysis was used to identify influencing factors for postoperative infection, and interaction terms were introduced to assess effect modification between variables. Results:Among the 97 patients, 46(47.42%) developed postoperative infections, of which 44(95.65%) were pulmonary infections. The proportion of hypertension in the infection group was 43.48%(20/46), which was higher than 23.53%(12/51) in the non-infection group, and the difference was statistically significant ( χ2=4.35, P=0.037). The preoperative glycosylated hemoglobin level in the infection group was 6.26%±0.85%, which was higher than that in the non-infection group (5.77%±0.57%), and the difference was statistically significant ( t=-2.81, P=0.007). Binary logistic regression analysis showed that male (odds ratio ( OR)=0.598, 95% confidence interval ( CI) 0.519 to 0.689, P<0.001), absence of diabetes ( OR=0.416, 95% CI 0.340 to 0.509, P<0.001), and absence of hypertension ( OR=0.647, 95% CI 0.569 to 0.735, P<0.001) were protective factors against postoperative infection. Age>60 years ( OR=1.159, 95% CI 1.031 to 1.304, P=0.014) and alcohol consumption ( OR=1.262, 95% CI 1.024 to 1.555, P=0.029) were risk factors for postoperative infection. Effect modification analysis found that males without diabetes ( OR=0.027, 95% CI 0.001 to 0.687, P=0.029) and the absence of both diabetes and hypertension ( OR=0.378, 95% CI 0.163 to 0.880, P=0.024) were also protective factors against postoperative infection. Conclusions:Risk factors for postoperative infection in OSCC include elder age, alcohol consumption, hypertension, and poor preoperative glycemic control. Therefore, clinical practice should enhance preoperative assessment, promote lifestyle modifications, optimize perioperative blood pressure management, implement glycemic control, and provide perioperative alcohol cessation interventions to reduce the risk of postoperative infection.

ObjectiveTo explore the therapeutic mechanism of Bushen Huoxue prescription from the perspective of bone metabolism by observing the clinical efficacy of this prescription in treating femoral head necrosis （ONFH， syndrome of liver and kidney deficiency） and its influences on bone metabolism indexes： N-terminal propeptide （PINP） and β-collagen degradation product （β-CTX）. MethodSixty-six ONFH patients with the syndrome of liver and kidney deficiency in Zhengzhou Traditional Chinese Medicine Hospital of Orthopedics from December 2021 to September 2022 were selected. The patients were randomized into an experimental group and a control group by the parallel control method， with 33 patients in each group. The experimental group received Bushen Huoxue prescription orally， while the control group received Xianlinggubao Capsules orally， with a treatment cycle of 6 months. The visual analogue scale （VAS） score， Harris score， Association Research Circulation Osseous （ARCO） staging， imaging changes， quantitative scores of TCM symptoms， and serum levels of PINP and β-CTX were determined before and after treatment. The occurrence of adverse events and reactions was recorded. ResultThe total response rate in the experimental group was 83.87% （26/31）， which was higher than that （68.75%， 22/32） in the control group （Z=-2.096， P<0.05）. After treatment， the single and total scores of TCM symptoms， VAS score， and β-CTX level decreased in the two groups （P<0.05）. Moreover， the decreases in the scores of hip pain， lower limb mobility， soreness of waist and knees， and lower limb flaccidity， total score of TCM symptoms， VAS score， and β-CTX level in the experimental were larger than those in the control group （P<0.05）. After treatment， the imaging results showed no significant improvement in the two groups. The Harris score and PINP level in both groups increased after treatment （P<0.05）， and the increases were more obvious in the experimental group than in the control group （P<0.05）. No serious adverse event or adverse reaction appeared during the observation period. ConclusionBushen Huoxue prescription can relieve pain and TCM symptoms and improve the hip joint function in treating ONFH patients with the syndrome of liver and kidney deficiency. It can inhibit the development of ONFH， increase PINP， and decrease β-CTX. No obvious side effect appears during the clinical observation period， which shows that Bushen Huoxue prescription has good safety.