Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) is a promising target for sensitizing solid tumors to immune checkpoint blockades. However, the highly polar active sites of PTPN2 hinder drug discovery efforts. Leveraging small interfering RNA (siRNA) technology, we developed a novel glutathione-responsive nano-platform HPssPT (HA/PEIss@siPtpn2) to silence PTPN2 and enhance immunotherapy efficacy in hepatocellular carcinoma (HCC). HPssPT showed potent transfection and favorable safety profiles. PTPN2 deficiency induced by HPssPT amplified the interferon γ signaling in HCC cells by increasing the phosphorylation of Janus-activated kinase 1 and signal transducer and activator of transcription 1, resulting in enhanced antigen presentation and T cell activation. The nano-platform was also able to promote the M1-like polarization of macrophages in vitro. The unique tropism of HPssPT towards tumor-associated macrophages, facilitated by hyaluronic acid coating and CD44 receptor targeting, allowed for simultaneous reprogramming of both tumor cells and tumor-associated macrophages, thereby synergistically reshaping tumor microenvironment to an immunostimulatory state. In HCC, colorectal cancer, and melanoma animal models, HPssPT monotherapy provoked robust antitumor immunity, thereby sensitizing tumors to PD-1 blockade, which provided new inspiration for siRNA-based drug discovery and tumor immunotherapy.

Objective:To investigate the incidence of postoperative complications in Chinese patients with gastric or colorectal cancer, and to evaluate the risk factors for postoperative complications.Methods:This was a national, multicenter, prospective, registry-based, cohort study of data obtained from the database of the Prevalence of Abdominal Complications After Gastro- enterological Surgery (PACAGE) study sponsored by the China Gastrointestinal Cancer Surgical Union. The PACAGE database prospectively collected general demographic characteristics, protocols for perioperative treatment, and variables associated with postoperative complications in patients treated for gastric or colorectal cancer in 20 medical centers from December 2018 to December 2020. The patients were grouped according to the presence or absence of postoperative complications. Postoperative complications were categorized and graded in accordance with the expert consensus on postoperative complications in gastrointestinal oncology surgery and Clavien-Dindo grading criteria. The incidence of postoperative complications of different grades are presented as bar charts. Independent risk factors for occurrence of postoperative complications were identified by multifactorial unconditional logistic regression.Results:The study cohort comprised 3926 patients with gastric or colorectal cancer, 657 (16.7%) of whom had a total of 876 postoperative complications. Serious complications (Grade III and above) occurred in 4.0% of patients (156/3926). The rate of Grade V complications was 0.2% (7/3926). The cohort included 2271 patients with gastric cancer with a postoperative complication rate of 18.1% (412/2271) and serious complication rate of 4.7% (106/2271); and 1655 with colorectal cancer, with a postoperative complication rate of 14.8% (245/1655) and serious complication rate of 3.0% (50/1655). The incidences of anastomotic leakage in patients with gastric and colorectal cancer were 3.3% (74/2271) and 3.4% (56/1655), respectively. Abdominal infection was the most frequently occurring complication, accounting for 28.7% (164/572) and 39.5% (120/304) of postoperative complications in patients with gastric and colorectal cancer, respectively. The most frequently occurring grade of postoperative complication was Grade II, accounting for 65.4% (374/572) and 56.6% (172/304) of complications in patients with gastric and colorectal cancers, respectively. Multifactorial analysis identified (1) the following independent risk factors for postoperative complications in patients in the gastric cancer group: preoperative comorbidities (OR=2.54, 95%CI: 1.51-4.28, P<0.001), neoadjuvant therapy (OR=1.42, 95%CI:1.06-1.89, P=0.020), high American Society of Anesthesiologists (ASA) scores (ASA score 2 points:OR=1.60, 95% CI: 1.23-2.07, P<0.001, ASA score ≥3 points:OR=0.43, 95% CI: 0.25-0.73, P=0.002), operative time >180 minutes (OR=1.81, 95% CI: 1.42-2.31, P<0.001), intraoperative bleeding >50 mL (OR=1.29,95%CI: 1.01-1.63, P=0.038), and distal gastrectomy compared with total gastrectomy (OR=0.65,95%CI: 0.51-0.83, P<0.001); and (2) the following independent risk factors for postoperative complications in patients in the colorectal cancer group: female (OR=0.60, 95%CI: 0.44-0.80, P<0.001), preoperative comorbidities (OR=2.73, 95%CI: 1.25-5.99, P=0.030), neoadjuvant therapy (OR=1.83, 95%CI:1.23-2.72, P=0.008), laparoscopic surgery (OR=0.47, 95%CI: 0.30-0.72, P=0.022), and abdominoperineal resection compared with low anterior resection (OR=2.74, 95%CI: 1.71-4.41, P<0.001). Conclusion:Postoperative complications associated with various types of infection were the most frequent complications in patients with gastric or colorectal cancer. Although the risk factors for postoperative complications differed between patients with gastric cancer and those with colorectal cancer, the presence of preoperative comorbidities, administration of neoadjuvant therapy, and extent of surgical resection, were the commonest factors associated with postoperative complications in patients of both categories.

Objective:To investigate the incidence of postoperative complications in Chinese patients with gastric or colorectal cancer, and to evaluate the risk factors for postoperative complications.Methods:This was a national, multicenter, prospective, registry-based, cohort study of data obtained from the database of the Prevalence of Abdominal Complications After Gastro- enterological Surgery (PACAGE) study sponsored by the China Gastrointestinal Cancer Surgical Union. The PACAGE database prospectively collected general demographic characteristics, protocols for perioperative treatment, and variables associated with postoperative complications in patients treated for gastric or colorectal cancer in 20 medical centers from December 2018 to December 2020. The patients were grouped according to the presence or absence of postoperative complications. Postoperative complications were categorized and graded in accordance with the expert consensus on postoperative complications in gastrointestinal oncology surgery and Clavien-Dindo grading criteria. The incidence of postoperative complications of different grades are presented as bar charts. Independent risk factors for occurrence of postoperative complications were identified by multifactorial unconditional logistic regression.Results:The study cohort comprised 3926 patients with gastric or colorectal cancer, 657 (16.7%) of whom had a total of 876 postoperative complications. Serious complications (Grade III and above) occurred in 4.0% of patients (156/3926). The rate of Grade V complications was 0.2% (7/3926). The cohort included 2271 patients with gastric cancer with a postoperative complication rate of 18.1% (412/2271) and serious complication rate of 4.7% (106/2271); and 1655 with colorectal cancer, with a postoperative complication rate of 14.8% (245/1655) and serious complication rate of 3.0% (50/1655). The incidences of anastomotic leakage in patients with gastric and colorectal cancer were 3.3% (74/2271) and 3.4% (56/1655), respectively. Abdominal infection was the most frequently occurring complication, accounting for 28.7% (164/572) and 39.5% (120/304) of postoperative complications in patients with gastric and colorectal cancer, respectively. The most frequently occurring grade of postoperative complication was Grade II, accounting for 65.4% (374/572) and 56.6% (172/304) of complications in patients with gastric and colorectal cancers, respectively. Multifactorial analysis identified (1) the following independent risk factors for postoperative complications in patients in the gastric cancer group: preoperative comorbidities (OR=2.54, 95%CI: 1.51-4.28, P<0.001), neoadjuvant therapy (OR=1.42, 95%CI:1.06-1.89, P=0.020), high American Society of Anesthesiologists (ASA) scores (ASA score 2 points:OR=1.60, 95% CI: 1.23-2.07, P<0.001, ASA score ≥3 points:OR=0.43, 95% CI: 0.25-0.73, P=0.002), operative time >180 minutes (OR=1.81, 95% CI: 1.42-2.31, P<0.001), intraoperative bleeding >50 mL (OR=1.29,95%CI: 1.01-1.63, P=0.038), and distal gastrectomy compared with total gastrectomy (OR=0.65,95%CI: 0.51-0.83, P<0.001); and (2) the following independent risk factors for postoperative complications in patients in the colorectal cancer group: female (OR=0.60, 95%CI: 0.44-0.80, P<0.001), preoperative comorbidities (OR=2.73, 95%CI: 1.25-5.99, P=0.030), neoadjuvant therapy (OR=1.83, 95%CI:1.23-2.72, P=0.008), laparoscopic surgery (OR=0.47, 95%CI: 0.30-0.72, P=0.022), and abdominoperineal resection compared with low anterior resection (OR=2.74, 95%CI: 1.71-4.41, P<0.001). Conclusion:Postoperative complications associated with various types of infection were the most frequent complications in patients with gastric or colorectal cancer. Although the risk factors for postoperative complications differed between patients with gastric cancer and those with colorectal cancer, the presence of preoperative comorbidities, administration of neoadjuvant therapy, and extent of surgical resection, were the commonest factors associated with postoperative complications in patients of both categories.

Objective To evaluate the influence of routine lateral release to the clinical outcomes after total knee arthroplasty without patellar resurfacing.Methods The study involved all patients divided into two groups using a randomised group method.During total knee arthroplasty(TKA),forty-three patients were treated with lateral release in the treatment group,while Forty-two patients in the control group were not treated with lateral release.Both groups were assessed for anterior knee pain,patient satisfaction,Knee Surgery Society(KSS)score,KSS function score,patella score,and incidence of postoperative complications.Results After 24 months of follow-up,the treatment group was found to have a lower incidence of anterior knee pain compared to the control group(P<0.05),and there were no statistically significant differences in postoperative satisfaction,complication rate,KSS knee score,KSS function score,and patella score between the two groups(P>0.05).Conclusion The study suggests that routine lateral release can reduce anterior knee pain and does not increase the risk of postoperative complications after total knee arthroplasty without patellar resurfacing.

Objective To analyze the setup errors during proton and heavy ion therapy for head and head neck tumor patients fixed by thermoplastic film combined with styrofoam.Methods Totally 20 patients undergoing proton and heavy ion therapy at some hospital from January to December 2018 were selected retrospectively,of whom 10 ones had head tumors with clinical targets located in the head and the other 10 cases had head and neck tumors with clinical targets distributed in the head and neck.All the 20 patients were fixed with thermoplastic film combined with styrofoam.The head and neck images of the patients acquired after image guidance were aligned with the CT localization-based digitally reconstructed radiograph images,and the setup errors at six-dimensional directions(left-right translation,head-foot translation,forward-backward translation,isocentric rotation,pitch rotation and transverse-roll rotation)were recorded in the first five and the last five times of radiotherapy treatment.The data were processed by using the SPSS 23.0 statistical software and EXCEL.Results There were no significant differences between the head tumor patients in the setup errors at the six directions during the first and last five times of radiotherapy(P＞0.05).The head and neck tumor patients did not have obvious differences in the setup errors at the the directions of left-right translation,forward-backward translation,isocentric rotation and transverse-roll rotation(P＞0.05),while did at the directions of head-foot translation and pitch rotation(P＜0.05).The head and head neck tumor patients with the fixation by thermoplastic film combined with styrofoam had their setup errors at the six directions meet clinical requirements after calibration by the six-dimensional treatment table.Conclusion The fixation mode by thermoplastic film and styrofoam behaves well to enhance the setup repeatability for head tumor patients at the six-dimensional directions,while not so well for head neck tumor patients at the directions of head-foot translation and pitch rotation.Proper measures have to be taken to decrease the setup errors during proton and heavy ion therapy for head and head neck tumor patients.[Chinese Medical Equipment Journal,2024,45(7):56-61]

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

ObjectiveTo explore the effect of Tongxie Yaofang on the immune microenvironment of colorectal cancer in mice under chronic stress and the underlying mechanism. MethodA total of 40 male SPF BABL/C mice were randomized into normal group， stress group， Tongxie Yaofang group （13.65 g·kg^-1）， and Tongxie Yaofang-stress group （13.65 g·kg^-1）， with 10 in each group. Chronic restraint stress was induced in mice and administration （ig） of Tongxie Yaofang began after 7 days of stress. On the 14^th day， forced swim and tail suspension tests were used to examine the behavioral changes of mice after stress and the subcutaneous colorectal tumor was implanted in each group of mice. The effect of this prescription on the body mass and tumor volume of mice was observed. After the last administration， mouse serum and tumor samples were collected. The content of T lymphocytes （CD3⁺， CD4⁺， CD8⁺， and CD4⁺/CD8⁺） in tumor was detected by immunohistochemistry and flow cytometry and levels of corticosterone （CORT） in peripheral blood， and interleukin （IL）-2， interferon-γ （IFN-γ）， IL-6， and IL-10 in the serum were determined by enzyme-linked immunosorbent assay （ELISA）. The protein expression of inhibitor of nuclear factor-κB（IκB） kinase α/β （IKKα/β）， nuclear factor-κB （NF-κB）α （IκBα）， NF-κB p65， and phosphorylated （p）-NF-κB p65 was measured by Western blot. ResultCompared with the normal group， the stress group had large tumor volume （P<0.05）， low content of CD3⁺， CD4⁺， and CD4⁺/CD8⁺ （P<0.05， P<0.01）， high content of CD8⁺， low content of T helper 1 （Th1）-secreted IFN-γ （P<0.05）， high content of T helper 2 （Th2）-secreted IL-10 （P<0.05） and CORT （P<0.05）， high protein expression of p-NF-κB p65， NF-κB p65， and IKKα/β （P<0.05）， and low protein expression of IκBα （P<0.05）. Compared with the normal group， the Tongxie Yaofang group showed slow tumor growth， high content of CD3⁺， CD4⁺， and CD4⁺/CD8⁺ （P<0.01）， low content of CD8⁺ （P<0.05）， high content of Th1-secreted IL-2 and IFN-γ （P<0.05）， low content of Th2-secreted IL-6 and IL-10 （P<0.05）， low content of CORT， low protein expression of p-NF-κB p65， NF-κB p65， and IKKα/β （P<0.05）， and high protein expression of IκBα （P<0.01）. Tongxie Yaofang-stress group demonstrated slower tumor growth， higher content of CD3⁺， CD4⁺， and CD4⁺/CD8⁺ （P<0.01）， smaller content of CD8⁺ （P<0.05）， higher content of IL-2 and IFN-γ （P<0.05）， lower content of IL-6， IL-10 （P<0.05）， and CORT （P<0.05）， lower protein expression of p-NF-κB p65， NF-κB p65， and IKKα/β （P<0.05，P<0.01）， and higher protein expression of IκBα （P<0.01） than the stress group. ConclusionTongxie Yaofang can delay the growth of colorectal cancer under chronic stress and alleviate the deterioration of the immune microenvironment， possibly by inhibiting NF-κB signaling pathway， regulating the function of T lymphocyte subsets， and thus suppressing the secretion of pro-inflammatory factors.

Objective To observe the effect of Tongxie Yaofang-containing serum on the cell cycle and apoptosis of colon cancer HCT116 cells,and to explore its possible biological mechanism.Methods Colon cancer HCT116 cells were divided into blank group and Tongxie Yaofang-containing serum group with different concentrations.Cell proliferation and activity detection-8(CCK8)was used to detect the effect of each group on the viability of HCT116 cells at 24,48 and 72 h;Flow cytometry was used to detect the apoptosis and cycle arrest of HCT116 cells induced by different concentrations of Tongxie Yaofang-containing serum;Western blot was used to detect the protein expression level of Cell Cycle Regulatory Protein P21(P21),Cyclin B1,cyclin-dependent protein kinases-1(CDK1),B-lymphoma-2(Bcl-2),Bcl-2-related X protein(Bax),phosphatidylinositol-3-kinase(PI3K),phosphorylated phosphatidylinositol-3-kinase(p-PI3K),protein kinase B(Akt)and phosphorylated protein kinase B(p-Akt)after different concentrations of Tongxie Yaofang-containing serum intervention.Results CCK8 showed that compared with the 10%blank group,10%Tongxie Yaofang-containing serum had a significant inhibitory effect on the viability of HCT116 cells only at 48 h(P<0.01);Compared with the 20%blank group,20%Tongxie Yaofang-containing serum could inhibit the viability of HCT116 cells at 48 and 72 h(P<0.01,P<0.05),and the increase of blank serum will not inhibit the viability of HCT116 cell,so 10%blank serum and 48 h were selected as the drug control and intervention time in the subsequent experiment.Flow Cytometry showed that,compared with the blank group,10%and 20%Tongxie Yaofang-containing serum could arrest HCT116 cell cycle in G2/M phase after 48 h of intervention(P<0.01),and induce HCT116 cell apoptosis.At the same time,Western blot showed that Tongxie Yaofang-containing serum could increase the expression of P21 and Bax to varying degrees,and reduces Cyclin B1,CDK1,Bcl-2,p-PI3K,p-Akt expression(P<0.05,P<0.01).Conclusion Tongxie Yaofang can inhibit the proliferation and induce apoptosis of colon cancer HCT116 cells,and its mechanism may be related to the inhibition of PI3K/Akt signaling pathway.

Objective: The survival of colorectal cancer in Qidong City, Jiangsu Province from 1972 to 2016 was analyzed to provide a basis for the evaluation of prognosis and the formulation of prevention and control measures. Methods: Colorectal cancer data were obtained from the Qidong Cancer Registration and Reporting System, and the follow-up was up to December 31, 2021. The observed survival rate (OSR) and relative survival rate (RSR) were calculated by SURV 3.01 software, and the trend test was performed by Hakulinen's likelihood ratio test. The Joinpoint regression model was used to calculate the average annual percentage change (AAPC) of survival, and the ARIMA model was used to predict the trend of colorectal cancer survival. Results: There were 8 637 new cases of colorectal cancer in Qidong from 1972 to 2016. Dividing 1972-2016 into 9 periods at 5-year intervals, the 5-year OSR from 1972-1976 to 2012-2016 increased from 21.86% to 48.86%, and the 5-year RSR increased from 26.45% to 59.91%. The increasing trend of RSR was statistically significant (χ(2)=587.47, P<0.001). From 1972 to 2016, the survival rates of colorectal cancer in different sexes in Qidong were similar, and the 5-year RSR was 44.63% for men and 44.07% for women. Since the 1990s, the 5-year OSR and RSR for men have been lower than those for women. From 1972 to 2016, the 5-year RSR of colorectal cancer in Qidong was significantly improved in the 65-74 and ≥75-year-old groups, but the survival rate of the ≥75-year-old group was still the lowest (36.78%), followed by the 35-44-year-old group ( 43.04%). The time trend showed that the overall AAPC of colorectal cancer 5-year RSR in Qidong from 1972 to 2016 was 2.50% (t=16.45, P<0.001). The upward trend of different sexes was consistent, and the increase was greater in women (AAPC for males=2.18%, AAPC for females=2.54%, both P<0.05). The 5-year RSR of colorectal cancer in each age group showed an upward trend, and the AAPCs of the 35-44, 45-54, 55-64, 65-74, and ≥75-year-old groups were 1.54%, 1.83%, 2.00%, 3.51% and 4.35%, respectively (all P<0.05). The prediction results of colorectal cancer survival rate showed that the 5-year RSR of colorectal cancer in Qidong will increase to 71.62% by 2026. Conclusions: The overall survival rate of colorectal cancer patients in Qidong has been greatly improved, but there is still room for improvement. We should continue to pay attention to the early diagnosis and early treatment of colorectal cancer.
Male ; Humans ; Female ; Aged ; Adult ; Survival Rate ; Prognosis ; Software ; Likelihood Functions ; Colorectal Neoplasms ; China/epidemiology* ; Incidence

The anterior cruciate ligament (ACL) injury is a common sports injury that has a significant impact on knee function and patients′ mobility. With the popularity of national fitness campaign in China, the incidence of ACL injury is increasing year by year. Currently, there still lacks clinical standards or guidelines on how to choose appropriate treatment methods, surgical plans and rehabilitation protocols for ACL injury. In order to timely reflect the new treatment concept of ACL injury, standardize its diagnosis and treatment and improve the curative effect, the Sports Medicine Society of Chinese Research Hospital Association and the Editorial Board of Chinese Journal of Trauma organized domestic orthopedic and sports medicine experts to formulate the "clinical evidence-based guideline for the diagnosis and treatment of anterior cruciate ligament injury (2022 version)" based on the level of evidence-based medicine and in compliance with the principle of scientificity, practicability and advancement. The present guideline includes 12 recommendations for the diagnosis, treatment and rehabilitation of ACL injury in order to provide guidance and assistance for the clinical diagnosis and treatment of ACL injury in China.