The cellular and molecular components of the tumor immune microenvironment (TIME) and their information exchange processes significantly influence the trends of anti-tumor immunity. In recent years, numerous studies have begun to evaluate TIME in the context of previous cancer treatment strategies. This review will systematically summarize the compositional characteristics of TIME and, based on this foundation, explore the impact of current cancer therapies on the remodeling of TIME, aiming to provide new insights for the development of innovative immune combination therapies that can convert TIME into an anti-tumor profile.
Tumor Microenvironment/immunology* ; Humans ; Neoplasms/therapy* ; Immunotherapy/methods* ; Animals

Objective To investigate the effect of FUNDC1 tyrosine phosphorylation site mutations on mitophagy in H9c2 myocardial cells by constructing tyrosine site mutant plasmids (Y11 and Y18) of the FUN14 domain-containing protein 1 (FUNDC1). Methods The mutant plasmids constructed by whole-gene synthesis were transfected into rat myocardial H9c2 cells and divided into five groups: empty plasmid group, FUNDC1 overexpression group, Y11 mutant group, Y18 mutant group, and Y11 combined with Y18 mutant group. The viability of H9c2 cells was assessed using the CCK-8 assay. Additionally, tetramethylrhodamine ethyl ester (TMRE) staining was utilized to detect mitochondrial membrane potential. The protein expression levels of FUNDC1, translocase of the outer mitochondrial membrane 20 (TOM20), and cytochrome c oxidase IV (COX IV) were detected by Western blot analysis. Confocal microscopy was used to evaluate transfection efficiency as well as the co-localization of mitochondria and lysosomes. Results The FUNDC1 overexpression, Y11, Y18, and Y11 combined with Y18 mutant plasmids were successfully constructed. After plasmid transfection, widespread GFP fluorescence expression was observed under confocal microscopy. Compared with the empty plasmid group, FUNDC1 protein expression levels were significantly increased in the FUNDC1 overexpression group, Y11 mutation group, Y18 mutation group, and Y11 combined with Y18 mutation group, while cell viability and mitochondrial membrane potential showed no significant changes. Compared to the empty plasmid group, cells transfected with Y18 and Y11 combined with Y18 mutant plasmids showed increased TOM20 and COX IV expression levels and decreased mitochondrial-lysosomal co-localization. Conclusion Transfection with FUNDC1 Y18 or Y11 combined with Y18 mutant plasmids inhibited mitophagy in H9c2 myocardial cells.
Animals ; Rats ; Mitophagy/genetics* ; Myocytes, Cardiac/cytology* ; Mitochondrial Proteins/metabolism* ; Mutation ; Phosphorylation ; Tyrosine/genetics* ; Cell Line ; Membrane Proteins/metabolism* ; Membrane Potential, Mitochondrial

Objective To investigate the common diseases and the causes of diseases in Chinese Antarctic researchers,so as to provide reference for the medical support.Methods Medical records of 1 127 people with injuries and diseases who participated in four Antarctic scientific expeditions(the 31st,35th,36th,and 39th time)were retrospectively analyzed.The causes of the injuries and diseases as well as the implications for nursing were investigated.Results The top 10 diseases in the four Antarctic expeditions were acute soft tissue injury,dermatomycosis,pharyngitis,insomnia,periodontitis,gastroenteritis,motion sickness,acute upper respiratory infection,primary hypertension,and frostbite.The causes of the diseases in the four Antarctic expeditions were analyzed,and the nursing of different diseases was proposed.Conclusion It is necessary to take preventive measures based on the characteristics of injuries and diseases during Antarctic expeditions,so as to effectively prevent and treat these diseases and provide more comprehensive medical support for Antarctic scientific expeditions.

Objective To investigate the efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with unresectable or advanced hepatocellular carcinoma(HCC).Methods A retrospective analysis was performed for the patients with unresectable/advanced HCC who attended six hospitals from January 1,2019 to March 31,2021,and all patients received camrelizumab monoclonal antibody treatment,among whom 84.8%also received targeted therapy.According to the age of the patients,they were divided into elderly group(≥65 years)and non-elderly group(＜65 years).The two groups were assessed in terms of overall survival(OS),progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),and immune-related adverse events(irAE).The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups;the independent samples t-test was used for comparison of normally distributed continuous data,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups.The Kaplan-Meier method was used for survival analysis,and the log-rank test was used for comparison of survival curves.Univariate and multivariate Cox proportional hazards regression analyses were used to determine the independent influencing factors for PFS and DCR at 6 months.Results A total of 99 HCC patients were enrolled,with 27 in the elderly group and 72 in the non-elderly group.The elderly group had an OS rate of 67.8%,an ORR of 44.4%,and a DCR of 74.1%at 12 months and a median PFS of 6.4(95%confidence interval[CI]:3.0-12.4)months,with no significant differences compared with the non-elderly group(all P＞0.05).The median OS was unavailable for the elderly group,while the non-elderly group had an OS of 18.9(95%CI:13.0-24.8)months;there was no significant difference between the two groups(P=0.485).The univariate and multivariate Cox regression analyses showed that major vascular invasion(MVI)was an independent risk factor for PFS(hazard ratio[HR]=2.603,95%CI:1.136-5.964,P=0.024)and DCR(HR=3.963,95%CI:1.671-9.397,P=0.002)at 6 months,while age,sex,etiology of HBV infection,presence of extrahepatic metastasis,Child-Pugh class B,and alpha-fetoprotein＞400 ng/mL were not associated with PFS or DCR at 6 months.For the elderly group,the incidence rates of any irAE and grade 3/4 irAE were 51.9%and 25.9%,respectively,with no significant differences compared with the non-elderly group(P＞0.05),and skin disease was the most common irAE in both groups(39.4%).Conclusion Camrelizumab monoclonal antibody combined with molecular-targeted therapy has similar efficacy and safety in patients with unresectable/advanced HCC aged≥65 years and those aged＜65 years.MVI is associated with suboptimal response to immunotherapy and poor prognosis.

BACKGROUND:After the treatment of femoral shaft fracture with the intramedullary nail,the third fracture open reduction indications are controversial.Some scholars believe that limited open reduction can achieve anatomical reduction,conducive to fracture healing;but some scholars believe that no open reduction of the third fracture still has a high fracture healing rate. OBJECTIVE:To investigate the effect of the circumference and displacement of the third fragment on fracture healing after intramedullary nailing of femoral shaft fractures with the third fragment. METHODS:A retrospective cohort study was conducted to analyze the clinical data of 142 patients suffered a femoral shaft fracture with a third fragment admitted to the Affiliated Lianyungang Hospital of Xuzhou Medical University from February 2016 to December 2021.The fracture were classified into three types according to the circumference of the third fracture with reference to the diaphyseal circumference at the fracture site:type 1 in 71 cases,type 2 in 52 cases,and type 3 in 19 cases.Referring to the diaphyseal diameter,the fractures were classified into three degrees according to the degree of the third fragment displacement:degree I in 95 cases,degree II in 31 cases,and degree III in 16 cases.All patients were treated with femoral interlocking intramedullary nails,and no intervention was performed for the displaced third fragment during the operation.Postoperative follow-up was performed to compare the fracture healing rate,healing time,and the modified Radiographic Union Scale for Tibia at month 9 after surgery in each group.The effect of third fracture fragment circumference and degree of displacement on fracture healing was assessed. RESULTS AND CONCLUSION:(1)All 142 patients were followed up for at least 12 months,with a mean of(14.7±4.1)months,and the overall healing rate was 73.4%.(2)When the third fragment was displaced by degree I,the healing rate,healing time,and modified Radiographic Union Scale for Tibia score at month 9 were not statistically significant among the three sub-groups of circumference classification.(3)When the third fragments were displaced by degree II or III,the healing rate and healing time were not statistically significant among the three subgroups of circumference classification;the modified Radiographic Union Scale for Tibia score at month 9 in the type 1 group was higher than that in the type 2 and 3 groups(P = 0.017).(4)Logistic regression analysis showed that a greater third fragment displacement and circumference were associated with lower fracture healing rates(P<0.05).(5)These findings indicate that in the treatment of femoral shaft fractures with third fragment by intramedullary nails,when the fracture fragment is displaced to degree I,the circumference size has little effect on fracture healing,and no intervention is required during surgery.When the third fragment is displaced to degree II or III and the circumference of which is type 1,a higher modified Radiographic Union Scale for Tibia score can still be obtained with no intervention of the third fragment.However,when the circumference is of type 2 or type 3,it significantly affects the fracture healing.Consequently,intraoperative intervention to reduce the distance of displacement of the fragment is required to lower the incidence of nonunion.The displacement of the third fracture fragments has a greater impact on fracture healing than their circumference.

OBJECTIVE To explore the expression of trefoil factor family peptide(TFF3)in chronic rhinosinusitis with nasal polyps(CRSwNP)and its regulation on mucin 5AC(MUC5AC)expression.METHODS The nasal polyp tissues of 16 patients in the CRSwNP group and the nasal mucosal tissues of 16 patients in the control group were selected,and the expressions of TFF3 and MUC5AC were detected by quantitative real-time polymerase chain reaction(RT-qPCR)and Western blot,and the correlation between them was analyzed.The human nasal epithelial cell(HNEpC)line with TFF3 knockdown was constructed,and the expression of MUC5AC in KD-TFF3 HNEpC was detected by RT-qPCR and immunofluorescence.RESULTS The expression level of TFF3 in nasal polyps was significantly lower than that of control group,and the expression level of MUC5AC was increased,and the expression level of both was negatively correlated(r=-0.556,P<0.05).The expression of MUC5AC in KD-TFF3 HNEpC was significantly higher than that in control group.CONCLUSION The expression of TFF3 decreases in CRSwNP and negatively regulates the expression of MUC5AC.This study provides a new idea for the treatment of abnormal hypersecretion of mucous in chronic nasal inflammatory diseases represented by CRSwNP.

Objective:To study the factors influencing survival after radical resection in patients with intrahepatic cholangiocarcinoma (ICC), and to construct a nomogram on survival prediction.Methods:The clinical data of 139 patients with ICC who underwent radical resection at the People's Hospital of Zhengzhou University from June 2018 to December 2021 were retrospectively analyzed. There are 69 males and 70 females, aged (59.5±10.2) years old. These patients were divided into two groups based on a 3: 1 ratio by using the random number method: the test group ( n=104) and the validation group ( n=35). Data from the test group was used to construct a nomagram and data from the validation group was used to validate the predictive power of the nomagram. Univariate and multivariate Cox regression analyses were used to analyse factors influencing survival on the test group patients and to construct a nomogram. The predictive accuracy of the nomogram was determined by receiver operating characteristic (ROC) curves, concordance index (C-index) and calibration curves. Results:The results of the multivariate regression analysis showed that a combined hemoglobin, albumin, lymphocyte and platelet immunoinflammation (HALP) score <37.1 ( HR=1.784, 95% CI: 1.047-3.040), CA19-9 > 35U/ml ( HR=2.352, 95% CI: 1.139-4.857), poorly differentiated tumor ( HR=2.475, 95% CI: 1.237-4.953) and vascular invasion ( HR=1.897, 95% CI: 1.110-3.244) were independent risk factors that affected prognosis of patients with ICC after radical resection (all P<0.05). The AUCs of the nomogram in the test group in predicting the overall survival at 1, 2 and 3 years of patients with ICC after radical resection were 0.808, 0.853 and 0.859, respectively. There was good consistency between the prediction of the nomogram and actual observation. The predicted C-index of the total survival period of the test group was 0.765 (95% CI: 0.704-0.826), and the C-index of the validation group was 0.759 (95% CI: 0.673-0.845). Conclusion:A HALP score <37.1, CA19-9>35 U/ml, poorly differentiated tumour and vascular invasion were independent risk factors for prognosis of ICC patients after radical resection. The nomogram was established based on the above factors and showed good performance in predicting overall survival after radical resection in patients with ICC.

Objective To predict the intervention targets of empagliflozin(EMPA),a specific inhibitor of sodium-glucose cotransporter 2(SGLT2),in gastric adenocarcinoma through comprehensive network pharmacology,and to validate the effects and the molecular mechanisms of EMPA through cellular and molecular biology experiments.Methods Bioinformatics analysis of gastric adenocarcinoma was conducted to assess the correlation between gastric adenocarcinoma prognosis and SGLT2 expression.Network pharmacology was utilized to identify shared targets of EMPA and gastric adenocarcinoma.AGS cells,a human gastric adenocarcinoma cells line,were incubated with EMPA at different concentrations for 24 h and,then,cell proliferation was assessed using the CCK8 assay.After AGS cells were incubated with EMPA at the doses of 0,3,and 6 mmol/L,real-time cell analysis(RTCA)and 5-ethynyl-2-deoxyuridine(EdU)incorporation were used to evaluate EMPA's inhibitory effects on the proliferation of the AGS cells.In addition,wound healing and Transwell assays were performed to assess the inhibitory effect of EMPA on the migration and invasion of the APC cells and Western blot analysis was conducted to examine the expression of mammalian target of rapamycin(mTOR)and phosphorylated mTOR(p-mTOR).BALB/c(nu/nu)nude mice were implanted with 5x106 AGS cells in the axilla.The mice were divided into three groups,a control group,a low-dose group,and a high-dose group,each consisting of 7 mice.After one week,the control group received daily intraperitoneal injections of normal saline,while the low-dose group and high-dose group received daily intraperitoneal injections of EMPA at the doses of 3 mg/kg and 5 mg/kg,respectively.The tumor volume was measured one week after the drug intervention started.Results Gastric adenocarcinoma patients with low expression of SGLT2 exhibited longer survival time and higher survival rate than those with high expression of SGLT2 did.A total of 104 EMPA-related potential targets and 2028 targets associated with gastric adenocarcinoma were identified.Among these,45 targets associated with gastric adenocarcinoma overlapped with potential targets of EMPA.Further analysis revealed 10 relevant pathways and 4 core genes.The core genes were cyclin-dependent kinase 4(CDK4),glyceraldehyde-3-phosphate dehydrogenase(GAPDH),mTOR,and cyclin El(CCNE1).CCK-8 assay revealed that EMPA at concentrations ranging from 0.39 to 50 mmol/L effectively inhibited the proliferation of AGS cells.RTCA results indicated a downward shift in the cell growth curve.In comparison to the findings for the control group,EdU assay demonstrated that EMPA at the concentrations of 3 mmol/L and 6 mmol/L significantly inhibited AGS cell proliferation(P＜0.05).Results from wound healing and Transwell assays indicated a decrease in the levels of cell migration and invasion(P＜0.05)and,notably,there was a significant difference between the high and low-dose EMPA groups(P＜0.05).Western blot showed no statistically significant difference in the expression of total mTOR protein between the groups.However,the expression of p-mTOR in the 3 mmol/L and 6 mmol/L EMPA groups decreased compared to that of the control group(P＜0.05),with the 6 mmol/L EMPA group exhibiting a more pronounced reduction(P＜0.05).Nude mice xenograft tumor experiment demonstrated that,compared to that of the control group,the tumor volumes in the EMPA-treatment groups were significantly reduced(P＜0.05),with the high-dose group showing a more pronounced reduction(P＜0.05).Conclusion EMPA inhibits the abnormal proliferation and migration of gastric adenocarcinoma cells,potentially through the modulation of mTOR protein activation.This study provides new potential medication and intervention targets for gastric adenocarcinoma treatment.

Objective:To investigate the anatomical characteristics of human hepatic anterior fissure vein.Methods:The retrospective and descriptive study was used. A total of 22 adult cadaver specimens were collected from the Department of Human Anatomy of Harbin Medical University from March 2018 to March 2021. There were 15 males and 7 females, aged 45(range, 18?75)years. Observation indicators: (1) recognition rate of hepatic anterior fissure vein and the location of hepatic anterior fissure vein merging into hepatic vein; (2) length of hepatic anterior fissure vein and the opening diameter of hepatic anterior fissure vein merging into hepatic vein; (3) location of hepatic anterior fissure vein and the ventral hepatic vein of segment Ⅷ of liver (V8v) as well as V8v condition; (4) relationship among hepatic anterior fissure vein, anterior ventral portal vein and anterior dorsal portal vein. Measurement data with normal distribution were represented as Mean± SD, and t test was used for comparison between groups. Measurement data with skewed distribution were represented as M(range), and count data were expressed as absolute numbers or percentages. Results:(1) Recognition rate of hepatic anterior fissure vein and the location of hepatic anterior fissure vein merging into hepatic vein. The recognition rate of hepatic anterior fissure vein of 22 liver samples was 90.9% (20/22). There were 9.1%(2/22) of liver samples without hepatic anterior fissure vein. The proportions of hepatic anterior fissure vein merging into proximal middle hepatic vein and proximal right hepatic vein were 19/20 and 1/20, respectively. There was no liver sample with hepatic anterior fissure vein merging into distal middle hepatic vein and distal right hepatic vein. (2) Length of hepatic anterior fissure vein and the opening diameter of hepatic anterior fissure vein merging into hepatic vein. In the 20 liver samples with hepatic anterior fissure vein, the length of hepatic anterior fissure vein was (6.41±1.26)cm, and the opening diameter of hepatic anterior fissure vein merging into hepatic vein was (0.38±0.10)cm. (3) Location of anterior fissure vein and the V8v and V8v condition. In the 22 liver samples, there were 25 V8v branches merging into the proximal middle hepatic vein, with the V8v length as (3.83±0.36)cm and the V8v diameter as (0.16±0.08)cm. In the 17 liver samples with both hepatic anterior fissure vein and V8v, the proportion of V8v merging into hepatic anterior fissure vein and then into middle hepatic vein was 14/17, the proportion of hepatic anterior fissure vein and V8v merging into middle hepatic vein separately was 3/17, and there was no liver sample with hepatic anterior fissure vein merging into right hepatic vein and V8v merging into middle hepatic vein. (4) Relationship among hepatic anterior fissure vein, anterior ventral portal vein and anterior dorsal portal vein. Of the 20 liver samples with hepatic anterior fissure vein, the hepatic anterior fissure vein of 16 liver samples could be used as the demarcation mark of anterior ventral segment and anterior dorsal segment of hepatic right anterior region. The distance between the hepatic anterior fissure vein and anterior ventral portal vein was (1.40±0.43)cm, and that between the hepatic anterior fissure vein and anterior dorsal portal vein was (1.46±0.63)cm, showing no significant difference between them ( t=1.00, P>0.05). Conclusion:The hepatic anterior fissure vein exists in most normal adult livers, and it mostly merges into proximal middle hepatic vein. The hepatic anterior fissure vein can be identified by the condition of V8v. The hepatic anterior fissure vein can be used as the demarcation mark of anterior ventral segment and anterior dorsal segment of hepatic right anterior region.

Fusion surgery has been an effective modality for the treatment of spinal disorders for more than 100 years. With the increasing understanding of the disease and the increasing maturity of surgical techniques, lumbar fusion has become more widely performed and its efficacy has been conclusively proven. However, fusion surgery inevitably disrupts the original physiologic motion of the spine and limits segmental motion, resulting in a significant increase in disc and joint protrusion stress in adjacent segments. When a newly identified degenerative change on imaging is present in an adjacent segment or an existing degeneration is more aggravated, this is known as adjacent segment degeneration. When clinical symptoms such as pain and numbness in the lower extremities are present that are consistent with degeneration, this is known as adjacent segment disease. Real world studies (RWS) have become a major focus in medical research in recent years. Since it is closer to clinical practice and more practical for decision-making compared with randomized controlled trail (RCT), it is gaining importance in clinical practice. By searching major national and international databases, this article provides a review of risk factors as well as advances in the treatment of lumbar adjacent segment disease in RWS. According to the retrieved literature, there are many factors that contribute to the development and progression of adjacent segment degeneration and disease, which are mainly divided into patient-related factors and surgery-related factors. In general, patient age, weight, spinal-pelvic sagittal parameters, and internal diseases influence the progression of adjacent segment degeneration. Surgery-related risk factors include the number of segments operated on, the surgical approach, interference with adjacent segments, and whether the spinal-pelvicsagittal imbalance is corrected. To prevent the development of adjacent segment disease, patients can slow the progression of adjacent segment degeneration by reducing their own weight and controlling their internal diseases. The physician can also avoid the influence of surgery-related factors through adequate surgical planning and careful intraoperative management. At the same time, surgeries may be performed in patients who have developed adjacent segmental disease and for whom conservative treatment has failed. The current revision surgical approaches include endoscopic simple decompression and posterior decompression with extended internal fixation.Short-term RWS revealed that the efficacy of endoscopic treatment of adjacent spondylosis might be equivalent to re-fusion internal fixation surgery. Studies with large samples and long-term follow-up are still needed to guide the treatment of adjacent segment disease in the future, in order to improve clinical decision-making.