[Aqueous extract of Chuan Xiong Rhizoma enhances inhibitory effect of temozolomide against brain metastasis of melanoma in mice].

OBJECTIVE: To investigate the effect of the aqueous extract of Chuan Xiong Rhizoma (CR) on brain metastasis of melanoma B16F10 cells in mice. METHODS: C57BL/6J mouse models of brain metastasis of melanoma were established by ultrasound-guided intraventricular injection of Luc-labeled B16F10 cells, and brain tumor growth was monitored by in vivo imaging. The mouse models were then randomized for daily gavage of saline or aqueous extract of CR (equivalent crude drug concentration of 1 mg/g). Behavioral tests were used to evaluate the neuroprotective effects of CR in the tumor-bearing mice, and the changes in proteins associated with blood-brain barrier integrity, neuronal cell proliferation and apoptosis, and microglial cell apoptosis and activation were observed using immunofluorescence assay. The efficacy of CR combined with temozolomide (25 mg/kg) against brain metastases of B16F10 cells was observed by in vivo imaging. RESULTS: CR-treated mouse models did not show obvious progression of brain metastases and had a reduced rate of body weight loss and lowered protein expressions of ZO-1, claudin-5, occludin, P-gp, TNF-α, AQP4 and PDGFRß. In the behavioral tests, the CR-treated mice showed prolonged stay on the wooden stick with a shortened time of sticky stick removal. Immunofluorescence assay showed increased proliferation and decreased apoptosis of neuronal cells and microglia in CR-treated mice. CR treatment significantly increased the levels of CD86, CD206, IL-4 and IL-10 and decreased the levels of CD163 and IL-1ß in the microenvironment of brain metastases. The mice receiving combined treatments with CR and temozolomide showed significantly lower intensity of fluorescent signals in the brain than those treated with temozolomide alone. CONCLUSION: CR does not promote brain metastasis of melanoma while inducing opening of the blood-brain barrier, and its combined use with TMZ results in enhanced inhibition against brain metastasis of melanoma B16F10 cells in mice.

Pan-cancer analysis of heterogeneity of tumor mutational burden and genomic mutation under treatment pressure.

BACKGROUND: High tumor mutational burden (TMB) is one of the widely researched predictive biomarkers of immune checkpoint inhibitors and has been shown to be closely related with response to immunotherapy in multiple cancer types. However, for patients who have failed conventional therapy and are about to undergo immunotherapy, there is no consensus recommendation on the timing of tumor sampling for TMB analysis, and the effects of different therapies on TMB have not been clarified. This retrospective observational study aimed to investigate the heterogeneity of TMB and genomic mutation under the treatment pressure. PATIENTS AND METHODS: We retrospectively collected the available genomic and therapeutic information from 8051 samples across 15 tumor types (>50 samples/tumor) found in 30 published studies and investigated the distribution and heterogeneity of TMB under treatment across diverse cohorts. RESULTS: This integrated analysis has shown anticancer treatments increased TMB. Significant effects of treatment on TMB were more frequently observed in tumor types with lower treatment-naïve TMB, including breast, prostate, and pediatric cancers. For different cancer therapies, chemotherapy was prone to be correlated with an increased TMB in most cancer types. Meanwhile, the fraction of the TMB-high category of breast, prostate, and bladder cancers and glioma increased significantly after chemotherapy. Several actionable genes including ERS1 and NF1 in breast cancer, as well as some prognostic markers including TERT in bladder cancer and IDH1 in glioma, were significantly changed in post-chemotherapy tumors compared to treatment-naïve tumors. CONCLUSION: Our study reveals the heterogeneity of TMB under treatment across diverse cancer types and provides evidences that chemotherapy was associated with increases in TMB as well as the fraction of TMB-high category, suggesting that resampling tumor tissues for calculating post-chemotherapy TMB could be a better option for predicting the response to immunotherapy, especially for tumors with initially low TMB.

Fabrication and evaluation of porous coatings doped with bioactive elements on titanium surfaces.

OBJECTIVE: Although pure titanium (PT) and its alloys exhibit excellent mechanical properties, they lack biological activity as implants. The purpose of this study was to improve the biological activity of titanium implants through surface modification. MATERIALS AND METHODS: Titanium was processed into titanium discs, where the titanium discs served as anodes and stainless steel served as cathodes, and a copper- and cobalt-doped porous coating [pure titanium model (PTM)] was prepared on the surface of titanium via plasma electrolytic oxidation. The surface characteristics of the coating were evaluated using field emission scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and profilometry. The corrosion resistance of PTM was evaluated with an electrochemical workstation. The biocompatibility and bioactivity of coated bone marrow mesenchymal stem cells (BMSCs) were evaluated through in vitro cell experiments. RESULTS: A copper- and cobalt-doped porous coating was successfully prepared on the surface of titanium, and the doping of copper and cobalt did not change the surface topography of the coating. The porous coating increased the surface roughness of titanium and improved its resistance to corrosion. In addition, the porous coating doped with copper and cobalt promoted the adhesion and spreading of BMSCs. CONCLUSIONS: A porous coating doped with copper and cobalt was prepared on the surface of titanium through plasma electrolytic oxidation. The coating not only improved the roughness and corrosion resistance of titanium but also exhibited good biological activity.

[Liver cancer treatment with mitochondrial homeostasis].

Systemic treatment, including molecular targeted therapy, immunotherapy, and chemotherapy, is an important means of achieving long-term survival in patients with intermediate-and advanced-stage liver cancer. However, some patients are insensitive to treatment and even develop drug resistance. Mitochondria are the center of cellular energy metabolism and, at the same time, are the priority targets for systemic therapy. Mitochondrial homeostasis plays an important role in the treatment of liver cancer. The relationship between the two advances is elucidated so as to provide better ideas for the clinical treatment of liver cancer.

[Progress in application of aspirin desensitization and maintenance therapy in aspirin-exacerbated respiratory disease].

Aspirin-exacerbated respiratory disease (AERD) is a clinical syndrome characterized by chronic rhinosinusitis with nasal polyps, asthma and the development of significant airway symptoms following the ingestion of aspirin and other nonsteroid anti-inflammatory drugs (NSAIDs). At present, aspirin challenge is the gold standard for diagnosis. Aspirin desensitization and aspirin therapy after desensitization (ATAD) is one of the classical therapies. This paper described the application of aspirin desensitization and ATAD in AERD and provided the reference for the comprehensive treatment of AERD.

[Multi-omics combined test performance effectiveness on opportunistic screening of high-risk liver cancer population].

Objective: To validate the performance of a multi-omics combined test for early screening of high-risk liver cancer populations. Methods: 173 high-risk patients with liver cancer were prospectively screened in a real-world setting, and 164 cases were finally enrolled. B-ultrasound, alpha-fetoprotein (AFP), and HCC screens were conducted in all patients. A multi-omics early screening test was performed for liver cancer in combination with multi-gene methylation, TP53/TERT/CTNNB1 mutations, AFP, and abnormal prothrombin (PIVKA-II). Differences in rates were compared using the chi-square test, adjusted chi-square test, or Fisher's exact probability method for count data. A non-parametric rank test (Mann-Whitney) was used to compare the differences between the two groups of data. Results: The HCCscreen detection had a sensitivity of 100% for liver cancer screening, 93.8% for liver cancer and precancerous diseases, 34.1% for positive predictive value, 99.2% for negative predictive value, and 0.89 for an area under the curve (AUC). Parallel detection of AFP, AFP+B-ultrasound, and methylation+mutation had a sensitivity/specificity and AUC of 31.3%/88.5% (AUC=0.78), 56.3%/88.2% (AUC=0.86), and 81.3%/82.4 % (AUC=0.84). At the same time, the disease severity range was significantly correlated with the methylation+mutation score, HCCscreen score, or positive detection rate (PDR). There was no significant correlation between AFP serum levels and methylation+mutation or HCCscreen scores, while there was a significant linear correlation between methylation+mutation scores and HCCscreen scores (r = 0.73, P < 0.001). Conclusion: In real-world settings, HCCscreen shows high sensitivity for screening opportunistic, high-risk liver cancer populations. Furthermore, it may efficaciously detect liver cancer and precancerous diseases, with superior performance to AFP and AFP+ultrasound. Hence, HCCscreen has the potential to become an effective screening tool that is superior to existing screening methods for high-risk liver cancer populations.

[Disease burden of colorectal cancer attributable to dietary risk factors from 1990 to 2019 in China].

Objective: To analyze the trend of mortality rate and disability-adjusted life year (DALY) of colorectal cancer attributable to dietary risk factors from 1990 to 2019 in China. Methods: Mortality rate and DALY rate of colorectal cancer attributable to dietary risk factors (diet high in processed meat, diet high in red meat, diet low in calcium, diet in low in fiber, diet low in milk, diet low in whole grains, dietary risks) were collected from the Global Burden of Disease study 2019 (GBD2019). Joinpoint regression model was selected to analyze the trend and an age-period-cohort model was used to estimate the effects of age, period and birth cohort. Results: Joinpoint regression analysis showed that the age-standardized mortality rate and age-standardized DALY rate of colorectal cancer attributable to diet high in processed meat, diet high in red meat, diet low in milk, diet low in whole grains and dietary risks showed an upward trend (P<0.05) from 1990 to 2019, while those attributable to diet low in calcium and diet low in fiber showed a downward trend (P<0.05). The mortality rate and DALY rate of colorectal cancer attributable to diet high in processed meat, diet high in red meat, diet low in milk, diet low in whole grains and dietary risks in age groups from 65 to 79 years showed a quicker upward trend than those in age groups from 25 to 64 years. The mortality rate and DALY rate attributable to diet low in calcium and diet low in fiber in age groups from 65 to 79 years showed a slower downward trend than those in age groups from 25 to 64 years. The mortality rate and DALY rate of colorectal cancer attributable to diet high in processed meat, diet high in red meat, diet low in calcium, diet low in fiber, diet low in milk, diet low in whole grains, and dietary risks increased with age after adjusting for period effect and cohort effect (P<0.05). The mortality rate and DALY rate attributable to diet high in processed meat, diet high in red meat, diet low in calcium, diet low in milk, diet low in whole grains and dietary risks increased with period or cohort, while those attributable to diet low in fiber decreased with period or cohort. Period and cohort effect of dietary risk factors in this study were statistically significant (P<0.001). Conclusions: Disease burden of colorectal cancer attributable to dietary risk factors in China showed an upward trend in general. Elderly population is high at risk and more attention should be paid to science popularization and education on dietary risk factors in prevention and treatment of colorectal cancer.

Association of serum lipids and abnormal lipid score with cancer risk: a population-based prospective study.

BACKGROUND: Serum lipid levels are associated with cancer risk. However, there still have uncertainties about the single and combined effects of low lipid levels on cancer risk. METHODS: A prospective cohort study of 33,773 adults in Shanghai between 2016 and 2017 was conducted. Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were measured. Cox proportional hazard models were used to assess the association of single and combined lipids with overall, lung, colon, rectal, thyroid gland, stomach, and female breast cancers. The effect of the combination of abnormal lipid score and lifestyle on cancer was also estimated. RESULTS: A total of 926 incident cancer cases were identified. In the RCS analysis, hazard ratios (HRs) of overall cancer for individuals with TC < 5.18 mmol/L or with LDL-C < 3.40 mmol/L were higher. Low TC was associated with higher colorectal cancer risk (HR [95% CI] = 1.76 [1.09-2.84]) and low HDL-C increased thyroid cancer risk by 90%. Abnormal lipid score was linearly and positively associated with cancer risk, and smokers with high abnormal lipid scores had a higher cancer risk, compared to non-smokers with low abnormal lipid scores (P < 0.05). CONCLUSIONS: Low TC levels were associated with an increased risk of overall and colorectal cancer. More attention should be paid to participants with high abnormal lipid scores and unhealthy lifestyles who may have a higher risk of developing cancer. Determining the specific and comprehensive lipid combinations that affect tumorigenesis remains a valuable challenge.

Efficacy and Safety of First-line Therapies for Advanced Unresectable Oesophageal Squamous Cell Cancer: a Systematic Review and Network Meta-analysis.

AIM: To compare the clinical efficacy and safety of first-line treatments for advanced unresectable oesophageal squamous cell cancer. MATERIALS AND METHODS: A systematic review and network meta-analysis was carried out by retrieving and retaining relevant literature from databases. The studies were randomised controlled trials comparing first-line treatments for advanced unresectable oesophageal squamous cell cancer. A Bayesian network meta-analysis was used to assess clinical outcomes. RESULTS: Nine studies including 4499 patients receiving first-line treatments were analysed. For all populations, toripalimab plus chemotherapy tended to provide the best overall survival (hazard ratio 0.58, 95% confidence intervals 0.43-0.78) and sintilimab plus chemotherapy provided the best progression-free survival (0.56, 0.46-0.68). Nivolumab plus chemotherapy presented the best objective response rate (odds ratio 2.45, 1.78-3.42) and camrelizumab plus chemotherapy (0.47, 0.29-0.74) appeared to be the safest. Sintilimab plus chemotherapy (0.55, 0.40-0.75) and nivolumab (0.54, 0.37-0.80) plus chemotherapy had the best overall survival in programmed death ligand 1 (PD-L1) tumour proportion score <1% and ≥1% subgroups. Toripalimab plus chemotherapy (0.61, 0.40-0.93) and pembrolizumab (0.57, 0.43-0.75) were the best in overall survival in combined positive score <10 and ≥10 subgroups, respectively. Toripalimab plus chemotherapy showed the best overall survival in the Asian group; pembrolizumab presented better overall survival in the Asian population than the non-Asian group. CONCLUSION: Most immunotherapy combined with chemotherapy showed superior clinical benefits and sintilimab plus chemotherapy, toripalimab plus chemotherapy and tislelizumab plus chemotherapy had better comprehensive clinical efficacy. PD-L1 expression detection and ethnicity differences are still of great significance and most suitable regimens varied from each subgroup.

A comprehensive prognostic analysis of cause-specific mortality in patients with ovarian serous cystadenocarcinoma using a competing-risks model: a case study of the SEER database.

OBJECTIVE: This retrospective study employed a competing-risks analysis utilizing the Surveillance, Epidemiology, and End Results (SEER) database to identify precise prognostic factors associated with ovarian serous cystadenocarcinoma (OSCC) in patients. PATIENTS AND METHODS: Patients with OSCC during 2004-2015 were identified in the SEER database, and their clinicopathological, demographic, and survival data were examined. Univariate analysis using Gray's test and the cumulative incidence function was used to evaluate the prognoses of events of interest. The multivariate analysis involved several models, including the Cox proportional hazards, Fine-Gray, and cause-specific (CS) hazard function models, to estimate the hazard functions of competing risks. Hazard ratios were analyzed to identify the reliability of the prognostic factors. RESULTS: Among the 10,400 individuals diagnosed with OSCC, 5,713 died from the illness, and 1,125 died from other causes. The cumulative incidence rate of events of interest was found to be significant for ethnicity, age at diagnosis, histological grade, American Joint Committee on Cancer (AJCC) stage, chemotherapy and surgery status, tumor size, marital status, and local lymph node metastases (p<0.05). The multivariate analysis revealed that ethnicity, histological grade, surgery and chemotherapy status, age at diagnosis, AJCC stage, marital status, and distant metastases were independent prognostic factors in the Cox model (p<0.05). Finally, the Fine-Gray and CS models demonstrated that ethnicity, histological grade, surgery and chemotherapy status, age at diagnosis, AJCC stage, tumor size, marital status, and combination summary stage were all identified as independent prognostic factors (p<0.05). CONCLUSIONS: This study determined the risk factors for OSCC using a competing risk analysis model established by the SEER database. The findings can help clinicians understand OSCC better and provide more accurate medical support to affected patients.

[Learning curve and clinical efficacy of aortic surgery through upper hemisternotomy].

OBJECTIVE: To investigate the learning curve and clinical efficacy of aortic dissection and non-dissection aortic surgeries through upper hemisternotomy. METHODS: We retrospectively analyzed the perioperative data of aortic dissection and non-dissection surgeries through upper hemisternotomy performed by the same surgical team. Based on cardiopulmonary bypass time and aortic cross-clamping time, the learning curves were plotted using cumulative (CUSUM) analysis and the fitting curve, and the learning process was divided into the improvement period and proficiency period. We compared the perioperative parameters in the two stages, and verified whether the critical point was the number of operations required to overcome the learning curve. The safety and short-term efficacy of the aortic surgeries were analyzed after achieving proficiency. RESULTS: A total of 107 patients were analyzed, including 47 undergoing aortic dissection (ascending aorta replacement + arch replacement + descending aorta stent implantation and/or aortic root treatment) and 60 undergoing non-dissection surgeries (artery root surgery and/or ascending aorta replacement). The optimal fitting equation was y=-0.019x3+0.251x2+28.852x-6.076 (R2=0.918, P < 0.05) for CPB time and y=-0.015x3-0.093x2+34.799x-27.316 (R2=0.92, P < 0.05) for aortic cross-clamping time. In the dissection group, with 27 cases as the boundary, the perioperative parameters were significantly better in the proficiency stage than in the improvement stage, and the critical point was the number of surgeries needed to overcome the learning curve. The best fitting equation was y=0.013x3-1.826x2 + 62.353x+193.189 (R2=0.906, P < 0.05) for CPB time and y= 0.009x3-1.416x2+49.389x+177.335 (R2=0.90, P < 0.05) for aortic cross-clamping time. In the non-dissecting aorta group, where 22 cases served as the boundary, the perioperative parameters were also better in the proficiency period than in the improvement period. CONCLUSION: Both aortic dissection and non-dissection surgeries through upper hemisternotomy are safe and can significantly improve the short-term postoperative efficacy after achieving proficiency, but the latter approach has a shorter learning curve.

[Analysis of the prevalence of dyslipidemia and correlative factors in Tajik population in Pamir Plateau of Xinjiang].

Objective: To investigate the prevalence of dyslipidemia and the level of blood lipids among Tajik people in Pamir Plateau, Xinjiang, and explore the related factors of dyslipidemia. Methods: It is a retrospective cross-sectional study. A multi-stage cluster random sampling survey was conducted among 5 635 Tajiks over 18 years old in Tashkorgan Tajik Autonomous County, Xinjiang Province from May to October 2021. Data were collected through questionnaire survey (general information, medical history, and personal history), physical examination (height, weight, waist, and blood pressure) and blood test (total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density cholesterol (HDL-C)) to analyze the dyslipidemia and its risk factors among Tajiks. Results: The age of Tajik participants was (41.9±15.0) years, including 2 726 males (48.4%). The prevalence of borderline high TC, high LDL-C and high TG levels were 17.2%, 14.7% and 8.9%, respectively. The prevalence of high TC, high LDL-C, high TG and low HDL-C were 4.1%, 4.9%, 9.4% and 32.4%, respectively, and the prevalence of dyslipidemia was 37.0%. There is a positive correlation between male,higher education level, higher body mass index (BMI) value,waist circumference, living in town, smoking and dyslipidemia. Conclusions: The low prevalence of high TC, high LDL-C, high TG and high prevalence of low HDL-C was a major characteristic of Tajik people in Pamir Plateau of Xinjiang. The lower rates of overweight and obesity may be one of the reasons for the lower prevalence of dyslipidemia among Tajik.

[Experimental study on the therapeutic effect and mechanism of erlotinib on non-proliferative diabetic retinopathy].

Objective: To investigate the therapeutic effect and mechanism of erlotinib, an epidermal growth factor receptor (EGFR) inhibitor, on non-proliferative diabetic retinopathy (NPDR). Methods: An experimental research was conducted. Human retinal Müller cells (RMC) were MIO-M1 cells from Moorfields Ophthalmology Hospital and the Institute of Ophthalmology at London University College. MIO-M1 cells were divided into normal, hypertonic, high glucose, high glucose+dimethyl sulfoxide (DMSO), high glucose+erlotinib 0.5 mmol/L, high glucose+erlotinib 1 mmol/L, and high glucose+erlotinib 2 mmol/L groups using a random number table method. Detection of the effect of erlotinib on the proliferation of MIO-M1 cells under high glucose conditions was performed by 5-ethynyl-2'-deoxyuridine (EdU) method. Western blotting (WB) was used to detect the effect of erlotinib on the activation markers of glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS) protein levels in MIO-M1 cells under high glucose conditions. WB was used to detect the effect of erlotinib on the protein levels of nerve growth factor receptor (p75NTR), vimentin, and cell retinol binding protein (CRALBP) in RMC under high glucose conditions. MIO-M1 cells were divided into normal group, high glucose group, high glucose+DMSO group, and high glucose+erlotinib (1 mmol/L) group using random number table method. The effect of erlotinib on EGFR nuclear translocation under high glucose conditions was detected by cell immunofluorescence staining. Immunoprecipitation was used to detect the effect of erlotinib on the interaction between EGFR and transcription intermediate factor 2 (TIF2) in MIO-M1 cells under high glucose conditions. MIO-M1 cells were randomly divided into normal group, high glucose group, high glucose+DMSO group, high glucose+Myc-DDK empty body group, high glucose+erlotinib group, high glucose+erlotinib+human doublet protein group, high glucose+erlotinib+TIF2 plasmid group, and high glucose+erlotinib+human doublet protein+TIF2 plasmid group. Cell immunofluorescence staining was used to detect the effect of erlotinib on the binding of EGFR and TIF2 in MIO-M1 cells under high glucose conditions through the EGFR/TIF2 axis. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the regulatory effect of EGFR and TIF2 binding on cyclin D1 transcription in MIO-M1 cells under high glucose conditions. The mouse model of diabetes retinopathy (DR) was constructed and divided into normal group, DR group, DR+DMSO group, DR+erlotinib 0.25 mg·kg-1·d-1 group, DR+erlotinib 0.5 mg·kg-1·d-1 group and DR+erlotinib 1 mg·kg-1·d-1 group. 25 mice in total, 5 in each group. Tissue immunofluorescence staining was used to detect the expression of RMC activation marker GFAP. The FITC-dextran injection experiment was used to detect the effect of erlotinib on retinal vascular leakage in a murine DR model. Results: Compared with the normal group (32.4%±3.0%), the proportion of EdU positive cells in RMC in the high glucose group (59.2%±3.8%) increased (P<0.001). Compared with the high glucose group (59.2%±3.8%), the proportion of EdU positive cells in the high glucose+1 mmol/L erlotinib group (37.6%±4.4%) decreased (P<0.001). Compared with the normal group, the expression of GFAP in RMC in the high glucose group increased (1 in the normal group, 2.27±0.11 in the high glucose group, P<0.001), while the expression of GS decreased (1 in the normal group, 0.32±0.03 in the high glucose group, P<0.001). 1 mmol/L erlotinib treatment reduced the expression of GFAP in RMC under high glucose conditions (1.32±0.13 and 2.27±0.11, respectively; P<0.001), and increased the expression of GS (0.71±0.06 and 0.32±0.03, respectively; P<0.001). The colocalization of EGFR and DAPI in RMC of the high glucose+1 mmol/L erlotinib group was lower than that of the high glucose group (52.2%±4.1% and 76.4%±5.7%, respectively; P<0.001). The expression of TIF2 or EGFR both increased while using EGF or TIF2 antibodies to precipitate TIF2 or EGFR under high glucose conditions compared to the normal group (1 in the normal group, 2.27±0.20 in the high glucose group, 2.17±0.21 in the EGFR, all P<0.05). And the expression of TIF2 (1.38±0.10) or EGFR (1.32±0.13) in the high glucose+erlotinib group was lower than that in the high glucose group (2.27±0.20) and the high glucose group (2.17±0.21) (all P<0.05). The colocalization of EGFR and TIF2 (17.2%±3.9%) and the mRNA level of Cyclin D1 (1.32±0.16) in the RMC of the high glucose+erlotinib group were lower than those in the high glucose group (54.6%±3.7% of EGFR and TIF2 colocalization ratio, 2.58±0.19 of Cyclin D1 mRNA level,all P<0.05). The high glucose+erlotinib+AREG (EGFR agonist) group, high glucose+erlotinib+Myc DDK-TIF2 plasmid group and high sugar+erlotinib+AREG+Myc-DDK-TIF2 plasmid group EGFR colocalization with TIF2 (colocalization ratios 24.1%±1.9%, 26.0%±2.3%, 35.3%±2.5%) and TIF2 mRNA levels (1.71±0.16, 1.72±0.18, 2.20±0.18). Compared with the high glucose+erlotinib group, The increases were statistically significant (all P<0.05). Compared to the normal group, the expression of GFAP in mouse retina tissue was increased in the DR group (1 in the normal group, 3.07±0.19 in the DR group, P<0.001), and 0.5 mg·kg-1·d-1 erlotinib (1.73±0.30) significantly reduced the expression of GFAP in the retina of DR group mice (P<0.05). Compared to the normal group (3.97±0.47), the DR group (23.13±2.15) showed an increase in fluorescein leakage, while the DR+erlotinib group (11.66±1.45) showed a significant decrease in leakage compared to the DR group (all P<0.05). Conclusions: Erlotinib inhibits the proliferation and activation of RMC induced by high glucose, inhibits the entry of EGFR into the nucleus, inhibits the binding of EGFR to TIF2 in RMC, and reduces the transcription of Cyclin D1 in RMC by inhibiting the interaction between EGFR and TIF2. At the same time, erlotinib inhibits the proliferation and activation of RMC in the mouse DR model, ameliorating retinal vascular leakage in mice. These results suggest that erlotinib inhibits the activation and proliferation of RMC by downregulating the EGFR/TIF2/Cyclin D1 pathway under high glucose conditions, thereby alleviating the progression of NPDR.

[Research progress on the mechanism and response strategies of molecular targeted drug resistance in liver cancer].

Molecular targeted drugs are one of the treatments for hepatocellular carcinoma (HCC), the primary factor influencing their therapeutic efficacy is drug resistance. Diminished drug intake, greater efflux, improved DNA damage repair capacity, aberrant signal pathways, hypoxia, epithelial-mesenchymal cell transition, and the cellular autophagy system are summarized herein as aspects of the drug resistance mechanism. Simultaneously, effective strategies for addressing drug resistance are elaborated, providing ideas for better clinical treatment of HCC.

[Management of radiation-induced intestinal injury:from multi-disciplinary team team to holistic integrative management].

Radiation-induced intestinal injury is a radiation injury of the colon and rectum after radiotherapy for pelvic malignant tumors. This condition affects multiple organs in the pelvis, making treatment challenging. In clinical practice, the most effective protocol is often determined through discussion by a multi-disciplinary team (MDT). However, due to the severity and complexity of radiation enteritis, many patients still experience poor diagnosis and treatment outcomes. Holistic integrative management (HIM) is a rapidly developing concept that has greatly enhanced clinical medicine in recent years. It improves the level of diagnosis, treatment, prevention, and rehabilitation from multiple dimensions of prevention, screening, diagnosis, treatment, and rehabilitation. In the context of radiation-induced intestinal injury, HIM also calls for the implementation of an individualized management system that focuses on the patient as a whole within the healthcare team. From the perspective of HIM, this article introduces some of the latest progress of radiation-induced intestinal injury in recent years.

[Prognostic significance and immune cell infiltration analysis of differentially expressed genes in malignant pleural mesothelioma].

Objective: To explore and analyze differential expressed genes in malignant pleural mesothelioma (MPM) by bioinformatics method, and to study their prognostic value in MPM and their potential role in immunotherapy. Methods: In January 2022, the dataset GSE51024 was downloaded from the GEO database, and MPM (55 cases) and normal tissue (41 cases) samples were obtained. Using R software and HMDD and miRNet database, MPM-related differential genes were screened and co-expressed genes were identified. Co-expressed genes were enriched and functionally annotated, and protein-protein interaction (PPI) networks were constructed and key genes were identified using the STRING database and Cytoscape software. TRRUST and GEPIA databases were used to predict transcription factors of key genes and to analyze prognosis and survival. The correlation between key genes and the degree of infiltration of immune cells was analyzed using TIMER. Results: A total of 435 co-expressed genes were obtained, which were mainly concentrated in the extracellular matrix tissue and the signaling pathways of cell adhesion molecules. Combined with PPI and TRRUST database, seven key MPM prognostic genes were identified. Among them, cyclin 20 (CDC20) , cell cycle checkpoint kinase 1 (CHEK1) , enhancer of Zeste homolog 2 (EZH2) , ribonucleotide reductase subunit M2 (RRM2) , topoisomerase 2A (TOP2A) , ubiquitin like plant homeodomain and ring finger domain 1 (UHRF1) were significantly up-regulated in MPM, while cyclin A1 (CCNA1) was significantly down-regulated. The expressions of CCNA1, CDC20, CHEK1, EZH2, RRM2, TOP2A and UHRF1 genes were significantly associated with MPM overall survival (P<0.05) . The expressions of CDC20, CHEK1, EZH2, RRM2 and TOP2A genes were positively correlated with B cells and dendritic cells (P<0.05) , and negatively correlated with neutrophils (P<0.05) . Conclusion: CCNA1, CDC20, CHEK1, EZH2, RRM2, TOP2A and UHRF1 may be potential prognostic markers in MPM patients, and their expressions may be related to MPM tumor immunity.

[Effects of free superficial peroneal artery perforator flap in repairing small and medium-sized thermal crush injury wounds in the hand].

Objective: To investigate the surgical methods and clinical effects of free superficial peroneal artery perforator flap in repairing small and medium-sized thermal crush injury wounds in the hand. Methods: A retrospective observational study was conducted. From August 2018 to December 2021, 12 patients (19 wounds) with small and medium-sized thermal crush injury in the hand who met the inclusion criteria were hospitalized in Suzhou Ruihua Orthopaedic Hospital, including 5 males and 7 females, aged from 30 to 54 years. The area of the wound was from 2.5 cm×2.0 cm to 14.0 cm×3.5 cm, and all the wounds were repaired by using free superficial peroneal artery perforator flaps from lower leg on one side (including single flap, multiple flaps, and multiple flaps with one pedicle resected from the same donor site). The area of the flap was from 3.5 cm×3.0 cm to 16.0 cm×4.0 cm. The wound in the donor site was sutured directly. The vascular crisis and survival of the flap were observed after operation. The texture, appearance, color, hyperpigmentation, sensation, and two-point discrimination of the flap repaired area were followed up, as well as the hyperplasia of scar and pain condition in the donor and recipient sites. At the last follow-up, the curative effect of flap repair was evaluated by the comprehensive evaluation scale, and the extension and flexion functions of the reserved digital joint were evaluated by the total active movement systematic evaluation method recommended by American Academy for Surgery of Hand. Results: One flap developed arterial crisis on the first day after operation but survived after timely exploration. The other 18 flaps survived successfully after operation. Follow-up of 4 to 24 months after operation showed good texture and appearance in the flap repaired area; the color of the flap repaired area was similar to that of the normal skin around the recipient site, without pigmentation; the protective sensation was restored in all cases, but there was no two-point discrimination; there was no obvious hypertrophic scarring or pain in the donor or recipient site. At the last follow-up, the curative effect of flap repair was evaluated with 3 flaps being excellent and 16 flaps being good; the extension and flexion functions of the reserved digital joint were also assessed, being excellent in 8 fingers, good in 9 fingers, and fair in 2 fingers. Conclusions: The blood supply of superficial peroneal artery perforator flap is sufficient and reliable, and multiple flaps of this type or multiple flaps with one pedicle can be resected from one donor site. The use of this flap to repair small and medium-sized thermal crush injury wounds in the hand results in minimal damage to the donor area, and good postoperative appearance and texture of the flap.