Objective:To observe and analyze the correlations between aqueous humor cytokine concentrations and disorganization of retinal inner layers (DRIL), as well as postoperative visual acuity, in patients with idiopathic epiretinal membrane (iERM).Methods:A prospective clinical study. From November 2022 to October 2024, 40 eyes of 40 patients diagnosed with iERM at Ophthalmology Center of Zhejiang Provincial People's Hospital (Affiliated People's Hospital) underwent cataract surgery alone or combined with pars plana vitrectomy (iERM group) were enrolled; 19 eyes of 19 patients undergoing cataract surgery alone during the same period served as the control group. All eyes underwent best-corrected visual acuity (BCVA) testing and swept-source optical coherence tomography (SS-OCT). BCVA was assessed using a logarithmic visual acuity chart and converted to the logarithm of the minimum angle of resolution (logMAR) for statistical analysis. Central macular thickness (CMT) was measured using SS-OCT. The iERM group was further subdivided into DRIL-positive and DRIL-negative subgroups (21 eyes and 19 eyes, respectively), based on the presence or absence of DRIL. Aqueous humor samples were collected preoperatively from eyes in both the iERM and control groups. Concentrations of transforming growth factor (TGF)-β1, TGF-β2, TGF-β3, platelet-derived growth factor (PDGF)-AB, hepatocyte growth factor, fibroblast growth factor, vascular endothelial growth factor-A (VEGF-A), placental growth factor (PLGF), glial cell line-derived neurotrophic factor (GDNF), intercellular adhesion molecule-1 (ICAM-1), angiopoietin (Ang)-1, Ang-2, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured. Follow-up examinations using the same equipment and methods were performed at 1 month postoperatively. Aqueous cytokine levels were compared between the iERM group, control group, DRIL-positive subgroup, and DRIL-negative subgroup. Correlations between aqueous cytokine levels in the iERM group and BCVA or CMT were also analyzed. Intergroup comparisons utilized the Mann-Whitney U test; correlations between variables were assessed using Spearman's rank correlation analysis. Results:Compared to the control group, the iERM group exhibited significantly higher aqueous concentrations of TGF-β1, TGF-β3, PDGF-AB, PLGF, GDNF, ICAM-1, Ang-1, and TNF-α ( P<0.05). Compared to the DRIL-negative subgroup, the DRIL-positive subgroup showed significantly elevated aqueous concentrations of TGF-β3, PDGF-AB, PLGF, GDNF, ICAM-1, Ang-1, Ang-2, TNF-α, and IL-6 ( P<0.05). Significant differences were observed in logMAR BCVA ( P=0.028) and CMT ( P<0.001) within the iERM group between preoperative and 1-month postoperative measurements. LogMAR BCVA differed significantly between the DRIL-positive and DRIL-negative subgroups ( P=0.048). Correlation analysis revealed that baseline aqueous levels of VEGF-A and IL-6 in eyes with DRIL were positively correlated with postoperative BCVA ( r=0.324, 0.452; P=0.042, 0.003). No significant correlation was found between CMT and any cytokine ( P>0.05). Conclusions:Aqueous humor cytokines are closely associated with DRIL in iERM patients. IL-6 and VEGF-A may serve as potential predictive biomarkers for early postoperative visual recovery.

Objective To investigate the potential mechanism of miR-21-5p in alleviating cerebral ischemia-reperfusion injury by targeting STAT3.Methods The HT22 cells were induced by OGD/R to construct a cell model of cerebral ischemia reperfusion injury.The expression of miR-21-5p was detected by RT-qPCR.The CCK-8 assay,TUNEL staining and flow cytometry were respectively used to detect the cell viability and apoptosis.ELISA assay was used to determine the contents of inflammatory factors IL-6,IL-10 and TNF-α in the cell supernatant.Western blot was used to detect the expression levels of p-STAT3/STAT3,Cleaved-Caspase-3,Bax and Bcl-2 proteins.The TargetScan database was used to predict the binding sites of miR-21-5p and STAT3.The dual-luciferase reporter gene assay was used to verify the targeting relationship between miR-21-5p and STAT3.Results The relative expression level of miR-21-5p was down-regulated in HT22 cells which induced by OGD/R(P<0.001).The cell viability(P<0.0001)was decreased and the apoptosis rate(P<0.001)was increased in OGD/R induced-HT22 cells.The contents of pro-inflammatory factors IL-6(P<0.001)and TNF-α(P<0.001)was increased,while the content of anti-inflammatory factor IL-10(P<0.001)decreased.After transfection with miR-21-5p mimic,cell viability was enhanced,apoptosis rate was reduced and neuroinflammation was inhibited.MiR-21-5p could target and bind to STAT3.After miR-21-5p inhibitor transfection,cell viability decreased,apoptosis was promoted,and neuroinflammation occurred;STAT3 inhibitor Stattic could reverse the effect of miR-21-5p inhibitor.Conclusion MiR-21-5p could specifically bind to STAT3 and reduce the neuroinflammation and apoptosis of OGD/R induced-HT22 cells.

Objective:To observe and analyze the correlations between aqueous humor cytokine concentrations and disorganization of retinal inner layers (DRIL), as well as postoperative visual acuity, in patients with idiopathic epiretinal membrane (iERM).Methods:A prospective clinical study. From November 2022 to October 2024, 40 eyes of 40 patients diagnosed with iERM at Ophthalmology Center of Zhejiang Provincial People's Hospital (Affiliated People's Hospital) underwent cataract surgery alone or combined with pars plana vitrectomy (iERM group) were enrolled; 19 eyes of 19 patients undergoing cataract surgery alone during the same period served as the control group. All eyes underwent best-corrected visual acuity (BCVA) testing and swept-source optical coherence tomography (SS-OCT). BCVA was assessed using a logarithmic visual acuity chart and converted to the logarithm of the minimum angle of resolution (logMAR) for statistical analysis. Central macular thickness (CMT) was measured using SS-OCT. The iERM group was further subdivided into DRIL-positive and DRIL-negative subgroups (21 eyes and 19 eyes, respectively), based on the presence or absence of DRIL. Aqueous humor samples were collected preoperatively from eyes in both the iERM and control groups. Concentrations of transforming growth factor (TGF)-β1, TGF-β2, TGF-β3, platelet-derived growth factor (PDGF)-AB, hepatocyte growth factor, fibroblast growth factor, vascular endothelial growth factor-A (VEGF-A), placental growth factor (PLGF), glial cell line-derived neurotrophic factor (GDNF), intercellular adhesion molecule-1 (ICAM-1), angiopoietin (Ang)-1, Ang-2, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured. Follow-up examinations using the same equipment and methods were performed at 1 month postoperatively. Aqueous cytokine levels were compared between the iERM group, control group, DRIL-positive subgroup, and DRIL-negative subgroup. Correlations between aqueous cytokine levels in the iERM group and BCVA or CMT were also analyzed. Intergroup comparisons utilized the Mann-Whitney U test; correlations between variables were assessed using Spearman's rank correlation analysis. Results:Compared to the control group, the iERM group exhibited significantly higher aqueous concentrations of TGF-β1, TGF-β3, PDGF-AB, PLGF, GDNF, ICAM-1, Ang-1, and TNF-α ( P<0.05). Compared to the DRIL-negative subgroup, the DRIL-positive subgroup showed significantly elevated aqueous concentrations of TGF-β3, PDGF-AB, PLGF, GDNF, ICAM-1, Ang-1, Ang-2, TNF-α, and IL-6 ( P<0.05). Significant differences were observed in logMAR BCVA ( P=0.028) and CMT ( P<0.001) within the iERM group between preoperative and 1-month postoperative measurements. LogMAR BCVA differed significantly between the DRIL-positive and DRIL-negative subgroups ( P=0.048). Correlation analysis revealed that baseline aqueous levels of VEGF-A and IL-6 in eyes with DRIL were positively correlated with postoperative BCVA ( r=0.324, 0.452; P=0.042, 0.003). No significant correlation was found between CMT and any cytokine ( P>0.05). Conclusions:Aqueous humor cytokines are closely associated with DRIL in iERM patients. IL-6 and VEGF-A may serve as potential predictive biomarkers for early postoperative visual recovery.

OBJECTIVE: To investigate the current status and influencing factors of feeding intolerance (FI) during enteral nutrition (EN) in intensive care unit (ICU) patients. METHODS: A retrospective case-control study was conducted, including patients from two ICU wards of a tertiary hospital in Guizhou Province from July 2019 to December 2022. Clinical data were collected using a self-designed data collection form, including general information [age, gender, acute physiology and chronic health evaluation II (APACHE II)], clinical treatment (mechanical ventilation, mild hypothermia therapy), medication use (vasoactive drugs, glucocorticoids, analgesics, sedatives), EN implementation (types of EN fluids, EN methods, tube feeding rate), EN tolerance, and blood glucose status. Patients were divided into EN tolerance and EN intolerance groups based on the FI criteria. Differences in the above-mentioned indicators between the two groups were compared, and statistically significant indicators were included in a binary multivariate Logistic regression analysis to explore the independent influencing factors of FI during EN in ICU patients. RESULTS: A total of 683 ICU patients were included, with 57.10% (390/683) incidence of FI during EN. The most common FI symptom was diarrhea (41.58%), followed by gastric retention, reflux, abdominal distension, nausea, abdominal pain, vomiting, and aspiration, with blood in stool being the least common (3.37%). Compared to the EN tolerance group, the EN intolerance group had significantly higher proportions of patients aged ≥60 years, undergoing mechanical ventilation, receiving analgesic and sedative medications, having hyperglycemia, using short-peptide EN fluids, receiving continuous EN, and having a feeding rate > 40 mL/h (all P < 0.05). The binary multivariate Logistic regression analysis revealed that age ≥60 years [odds ratio (OR) = 1.738, 95% confidence interval (95%CI) was 1.241-2.436, P = 0.001], continuous EN (OR = 0.534, 95%CI was 0.377-0.756, P < 0.001), use of analgesic medications (OR = 1.701, 95%CI was 1.139-2.539, P = 0.009), hyperglycemic state (OR = 2.794, 95%CI was 1.999-3.907, P < 0.001), and tube feeding rate > 40 mL/h (OR = 1.018, 95%CI was 1.009-1.027, P < 0.001) were independent risk factors for FI during EN in ICU patients. CONCLUSIONS The incidence of FI during EN in ICU patients is relatively high and influenced by age, EN methods, analgesic medications, hyperglycemic state, and tube feeding rate. Therefore, healthcare professionals need to accurately identify the risk factors for FI and actively implement effective intervention measures to reduce the incidence of FI and improve patient outcomes.
Humans ; Retrospective Studies ; Enteral Nutrition/methods* ; Intensive Care Units ; Case-Control Studies ; Male ; Female ; APACHE ; Logistic Models ; Diarrhea/epidemiology* ; Respiration, Artificial/adverse effects* ; Middle Aged ; Aged

Objective To investigate the value of peripheral blood soluble interleukin-2 receptor(sIL-2R),CD4+lymphocyte percentage/CD8+lymphocyte percentage ratio(hereinafter referred to as CD4+/CD8+)and tumor necrosis factor-α(TNF-α)in evaluating the efficacy of chemotherapy in elderly patients with newly treated active pulmonary tuberculosis.Methods A total of 102 elderly patients with newly treated active tu-berculosis admitted to the hospital from December 2019 to December 2022 were enrolled in the study as the observation group,and 102 healthy people aged 60 and older who underwent physical examination in the hos-pital during the same period were enrolled as the control group.The levels of sIL-2R,TNF-α and CD4+/CD8+in peripheral blood were compared between the two groups,and the correlations between sIL-2R,TNF-α and CD4+/CD8+were analyzed.The observation group was treated with 2HRZE/4HR anti-tuberculosis treatment regimen.The levels of sIL-2R,TNF-α and CD4+/CD8+in peripheral blood of patients with different efficacy before treatment,1 month and 6 months after treatment in the observation group were compared.The correla-tion between sIL-2R,CD4+/CD8+,TNF-α levels and therapeutic effect was analyzed.The receiver operating characteristic(ROC)curve was used to analyze the efficacy of indicators in evaluating the efficacy of chemo-therapy in elderly patients.Results The levels of sIL-2R and TNF-α in the observation group were higher than those in the control group,while CD4+/CD8+was lower than that in the control group,and the differ-ences were statistically significant(P＜0.05).In the observation group,sIL-2R and TNF-α were negatively correlated with CD4+/CD8+(P＜0.05),sIL-2R was positively correlated with TNF-α(P＜0.05).After 1 month and 6 months of treatment,the levels of sIL-2R and TNF-α in patients with apparent efficacy were low-er than those in patients with efficacy,and the latter were lower than those in patients with no effect,while the CD4+/CD8+in patients with apparent efficacy was higher than that in patients with efficacy,and the latter was higher than that in patients with no efficacy,and the differences were statistically significant(P＜0.05).The levels of sIL-2R and TNF-α were negatively correlated with the efficacy(P＜0.05),and CD4+/CD8+was positively correlated with the efficacy(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of sIL-2R,CD4+/CD8+,and TNF-α used in combination to assess efficacy was significantly greater than the AUCs of the single indicators used in the assessment at each time point of treatment(P＜0.05),and the AUC of the combination of the indicators was greater after 6 months of treatment than after 1 month of treatment(P＜0.05).Conclusion The levels of sIL-2R,CD4+/CD8+and TNF-α are closely related to the ef-ficacy of chemotherapy in elderly patients with newly treated active pulmonary tuberculosis,and the combina-tion of the above indicators has certain reference value in evaluating the efficacy of chemotherapy in patients.

Objective:To explore the application effect of pathway nursing combined with multimodal exercise intervention in patients with tumor-associated sarcopenia under multi-disciplinary team.Methods:Using the convenient sampling method, a total of 120 patients with tumor-associated sarcopenia who visited Cancer Center of Henan Provincial People 's Hospital from January 2020 to December 2021 were selected as the research objects. They were divided into the observation group ( n=60) and the control group ( n=60) according to the random number table method. The control group received routine nursing care, while the observation group received multi-disciplinary team pathway nursing combined with multimodal exercise. Skeletal Muscle Mass Index (SMI) , Hand Grip Strength (HGS) , daily walking speed, Cancer Fatigue Scale (CFS) and Irritability, Depression and Anxiety Scale (IDA) scores were compared and analyzed between the two groups. Results:After 4 weeks of intervention, HGS and daily walking speed in the observation group were higher than those in the control group, and the differences were statistically significant ( P<0.05) . After 4 weeks of intervention, the total score of CFS in the observation group was lower than that in the control group, and the scores of physical fatigue, emotional fatigue and cognitive fatigue in the observation group were lower than those in the control group, and the differences were statistically significant ( P<0.05) . After 4 weeks of intervention, the total IDA score of the observation group was lower than that of the control group, and the scores of anxiety, depression, extroversion and introversion stimulation were lower than those of the control group, and the differences were statistically significant ( P<0.05) . Conclusions:Multi-disciplinary team pathway care combined with multimodal exercise can improve the physical fitness of patients with tumor-associated sarcopenia, increase the level of physical activity, relieve fatigue and reduce negative emotions such as anxiety, depression and irritation.

Objective To study the pathological types,expression of mismatch repair protein,human epidermal growth factor receptor 2(HER2),and Pan-TRK,and Epstein-Barr virus(EBV)infection in patients with colorectal cancer resected in Tibet. Methods A total of 79 patients with colorectal cancer resected in Tibet Autonomous Region People's Hospital from December 2013 to July 2021 were enrolled in this study.The clinical and pathological data of the patients were collected.The expression of mismatch repair protein,HER2,and Pan-TRK was detected by immunohistochemical(IHC)staining,and detection of HER2 gene by fluorescence in situ hybridization(FISH)in the patients with HER2 IHC results of 2+ or above.EBV was detected by in situ hybridization with EBV-encoded small RNA. Results A total of 79 colorectal cancer patients were included in this study,with the male-to-female ratio of 1.26:1 and the mean age of(57.06±12.74)years(24-83 years).Among them,4 patients received preoperative neoadjuvant therapy.Colonic cancer and rectal cancer occurred in 57(57/79,72.15%,including 31 and 26 in the right colon and left colon,respectively)and 22(22/79,27.85%)patients,respectively.The maximum diameter of tumor varied within the range of 1-20 cm,with the mean of(6.61±3.33)cm.Among the 79 colorectal cancer patients,75(75/79,94.94%)patients showed adenocarcinoma.Lymph node metastasis occurred in 12(12/21,57.14%)out of the 21 patients with severe tumor budding,13(13/23,56.52%)out of the 23 patients with moderate tumor budding,and 2(2/31,6.45%)out of the 31 patients with mild tumor budding,respectively.The lymph node metastasis rate showed differences between the patients with severe/moderate tumor budding and the patients with mild tumor budding(all P<0.001).The IHC staining showed that mismatch repair protein was negative in 10(10/65,15.38%)patients,including 5 patients with both MSH2 and MSH6 negative,4 patients with both MLH1 and PMS2 negative,and 1 patient with MSH6 negative.Pan-TRK was negative in 65 patients.The IHC results of HER2 showed 0 or 1+ in 60 patients and 2+ in 5 patients.FISH showed no positive signal in the 5 patients with HER2 IHC results of 2+.The detection with EBV-encoded small RNA showed positive result in 1(1/65,1.54%)patient. Conclusions Non-specific adenocarcinoma of the right colon is the most common in the patients with colorectal cancer resected in Tibet,and 15% of the patients showed mismatch repair protein defects.EBV-associated colorectal carcer is rare,Pan-TRK expression and HER2 gene amplification are seldom.The colorectal cancer patients with moderate and severe tumor budding are more likely to have lymph node metastasis.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Adenocarcinoma ; Biomarkers, Tumor/genetics* ; Colorectal Neoplasms/pathology* ; DNA Mismatch Repair ; DNA-Binding Proteins/genetics* ; Epstein-Barr Virus Infections/diagnosis* ; Herpesvirus 4, Human/metabolism* ; In Situ Hybridization, Fluorescence ; Lymphatic Metastasis ; Tibet ; Young Adult ; Aged, 80 and over

OBJECTIVE To provide a reference for further improvement of the essential medicine system. METHODS Statistical analysis method and comparative analysis method were used to explain the necessity of coordination between the two systems from the direct correlation and indirect impact of centralized volume-based procurement on the essential medicine system at the present stage. The relevant suggestions were put forward for the development of the essential medicine system in the new era from the perspective of improving institutional synergy. RESULTS & CONCLUSIONS There was a direct correlation between the policy of centralized procurement and the essential medicine system in terms of policy objectives and medicines selection. However， it also indirectly affects the use of essential medicines in medical institutions through production and supply， coincidence degree between the essential medicine list and the selected variety， and the consistency evaluation of generic drugs. It is suggested that in the selection of essential medicine list in the future， priority should be given to the selection of varieties through centralized procurement， and improve the drug supply guarantee capacity under the dual policy linkage； at the same time， incentive assessments for the allocation and use of essential medicines by various entities should be further strengthened to promote the further improvement and development of the essential medicine system.

OBJECTIVE: To investigate the mechanism of shikonin-induced death of human hepatocellular carcinoma SMMC-7721 cells. METHODS: Cultured SMMC-7721 cells and normal hepatocytes (L-02 cells) were treated with 4, 8, or 16 μmol/L shikonin, and the changes in cell viability was assessed using MTT assay. The levels of ATP and lactic acid in the cell cultures were detected using commercial kits. Co-immunoprecipitation and immunofluorescence staining were used to determine the relationship among pyruvate kinase M2 (PKM2), prolyl hydroxylase 3 (PHD3), and hypoxia-inducible factor-1α (HIF-1α). The expressions of PHD3, PKM2, HIF-1α, Bax, cleaved caspase-3, and Bcl-2 in SMMC-7721 cells were detected with Western blotting, and cell apoptosis was analyzed with annexin V-FITC/PI staining. The effects of RNA interference of PKM2 on PHD3 and HIF-1α expressions in SMMC-7721 cells were detected using Western blotting. RESULTS: The IC₅₀ of shikonin against SMMC-7721 and L-02 cells was 8.041 μmol/L and 31.75 μmol/L, respectively. Treatment with shikonin significantly inhibited the protein expressions of PKM2, HIF-1α and PHD3 and nuclear translocation of PKM2 and HIF-1α in SMMC-7721 cells. Coimmunoprecipitation and immunofluorescence staining confirmed that shikonin inhibited the formation of PKM2/PHD3/HIF-1α complex and significantly reduced the contents of lactic acid and ATP in SMMC-7721 cells (P < 0.05). The expressions of PHD3 and HIF-1α decreased significantly after PKM2 knockdown (P < 0.05). Shikonin treatment significantly increased the apoptosis rate, enhanced the expressions of Bax and cleaved caspase-3, and decreased Bcl-2 expression in SMMC-7721 cells (P < 0.05). CONCLUSIONS Shikonin induces apoptosis of SMMC-7721 cells possibly by inhibiting aerobic glycolysis through the PKM2/PHD3/HIF-1α signaling pathway to cause energy supply dysfunction in the cells.
Humans ; Prolyl Hydroxylases ; Carcinoma, Hepatocellular ; Caspase 3 ; bcl-2-Associated X Protein ; Liver Neoplasms ; Signal Transduction ; Apoptosis ; Adenosine Triphosphate

OBJECTIVE: To compare the clinical efficacy of initial periodontal therapy in periodontitis patients with or without type 2 diabetes mellitus and its correlation with white blood cell counts. METHODS: In this study, 32 chronic periodontitis patients without systemic disease (CP group) and 27 chronic periodontitis patients with type 2 diabetes mellitus (CP+DM group) were enrolled. At admission, all the patients went through periodontal examination and fasting blood examination(baseline). Probing depth (PD), attachment loss (AL), bleeding index (BI), plaque index (PLI), white blood cells (WBC) counts and fasting blood glucose (FBG) were recorded respectively, while hemoglobin A1c (HbA1c) was recorded only in CP+DM group. After that, initial periodontal therapy was performed. All the tests were repeated 3 and 6 months after treatment. The changes of periodontal clinical indexes and WBC levels were compared between the two groups before and after treatment, and the correlation between WBC and periodontal clinical indexes and glucose metabolism indexes were analyzed by generalized linear mixed model. RESULTS: At baseline, the periodontal inflammation and destruction were similar in CP and CP+DM group, but the WBC level was significantly higher in CP+DM groups [(6.01±1.26)×10⁹/L vs. (7.14±1.99)×10⁹/L, P=0.01]. After 3 and 6 months of initial periodontal therapy, the mean PD, AL, BI, and PLI in CP+DM and CP groups were significantly lower than the baseline, and the PD in CP+DM group was further decreased by 6 months compared with 3 months [(3.33±0.62) mm vs. (3.61±0.60) mm, P < 0.05]. However, none of these periodontal indexes showed significant difference between the two groups by 3 or 6 months. In CP+DM group, HbA1c at 3 months and 6 months were significantly lower than the baseline [(7.09±0.79)% vs. (7.64±1.16)%, P < 0.05; (7.06±0.78)% vs. (7.64±1.16)%, P < 0.05], and FBG was significantly lower than the baseline by 6 months [(7.35±1.14) mmol/L vs. (8.40±1.43) mmol/L, P < 0.05]. The WBC level in CP group was significantly lower than the baseline level by 3 months [(5.35±1.37)×10⁹/L vs. (6.01±1.26)×10⁹/L, P < 0.05], while that in CP+DM group was significantly lower than the baseline level by 6 months [(6.00±1.37)×10⁹/L vs. (7.14±1.99)×10⁹/L, P < 0.05]. The analysis of genera-lized linear mixed model showed that WBC level was significantly positively correlated with PD and FBG (P < 0.05). CONCLUSION Initial periodontal therapy can effectively improve the periodontal clinical status of patients with or without type 2 diabetes mellitus, and have benefits on glycemic control in diabetic patients. However, the response of periodontal indexes and WBC level to initial therapy were relatively delayed in diabetic patients. WBC plays an important role in the correlation between diabetes mellitus and periodontitis.
Chronic Periodontitis/therapy* ; Diabetes Mellitus, Type 2/complications* ; Glycated Hemoglobin A/analysis* ; Humans ; Leukocytes/chemistry* ; Periodontal Index