ObjectiveTo investigate the triglyceride-glucose (TyG) index and the level of serum homocysteine (Hcy) in association with the incidence of stroke in type 2 diabetes mellitus (T2DM) patients. MethodsBased on the chronic disease risk factor surveillance cohort in Pudong New Area, Shanghai, excluding those with stroke in baseline survey, T2DM patients who joined the cohort from January 2016 to October 2020 were selected as the research subjects. During the follow-up period, a total of 318 new-onset ischemic stroke patients were selected as the case group, and a total of 318 individuals matched by gender without stroke were selected as the control group. The Cox proportional hazards regression model was used to adjust for confounding factors and explore the serum TyG index and the Hcy biochemical indicator in association with the risk of stroke. ResultsThe Cox proportional hazards regression results showed that after adjusting for confounding factors, the risk of stroke in T2DM patients with 10 μmol·L⁻¹-¹ and Hcy>15 μmol·L⁻¹ was 1.532 times (95%CI: 1.017‒2.309 times, P=0.041) and 1.738 times (95%CI: 1.119‒2.699 times, P=0.014) higher respectively, compared to T2DM patients with Hcy≤10 μmol·L⁻¹. T2DM patients with TyG>9.074 had 1.396 times higher risk of stroke (95%CI: 1.091‒1.787, P=0.008) compared to those with TyG≤9.074. The study found that urea and α1-antitrypsin (α1-AT) were independent risk factors for the incidence of stroke in T2DM patients. For every unit increase in urea andα1-AT, the risk of stroke in T2DM patients increased by 233.6% (HR=3.336, 95%CI: 1.588‒7.009, P=0.001) and 11.3% (HR=1.113, 95%CI: 1.028‒1.205, P=0.008), respectively. Cumulative risk curves showed that Hcy>10 μmol·L⁻¹ and TyG>9.074 accelerated the time to stroke occurrence in T2DM patients. ConclusionElevated levels of Hcy>10 μmol·L⁻¹ and a higher TyG index are risk factors for stroke in T2DM patients. Effective interventions for Hcy and TyG should be conducted for diabetic patients to reduce the incidence of stroke.

ObjectiveTo evaluate the intervention effect of meteorological risk forecasting service on acute onset and medical expenses of chronic obstructive pulmonary disease（COPD） patients， and to provide scientific basis for the establishment of health management model for chronic obstructive pulmonary disease（COPD） patients. MethodsStudy subjects were recruited from chronic obstructive pulmonary patients aged ≥40 in Pudong New Area. Propensity score matching method was used to determine the intervention group and the control group. The control group received regular health education and follow-up management， and the intervention group was provided with meteorological and environmental risk forecasting services through WeChat， mobile phone short message service（SMS）and telephone. Finally， a total of2 589 subjects were included in the analysis， including 1 300 in the intervention group and 1 289 in the control group. General demographic data， past medical history and family history of COPD， COPD related knowledge and practice survey， COPD related symptom assessment， acute onset， health service utilization and medical expenses before and after intervention were collected through questionnaire survey. The differences of acute attack， health service utilization and related medical expenses between the two groups before and after intervention were compared to evaluate the intervention effect. ResultsIn terms of acute attacks， after intervention， the incidence of acute attacks in the intervention group was lower than that before intervention（χ²=52.901， P<0.001）， and the incidence of acute attacks in the groups with different intervention methods was lower than that before intervention （P<0.001）. WeChat had the best effect， decreasing the incidence by 14.4%， followed by mobile phone SMS SMS decreasing by 12.3%. In terms of utilization of health services， the outpatient rate due to acute attack was lower in the intervention group after intervention than that before intervention （χ²=7.129， P=0.008）， and the outpatient rate due to acute attack was lower in the subjects who received the forecast service through mobile phone SMS than that before intervention （χ²=4.675， P<0.001）. In terms of medical expenses， there was no significant difference between control group and intervention group with different intervention methods before intervention （P>0.05）. After intervention， the difference between the control group and the intervention group with different intervention methods was statistically significant （H=11.864， P<0.05）. The results of multiple comparisons showed that compared with the control group， the average annual medical expenses of patients receiving mobile phone SMS and telephone forecasting services after intervention were lower than those of the control group， and the difference was statistically significant （P<0.05）. ConclusionMeteorological risk forecasting service can reduce the acute onset of COPD， reduce the rate of consultation and medical expenses due to acute onset， and provide scientific basis for the basic COPD health management model.

Objective To explore the relationship between baseline urinary protein levels and the onset of chronic obstructive pulmonary disease (COPD). Methods A questionnaire survey, blood and urine sample collection, physical examination, and pulmonary function test were conducted among permanent residents over 40 years old in Pudong New Area, Shanghai. The subjects were divided into four groups based on the baseline urine albumin-to-creatinine ratio (ACR) quartiles (0~1.65 mg/g, 1.65~4.89 mg/g, 4.89~10.78 mg/g, and ≥10.78 mg/g). Cox regression analysis was used to explore the relationship between ACR levels and the incidence of COPD in middle-aged and elderly people. Results Among the 3 105 subjects, the median follow-up time was 3.212 years (P25~P75：3.102~3.473). 116 new cases of COPD were observed, with an incidence density of 10.423 per 1000 person-years. The incidence densities for COPD at four ACR levels were 7.922 per 1 000 person-years, 8.300 per 1 000 person-years , 11.419 per 1 000 person-years, and 13.843 per 1 000 person-years, respectively. Cox regression analysis revealed that as the ACR level increased, there was a rising trend in the incidence rate of COPD (χ²=4.396, P=0.036). After adjusting for gender, age, education level, occupational exposure to dust, history of childhood pneumonia, smoking, family history of COPD, central obesity, and hypertension, the risk of developing COPD was 2.499 times higher (95% CI: 1.460~4.276) for ACR levels ≥10.78 mg/g compared to the reference group with a baseline ACR level of 0~1.65 mg/g. Conclusion Elevated ACR levels in middle-aged and elderly population may increase the risk of COPD, and early monitoring of urine protein levels is beneficial for COPD prevention.

Objective To assess the value of cone-beam computed tomography (CBCT) in evaluating the response of unresectable liver cancer to transarterial chemoembolization (TACE). Methods A total of 55 unresectable liver cancer patients with 90 lesions who received TACE at the First People’s Hospital of Liangshan Yi Autonomous Prefecture between July 2021 and July 2023 were enrolled in the study. The response to TACE was evaluated using the modified Response Evaluation Criteria in Solid Tumors one month post-treatment. The value of lesion diameter, volume, and density on CBCT images in predicting the response to TACE was assessed using the area under the receiver operating characteristic curve. Results Of the 55 patients treated with TACE, 26 achieved complete response, 17 achieved partial response, 9 showed stable disease, and 3 had progressive disease. Of the 90 lesions, 48 achieved complete response, 20 achieved partial response, 17 showed stable disease, and 5 had progressive disease. On CBCT images, the mean diameter, volume, and density of lesions with complete and non-complete responses were (20.9 ± 9.9) mm, (1719.3 ± 777.9) mm³, and (143.7 ± 87.9) HU, versus (10.9 ± 7.7) mm, (890.0 ± 327.4) mm³, and (38.8 ± 33.3) HU, respectively, with significant differences between the two groups (t=10.6, 79.8, and 65.5; all P < 0.01). One month post-treatment, CT scans displayed no enhanced areas in lesions with complete response and visible enhanced areas in lesions with non-complete response, with mean lesion diameter and density of (14.1 ± 6.2) mm and (78.8 ± 30.3) HU, respectively. In addition, the areas under the receiver operating characteristic curves of lesion diameter, volume, and density on CBCT images were 0.935, 0.955, and 0.981, respectively, in distinguishing between complete and non-complete responses following TACE. Using a cut-off value of 82.5 HU for predicting response to TACE, the lesion density had sensitivity, specificity, positive predictive value, and negative predictive value of 95.5%, 100.0%, 100.0%, and 95.0%, respectively. Conclusion CBCT is effective in predicting the short-term response of liver cancer to TACE.

Objective:To evaluate the clinical efficacy of a single-session implantation of spinal cord electrical stimulation with neurophysiological monitoring a spinal cord electrical stimulator under general anesthesia with neurophysiological monitoring for the treatment of high-risk diabetic foot.Methods:The clinical data of seven patients with high-risk diabetic foot who underwent spinal cord electrical stimulation in neurosurgery ward nine of Tianjin Huanhu Hospital from May 2022 to May 2023 were collected. The operation was performed under general anesthesia with the "C" arm X ray machine guidance and neurophysiological monitoring. The arterial diameter and peak flow rate of lower extremity, lower extremity skin temperature (calf skin temperature, foot skin temperature), visual analog scale (VAS), continuous distance of movement, blood glucose level and toe wound were compared between patients before and after surgery.Results:A total of seven patients with high-risk diabetic foot were included. The diameters and peak flow rates of femoral artery, popliteal artery, anterior tibial artery, posterior tibial artery and dorsal foot artery in both lower limbs were significantly improved after surgery. All patients had different degrees of lower limb pain before operation. After operation, VAS score decreased significantly (1.1±0.9 vs. 6.8±3.4), the pain was significantly relieved, and the calf skin temperature and foot skin temperature were significantly higher than those before surgery [calf skin temperature (℃): 33.3±0.9 vs. 30.9±0.7, foot skin temperature (℃): 31.4±0.8 vs. 29.1±0.6], fasting blood glucose and postprandial blood glucose were significantly lower than those before surgery [fasting blood glucose (mmol/L): 7.6±1.4 vs. 10.5±1.2, postprandial blood glucose (mmol/L): 9.3±2.3 vs. 13.5±1.1], the differences were statistically significant (all P < 0.01). The lower limb movement of all seven patients was significantly improved after surgery, including one patient who needed wheelchair travel before surgery, and one patient who had intermittent claudication before surgery. Among them, one patient needed wheelchair travel and one patient had intermittent claudication before surgery. All patients could walk normally at 2 weeks after operation. Among the seven patients, two patients had the diabetic foot wound ulceration before surgery, which could not heal for a long time. One month after surgery, blood flow around the foot wound recovered and the healing was accelerated. The wound was dry and crusted around the wound, and the wound healed well. Conclusion:For diabetic high-risk foot patients who are intolerant to diabetic peripheral neuralgia and local anesthesia spinal cord electrical stimulation test, one-time implantation of spinal cord electrical stimulator under general anesthesia under neurophysiological monitoring can effectively alleviate peripheral neuralgia and other diabetic foot related symptoms, improve lower limb blood supply, and reduce the risk of toe amputation. Clinical practice has proved the effectiveness of this technique, especially for the early treatment of diabetic high-risk foot patients.

Objective: The study aimed to investigate the role of N6-methyladenosine (m6A) modification in spinal cord injury (SCI) and its underlying mechanism, focusing on the interplay between m6A methyltransferase-like 3 (METTL3), miR-30c, and autophagy-related proteins. Methods: An SCI model was established in rats, and changes in autophagy-related proteins, m6A methylation levels, and miR-30c levels were analyzed. Hydrogen peroxide (H2O2)-stimulated spinal cord neuron cells (SCNCs) were used to assess the impact of METTL3 overexpression. The effects of STM2457, an antagonist of METTL3, were evaluated on cell viability, apoptosis, and autophagy markers in H2O2-stimulated SCNCs. Results: In the SCI model, decreased levels of autophagy markers and increased m6A methylation, miR-30c levels, and METTL3 were observed. Overexpression of METTL3 in SCNCs led to reduced cell viability, increased apoptosis, and suppressed autophagy. Conversely, co-overexpression of autophagy-related protein 5 (ATG5) or miR-30c inhibition reversed these effects. Knocking out METTL3 yielded opposite results. STM2457 treatment improved cell viability, reduced apoptosis, and upregulated autophagy markers in SCNCs, which also enhanced functional recovery in rats as measured by the Basso-Beattie-Bresnahan score and inclined plate test. Conclusion STM2457 alleviated SCI by suppressing METTL3-mediated m6A modification of miR-30c, which in turn induces ATG5-mediated autophagy. This study provides insights into the role of m6A modification in SCI and suggests a potential therapeutic approach through targeting METTL3.

Objective:To investigate the role of an inflammatory microenvironment induced by Porphyromonasgingivalis ( P. gingivalis) in the occurrence of esophageal squamous cell carcinoma (ESCC) in mice. Methods:A total of 180 C57BL/6 mice were randomly divided into 6 groups, i.e. control group, P. gingivalis group, 4NQO group, 4NQO + P. gingivalis group, 4NQO + P. gingivalis + celecoxib group, and 4NQO + P. gingivalis + antibiotic cocktail (ABC, including metronidazole, neomycin, ampicillin, and vancomycin) group, with 30 mice in each group, using the random number table. All mice were normalized by treatment with ABC in drinking water for 2 weeks. In the following 2 weeks, the mice in the control group and the P. gingivalis group were given drinking water, while the other 4 groups were treated with 30 μg/ml 4NQO in the drinking water. In weeks 11-12, the mice in the P. gingivalis group, the 4NQO + P. gingivalis group, the 4NQO + P. gingivalis + celecoxib group, and the 4NQO + P. gingivalis + ABC group were subjected to ligation of the second molar in oral cavity followed by oral P. gingivalis infection thrice weekly for 24 weeks in weeks 11-34. In weeks 13-34, the mice in 4NQO + P. gingivalis+celecoxib group and 4NQO + P. gingivalis + ABC group were administered with celecoxib and ABC for 22 weeks, respectively. At the end of 34 weeks, gross and microscopic alterations were examined followed by RT-qPCR and immunohistochemistry to examine the expression profiles of inflammatory- and tumor-molecules in esophagi of mice. Results:At 34 weeks, 4NQO treatment alone did not affect the foci of papillary hyperproliferation, diseased area, and the thickness of the esophageal wall, but significantly enhanced the foci of hyperproliferation (median 1.00, P＜0.05) and mild/moderate dysplasia (median 2.00, P＜0.01). In addition, the expression levels of IL-6 [8.35(3.45,8.99)], IL-1β [6.90(2.01,9.72)], TNF-α [12.04(3.31,14.08)], c-myc [2.21(1.80,3.04)], pSTAT3, Ki-67, and pH2AX were higher than those in the control group. The pathological changes of the esophageal mucosa were significantly more overt in the 4NQO + P. gingivalis group in terms of the foci of papillary hyperproliferation (median 2.00), diseased area (median 2.51 mm 2), the thickness of the esophageal wall (median 172.52 μm), the foci of hyperproliferation (median 1.00, P＜0.05), and mild/moderate dysplasia (median 1.00, P＜0.01). In mice of the 4NQO + P. gingivalis group, the expression levels of IL-6 [12.27(5.35,22.08)], IL-1β [13.89(10.04,15.96)], TNF-α [19.56(6.07,20.36)], IFN-γ [11.37(8.23,20.07)], c-myc [2.62(1.51,4.25)], cyclin D1 [4.52(2.68,7.83)], nuclear pSTAT3, COX-2, Ki-67, and pH2AX were significantly increased compared with the mice in the control group. In mice of the 4NQO + P. gingivalis group, the diseased area, invasive malignant foci as well as pSTAT3 and pH2AX expression were significantly blunted by celecoxib. Treatment with ABC markedly reduced the papillary hyperproliferative foci, invasive malignant foci, and pSTAT3 expression but not pH2AX. Conclusions:P. gingivalis promotes the occurrence of esophageal squamous cell carcinoma in mice by inducing an inflammatory microenvironment primed with 4NQO induced DNA damage. Clearance of P. gingivalis with ABC or anti-inflammatory intervention holds promise for prevention of esophageal squamous cell malignant pathogenesis via blockage of IL-6/STAT3 signaling and amelioration of inflammation.

Objective:To investigate the role of an inflammatory microenvironment induced by Porphyromonasgingivalis ( P. gingivalis) in the occurrence of esophageal squamous cell carcinoma (ESCC) in mice. Methods:A total of 180 C57BL/6 mice were randomly divided into 6 groups, i.e. control group, P. gingivalis group, 4NQO group, 4NQO + P. gingivalis group, 4NQO + P. gingivalis + celecoxib group, and 4NQO + P. gingivalis + antibiotic cocktail (ABC, including metronidazole, neomycin, ampicillin, and vancomycin) group, with 30 mice in each group, using the random number table. All mice were normalized by treatment with ABC in drinking water for 2 weeks. In the following 2 weeks, the mice in the control group and the P. gingivalis group were given drinking water, while the other 4 groups were treated with 30 μg/ml 4NQO in the drinking water. In weeks 11-12, the mice in the P. gingivalis group, the 4NQO + P. gingivalis group, the 4NQO + P. gingivalis + celecoxib group, and the 4NQO + P. gingivalis + ABC group were subjected to ligation of the second molar in oral cavity followed by oral P. gingivalis infection thrice weekly for 24 weeks in weeks 11-34. In weeks 13-34, the mice in 4NQO + P. gingivalis+celecoxib group and 4NQO + P. gingivalis + ABC group were administered with celecoxib and ABC for 22 weeks, respectively. At the end of 34 weeks, gross and microscopic alterations were examined followed by RT-qPCR and immunohistochemistry to examine the expression profiles of inflammatory- and tumor-molecules in esophagi of mice. Results:At 34 weeks, 4NQO treatment alone did not affect the foci of papillary hyperproliferation, diseased area, and the thickness of the esophageal wall, but significantly enhanced the foci of hyperproliferation (median 1.00, P＜0.05) and mild/moderate dysplasia (median 2.00, P＜0.01). In addition, the expression levels of IL-6 [8.35(3.45,8.99)], IL-1β [6.90(2.01,9.72)], TNF-α [12.04(3.31,14.08)], c-myc [2.21(1.80,3.04)], pSTAT3, Ki-67, and pH2AX were higher than those in the control group. The pathological changes of the esophageal mucosa were significantly more overt in the 4NQO + P. gingivalis group in terms of the foci of papillary hyperproliferation (median 2.00), diseased area (median 2.51 mm 2), the thickness of the esophageal wall (median 172.52 μm), the foci of hyperproliferation (median 1.00, P＜0.05), and mild/moderate dysplasia (median 1.00, P＜0.01). In mice of the 4NQO + P. gingivalis group, the expression levels of IL-6 [12.27(5.35,22.08)], IL-1β [13.89(10.04,15.96)], TNF-α [19.56(6.07,20.36)], IFN-γ [11.37(8.23,20.07)], c-myc [2.62(1.51,4.25)], cyclin D1 [4.52(2.68,7.83)], nuclear pSTAT3, COX-2, Ki-67, and pH2AX were significantly increased compared with the mice in the control group. In mice of the 4NQO + P. gingivalis group, the diseased area, invasive malignant foci as well as pSTAT3 and pH2AX expression were significantly blunted by celecoxib. Treatment with ABC markedly reduced the papillary hyperproliferative foci, invasive malignant foci, and pSTAT3 expression but not pH2AX. Conclusions:P. gingivalis promotes the occurrence of esophageal squamous cell carcinoma in mice by inducing an inflammatory microenvironment primed with 4NQO induced DNA damage. Clearance of P. gingivalis with ABC or anti-inflammatory intervention holds promise for prevention of esophageal squamous cell malignant pathogenesis via blockage of IL-6/STAT3 signaling and amelioration of inflammation.

Objective To evaluate the efficacy,safety and economics of romiplostim for treating primary immune thrombocytopenia(ITP)by rapid health technology assessment,and to provide an evidence-based basis for policy makers and clinical practice.Methods PubMed,Cochrane Library,Embase,CNKI,WanFang Data and VIP databases and the official websites of health technology assessment agency were electronically searched to collect high-quality clinical evidence and pharmacoeconomics evaluation literature of romiplostim for the treatment of ITP from inception to January 18,2024.Two researchers independently screened the literature,extracted information,and accessed the quality of included the literature,the extracted results were categorized and evaluated.Results A total of 14 literature were included,in which 8 systematic reviews/Meta-analysis and 6 pharmacoeconomic studies.In terms of efficacy,treatment with romiplostim significantly elevated platelet response rate,sustained platelet response rate,and mean platelet count in patients with ITP compared with placebo(P＜0.05).Romiplostim did not show a significant advantage in elevating patients'platelet response rate and sustained platelet response rate compared with other agents used to treat ITP(P＞0.05).In terms of safety,the incidence of serious adverse events was statistically lower with romiplostim compared to placebo(P＜0.05),while no significant differences were seen in the incidence of adverse events,bleeding events and thrombotic events(P＞0.05).There were no significant differences in the incidence of adverse events,serious adverse events,bleeding events,or thrombotic events when comparing romiplostim to other drugs for the treatment of ITP(P＞0.05).From an economic standpoint,most studies considered eltrombopag to be more economic advantages than romiplostim.Conclusion Romiplostim has good efficacy and safety in the treatment of ITP,and no advantage was shown in terms of economy.

Objective:To explore the value of conventional magnetic resonance imaging (MRI), diffusion weighted imaging (DWI), diffusion kurtosis imaging (DKI) sequence and pathological examination in predicting the efficacy of neoadjuvant chemotherapy (NAC) in advanced breast cancer.Methods:The clinical data of 65 cases of advanced breast cancer with NAC confirmed by pathology in the Affiliated Hospital of Jining Medical University from March 2022 to May 2023 were retrospectively analyzed, including 20 cases in the pathological complete remission (pCR) group and 45 cases in the non pCR group; All patients underwent routine MRI, DWI, DKI examinations and pathological analysis. The clinical pathological data, routine MRI features, apparent diffusion coefficient (ADC) values, mean kurtosis coefficient (MK), and mean diffusion coefficient (MD) between the two groups were analyzed; We compared the differences in various parameters between two groups and plotted receiver operating characteristic (ROC) curves to compare their diagnostic efficacy of NAC in breast cancer.Results:There were significant differences in molecular typing, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her-2) and Ki-67 between pCR group and non pCR group (all P<0.05). In pCR group, Her-2 overexpression type and triple negative breast cancer (TNBC) type breast cancer were more common. ER and PR were mostly negative, Her-2 was mostly positive, and Ki 67 was mainly positive. The difference in tumor T2WI signal between the pCR group and the non pCR group was statistically significant ( P<0.05), with the pCR group showing mostly moderate/low T2WI signal. The ADC and MD values of the pCR group were lower than those of the non pCR group, while the MK value of the pCR group was higher than that of the non pCR group, and the differences were statistically significant (all P<0.001). The area under the ROC curve (AUC) for predicting the efficacy of NAC using a clinical pathological model was 0.829, which was higher than the AUC of molecular subtypes, ER, PR, Her-2, and Ki-67 ( Z=3.008, 2.697, 2.815, 2.131, 2.376, all P<0.05); The AUC of the DKI+ DWI predicting the efficacy of NAC was 0.934, which was higher than that of the DWI single sequence model, and the difference in type was statistically significant ( Z=2.396, P=0.017). The diagnostic efficacy of the DKI+ DWI model was higher than that of the single parameter ADC, MD, and MK, and the differences were statistically significant ( Z=2.396, 2.219, 2.161, all P<0.05); The AUC of the combined imaging and pathology model was 0.983, and its diagnostic efficacy was higher than that of the conventional MRI feature model, pathology model, DWI model, and DKI model, with statistically significant differences ( Z=5.877, 2.961, 3.240, 2.264, all P<0.05). Conclusions:The results of pathology, conventional MRI, DWI and DKI parameters of pCR and non pCR breast cancer patients are significantly different, and the combined model is better than the single model in predicting the efficacy of NAC.