Background: Diabetic macrovascular and microvascular complications often coexist and may share similar risk factors and pathological pathways. We aimed to investigate whether 10-year atherosclerotic cardiovascular disease (ASCVD) risk, which is commonly assessed in diabetes management, can predict incident diabetic nephropathy (DN) and retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). Methods: This prospective cohort study enrolled 2,891 patients with clinically diagnosed T2DM who were free of ASCVD, nephropathy, or retinopathy at baseline in the Guangzhou (2017–2022) and Shaoguan (2019–2021) Diabetic Eye Study in southern China. The 10-year ASCVD risk was calculated by the Prediction for ASCVD Risk in China (China-PAR) equations. Multivariable- adjusted Cox proportional hazard models were developed to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). The area under the receiver operating characteristic curve (AUC) was used to evaluate predictive capability. Results: During follow-up, a total of 171 cases of DN and 532 cases of DR were documented. Each 1% increment in 10-year ASCVD risk was associated with increased risk of DN (pooled HR, 1.122; 95% CI, 1.094 to 1.150) but not DR (pooled HR, 0.996; 95% CI, 0.979 to 1.013). The model demonstrated acceptable performance in predicting new-onset DN (pooled AUC, 0.670; 95% CI, 0.628 to 0.715). These results were consistent across cohorts and subgroups, with the association appearing to be more pronounced in women. Conclusion Ten-year ASCVD risk predicts incident DN but not DR in our study population with T2DM. Regular monitoring of ASCVD risk in routine diabetes practice may add to the ability to enhance population-based prevention for both macrovascular and microvascular diseases, particularly among women.

Background: Diabetic macrovascular and microvascular complications often coexist and may share similar risk factors and pathological pathways. We aimed to investigate whether 10-year atherosclerotic cardiovascular disease (ASCVD) risk, which is commonly assessed in diabetes management, can predict incident diabetic nephropathy (DN) and retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). Methods: This prospective cohort study enrolled 2,891 patients with clinically diagnosed T2DM who were free of ASCVD, nephropathy, or retinopathy at baseline in the Guangzhou (2017–2022) and Shaoguan (2019–2021) Diabetic Eye Study in southern China. The 10-year ASCVD risk was calculated by the Prediction for ASCVD Risk in China (China-PAR) equations. Multivariable- adjusted Cox proportional hazard models were developed to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). The area under the receiver operating characteristic curve (AUC) was used to evaluate predictive capability. Results: During follow-up, a total of 171 cases of DN and 532 cases of DR were documented. Each 1% increment in 10-year ASCVD risk was associated with increased risk of DN (pooled HR, 1.122; 95% CI, 1.094 to 1.150) but not DR (pooled HR, 0.996; 95% CI, 0.979 to 1.013). The model demonstrated acceptable performance in predicting new-onset DN (pooled AUC, 0.670; 95% CI, 0.628 to 0.715). These results were consistent across cohorts and subgroups, with the association appearing to be more pronounced in women. Conclusion Ten-year ASCVD risk predicts incident DN but not DR in our study population with T2DM. Regular monitoring of ASCVD risk in routine diabetes practice may add to the ability to enhance population-based prevention for both macrovascular and microvascular diseases, particularly among women.

Background: Diabetic macrovascular and microvascular complications often coexist and may share similar risk factors and pathological pathways. We aimed to investigate whether 10-year atherosclerotic cardiovascular disease (ASCVD) risk, which is commonly assessed in diabetes management, can predict incident diabetic nephropathy (DN) and retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). Methods: This prospective cohort study enrolled 2,891 patients with clinically diagnosed T2DM who were free of ASCVD, nephropathy, or retinopathy at baseline in the Guangzhou (2017–2022) and Shaoguan (2019–2021) Diabetic Eye Study in southern China. The 10-year ASCVD risk was calculated by the Prediction for ASCVD Risk in China (China-PAR) equations. Multivariable- adjusted Cox proportional hazard models were developed to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). The area under the receiver operating characteristic curve (AUC) was used to evaluate predictive capability. Results: During follow-up, a total of 171 cases of DN and 532 cases of DR were documented. Each 1% increment in 10-year ASCVD risk was associated with increased risk of DN (pooled HR, 1.122; 95% CI, 1.094 to 1.150) but not DR (pooled HR, 0.996; 95% CI, 0.979 to 1.013). The model demonstrated acceptable performance in predicting new-onset DN (pooled AUC, 0.670; 95% CI, 0.628 to 0.715). These results were consistent across cohorts and subgroups, with the association appearing to be more pronounced in women. Conclusion Ten-year ASCVD risk predicts incident DN but not DR in our study population with T2DM. Regular monitoring of ASCVD risk in routine diabetes practice may add to the ability to enhance population-based prevention for both macrovascular and microvascular diseases, particularly among women.

Background: Diabetic macrovascular and microvascular complications often coexist and may share similar risk factors and pathological pathways. We aimed to investigate whether 10-year atherosclerotic cardiovascular disease (ASCVD) risk, which is commonly assessed in diabetes management, can predict incident diabetic nephropathy (DN) and retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). Methods: This prospective cohort study enrolled 2,891 patients with clinically diagnosed T2DM who were free of ASCVD, nephropathy, or retinopathy at baseline in the Guangzhou (2017–2022) and Shaoguan (2019–2021) Diabetic Eye Study in southern China. The 10-year ASCVD risk was calculated by the Prediction for ASCVD Risk in China (China-PAR) equations. Multivariable- adjusted Cox proportional hazard models were developed to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). The area under the receiver operating characteristic curve (AUC) was used to evaluate predictive capability. Results: During follow-up, a total of 171 cases of DN and 532 cases of DR were documented. Each 1% increment in 10-year ASCVD risk was associated with increased risk of DN (pooled HR, 1.122; 95% CI, 1.094 to 1.150) but not DR (pooled HR, 0.996; 95% CI, 0.979 to 1.013). The model demonstrated acceptable performance in predicting new-onset DN (pooled AUC, 0.670; 95% CI, 0.628 to 0.715). These results were consistent across cohorts and subgroups, with the association appearing to be more pronounced in women. Conclusion Ten-year ASCVD risk predicts incident DN but not DR in our study population with T2DM. Regular monitoring of ASCVD risk in routine diabetes practice may add to the ability to enhance population-based prevention for both macrovascular and microvascular diseases, particularly among women.

OBJECTIVE: To investigate the clinical effect of minimally invasive technique in the treatment of moderate and severe gluteal muscle contracture. METHODS: A retrospective study was conducted on 85 patients (170 sides) with bilateral gluteal muscle contracture admitted from January 2016 to December 2019. All patients were treated with minimally invasive release of tendon knife. There were 32 males and 53 females, ranging in age from 15 to 37 years old, with an average age of (22.3±6.3) years old. Operation time, intraoperative blood loss, incision length, first postoperative ambulation time, complication rate, recurrence rate, and Harris hip score (HHS) were analyzed and evaluated. RESULTS: The average follow-up time was (16.2±4.6) months, ranging from 12 to 30 months. The operation time ranged from 7 to 15 min, with an average of (10.2±3.1) min. Intraoperative blood loss ranged from 2 to 20 ml, with an average of (8.4±2.2) ml. The incision length ranged from 0.6 to 2.0 cm, with an average of (0.8±0.3) cm. The time to postoperative ambulation ranged from 12 to 28 h, with an average of (20.0±3.2) h. All patients achieved primary wound healing without sciatic nerve injury or recurrence. HHS hip function scores ranged from 90 to 98, with an average score of (96.2±1.4). Complications included intraoperative tendon blade tip fracture in two cases (removed under fluoroscopic guidance) and subcutaneous hematoma in three cases-two resolved with compression and one with open evacuation.. Twenty-nine patients exhibited transient swaying gait postoperatively, of which 24 patients returned to normal after 4 weeks and 5 patients returned to normal after 6 weeks. CONCLUSION Minimally invasive tendon blade release is a safe and effective technique for treating gluteal muscle contracture, offering minimal trauma, rapid recovery, and excellent cosmetic and functional outcomes. However, it exhibits a low risk of blade tip fracture and sciatic nerve injury, warranting experienced surgical handling.
Humans ; Male ; Female ; Adult ; Minimally Invasive Surgical Procedures/methods* ; Adolescent ; Retrospective Studies ; Buttocks/surgery* ; Young Adult ; Contracture/surgery* ; Tendons/surgery* ; Muscle, Skeletal/surgery*

Multi-target analgesics with minimal side effects and high efficacy are a key research focus in addressing the global pain crisis. Using a molecular networking approach, five pairs of potent analgesic alkaloid enantiomers were isolated from the roots of Anacyclus pyrethrum (A. pyrethrum). Their structures were elucidated by comprehensive spectroscopic data analysis, including LR-HSQMBC and ¹H-¹⁵N HMBC, quantum ¹³C NMR DP4+ and ECD calculations, and single-crystal X-ray diffraction analysis. Anacyphrethines A (1) and B (2) are highly conjugated and polymethylated 6/6/6/6/5/7/5/5-fused octacyclic tetraazabic alkaloids possessing an unprecedented 8,14,18,24-tetraaza-octacyclo[16.8.2.1^1,23.0^4,28.0^5,17.0^9,16.0^11,15.0^21,27] nonacosane motif. Their biosynthetic pathways are proposed involving key aldol, hydroamination, and Schiff base reactions. All isolates showed potent analgesic effects in vivo. Even at a lower dose of 0.2 mg/kg, (±)-1 and (+)-1 still exhibited more potent analgesic activities than morphine. Interestingly, the racemic mixture (±)-1 showed stronger analgesic effect than either pure enantiomer alone at higher doses of 5 and 1 mg/kg; while, (±)-1 showed significant analgesic activities comparable to (+)-1 at lower doses of 0.2 and 0.04 mg/kg. (+)-1 had stronger analgesic effect than (-)-1 at five tested does. Further tests on 44 analgesic-related targets demonstrated that (+)-1 showed significant inhibitory effects against many ion channels such as TRPM8, Kv1.2, Kv1.3, and Ca_v2.1 with IC₅₀ values of 1.10 ± 0.26, 4.20 ± 0.07, 2.20 ± 0.24, and 10.40 ± 0.69 μmol/L, respectively, while (-)-1 primarily inhibited TRPC6, Kv1.2, and Kv1.3 ion channels with IC₅₀ values of 0.81 ± 0.05, 0.91 ± 0.04, and 1.50 ± 0.13 μmol/L, respectively, without affecting the opioid receptors, suggesting their non-opioid analgesic potentials. The molecular dockings provided structural guidance to develop potent non-opioid analgesics.

Objective:To investigate the role of RNA m6A reader YTHDF2 in neurodegeneration of the aged mice.Methods:Eighteen 18-month-old control C57BL/6 mice and 22 Ythdf2 conditional knockout (cKO) mice of the same age (that exhibited significant aging characteristics) were used. Five pairs of mice were used for morphological analysis. Thirteen control mice and 17 cKO mice were used for behavioral experiments. Immunofluorescence analysis was performed to detect the expression of YTHDF2 in the brains of 18-month-old C57BL/6 mice. After establishing the neural progenitor cell-specific knockout mice of Ythdf2, their phenotypes were analyzed through comparison of body weight, brain weight and H&E staining. Subsequently, immunohistochemistry and immunofluorescence analyses were used to detect the expression of various neural cell-specific markers in the aged control mice and Ythdf2 cKO mice. Finally, behavioral tests, including the open field test, new object recognition, and water maze, were used to assess the levels of anxiety, depression, learning and memory abilities.Results:Immunofluorescence staining showed that YTHDF2 was mainly expressed in the neurons. Compared with the age-matched control mice, there was no significant change in the body weight of the Ythdf2 cKO mice, but the brain weight decreased significantly ( P<0.05). The immunostaining showed that Ythdf2 cKO mice had fewer neurons, fewer astrocytes with defective morphology, more microglia and activation of microglia ( P<0.05). Behavioral tests showed that the aged Ythdf2 cKO mice exhibited impaired movement, learning and memory abilities ( P<0.05). Conclusions:YTHDF2 is mainly expressed in the neurons of the aged brain. Conditional knockout of Ythdf2 causes quantitative and structural abnormalities in hippocampal neuronal cells, and impairs motor ability and learning and memory of the aged mice, suggesting that YTHDF2 plays an important role in neurodegeneration of the aged mice.

Objective To investigate the therapeutic effects of bone marrow mesenchymal stem cells (BMSCs) for radiation-induced lung injury (RILI) and the underlying mechanism. Methods Forty-five healthy adult male C57BL/6 mice were randomly divided into control, model, and BMSCs groups. The model and BMSCs groups received a single irradiation dose of 20 Gy to the chest, while the control group did not receive X-ray irradiation. For the BMSCs group, an injection of 1 × 10⁶ BMSCs cells was administered via the tail vein within 6 h after irradiation. In the 5th week, the lung tissue was taken to observe pathological changes with HE staining; examine the expression of the inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) with immunohistochemical staining; observe the polarization of macrophages with immunofluorescence staining; and measure the expression of the epithelial-mesenchymal transition markers E-cadherin, N-cadherin, and vimentin proteins by Western blot. Results After radiation, the model group developed pulmonary vasodilation and congestion with septal thickening and inflammatory cell infiltration, and these changes were markedly reduced in the BMSCs group. The model group showed significantly down-regulated expression of IL-6 and TNF-α compared with significantly increased levels in the model group (P < 0.01, P < 0.05). Treatment with BMSCs significantly increased the polarization of lung macrophages towards the M2 type, while significantly decreasing the abnormally increased N-cadherin and vimentin levels in RILI mice (P < 0.05, P < 0.01). Conclusion BMSCs have therapeutic effects for RILI mice, which may be through promoting macrophage polarization from M1 to M2.

BACKGROUND:Establishing a stable and reliable animal model of acute pancreatitis is of great significance for understanding its pathogenesis,pathophysiological characteristics,and clinical medication.Domestic and foreign studies have shown that cerulein,L-arginine,and sodium taurocholate can induce acute pancreatitis,but their pathophysiological characteristics and model characteristics are still unclear. OBJECTIVE:To establish an acute pancreatitis rat model using cerulein,L-arginine,and sodium taurocholate and to observe the changing patterns of model features at different time points. METHODS:Ninety-six healthy male Sprague-Dawley rats were randomly divided into normal group,cerulein group,L-arginine group,and sodium taurocholate group,with 24 rats in each group.Within each group,there were three subgroups(n=8 per group):12-,24-,and 48-hour subgroups.Cerulein was administered via intraperitoneal injection six times with a 1-hour interval.L-arginine was administered through two intraperitoneal injections with a 1-hour interval.Sodium taurocholate was injected for inducing acute pancreatitis models through retrograde injection into the bile-pancreatic duct.By examining the rat survival rate,gross morphology of the pancreas,calculating the pancreatic organ index,and measuring levels of amylase,lipase,alanine transaminase,aspartate transaminase,blood urea nitrogen,and creatinine,as well as observing pancreatic tissue pathological features through hematoxylin-eosin staining and conducting a pancreatic injury scoring,we evaluated the changing patterns of model features at different time points. RESULTS AND CONCLUSION:Compared with the normal group,the overall survival rate of rats was 100%in the cerulein group,88%in the L-arginine group,and 96%in the sodium taurocholate group.The pancreatic organ index was increased in all groups.Gross observation indicated that,In the cerulein group,pancreatic edema,blurred lobes,and looseness were visible.In the L-arginine group,the pancreatic glands were enlarged and thickened with patchy bleeding.In the sodium taurocholate group,pancreatic tissue showed varying degrees of congestion and edema accompanied by scattered flakes of hemorrhage and necrosis.The levels of serum alanine transaminase,aspartate transaminase,blood urea nitrogen,creatinine,amylase,and lipase in rats exhibited consistent changes.In the cerulein group,these parameters possibly peaked at 12 hours(P<0.05)and then showed a declining trend.In the L-arginine group,they reached the highest levels at 24 hours(P<0.05)and significantly decreased at 48 hours.In the sodium taurocholate group,serum amylase and lipase remained at higher levels at 12 hours with a slow decline trend(P<0.05).Compared with the normal group,microscopic examination revealed mild acinar edema and widened interlobular spaces in the cerulein group,with a higher presence of inflammatory cells.In the L-arginine group,there was widening of interlobular spaces,extensive infiltration of inflammatory cells,and patchy necrotic areas.In the sodium taurocholate group,significant pancreatic edema,structural disarray,extensive necrotic foci,and inflammatory cell infiltration were observed.Compared with the normal group,the pathological scores of induced acute pancreatitis in all three models were significantly different at each time point(P<0.05).Moreover,the pathological scores in each group increased over time,indicating a gradual worsening of pancreatic tissue damage.When comparing different models at the same time,there were differences in pathological scores,with the sodium taurocholate group having the highest scores,followed by the L-arginine group,and the cerulein group having the lowest scores.Analyzing the three models at the same time point,the most severe condition was in the sodium taurocholate group,which was characterized by pancreatic hemorrhage and necrosis,followed by the L-arginine group,which was characterized by necrosis,and the least severe condition was in the cerulein group,mainly characterized by edema.The serum biochemical index levels of the cerulein and L-arginine groups decreased at 48 hours,indicating that these two models may have a tendency to self-heal and belong to a self-limiting disease course.The serum biochemical index levels of the sodium taurocholate group decreased slowly after 12 hours.Therefore,pancreatic injury in the sodium taurocholate group might not be relieved after 48 hours or longer.