Objective:To evaluate the efficacy of Tongdu Tiaoshen acupuncture combined with low-frequency electrical pulse in the treatment of neurogenic bladder (NB) caused by spinal cord injury (SCI); To explore its effects on urodynamics.Methods:A randomized controlled trial study was conducted. A total of 116 patients with NB caused by SCI in the First Affiliated Hospital of Hunan University of Chinese Medicine from January 2022 to June 2024 were selected as the observation objects and divided into 2 groups with random number table method, with 58 cases in each group. On the basis of conventional bladder function training, the control group was given low-frequency electronic pulse therapy, while the observation group was treated with the Tongdu Tiaoshen method on the basis of the control group. Both groups were treated continuously for 3 months. The urination conditions of the patients were observed before and after the treatment respectively, and the residual urine volume, single urine volume within 24 hours, the number of urine leaks within 24 hours, and the number of urinations within 24 hours were recorded; urodynamic parameters such as bladder volume, urine flow rate, detrusor pressure, bladder compliance, and detrusor contractility were measured using a urodynamic analyzer; the severity of NB symptoms was evaluated using the Chinese version of the Neurogenic Bladder Symptom Scale (NBSS), and the quality of life was evaluated using the Chinese version of the Short Form Health Assessment Scale (SF-Qualiveen). The levels of IL-1β, IL-6 and TNF-α were detected by ELISA. Adverse reactions were recorded during the treatment period and the clinical efficacy was evaluated.Results:The total effective rate was 91.38% (53/58) in the observation group and 75.86% (44/58) in the control group. There was a statistically significant difference between the two groups ( χ2=5.10, P=0.024). After treatment, the residual urine volume, single urine volume within 24 hours, frequency of urine leakage within 24 hours, and frequency of urination within 24 hours in the observation group were lower than those in the control group ( t values were -15.68, 3.75, -3.81, and -7.54 respectively, P<0.01). The bladder capacity, urine flow rate, detrusor pressure, bladder compliance and detrusor contractility were higher than those of the control group ( t values were 11.04, 7.49, 9.76, 5.65 and 4.36 respectively, P<0.01), while the NBSS score and SF-Qualiveen score were lower than those of the control group ( t values were -10.82 and -9.83 respectively, P<0.01). No obvious adverse reactions occurred in either group during the treatment period. Conclusion:Tongdu Tiaoshen acupuncture combined with low-frequency electrical pulses can improve the bladder function of NB caused by SCI, restore urodynamics, and improve the quality of life. Its mechanism may be related to the inhibition of inflammatory responses.

Objective To analyze the influence of clinical indicators and PPARD gene polymorphism on the hypoglycemic efficacy of dapagliflozin(DAPA)in patients with type 2 diabetes mellitus(T2DM).Methods A total of 102 patients with T2DM who visited the Affiliated Hospital of Jiangnan University and the Affiliated Hospital of Xuzhou Medical University from June 2021 to December 2023 were selected as the study subjects,an observational cohort of T2DM patients treated with DAPA was established,and DAPA tablets of 10 mg were administered orally once a day for 12 weeks,the venous blood and clinical data of the patients were col-lected.PPARD gene polymorphism typing was performed by using the Snapshot method.The differences in clinical indicators among patients with different genotypes were compared and the influencing factors of DA-PA in improving insulin resistance index(HOMA-IR)were analyzed.Results Eighty-two patients completed the 12-week follow-up.Before DAPA treatment,the differences in the clinical indicators of patients with dif-ferent PPARD rs3777744 genotypes were not statistically significant(P＞0.05).After 12 weeks of DAPA treatment,compared with patients with AA genotype,patients carried of G allele(GG+AG genotype)had lower levels of fasting blood glucose(FPG),HOMA-IR and its decrease,and the differences were statistically significant(P＜0.05).The results of multiple linear regression analysis showed that the genotype of PPARD rs3777744 locus and baseline HOMA-IR were correlated with the improvement of HOMA-IR after 12 weeks of DAPA treatment,and the improvement of HOMA-IR in G allele carriers was not as significant as that in AA genotype patients,and the higher the baseline HOMA-IR,the more significant the improvement of HO-MA-IR.Conclusion Different genotypes of PPARD rs3777744,baseline HOMA-IR are important influencing factors for DAPA to improve insulin resistance of T2DM patients.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Aim To explore the relationship between serum levels of proprotein convertase subtilisin/kexin type 9(PCSK9),macrophage migration inhibitory factor(MIF)and the severity of coronary artery lesions in patients with coro-nary heart disease(CHD).Methods A cross-sectional study was conducted involving 139 patients with CHD and 69 control subjects who underwent coronary angiography during the same period,all of whom were admitted to the People's Hospital of Xinjiang Uygur Autonomous Region from November 2023 to May 2024.Clinical data and coronary angiography results were collected,and the severity of coronary artery stenosis was quantitatively assessed using the Gensini score.Pa-tients with the Gensini scores＞0 were classified into three groups based on tertiles:the mild stenosis group(1～18 points,54 cases),the moderate stenosis group(19～36 points,54 cases),and the severe stenosis group(＞36 points,54 ca-ses).Serum levels of PCSK9 and MIF were measured by ELISA kit.Results Serum levels of PCSK9 and MIF were significantly higher in the CHD group than those in the control group(P＜0.05).Multivariable Logistic regression analy-sis revealed that high levels of serum PCSK9 and MIF were independent risk factors for CHD.Spearman correlation analy-sis showed that serum PCSK9 and MIF levels were positively correlated with Gensini score(rs=0.619 6 and r,=0.411 4,both P＜0.001).Further subgroup analysis showed that serum total cholesterol and low density lipoprotein cholesterol lev-els were significantly increased in patients with high-level PCSK9,while patients with high-level MIF had higher inflamma-tory coefficients such as systemic inflammatory response index(SIRI)and systemic immune-inflammation index(SII)(all P＜0.05).Conclusion Serum levels of PCSK9 and MIF are positively correlated with the severity of coronary artery stenosis.High levels of serum PCSK9 and MIF are independent risk factors for CHD.

Locomotion, a fundamental motor function encompassing various forms such as swimming, walking, running, and flying, is essential for animal survival and adaptation. The mesencephalic locomotor region (MLR), located at the midbrain-hindbrain junction, is a conserved brain area critical for controlling locomotion. This review highlights recent advances in understanding the MLR’s structure and function across species, from lampreys to mammals and birds, with a particular focus on insights gained from optogenetic studies in mammals. The goal is to uncover universal strategies for MLR-mediated locomotor control. Electrical stimulation of the MLR in species such as lampreys, salamanders, cats, and mice initiates locomotion and modulates speed and patterns. For example, in lampreys, MLR stimulation induces swimming, with increased intensity or frequency enhancing propulsive force. Similarly, in salamanders, graded stimulation transitions locomotor outputs from walking to swimming. Histochemical studies reveal that effective MLR stimulation sites colocalize with cholinergic neurons, suggesting a conserved neurochemical basis for locomotion control. In mammals, the MLR comprises two key nuclei: the cuneiform nucleus (CnF) and the pedunculopontine nucleus (PPN). Both nuclei contain glutamatergic and GABAergic neurons, with the PPN additionally housing cholinergic neurons. Optogenetic studies in mice by selectively activating glutamatergic neurons have demonstrated that the CnF and PPN play distinct roles in motor control: the CnF drives rapid escape behaviors, while the PPN regulates slower, exploratory movements. This functional specialization within the MLR allows animals to adapt their locomotion patterns and speed in response to environmental demands and behavioral objectives. Similar to findings in lampreys, the CnF and PPN in mice transmit motor commands to spinal effector circuits by modulating the activity of brainstem reticular formation neurons. However, they achieve this through distinct reticulospinal pathways, enabling the generation of specific behaviors. Further insights from monosynaptic rabies viral tracing reveal that the CnF and PPN integrate inputs from diverse brain regions to produce context-appropriate behaviors. For instance, glutamatergic neurons in the PPN receive signals from other midbrain structures, the basal ganglia, and medullary nuclei, whereas glutamatergic neurons in the CnF rarely receive inputs from the basal ganglia but instead are strongly influenced by the periaqueductal grey and inferior colliculus within the midbrain. These differential connectivity patterns underscore the specialized roles of the CnF and PPN in motor control, highlighting their unique contributions to coordinating locomotion. Birds exhibit exceptional flight capabilities, yet the avian MLR remains poorly understood. Comparative studies suggest that the pedunculopontine tegmental nucleus (PPTg) in birds is homologous to the mammalian PPN, which contains cholinergic neurons, while the intercollicular nucleus (ICo) or nucleus isthmi pars magnocellularis (ImC) may correspond to the CnF. These findings provide important clues for identifying the avian MLR and elucidating its role in flight control. However, functional validation through targeted experiments is urgently needed to confirm these hypotheses. Optogenetics and other advanced techniques in mice have greatly advanced MLR research, enabling precise manipulation of specific neuronal populations. Future studies should extend these methods to other species, particularly birds, to explore unique locomotor adaptations. Comparative analyses of MLR structure and function across species will deepen our understanding of the conserved and evolved features of motor control, revealing fundamental principles of locomotion regulation throughout evolution. By integrating findings from diverse species, we can uncover how the MLR has been adapted to meet the locomotor demands of different environments, from aquatic to aerial habitats.

Objective:To explore the correlation of bone metabolism with vitamin D and vitamin K levels in children with glucocorticoid-induced osteoporosis (GIOP) .Methods:A total of 120 GIOP children admitted to Neonatal Department of the First People’s Hospital of Chenzhou City, Hunan Province from Oct. 2022 to Dec. 2024 (GIOP group) and children without osteoporosis who received glucocorticoid therapy during the same period (the control group) were studied. Bone mineral density (BMD), biochemical indexes of bone metabolism and serum 25-hydroxyvitamin D (25 (OH) D), vitamin K1 (VitK1) and VitK2 were determined. BMD and bone metabolism indexes of GIOP children with different levels of 25 (OH) D, VitK1 and VitK2 were compared and their correlation was analyzed. Multiple linear regression analysis was conducted to analyze the independent factors affecting low BMD in GIOP children.Results:GIOP group had lower BMD, serum 25 (OH) D, VitK1 and VitK2 levels ( t=33.03, 42.22, 65.30, 86.16, P<0.05), while higher PINP, β-CTX and N-MID levels ( t=17.98, 34.78, 2.58, P<0.05); The levels of VitK1, VitK2, BMD, PINP, β-CTX and N-MID in GIOP children with different vitamin D and K levels were statistically significant ( F =54.31, 36.77, 82.32, 32.40, 22.80, 5.23), among which BMD was the lowest and PINP, β-CTX and N-MID levels were the highest ( P<0.05); The levels of 25 (OH) D, VitK1 and VitK2 were positively correlated with BMD ( r=0.54, 0.39, 0.47, P<0.05), but negatively correlated with PINP, β-CTX and N-MID ( r = -0.43, -0.34, -0.38, -0.39, -0.45, -0.44, -0.29, -0.32, -0.51, P<0.05); 25 (OH) D, VitK1 and VitK2 were protective factors for low BMD ( t=-2.76, -2.55, -3.51, P<0.05), while PINP, β-CTX, N-MID and hormone use time were risk factors ( t=2.48, 2.19, 2.22, 2.06, P<0.05) . Conclusions:The level of bone metabolism in children with GIOP is closely related to the levels of vitamin D and vitamin K. With the decrease of vitamin D and vitamin K levels, the decrease of BMD is more obvious. Therefore, vitamin D and vitamin K should be supplemented in a timely and reasonable manner for such children.

Objective To analyze the related factors of recurrent readmission in patients with hypertriglyceridemic acute pancreatitis(HTG-AP)in the short term,and to construct and verify the risk early warning model.Methods A total of 176 patients with HTG-AP admitted from January to November 2023 were selected as the research objects.According to whether they were readmitted and recurred in the short term,they were divided into recurrent readmission group(n=53)and non-recurrent readmission group(n=123).Univariate and multivariate Logistic regression were used to construct the risk prediction model.A total of 53 HTG-AP patients admitted from December 2023 to April 2024 were selected for external validation of the model.Results The probability of recurrence and readmission in 176 patients with HTG-AP in the short term was 30.11％.According to univariate and Logistic multivariate analysis,the results showed acute physiology and chronic health evaluation Ⅱ score ≥ 8 points,Ranson score ≥ 3 points,neutrophil to lymphocyte ratio,serum amylase and lactic dehydrogenase were independent risk factors for recurrence and readmission in HTG-AP patients in the short term,while Ca2+was the protective factor(P＜0.05).According to the H-L goodness of fit test results of 176 patients with HTG-AP,x2=5.212,P=0.735;Area under the curve(AUC)was 0.877(P＜0.001,95％CI:0.824-0.931),the sensitivity was 86.80％,the specificity was 73.20％,and the maximum Youden index was 0.600.According to the H-L goodness of fit test results of 53 patients with HTG-AP,x2=3.391,P=0.907;AUC was 0.881(P＜0.001,95％CI:0.791-0.971),the sensitivity was 78.10％,the specificity was 81.00％,and the maximum Youden index was 0.591.The results showed that the model had good goodness of fit and good predictive efficacy in predicting the short-term recurrence of HTG-AP patients.Conclusion The short-term recurrence and readmission of HTG-AP patients are affected by multiple factors,and the risk prediction model has good consistency and discrimination.

Aim To explore the relationship between serum levels of proprotein convertase subtilisin/kexin type 9(PCSK9),macrophage migration inhibitory factor(MIF)and the severity of coronary artery lesions in patients with coro-nary heart disease(CHD).Methods A cross-sectional study was conducted involving 139 patients with CHD and 69 control subjects who underwent coronary angiography during the same period,all of whom were admitted to the People's Hospital of Xinjiang Uygur Autonomous Region from November 2023 to May 2024.Clinical data and coronary angiography results were collected,and the severity of coronary artery stenosis was quantitatively assessed using the Gensini score.Pa-tients with the Gensini scores＞0 were classified into three groups based on tertiles:the mild stenosis group(1～18 points,54 cases),the moderate stenosis group(19～36 points,54 cases),and the severe stenosis group(＞36 points,54 ca-ses).Serum levels of PCSK9 and MIF were measured by ELISA kit.Results Serum levels of PCSK9 and MIF were significantly higher in the CHD group than those in the control group(P＜0.05).Multivariable Logistic regression analy-sis revealed that high levels of serum PCSK9 and MIF were independent risk factors for CHD.Spearman correlation analy-sis showed that serum PCSK9 and MIF levels were positively correlated with Gensini score(rs=0.619 6 and r,=0.411 4,both P＜0.001).Further subgroup analysis showed that serum total cholesterol and low density lipoprotein cholesterol lev-els were significantly increased in patients with high-level PCSK9,while patients with high-level MIF had higher inflamma-tory coefficients such as systemic inflammatory response index(SIRI)and systemic immune-inflammation index(SII)(all P＜0.05).Conclusion Serum levels of PCSK9 and MIF are positively correlated with the severity of coronary artery stenosis.High levels of serum PCSK9 and MIF are independent risk factors for CHD.

Objective To analyze the related factors of recurrent readmission in patients with hypertriglyceridemic acute pancreatitis(HTG-AP)in the short term,and to construct and verify the risk early warning model.Methods A total of 176 patients with HTG-AP admitted from January to November 2023 were selected as the research objects.According to whether they were readmitted and recurred in the short term,they were divided into recurrent readmission group(n=53)and non-recurrent readmission group(n=123).Univariate and multivariate Logistic regression were used to construct the risk prediction model.A total of 53 HTG-AP patients admitted from December 2023 to April 2024 were selected for external validation of the model.Results The probability of recurrence and readmission in 176 patients with HTG-AP in the short term was 30.11％.According to univariate and Logistic multivariate analysis,the results showed acute physiology and chronic health evaluation Ⅱ score ≥ 8 points,Ranson score ≥ 3 points,neutrophil to lymphocyte ratio,serum amylase and lactic dehydrogenase were independent risk factors for recurrence and readmission in HTG-AP patients in the short term,while Ca2+was the protective factor(P＜0.05).According to the H-L goodness of fit test results of 176 patients with HTG-AP,x2=5.212,P=0.735;Area under the curve(AUC)was 0.877(P＜0.001,95％CI:0.824-0.931),the sensitivity was 86.80％,the specificity was 73.20％,and the maximum Youden index was 0.600.According to the H-L goodness of fit test results of 53 patients with HTG-AP,x2=3.391,P=0.907;AUC was 0.881(P＜0.001,95％CI:0.791-0.971),the sensitivity was 78.10％,the specificity was 81.00％,and the maximum Youden index was 0.591.The results showed that the model had good goodness of fit and good predictive efficacy in predicting the short-term recurrence of HTG-AP patients.Conclusion The short-term recurrence and readmission of HTG-AP patients are affected by multiple factors,and the risk prediction model has good consistency and discrimination.