Metformin has been demonstrated to attenuate hyperglycaemia by modulating the gut microbiota. However, the mechanisms through which the microbiome mediates metformin monotherapy failure (MMF) are unclear. Herein, in a prospective clinical cohort study of newly diagnosed type 2 diabetes mellitus (T2DM) patients treated with metformin monotherapy, metagenomic sequencing of faecal samples revealed that Phocaeicola vulgatus abundance was approximately 12 times higher in nonresponders than in responders. P. vulgatus rapidly hydrolysed taurine-conjugated bile acids, leading to ceramide accumulation and reversing the improvements in glucose intolerance conferred by metformin in high-fat diet-fed mice. Interestingly, C22:0 ceramide bound to mitochondrial fission factor to induce mitochondrial fragmentation and impair hepatic oxidative phosphorylation in P. vulgatus-colonized hyperglycaemic mice, which could be exacerbated by metformin. This work suggests that metformin may be unsuitable for P. vulgatus-rich T2DM patients and that clinicians should be aware of metformin toxicity to mitochondria. Suppressing P. vulgatus growth with cefaclor or improving mitochondrial function using adenosylcobalamin may represent simple, safe, effective therapeutic strategies for addressing MMF.

Leishmania is a protozoan parasite that causes leishmaniasis,a disease prevalent in tropical regions.Vis-ceral leishmaniasis,also known as kala-azar in Asian countries,and cutaneous leishmaniasis are distributed world-wide.Chemotherapy with sodium stibogluconate and amphotericin B has shown significant effects.However,cur-rent treatment methods for leishmaniasis have various defects,including multiple side effects,prolonged treat-ment duration,varying efficacy across different regions,and the emergence of drug resistance.To address this ur-gent need,it is imperative to identify safer and more effective alternative treatment methods and seek for appropri-ate pharmacological targets.This review discusses key metabolic pathways that represent potential pharmacologi-cal targets,as well as emerging therapeutic strategies for leishmaniasis.

Objective:To prepare a novel ginseng polypeptide thermosensitive hydrogel,and to investigate its repair effect on heat-induced skin injury in the rats and explore the underlying mechanisms.Methods:Thermosensitive hydrogels were formulated using Pluronic F127 and β-sodium glycerophosphate(β-GP),and their phase transition temperatures,spatial structures,elemental compositions,and water retention capacities were evaluated.The rat models of heat-induced skin injury were established and the model rats were divided into PBS group,Gel group,and ginseng polypeptide gel(GP-Gel)group.After 11 d of treatment,the morphological changes of wound and collagen deposition in the wound of the rats in various groups were observed by HE and Masson staining.Immunohistochemistry was used to detect the expression levels of α-smooth muscle actin(α-SMA),connective tissue growth factor(CTGF),basic fibroblast growth factor(bFGF),proliferating cell nuclear antigen(PCNA),cell proliferation marker Ki67,epidermal growth factor(EGF),CD31,vascular endothelial growth factor(VEGF),P50 and P65 proteins in the skin wound tissue of the rats in various groups.Western blotting method was used to detect the expression levels of Toll-like receptor 4(TLR4)in the skin wound tissue of the rats in various groups.ELISA method was used to measure the levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),interleukin-15(IL-15),and interleukin-10(IL-10)in the serum of the rats in various groups.Results:Compared with PBS and Gel groups,the wound area of the rats in GP-Gel group was reduced(P＜0.01),the expression levels of PCNA,Ki67,EGF,CD31,VEGF,α-SMA,and CTGF proteins in the skin wound tissue were increased(P＜0.05 or P＜0.01),and the expression levels of P65 and TLR4 proteins were decreased(P＜0.01);the level of anti-inflammatory factor IL-10 in serum was increased(P＜0.01),while the levels of pro-inflammatory factors TNF-α,IL-1β,IL-6 and IL-15 were decreased(P＜0.05 or P＜0.01).Conclusion:The ginseng polypeptide thermosensitive hydrogel promotes the repair of heat-induced skin injury by enhancing cell proliferation,collagen synthesis,angiogenesis,and reducing inflammatory responses.

Leishmania is a protozoan parasite that causes leishmaniasis,a disease prevalent in tropical regions.Vis-ceral leishmaniasis,also known as kala-azar in Asian countries,and cutaneous leishmaniasis are distributed world-wide.Chemotherapy with sodium stibogluconate and amphotericin B has shown significant effects.However,cur-rent treatment methods for leishmaniasis have various defects,including multiple side effects,prolonged treat-ment duration,varying efficacy across different regions,and the emergence of drug resistance.To address this ur-gent need,it is imperative to identify safer and more effective alternative treatment methods and seek for appropri-ate pharmacological targets.This review discusses key metabolic pathways that represent potential pharmacologi-cal targets,as well as emerging therapeutic strategies for leishmaniasis.

Objective To investigate the correlation between telomere length of peripheral white blood cells and the levels of advanced glycosylation end products,as well as bone mineral density in patients with type 2 diabetes mellitus,and to assess the impact of advanced glycosylation end product levels on telomere length.Methods From May 1,2023,to May 1,2024,174 patients with T2DM who underwent dual-energy X-ray BMD examination at the Department of Endocrinology,Zhengzhou Central Hospital,were selected.T2DM patients were divided into osteoporosis group,osteopenia group,and normal bone mass group based on the T-value in BMD.qPCR method was used to measure telomere length in peripheral blood leukocytes,and ELISA method was used to determine AGEs levels.General patient data were collected along with measurements for blood glucose,blood lipid levels,25-hydroxy-vitamin D,and other indicators.Bone mineral density was evaluated using dual-energy X-ray imaging while plasma CTX and PINP levels were measured via ELISA.SPSS 26.0 statistical software was utilized to analyze differences and correlations among all indicators.Results(1)The telomere length of OP group,osteopenia group and normal bone mass group was different,and the telomere length of the three groups increased successively.(2)In individuals with type 2 diabetes mellitus,telomere length exhibited a positive correlation with BMD and a negative correlation with CTX and PINP.Plasma AGEs level showed a negative correlation with BMD and a positive correlation with CTX and PINP,while telomere length demonstrated a negative correlation with AGEs level.(3)Telomere length was an independent factor of BMD,and AGEs level was an independent factor of BMD(P<0.05).Conclusion The reduction of telomere length and the increase of AGEs in patients with type 2 diabetes are related to the decrease of bone mineral density,and the reduction of telomere length is related to the increase of AGEs.Telomere length of peripheral leucocytes and plasma AGEs level can jointly evaluate the bone metabolism status of T2DM patients.

Objective To investigate the effects of atorvastatin calcium on thyroid function, immune response and C-Jun N-terminal kinase/p38 mitogen-activated protein kinase (JNK/p38 MAPK) signaling pathway in rats with hypothyroidism. Methods A total of 30 healthy adult male SD rats were randomly divided into control group, hypothyroid group (PTU group) and atorvastatin calcium treatment group (ACT group), with 10 rats in each group. Rats in the PTU group and the ACT group were injected with PTU subcutaneously at the dorsum of the neck every day for 28 consecutive days; instead of PTU, rats in the control group were injected subcutaneously with 0.3 mL of saline. After 2 weeks of PTU treatment, rats in the ACT group were gavaged with 3 mL of atorvastatin calcium saline solution (containing 5 mg/kg of atorvastatin calcium), which was administered once daily; the control group was gavaged with an equal amount of saline in the same way. The body weight, food intake and water intake of rats were measured weekly. The histopathological changes of the thyroid gland were observed in histopathological sections of rats in each group. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the levels of triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), interferon γ (IFN-γ) and interleukin-4 (IL-4) in serum; quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed to detect the mRNA expression levels of IFN-γ, IL-10, Foxp3 and IL-4; western blot was performed to determine the levels of p-JNK/JNK and p-p38/p38 MAPK. Results Compared with control group, PTU-induced hypothyroidism rats showed a significant decrease in body mass and food and water consumption (P < 0.05). After 2 weeks of treatment with atorvastatin calcium, the body mass loss of PTU rats was inhibited, food and water consumption was improved, and the differences were statistically significant (P < 0.05). Atorvastatin calcium was able to significantly increase the serum T3 and T4 levels and decrease the serum TSH level in hypothyroid rats (P < 0.05). Atorvastatin calcium treatment was able to significantly alleviate histopathological changes such as follicular cell proliferation and related hypertrophy induced by PTU, and increase follicular size (P < 0.05). After treatment with atorvastatin calcium, the spleen mass of PTU rats increased significantly, and the expression of IFN-γ mRNA in hypothyroid rats decreased significantly, but the expression levels of IL-10 mRNA, Foxp3 mRNA and IL-4 mRNA increased significantly (P < 0.05). After treatment with atorvastatin calcium, the levels of p-JNK/JNK and p-p38/p38 MAPK in thyroid tissue of hypothyroid rats decreased significantly (P < 0.05). Conclusion Atorvastatin calcium treatment for hypothyroidism has the function of promoting the normalization of thyroid hormone imbalance, balancing Th1/Th2 cytokines, and inhibiting the activation of JNK/p38 MAPK signaling pathway.

OBJECTIVES: This study aimed to construct the finite element model of the mandibular first molar with the invisible appliance and explore the dentition movement characteristics of the mandibular first molar when using micro-implant anchorage and different initial positions of the first molar. METHODS: Models of the mandible, tooth, periodontal membrane, and invisible appliance were constructed using cone beam computed tomography (CBCT) data. The two groups were divided into the non-anchorage group and the micro-implant group (between the roots of the first molar and the second molar) based on whether the elastic traction of the micro-implant was assisted or not. The two groups were divided into the following conditions based on the starting position of the first molar: Working condition 1: the distance between the first molar and the second premolar was 0 mm; working condition 2: the distance between the first molar and the second premolar was 1 mm; working condition 3: the distance between the first molar and the second premolar was 2 mm; working condition 4: the distance between the first molar and the second premolar was 3 mm. The data characte-ristics of total displacement and displacement in each direction of dentition were analyzed. RESULTS: In the non-ancho-rage group, all the other teeth showed reverse movement except for the first molar which was moved distally. Meanwhile, in the micro-implant group, except for a small amount of mesial movement of the second molar in wor-king condition 1, the whole dentition in other working conditions presented distal movement and anterior teeth showed lingual movement, among which the distal displacement of the first molar in working condition 4 was the largest. With the change of the initial position of the first molar to the distal, the movement of the first molar to the distal, the premolar to the mesial, and the anterior to the lip increased, while the movement of the second molar to the mesial decreased. CONCLUSIONS The micro-implant can effectively protect the anterior anchorage, increase the expression rate of molar distancing, and avoid the round-trip movement of the second molar. The initial position of the first molar movement is related to the amount of distancing and the remaining tooth movement.
Finite Element Analysis ; Molar ; Bicuspid ; Periodontal Ligament ; Tooth Movement Techniques/methods* ; Orthodontic Appliances, Removable

Objective:To investigate the application value of percutaneous coronary intervention in patients with acute coronary syndrome in county-level hospitals.Methods:The clinical data of 51 patients with acute coronary syndrome who received treatment in Feng Tai People's Hospital from January 2020 to January 2022 were retrospectively analyzed. They were divided into a control group ( n = 25) and an observation group ( n = 26). The control group was given standard dual antiplatelet and statin drugs. The observation group underwent percutaneous coronary intervention and stent implantation based on conventional drug treatment. All patients were followed up for 1 year. Cardiac function indexes left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDD) were compared between the two groups. The number of readmissions, length of hospital stay, quality of life score, medication, the incidence of complications, and the incidence of adverse cardiovascular events were compared between the two groups. Results:Before treatment, there were no significant differences in LVEF and LVEDD between the two groups (both P > 0.05). After treatment, LVEF was increased, and LVEDD was decreased in each group compared with before treatment. After treatment, LVEF and LVEDD in the observation group were (50.34 ± 5.97)% and (49.01 ± 5.02) mm, respectively, which were significantly superior to (45.61 ± 5.42)% and (52.12 ± 5.24) mm in the control group ( t = -2.96, 2.17, both P < 0.05). After treatment, the number of readmissions in the observation group was significantly less than that in the control group [(0.8 ± 0.1) times vs. (2.1 ± 0.3) times, t = 20.14, P < 0.001]. The length of hospital stay in the observation group was significantly shorter than that in the control group [(12.4 ± 3.1) days vs. (25.3 ± 3.9) days, t = 13.10, P < 0.001]. Quality of life score in the observation group was significantly higher than that in the control group [(85.3 ± 5.9) points vs. (72.5 ± 5.2) points, t = -8.19, P < 0.001]. After treatment, the incidence of adverse cardiovascular events in the observation group was significantly lower than that in the control group [3.9% (1/26) vs. 28.0% (7/25), χ2 = 3.94, P = 0.041). Conclusion:Use of percutaneous coronary intervention in patients with acute coronary syndrome in county-level hospitals is feasible. It can improve patients' cardiac function and has a remarkable clinical effect with a low incidence of adverse cardiovascular events.

BACKGROUND/OBJECTIVES: This study aimed to investigate cancer-specific survival (CSS) and associated risk factors in elderly gastric cancer (EGC) patients. SUBJECTS/METHODS: EGC patients (≥ 70 yrs) who underwent curative gastrectomy between January 2013 and December 2017 at our hospital were included. Clinicopathologic characteristics and survival data were collected. Receiver operating characteristic (ROC) analysis was used to extract the best cutoff point for body mass index (BMI). A Cox proportional hazards model was used to determine the risk factors for CSS. RESULTS: In total, 290 EGC patients were included, with a median age of 74.7 yrs. The median follow-up time was 31 (1–77) mon. The postoperative 1-yr, 3-yr and 5-yr CSS rates were 93.7%, 75.9% and 65.1%, respectively. Univariate analysis revealed risk factors for CSS, including age (hazard ratio [HR] = 1.08; 95% confidence interval [CI], 1.01–1.15), intensive care unit (ICU) admission (HR = 1.73; 95% CI, 1.08–2.79), nutritional risk screening (NRS 2002) score ≥ 5 (HR = 2.33; 95% CI, 1.49–3.75), and preoperative prognostic nutrition index score < 45 (HR = 2.06; 95% CI, 1.27–3.33). The ROC curve showed that the best BMI cutoff value was 20.6 kg/m 2 . Multivariate analysis indicated that a BMI ≤ 20.6 kg/m 2 (HR = 2.30; 95% CI, 1.36–3.87), ICU admission (HR = 1.97; 95% CI, 1.17–3.30) and TNM stage (stage II: HR = 5.56; 95% CI, 1.59–19.43; stage III: HR = 16.20; 95% CI, 4.99–52.59) were significantly associated with CSS. CONCLUSIONS Low BMI (≤ 20.6 kg/m2 ), ICU admission and advanced pathological TNM stages (II and III) are independent risk factors for CSS in EGC patients after curative gastrectomy. Nutrition support, better perioperative management and early diagnosis would be helpful for better survival.