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.

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.

Objective:To investigate the diagnosis and treatment of posterolateral elbow dislocation in children.Methods:A total of 19 children with posterolateral elbow dislocation were diagnosed and treated at Department of Children's Orthopedics, Sichuan Orthopedic Hospital from April 2018 to April 2021. They were 12 boys and 7 girls, aged from 7 to 14 years (average, 10.9 years). Internal epicondyle avulsion fracture of the humerus was complicated in 11 cases, external epicondyle avulsion fracture of the humerus in 5 cases, capitulum avulsion fracture of the humerus in 3 cases, and fracture of the ulna coronoid process in 4 cases. After evaluation of the elbow stability, stable elbows were treated nonsurgically while the unstable ones complicated with fracture were treated with open reduction and internal fixation. After treatment, the injured limbs were fixated with elbow flexion 90° in forearm pronation position for 4 to 6 weeks.Results:In this group, 4 children received nonsurgical treatment and 15 ones were treated surgically. Internal epicondyle fractures of the humerus were treated by open reduction and internal fixation with Kirschner wire and hollow screws, and external epicondyle avulsion fractures or capitulum avulsion fractures of the humerus by suture fixation with Kirschner wire tension band or absorbable anchors. Three coronal process fractures were treated with plate internal fixation but one coronal process fracture was not treated with internal fixation. All the children were followed up for 6 to 30 months (average, 13.3 months). The last follow-up showed that fractures got united in all children, with no ectopic ossification, fine anatomical relationship of the elbow, and no recurrence of elbow dislocation or instability. The last follow-up showed that the Mayo elbow performance scores (MEPS) ranged from 75 to 100 points, averaging 93.2 points.Conclusions:In the treatment of posterolateral elbow dislocation in children, the key point is to rebuild the stability of the elbow. Non-surgical treatment is recommended for cases of a stable elbow with posterolateral rotation and dislocation while surgical treatment for cases of an unstable elbow because surgery leads to fine functional recovery and efficacy in children.

Plasticity in the glutamatergic synapses on striatal medium spiny neurons (MSNs) is not only essential for behavioral adaptation but also extremely vulnerable to drugs of abuse. Modulation on these synapses by even a single exposure to an addictive drug may interfere with the plasticity required by behavioral learning and thus produce impairment. In the present work, we found that the negative reinforcement learning, escaping mild foot-shocks by correct nose-poking, was impaired by a single in vivo exposure to 20 mg/kg cocaine 24 h before the learning in mice. Either a single exposure to cocaine or reinforcement learning potentiates the glutamatergic synapses on MSNs expressing the striatal dopamine 1 (D1) receptor (D1-MSNs). However, 24 h after the cocaine exposure, the potentiation required for reinforcement learning was disrupted. Specific manipulation of the activity of striatal D1-MSNs in D1-cre mice demonstrated that activation of these MSNs impaired reinforcement learning in normal D1-cre mice, but inhibition of these neurons reversed the reinforcement learning impairment induced by cocaine. The results suggest that cocaine potentiates the activity of direct pathway neurons in the dorsomedial striatum and this potentiation might disrupt the potentiation produced during and required for reinforcement learning.

Objective:To investigate the risk factors for early complications after laparoscopy-assisted gastrectomy in patients with gastric cancer.Methods:The retrospective case-control study was conducted. The clinicopathological data of 196 patients who underwent laparos-copy-assisted radical gastrectomy at Peking Union Medical College Hospital from March 2016 to March 2019 were collected. There were 144 males and 52 females, aged (61±10)years. Observation indicators: (1) early complications after laparoscopy-assisted radical gastrectomy and treatment; (2) analysis of risk factors for early complications after laparoscopy-assisted radical gastrectomy.Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( P25,P75). Count data were represented as absolute numbers. Univariate analysis was conducted using the t test, Mann-Whitney U test or chi-square test. Multivariate analysis was conducted using the Logistic regressional model. Results:(1) Early complications after laparoscopy-assisted radical gastrectomy and treatment: 51 of 196 patients had early postoperative complications, including 7 cases of grade Ⅰ according to Clavien-Dindo classi-fication system, 32 cases of grade Ⅱ, 9 cases of grade Ⅲa, 3 cases of grade Ⅲb. There was no grade Ⅳ or Ⅴ complication. There were 25 cases with abdominal complications, 7 cases with thoracic complications, 3 cases with internal/catheter related complications and 16 cases with other unclassified complications. All patients with complications were improved after symptomatic and supportive treatments. (2) Analysis of risk factors for early complications after laparoscopy-assisted radical gastrectomy: results of univariate analysis showed that the lymphocyte count, neutrophil-to-lymphocyte ratio, radiotherapy, operation time, volume of intraoperative blood loss, T stage, lymph node metastasis were related factors for early complications after laparoscopy-assisted radical gastrectomy in patients with gastric cancer ( Z=?2.048, χ2=6.385, 4.168, 8.068, 6.336, 12.497, 7.522, P<0.05). Results of multivariate analysis showed that the neutrophil/lymphocyte ratio ≥1.96, operation time ≥222 minutes, and lymph node metastasis were independent risk factors for early complica-tions after laparoscopy-assisted radical gastrectomy in patients with gastric cancer ( odds ratio=2.279, 2.245, 2.226, 95% confidence interval as 1.149-4.519, 1.116-4.517, 1.125-4.402, P<0.05). Conclusions:The abdominal complications are the most common early complications after laparoscopy-assisted radical gastrectomy. The neutrophil-to-lymphocyte ratio ≥1.96, operation time ≥222 minutes, and lymph node metastasis are independent risk factors for early complications after laparoscopy-assisted radical gastrectomy in patients with gastric cancer.