OBJECTIVES: To investigate the effects of quercetin on cuproptosis and L-type calcium currents in the myocardium of diabetic rats. METHODS: Forty SD rats were randomized into control group and diabetic model groups. The rat models of diabetes mellitus (DM) induced by high-fat and high-sugar diet combined with streptozotocin (STZ) injection were further divided into DM model group, quercetin treatment group, and empagliflozin treatment group (n=10). Blood glucose and body weight were measured every other week, and cardiac function of the rats was evaluated using echocardiography. HE staining, Sirius red staining, and wheat germ agglutinin (WGA) analysis were used to observe the changes in myocardial histomorphology, and serum copper levels and myocardial FDX1 expression were detected. In cultured rat cardiomyocyte H9c2 cells with high-glucose exposure, the effects of quercetin and elesclomol, alone or in combination, on intracellular CK-MB and LDH levels and FDX1 expression were assessed, and the changes in L-type calcium currents were analyzed using patch-clamp technique. RESULTS: The diabetic rats exhibited elevated blood glucose, reduced body weight, impaired left ventricular function, increased serum copper levels and myocardial FDX1 expression, decreased L-type calcium currents, and prolonged action potential duration. Quercetin and empagliflozin treatment significantly lowered blood glucose, improved body weight, and restored cardiac function of the diabetic rats, and compared with empagliflozin, quercetin more effectively reduced serum copper levels, downregulated FDX1 expression, and enhanced myocardial L-type calcium currents in diabetic rats. In H9c2 cells, high glucose exposure significantly increased myocardial expressions of FDX1, CK-MB and LDH, which were effectively lowered by quercetin treatment; Elesclomol further elevated FDX1, CK-MB and LDH levels in the exposed cells, and these changes were not significantly affected by the application of quercetin. CONCLUSIONS Quercetin ameliorates myocardial injury in diabetic rats possibly by suppressing myocardial cuproptosis signaling and restoring L-type calcium channel activity.
Animals ; Quercetin/pharmacology* ; Calcium Channels, L-Type/metabolism* ; Diabetes Mellitus, Experimental/metabolism* ; Rats, Sprague-Dawley ; Rats ; Myocytes, Cardiac/drug effects* ; Myocardium/pathology* ; Male

Objective To discuss the efficacy of direct resin filling restoration,improved atraumatic restorative treatment(ART),and Hall technique in treating deciduous molars in children.Methods A total of 120 children with 180 deciduous molars who came to the Department of Oral Surgery of our hospital from January 2023 to August 2023 were selected and randomly divided into three groups:direct resin filling restoration group(40 people,60 teeth),improved ataumatic restorative treatment group(40 people,62 teeth),and Hall technique group(40 people,58 teeth).The behavioral performance classification and degree of anxiety of the children during the treatment process and the treatment time were compared among the three groups.The clinical efficacy after 3 months,6 months,and 12 months of treatment was compared and the reasons for failure were analyzed.Results The treatment time of the Hall technique group was significantly shorter than that of the improved ART group and direct filling group,and the differences in treatment time of the three groups had statistical significance(P＜0.05).The Hall technique and improved ART technique were more easily accepted by the chil-dren,and the degree of anxiety and behavioral performance classification of the three groups had statistically significant differences(P＜0.05).At the 12-month follow-up,the success rate of the direct filling restoration group was significantly different from that of the im-proved ART technique group and the Hall technique group,and the difference was statistically significant(P＜0.05).However,the suc-cess rate of the improved ART technique group was not significantly different from that of the Hall technique group(P＞0.05).Conclu-sion The success rate of the improved ART technique group and the Hall technique group is higher than that of the direct filling resto-ration group,and is more easily accepted by children.The pain level and degree of anxiety are lighter,and the treatment time of the Hall technique is shorter,which is more conducive to the repair of tooth decay.

Objective To discuss the efficacy of direct resin filling restoration,improved atraumatic restorative treatment(ART),and Hall technique in treating deciduous molars in children.Methods A total of 120 children with 180 deciduous molars who came to the Department of Oral Surgery of our hospital from January 2023 to August 2023 were selected and randomly divided into three groups:direct resin filling restoration group(40 people,60 teeth),improved ataumatic restorative treatment group(40 people,62 teeth),and Hall technique group(40 people,58 teeth).The behavioral performance classification and degree of anxiety of the children during the treatment process and the treatment time were compared among the three groups.The clinical efficacy after 3 months,6 months,and 12 months of treatment was compared and the reasons for failure were analyzed.Results The treatment time of the Hall technique group was significantly shorter than that of the improved ART group and direct filling group,and the differences in treatment time of the three groups had statistical significance(P＜0.05).The Hall technique and improved ART technique were more easily accepted by the chil-dren,and the degree of anxiety and behavioral performance classification of the three groups had statistically significant differences(P＜0.05).At the 12-month follow-up,the success rate of the direct filling restoration group was significantly different from that of the im-proved ART technique group and the Hall technique group,and the difference was statistically significant(P＜0.05).However,the suc-cess rate of the improved ART technique group was not significantly different from that of the Hall technique group(P＞0.05).Conclu-sion The success rate of the improved ART technique group and the Hall technique group is higher than that of the direct filling resto-ration group,and is more easily accepted by children.The pain level and degree of anxiety are lighter,and the treatment time of the Hall technique is shorter,which is more conducive to the repair of tooth decay.

Objective To screen the specific cytokines of tuberculous pleural effusion(plTB)by using liquid array technique to establish a diagnostic model and discuss its application value.Methods A total of 86 patients with plTB(plTB group)were included,including 41 patients in the confirmed plTB group and 45 patients in the clinically diagnosed plTB group.There were 42 other patients with pleural effusion in the control group.Seventeen cytokines in pleural effusion were analyzed by liquid array technology.Interleukin(IL)-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-9,IL-10,gamma-interferon-induced protein 10(IP-10),IL-15,IL-17F,IL-27,tumor necrosis factor(TNF)-α,monocyte chemotactic protein-1(MCP-1),the expression levels of macrophage inflammatory protein-3a(MIP-3α),macrophage colony-stimulating factor(M-CSF)and β-interferon(IFN-β)were detected.Difference factors between the confirmed plTB group and the control group were screened,and the receiver operating characteristic(ROC)curve was drawn in the confirmed plTB patients.IP-10,IL-27 and MCP-1 with AUC>0.850 and specificity>80%were combined to diagnose plTB,and were compared with adenylate deaminase(ADA)and T-SPOT.TB in pleural effusion to evaluate the diagnostic efficacy.Results The levels of IL-2,IP-10,IL-27,TNF-α and MCP-1 were higher in the confirmed plTB group than those in the control group(P＜0.05).The sensitivity and specificity of IP-10,IL-27 and MCP-1 in the diagnosis of plTB were 87.8%and 81.0%.The sensitivity of three-factor combined diagnosis in 45 patients with plTB was still as high as 86.7%,and there was no significant difference in sensitivity compared with that in the diagnosed plTB group(P＞0.05).In the plTB group,the sensitivity of IP-10,IL-27 and MCP-1 combined detection was 87.2%,which was higher than that of T-SPOT.TB(81.4%)and ADA(54.7%).Conclusion The application of liquid array technology to the joint detection of pleural effusion IP-10,IL-27 and MCP-1 can provide help for the diagnosis of plTB.

Objective To investigate the effect of T cell immunoreceptor with Ig and ITIM domains (TIGIT) on the function of CD8⁺ T cells in the lungs of Plasmodium infected mice. Methods The lungs of the mice infected with Plasmodium yoelii were isolated, weighed and photographed after 12 days' infection. After dissolution, lung lymphocytes were isolated, counted and stained, and then the contents of CD8⁺ and TIGIT⁺CD8⁺ T cells were detected by flow cytometry. The expressions of L selectin (CD62L), CD69, programmed death 1 (PD-1), CD25, and C-X3-C motif chemokine receptor 1 (CX3CR1) on TIGIT⁺CD8⁺ T cells were detected by flow cytometry. After stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin, the ability of TIGIT⁺CD8⁺T cells to secrete interferon γ(IFN-γ), interleukin 21 (IL-21), IL-4, IL-17, and IL-10 was detected. Results The body mass of mice with Plasmodium infection was reduced. The lungs became darker, and the ratio of the lung mass to body mass was significantly increased. Compared with the normal mice, the percentages and absolute quantity of CD8⁺ and TIGIT⁺CD8⁺ T cells in the lungs of the infected mice were significantly increased. The percentage of TIGIT⁺CD8⁺ T cells expressing CD62L in the infected group was significantly lower, while the percentage of the CD69, PD-1, and CX3CR1 cells were significantly higher than that of TIGIT⁺CD8⁺ T cells from the normal mice. The percentages of TIGIT⁺CD8⁺ T cells secreting IL-21, IL-4, IL-17 and IL-10 cells in the infected group were significantly lower. Conclusion The lung lesions from mice with Plasmodium infection are obvious, the numbers of TIGIT⁺CD8⁺ T cells increase, and these cells express a variety of activation-related molecules, but the ability to secrete cytokines is reduced.
Animals ; Mice ; CD8-Positive T-Lymphocytes ; Cytokines/metabolism* ; Interferon-gamma/metabolism* ; Interleukin-10/metabolism* ; Interleukin-17/metabolism* ; Interleukin-4/metabolism* ; Lung/metabolism* ; Malaria/metabolism* ; Plasmodium yoelii/metabolism* ; Programmed Cell Death 1 Receptor/metabolism*

Objective:To explore the therapeutic effect and mechanism of Dachengqi decoction on patients with mild acute pancreatitis (MAP).Methods:A parallel randomized controlled trial was conducted. Sixty-eight patients with acute pancreatitis (AP) admitted to Shanghai Traditional Chinese Medicine (TCM)-Integrated Hospital from March 2018 to February 2021 were enrolled. Referring to the condition on admission of the patients and whether they agreed to receive the Dachengqi decoction or not, they were divided into conventional treatment group and Dachengqi decoction group according to the principle of 1∶1 equal randomness. Meanwhile, 20 healthy volunteers were recruited as controls. Both groups of patients were treated with octreotide, fasting, gastrointestinal decompression, antipyretic and analgesic, anti-inflammatory, inhibition of gastric acid and pancreatic juice secretion, maintenance of electrolyte balance and other western conventional medicine. The patients in the Dachengqi decoction group received Dachengqi decoction orally on the basis of routine treatment, 100 mL each time, twice a day, for seven consecutive days. The inflammation parameters [white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6)] before and after treatment and the recovery time of gastrointestinal function (first exhaust time, time to recover bowel sounds, first defecation time) of patients were recorded. 16S rRNA gene sequencing of stool samples was recorded, and normalized data were obtained after quality control and other related processing. The data were subjected to diversity analysis (Alpha diversity and Beta diversity) and linear discriminant analysis effect size analysis (LEfSe analysis) to observe changes in the gut microbiota of MAP patients. Spearman rank correlation coefficient was used to analyze the correlation between inflammatory indexes and microorganisms at the intestinal genus level. Blood, urine, stool samples, renal function, and electrocardiogram (ECG) during treatment of MAP patients were detected to assess the safety of the treatment.Results:Of the 68 patients with AP, 16 were excluded from moderate-severe AP, 4 were not collected or voluntarily abandoned treatment. Finally, 48 patients with MAP were enrolled, 24 in the conventional treatment group and 24 in the Dachengqi decoction group. The inflammation parameters levels at 7 days of treatment in both groups were significantly lower than those before treatment. CRP, PCT and IL-6 levels in the Dachengqi decoction group were significantly lower than those in the conventional treatment group [CRP (mg/L): 8.50 (3.50, 13.00) vs. 16.00 (9.25, 29.75), PCT (μg/L): 0.06 (0.03, 0.08) vs. 0.09 (0.05, 0.11), IL-6 (ng/L): 6.36 (3.96, 10.79) vs. 13.24 (6.69, 18.87), all P < 0.05]. The first exhaust time, time to recover bowel sounds and first defecation time in the Dachengqi decoction group were significantly shorter than those in the conventional treatment group [first exhaust time (days): 1.62±0.65 vs. 2.80±0.65, time to recover bowel sounds (days): 1.13±0.58 vs. 2.31±0.76, first defecation time (days): 3.12±0.75 vs. 4.39±0.76, all P < 0.05]. The analysis of intestinal microflora diversity showed that both the diversity and abundance of microbial communities were the highest in the healthy control group and the lowest in the conventional treatment group. In addition, the coincidence degree of microbial communities in healthy controls and MAP patients was small, while the coincidence degree of MAP patients among different treatment methods was relatively large. LEfSe analysis showed that Dachengqi decoction reduced the relative abundance of Escherichia coli-Shigella and Clostridium erysipelae, and increased the relative abundance of three beneficial bacteria, namely Lactobacillus, Rombutzia and Brutella. In the intestines of MAP patients, Lactobacillus mucilaginus and Lactobacillus conjunctus were significantly enriched. Correlation analysis showed that positive correlations between Escherichia coli- Shigella and the four inflammatory indicators including WBC, CRP, PCT, IL-6 were statistically significant ( r value was 0.31, 0.41, 0.57, 0.43, respectively, all P < 0.05). There was no significant correlation between other bacteria and inflammatory indicators. During the treatment, there was no obvious abnormality in blood, urine and feces, renal function and ECG of MAP patients. Conclusions:Dachengqi decoction could reduce inflammatory responses and promote recovery of intestinal microecological balance and gastrointestinal function in patients with MAP by regulating the composition of intestinal flora. No significant adverse effects were observed during the treatment period.

OBJECTIVE: To explore the genetic etiology of a Chinese pedigree affected with pseudohypoparathyroidism. METHODS: Peripheral blood samples of the proband and his parents were collected and subjected to trio-whole exome sequencing (trio-WES). Candidate variants were verified among the pedigree and 50 randomly selected healthy individuals through analysis of restriction fragment length polymorphism. Short tandem repeat (STR) linkage analysis was used to verify the parental origin of the pathogenic variants. RESULTS: Trio-WES and Sanger sequencing showed that the proband and his mother had both harbored a c.121C>G (p.His41Asp) variant of the GNAS gene, which was not found in other family members and the 50 healthy controls. The variant was not found in international databases. Based on guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be likely pathogenic. CONCLUSION The novel c.121C>G variant of the GNAS gene probably underlay the disease in this pedigree. Above finding has enriched the spectrum of GNAS gene variants.
Female ; Humans ; Pedigree ; East Asian People ; Mothers ; Exome Sequencing ; Pseudohypoparathyroidism/genetics* ; Mutation ; China ; Chromogranins/genetics* ; GTP-Binding Protein alpha Subunits, Gs/genetics*

A 69-year-old male patient with depression was treated with amfebutamone and mirtazapine for a long time. Because of poor control of symptoms, the treatment plan was adjusted to oral duloxetine (60 mg in the morning) and mirtazapine (15 mg at night). After 13 days of treatments, the patient developed high fever (41.0 ℃) with disturbance of consciousness, followed by muscle rigidity and dyspnea. His heart rate was 180 beats/min and blood oxygen saturation was 0.84. Laboratory tests showed serum creatinine (Scr) 609 μmol/L, creatine kinase (CK) 7 102 U/L, myoglobin (MYO) >3 000 μg/L, aspartate aminotransferase (AST) 88 U/L, and total bilirubin (TBil) 33.7 μmol/L. ECG monitoring showed rapid atrial fibrillation. The patient was diagnosed with malignant syndrome caused by duloxetine after excluding infection and other conditions. Duloxetine and mirtazapine were stopped immediately, and symptomatic and supportive treatments including endotracheal intubation, hemofiltration, improvement of water-electrolyte balance, and hepatoprotection were given. On the 6th day of drug withdrawal, the patient′s temperature was 38.2 ℃, the blood oxygen saturation was 0.96, muscle tone was improved, and muscle tremor disappeared. On the 16th day of drug withdrawal, the patient′s condition was obviously improved, the consciousness was clear, the temperature was normal, the call could be answered, and no limb convulsion and muscle tremor occurred. Laboratory tests showed Scr 116 μmol/L, CK 250 U/L, MYO 148 μg/L, AST 38 U/L, and TBil 21.4 μmol/L.

A 69-year-old male patient with depression was treated with amfebutamone and mirtazapine for a long time. Because of poor control of symptoms, the treatment plan was adjusted to oral duloxetine (60 mg in the morning) and mirtazapine (15 mg at night). After 13 days of treatments, the patient developed high fever (41.0 ℃) with disturbance of consciousness, followed by muscle rigidity and dyspnea. His heart rate was 180 beats/min and blood oxygen saturation was 0.84. Laboratory tests showed serum creatinine (Scr) 609 μmol/L, creatine kinase (CK) 7 102 U/L, myoglobin (MYO) >3 000 μg/L, aspartate aminotransferase (AST) 88 U/L, and total bilirubin (TBil) 33.7 μmol/L. ECG monitoring showed rapid atrial fibrillation. The patient was diagnosed with malignant syndrome caused by duloxetine after excluding infection and other conditions. Duloxetine and mirtazapine were stopped immediately, and symptomatic and supportive treatments including endotracheal intubation, hemofiltration, improvement of water-electrolyte balance, and hepatoprotection were given. On the 6th day of drug withdrawal, the patient′s temperature was 38.2 ℃, the blood oxygen saturation was 0.96, muscle tone was improved, and muscle tremor disappeared. On the 16th day of drug withdrawal, the patient′s condition was obviously improved, the consciousness was clear, the temperature was normal, the call could be answered, and no limb convulsion and muscle tremor occurred. Laboratory tests showed Scr 116 μmol/L, CK 250 U/L, MYO 148 μg/L, AST 38 U/L, and TBil 21.4 μmol/L.

OBJECTIVE To study the components of ethyl acetate fraction in Qubai tablet ，and its pharmacodynamics on de melanocyte model ，and explore the material basis for anti-vitiligo effect of Qubai tablet. METHODS The ethyl acetate fraction of Qubai tablets was obtained by extraction ，and its components were analyzed by ultra performance liquid chromatography-mass spectrometry（UPLC-MS）. Model control group ，vehicle control group and 8-methoxypsoralen（8-MOP）administration groups （10，50，100，150，200 μmol/L），ethyl acetate fraction administration groups of Qubai tablet （10，50，100，150，200 μg/mL） were set up in the experiment. By establishing the de melanocyte model ，the effects of ethyl acetate fraction of Qubai tablet on de melanocyte were studied from four aspects ：cell number ，cell viability ，melanin formation and tyrosinase activity. RESULTS UPLC-MS component analysis preliminarily determined the structure of 64 compounds in the ethyl acetate fraction of Qubai tablet ， of which 14 compounds were detected in positive and negative ion mode ；psoralen compounds accounted for the largest proportion ， and the content of psoralen chromone chalcone was the highest in positive and negative ion mode. The results of pharmacodynamic study showed that the ethyl acetate fraction of Qubai tablet could increase the number of de melanocytes ，and significantly improve the cell proliferation rate ，the rate of promoting melanin formation and the rate of promoting tyrosinase activity in the process of melanin formation （P＜0.01）. CONCLUSIONS Psoralen compounds may be the material basis for the anti-vitiligo effect of ethyl acetate fraction of Qubai tablet ；good anti-vitiligo effect of ethyl acetate fraction of Qubai tablet may be related to the promotion of tyrosinase activity.