This study aims to investigate the mechanism of Qingrun Decoction in alleviating hepatic insulin resistance in type 2 diabetes mellitus(T2DM) rats through the reprogramming of amino acid metabolism. A T2DM rat model was established by inducing insulin resistance through a high-fat diet combined with intraperitoneal injection of streptozotocin. The model rats were randomly divided into five groups: model group, high-, medium-, and low-dose Qingrun Decoction groups, and metformin group. A normal control group was also established. The rats in the normal and model groups received 10 mL·kg~(-1) distilled water daily by gavage. The metformin group received 150 mg·kg~(-1) metformin suspension by gavage, and the Qingrun Decoction groups received 11.2, 5.6, and 2.8 g·kg~(-1) Qingrun Decoction by gavage for 8 weeks. Blood lipid levels were measured in different groups of rats. Pathological damage in rat liver tissue was assessed by hematoxylin-eosin(HE) staining and oil red O staining. Transcriptome sequencing and untargeted metabolomics were performed on rat liver and serum samples, integrated with bioinformatics analyses. Key metabolites(branched-chain amino acids, BCAAs), amino acid transporters, amino acid metabolites, critical enzymes for amino acid metabolism, resistin, adiponectin(ADPN), and mammalian target of rapamycin(mTOR) pathway-related molecules were quantified using quantitative real-time polymerase chain reaction(qRT-PCR), Western blot, and enzyme-linked immunosorbent assay(ELISA). The results showed that compared with the normal group, the model group had significantly increased serum levels of total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), and resistin and significantly decreased ADPN levels. Hepatocytes in the model group exhibited loose arrangement, significant lipid accumulation, fatty degeneration, and pronounced inflammatory cell infiltration. In liver tissue, the mRNA transcriptional levels of solute carrier family 7 member 2(Slc7a2), solute carrier family 38 member 2(Slc38a2), solute carrier family 38 member 4(Slc38a4), and arginase(ARG) were significantly downregulated, while the mRNA transcriptional levels of solute carrier family 1 member 4(Slc1a4), solute carrier family 16 member 1(Slc16a1), and methionine adenosyltransferase(MAT) were upregulated. Furthermore, the mRNA transcription and protein expression levels of branched-chain α-keto acid dehydrogenase E1α(BCKDHA) and DEP domain-containing mTOR-interacting protein(DEPTOR) were downregulated, while mRNA transcription and protein expression levels of mTOR, as well as ribosomal protein S6 kinase 1(S6K1), were upregulated. The levels of BCAAs and S-adenosyl-L-methionine(SAM) were elevated. The serum level of 6-hydroxymelatonin was significantly reduced, while imidazole-4-one-5-propionic acid and N-(5-phospho-D-ribosyl)anthranilic acid levels were significantly increased. Compared with the model group, Qingrun Decoction significantly reduced blood lipid and resistin levels while increasing ADPN levels. Hepatocytes had improved morphology with reduced inflammatory cells, and fatty degeneration and lipid deposition were alleviated. Differentially expressed genes and differential metabolites were mainly enriched in amino acid metabolic pathways. The expression levels of Slc7a2, Slc38a2, Slc38a4, and ARG in the liver tissue were significantly upregulated, while Slc1a4, Slc16a1, and MAT expression levels were significantly downregulated. BCKDHA and DEPTOR expression levels were upregulated, while mTOR and S6K1 expression levels were downregulated. Additionally, the levels of BCAAs and SAM were significantly decreased. The serum level of 6-hydroxymelatonin was increased, while those of imidazole-4-one-5-propionic acid and N-(5-phospho-D-ribosyl)anthranilic acid were decreased. In summary, Qingrun Decoction may improve amino acid metabolism reprogramming, inhibit mTOR pathway activation, alleviate insulin resistance in the liver, and mitigate pathological damage of liver tissue in T2DM rats by downregulating hepatic BCAAs and SAM and regulating key enzymes involved in amino acid metabolism, such as BCKDHA, ARG, and MAT, as well as amino acid metabolites and transporters.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Insulin Resistance ; Diabetes Mellitus, Type 2/genetics* ; Male ; Liver/drug effects* ; Amino Acids/metabolism* ; Rats, Sprague-Dawley ; Humans ; Metabolic Reprogramming

The medicinal materials of Bawei Chenxiang Pills(BCPs) were extracted via three methods: reflux extraction by water, reflux extraction by 70% ethanol, and extraction by pure water following reflux extraction by 70% ethanol, yielding three extracts of ST, CT, and CST. The efficacy of ST(760 mg·kg~(-1)), CT(620 mg·kg~(-1)), and CST(1 040 mg·kg~(-1)) were evaluated by acute myocardial ischemia(AMI) and p-chlorophenylalanine(PCPA)-induced insomnia in mice, respectively. Western blot was further utilized to investigate their hypnosis mechanisms. The main chemical components of different extracts were identified by the UPLC-Q-Exactive-MS technique. The results showed that CT and CST significantly increased the ejection fraction(EF) and fractional shortening(FS) of myocardial infarction mice, reduced left ventricular internal dimension at end-diastole(LVIDd) and left ventricular internal dimension at end-systole(LVIDs). In contrast, ST did not exhibit significant effects on these parameters. In the insomnia model, CT significantly reduced sleep latency and prolonged sleep duration, whereas ST only prolonged sleep duration without shortening sleep latency. CST showed no significant effects on either sleep latency or sleep duration. Additionally, both CT and ST upregulated glutamic acid decarboxylase 67(GAD67) protein expression in brain tissue. A total of 15 main chemical components were identified from CT, including 2-(2-phenylethyl) chromone and 6-methoxy-2-(2-phenylethyl) chromone. Six chemical components including chebulidic acid were identified from ST. The results suggested that chromones and terpenes were potential anti-myocardial ischemia drugs of BCPs, and tannin and phenolic acids were potential hypnosis drugs. This study enriches the pharmacological and chemical research of BCPs, providing a basis and reference for their secondary development, quality standard improvement, and clinical application.
Animals ; Drugs, Chinese Herbal/isolation & purification* ; Mice ; Male ; Sleep Initiation and Maintenance Disorders/physiopathology* ; Humans ; Myocardial Infarction/drug therapy* ; Myocardial Ischemia/drug therapy*

In this study, fluvoxamine maleate sustained-release pellet system tablets were prepared and were used to evaluate their release behaviors in vitro. Fluvoxamine maleate pellets were prepared using centrifugal-spherization method and coated by fluidized bed as bottom-spray. The multi-unit sustained-release pellets and appropriate excipients for prescription volumes were mixed uniformly and then compressed to tablets. Screening and determining the optimal formulation of drug loaded pellets through L8 (2⁴) Taguchi experiment. Using Minitab software to design a DOE experiment with 2⁴ partial factors, including material temperature, fan speed, atomization pressure, and spray rate to optimize the bottom spray coating process. Taking monostearate glycerol ester with a particle size of 24-40 mesh as the main diluent for tableting to relieve the delamination phenomenon between pellets and excipients during tablet pressing and reduce mechanical damage to the coating film. By examining the powder fluidity indexes such as angle of repose, bulk density, tapped density, and Hausner ratio of mixed particles, it was found that the flowability and compressibility are good and suitable for direct compression. Evaluate the basic properties of the sustained-release tablets, investigate the in vitro release behavior and study the release mechanism. The results of in vitro release test showed that the self-made sustained-release tablets could disintegrate into independent pellet units in phosphate buffer at pH 6.8 and release slowly within 24 h, which conformed to the first-order drug release model. The fluvoxamine maleate sustained-release pellet system tablets meet the requirements of preparation design and has a great commercial prospect.

Objective: To explore the treatment options for congenitally missing teeth in patients with ectodermal dysplasia and provide a clinical reference. Methods: A patient with ectodermal dysplasia with a concave midface, anterior protrusion of the chin, and underdevelopment of the lower third of the face presented with congenital loss of multiple maxillary teeth, malocclusion of the remaining teeth, congenital loss of mandibular dentition, small dental arches, and upper and lower alveolar bone hypoplasia. The patient was treated by means of a removable partial maxillary prosthesis, implants in the anterior region of the lower mandible designed with the assistance of digital guides, and bar-clamped implant-overlay prostheses. A literature review of the protocol for the treatment of this condition was also conducted. Results: In addition to good retention and stability after denture wear, an excellent occlusal relationship, improvement of the patient's facial appearance, including upper and lower lip fullness, more equal balancing of the lower and middle 1/3 of the face, and improved masticatory function were achieved. The results of the literature review showed that patients with ectodermal dysplasia who are congenitally edentulous usually have a complex intraoral situation that makes restoration difficult, and common restorative modalities for these patients include fixed bridges, removable partial dentures, complete dentures, overdentures, and implant prostheses, which need to be selected according to the actual intraoral situation of each patient. Currently, there is no consensus on the treatment of congenitally missing teeth in patients with ectodermal dysplasia, and some scholars have suggested that fixed restorations be recommended for patients with fewer missing teeth, while the option of removable or implant-covered denture restorations should be given to patients with more missing teeth, with removeable prostheses for underage patients that are replaced with permanent fixed prostheses when the jaws have stabilized. Conclusion In patients with ectodermal dysplasia with congenital tooth loss, all factors should be taken into account, and an individualized restorative plan should be developed.

Objective To investigate the application value of combining the Demirjian's method with ma-chine learning algorithms for dental age estimation in northern Chinese Han children and adolescents.Methods Oral panoramic images of 10 256 Han individuals aged 5 to 24 years in northern China were collected.The development of eight permanent teeth in the left mandibular was classified into different stages using the Demirjian's method.Various machine learning algorithms,including support vector re-gression(SVR),gradient boosting regression(GBR),linear regression(LR),random forest regression(RFR),and decision tree regression(DTR)were employed.Age estimation models were constructed based on total,female,and male samples respectively using these algorithms.The fitting performance of different machine learning algorithms in these three groups was evaluated.Results SVR demonstrated superior estimation efficiency among all machine learning models in both total and female samples,while GBR showed the best performance in male samples.The mean absolute error(MAE)of the op-timal age estimation model was 1.246 3,1.281 8 and 1.153 8 years in the total,female and male samples,respectively.The optimal age estimation model exhibited varying levels of accuracy across dif-ferent age ranges,which provided relatively accurate age estimations in individuals under 18 years old.Conclusion The machine learning model developed in this study exhibits good age estimation effi-ciency in northern Chinese Han children and adolescents.However,its performance is not ideal when applied to adult population.To improve the accuracy in age estimation,the other variables can be con-sidered.

Objective By population survey,to explore the epidemiological characteristics of gastric precancerous lesions in Lishui District of Nanjing and provide objective basis for the prevention and treatment of early gastric cancer.Methods From July 2021 to December 2022,21 977 patients who received endoscopy and/or 13C-UBT in Lishui District People's Hospital and 6 medical community units in Nanjing City were retrospectively analyzed for demography characteristics,detection rate of gastric precancerous lesions,and H.Pylori infection rate.Results(1)590 cases of gastric precancerous lesions were detected(detection rate 2.68%);(2)The total detection rate of precancerous lesions and three pathological types in males were all higher than those in females(all P<0.001);(3)The minimum age for the total detection rate of precancerous lesions in males and the mini-mum age for each pathological type were lower than in females(P<0.001,0.009,0.005,0.002);(4)The popu-lation total H.pylori infection rate was 23.10%,the H.pylori infection rate in patients with precancerous lesions was higher than that in non-precancerous lesions(P<0.001),both H.pylori infection rate of male and female in precancerous lesions were all higher than those of non-precancerous lesions of the same sex(all P<0.001),in addition,the H.pylori infection rate of male whether in precancerous or non-precancerous lesions was higher than that of female(all P<0.001);(5)The precancerous lesions detection rate in male,female,and the overall age range of 20～29 to 70～79 years is positively correlated with age growth(P<0.001),and rapidly decreases after the age of 79,the of H.pylori infection rate was also positively correlated with age growth(P<0.001),and the trend of age change(P<0.001)was parallel to the precancerous lesions detection rate.Conclusions The detec-tion rate of gastric precancerous lesions in this region is above the average level in China;the total H.pylori infec-tion rate is at a relatively low level in China;the H.pylori infection rate is parallel to the age trend of the detection rate of gastric precancerous lesions,and increases with age.

Aim To construct a diabetic atherosclerosis mouse model and study the pathological characteristics of diabetic atherosclerosis.Methods Fifty 8-week-old male LDLR-/-mice were fed with standard diet for 2 weeks and then changed to high-fat diet,they were randomly divided into two groups.The diabetic atherosclerosis group was given intraperitoneal injection of low dose streptozotocin(STZ)for 5 days continuouly to establish the model,and the atheroscle-rosis group was given citrate buffer injection at the same time.The body mass,blood glucose and blood lipids of the mice in the two groups were detected for many times.At the age of 23 weeks,the mice were euthanized after glucose tolerance test.HE staining and oil red O staining were used to detect the gross and aortic root atherosclerosis,immunohistochemical staining was used to detect CD4,α-smooth muscle actin(α-SMA),EGF-like module-containing mucin-like hormone re-ceptor-like 1(EMR1),monocyte chemotactic protein-1(MCP-1),NOD-like receptor protein 3(NLRP3),vascular cell adhesion molecule-1(VCAM-1),matrix metalloproteinase-2(MMP-2)and tissue inhibitor of metalloproteinase-1(TIMP-1),Western blot was used to detect α-SMA,CD4,tumor necrosis factor-α(TNF-α),NLPR3,intercellular adhesion molecule-1(ICAM-1),and type Ⅰ and Ⅲ collagen.Results Compared with the atherosclerosis group,the body mass decreased,the levels of total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDLC)increased,and the levels of high density lipoprotein cholesterol(HDLC)decreased(P＜0.05)in the diabetic atherosclerosis group.Compared with the atherosclerosis group,the distribution of atherosclerotic plaques was diffuse and the area was increased in the diabetic atherosclerosis group,and the contents of lipids,T cells,macrophages,smooth muscle cells,type Ⅰ and Ⅲ colla-gen were increased(P＜0.05);the protein levels of TNF-α,MCP-1,MMP-2,NLRP3,ICAM-1 and VCAM-1 in vascular tissues were increased,while the content of TIMP-1 were decreased and MMP2/TIMP-1 were increased(P＜0.05).Conclusions LDLR-mouse model of diabetic atherosclerosis can be successfully established by STZ induction combined with high-fat diet,which can reflect the plaque composition and inflammatory characteristics of diabetes promoting atheroscle-rosis.It can be used as a relatively ideal pathological model for the study of diabetic macroangiopathy.

A case of paraneoplastic cerebellar ataxia syndrome caused by immune checkpoint inhibitors(ICI)was treated with ofatumumab(OFA).The patient is a 57-year-old male.He used"Camrelizumab"immunotherapy for his previous history of small cell lung cancer.The main reason was"walking unsteadily for more than one year and shaking his head involuntarily for more than one month".After admission,the head MRI,chest CT,electroencephalogram,lumbar puncture and other related examinations were improved.The antibody spectrum of paraneoplastic neurological syndrome was anti-GAD65 antibody IgG(+),and the case was then diagnosed as the immune checkpoint inhibitor-related paraneoplastic neurological syndromes(PNS)of nervous system.After OFA treatment(20 mg/time),the symptoms were obviously improved.This paper analyzes the clinical features and diagnosis and treatment approaches of this case,in order to improve clinicians'understanding of the disease and provide reference for clinical diagnosis and treatment of similar cases.

Objective:To evaluate the risk factors for the formation of parastomal Hernias(PSH)using meta-analysis,and to provide a theoretical basis for the prevention and treatment of PSH.Methods:Case control or Cohort study of PSH risk factors were collected by searching PubMed,CNKI,Wanfang data and other databases.Extract relevant data and perform meta-analysis using RevMan 5.3.Results:The results included a total of 16 studies,with a total sample size of 2411 cases,including 670 in the PSH group and 1741 in the non PSH group.The results showed that advanced age,female gender,BMI≥25,hypertension,COPD/chronic cough,diabetes,and postoperative Hypoproteinemia could increase the risk of PSH(P＜0.05);Smoking,previous ab-dominal surgery history,preoperative radiotherapy/chemotherapy etc.,were not significantly asso-ciated with the occurrence of PSH(P＞0.05).Conclusion:The current evidence shows that ad-vanced age,female gender,BMI≥25,hypertension,COPD/chronic cough,diabetes,postoperative Hypoproteinemia are risk factors for PSH,and extraperitoneal stoma can reduce the occurrence of PSH.

Opsoclonus-myoclonus syndrome （OMS） is a rare neurological syndrome associated with tumors， which is more common in children than in adults. It is characterized by involuntary， arrhythmic， chaotic， multidirectional saccades， usually accompanied by limb and trunk myoclonic seizures and ataxia. Case reports are even rare on OMS complicated by autoimmune encephalitis with overlapping antibodies against the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor （AMPAR） and N-methyl-D-aspartate receptor （NMDAR）， and its clinical manifestations and treatment are poorly understood. We report a case of autoimmune encephalitis with OMS positive for both NMDAR and AMPAR antibodies， and also review relevant literature to help improve the understanding of the condition.