Ulcerative colitis （UC）， which is characterized by a complex and multifactorial etiology， remains one of the challenging disorders in the international field of digestive system diseases. In recent years， rectal administration preparations have made rapid progress in UC therapeutic applications. This study systematically reviews the dosage forms， mechanisms of action， and clinical applications of rectally-administered preparations for the treatment of UC. It is found that suppositories are the most commonly used dosage forms for rectal administration. The newer suppositories have the advantages of high bioavailability and good stability. Enemas can retain the drug in the intestine as much as possible to achieve the effects of diluting intestinal toxins， cleansing the bowel， and reducing inflammation. Gels can achieve a drug-sustained-release effect and effectively improve intestinal mucosal damage. The mechanism of action of this type of preparation is mainly to inhibit inflammatory cell infiltration， regulate intestinal microbial homeostasis， and increase the expression of tight-junction proteins， so as to play anti-inflammatory， regulate the intestinal bacterial flora， repair the intestinal mucosa， and other efficacies. The diversity of rectal administration forms provides a wide range of choices for the clinical treatment of UC， such as Mesalazine suppositories， Lianshao enemas， and temperature- sensitive gels loaded with drugs for UC.

OBJECTIVE To investigate the antidepressant mechanism of Shugan hewei tang （SGHWT） based on the metabolomics of prefrontal cortex （PFC）-nucleus accumbens （NAc）-ventral tegmental area （VTA） neural circuit. METHODS Male SD rats were randomly divided into blank group， model group， SGHWT low-， medium- and high-dose groups [3.67， 7.34， 14.68 g/（kg·d）， by raw material]， and fluoxetine group [1.58 mg/（kg·d）， positive control]， with 12 rats in each group. Except for the blank group， the depression model was established by chronic unpredictable mild stress combined with individual cage housing in the remaining groups， and the corresponding drug solution or normal saline was administered via gavage during modeling， once a day， for 6 consecutive weeks. After the last administration， the body weight， sucrose preference rate， total moving distance， frequency into the center and immobility time of rats in each group were detected. Samples of PFC， NAc and VTA areas of rats in the blank group， model group， SGHWT medium-dose group and fluoxetine positive control groups were collected，and their histomorphological features were observed， and non-targeted metabolomics analysis （except for fluoxetine group）were performed and validated. RESULTS Compared with model group， the cytolysis， structural damage and other pathological damages in three brain regions of rats were significantly alleviated in each drug group， while their body weight， sucrose preference rate， total moving distance and frequency into the center were all significantly higher or longer （P＜0.05）， and immobility time was significantly shorter （P＜0.05）. The results of non-targeted metabolomics showed that a total of 78 endogenous differential metabolites were identified， with 40， 35 and 24 in the PFC， NAc and VTA regions respectively， mainly involved in amino acid， lipid and sphingolipid metabolism. The results of metabolic pathway enrichment analysis showed that SGHWT affected the neural circuits of depressed rats by regulating sphingolipid metabolism， alanine， aspartic acid and glutamic acid metabolism， saturated fatty acid biosynthesis， among which alanine， aspartic acid and glutamic acid metabolism was predominantly involved. Validation experiments showed that SGHWT significantly increased the phosphorylation levels of protein kinase B （Akt） and mammalian target of rapamycin （mTOR）， and decreased the protein expression of N-methyl-D-aspartic acid receptor 1 （NMDAR1） in the NAc region of rats. CONCLUSIONS SGHWT significantly improves the depression-like behavior and attenuates pathological damage of PFC-NAc-VTA neural circuit of model rats， the mechanism of which is associated with inhibiting NMDAR1 expression and activating the Akt/mTOR signaling pathway.

Objective:To investigate the impact of various mutations in the gD protein of PRV-2022 strain on its binding to the Nectin-1 receptor.Methods:We employed PCR, RT-qPCR and gene sequencing techniques for identification of the PRV-2022 strain. Furthermore, bioinformatics method were utilized to analyze the genetic evolution of the gD gene in PRV-2022 strain. Recombinant expression plasmid containing mutations at amino acids positions 69 and 82 within the extracellular domain of gD protein from PRV-2022 strain was constructed and expressed in vitro. The binding ability between different mutant forms of recombinant gD protein and Nectin-1 receptor was compared using His-pull down and biolayer interference techniques. Results:The gD gene of the PRV-2022 strain was obtained, and genetic evolution analysis revealed that the PRV-2022 strain belonged to the same branch as strains isolated prior to 2011, with a close genetic distance. The expression plasmids for gD extracellular domain containing A69V and S82N amino acid mutations were successfully constructed, enabling the expression and purification of recombinant PRV gD extracellular domain protein. Interaction studies demonstrated that gD-69, gD-82, gD-2022, and gD-Bartha proteins interacted with human Nectin-1. Notably, compared to the classical PRV vaccine strain Bartha, double mutation of amino acids 69 and 82 in the gD protein exhibited the highest affinity to human Nectin-1 receptor, whereas individual mutations at either site decreased this affinity.Conclusions:Introduction of A69V and S82N mutations in the gD protein significantly affected its binding ability to human Nectin-1 receptor. Simultaneous occurrence of A69V and S82N mutations resulted in the highest affinity towards human Nectin-1 receptor.

Gait deficits and balance disturbances are prevalent clinical features in Parkinson′s disease (PD). There is an increasing body of evidence pointing towards the degeneration of central cholinergic neurons as a crucial factor leading to these disturbances in PD. This paper presents a comprehensive review of the relevant research on the involvement of the central cholinergic system in the mechanisms underlying gait deficits and balance disturbance in PD. The aim is to provide new perspectives and insights for the treatment of gait deficits and balance disturbances in PD.

Objective To investigate correlation between preoperative thyroid-related serological indicators and benign and malignant thyroid nodules.Methods Clinical data of 401 patients with thyroid nodules underwent surgical treatment in Guizhou Provincial People's Hospital from January to December 2020 were retrospectively analyzed.According to the results of postoperative pathological examination,they were divided into benign group(129 cases)and malignant group(272 cases).Clinical data and preoperative thyroid-related serological indicators were compared between two groups.Results Age and preoperative serum thyroglobulin(Tg)level in malignant group were significantly lower than those in benign group,and proportion of males was significantly higher than that in benign group(P<0.05).The receiver operating characteristic(ROC)curve showed that preoperative serum Tg value of 35.41ng/ml was cut-off point for the risk factor of distinguishing benign and malignant thyroid nodules.Subgroup analysis showed that serum Tg level in malignant group of patients≤40 years old was significantly lower than that in benign group,thyroid stimulating hormone(TSH)×thyroglobulin antibodies(TGAb),TGAb/thyroid peroxidase antibodies(TPOAb)values in malignant group of patients≤40 years old were significantly higher than those in benign group(P<0.05).Among patients over 40 years old,serum Tg level in malignant group was significantly lower than that in benign group(P<0.05).Serum Tg and TPOAb levels in malignant group of male patients were significantly lower than those in benign group(P<0.05).Serum Tg level in malignant group of female patients was significantly lower than that in benign group(P<0.05).ROC curve showed that preoperative serum TSH×TGAb value of 15.87,TGAb/TPOAb value of 1.06 were risk factor cut-off points for distinguishing benign and malignant thyroid nodules in young adults,and preoperative serum TPOAb value of 9.40IU/ml was risk factor cut-off point for distinguishing benign and malignant thyroid nodules in males.Conclusion Male,young age and decreased Tg value are independent risk factors for thyroid cancer.Serum Tg value has certain diagnostic value for differentiating benign and malignant thyroid nodules.Decrease of preoperative serum TPOAb level is a risk factor for male thyroid cancer.Preoperative elevated TSH×TGAb and TGAb/TPOAb are independent risk factors for development of thyroid cancer in young adults.

Objective To explore the causal relationship between educational attainment and chronic kidney disease(including chronic glomerulonephritis,nephrotic syndrome,diabetic nephropathy,chronic renal failure,and other clinical diagnoses of chronic kidney disease),and provide targeted guidance support for different populations in the prevention and treatment of chronic kidney disease.Methods The study used four regression models,random-effects inverse-variance weighted(IVW),MR-Egger regression,weighted median method,and weighted model,to perform Mendelian randomization analysis of the causal relationship between educational attainment and chronic kidney disease.Results All four regression models showed no statistical significance for the three models of chronic kidney disease,chronic glomerulonephritis,and nephrotic syndrome with P>0.05.The diabetic nephropathy model was seen to be statistically significant as the results of the three methods except IVW method(OR=0.520,P<0.05)were not significant,while the scatter plot showed that the direction of the total effect value was the same for all methods.Chronic renal failure model IVW method(OR=0.487,P<0.001),weighted median method(OR=0.503,P<0.001)showed a significant effect and the scatter plot showed that the direction of the total effect value was the same in all methods,which was statistically significant.Conclusion Using two-sample Mendelian randomization method to exclude confounding factors and reverse causal associations,unbiased estimation results were obtained to get that the education level is not related to the overall chronic kidney disease incidence,but has reverse causality for diabetic nephropathy and chronic renal failure among them.

Objective This paper discusses the role of pre-audit management in the quality management of the first page of medical records,and studies the feasible measures to improve the quality of the first page of medical records and assist DRG payment.Methods This paper analyzes the new measures to improve the quality of the first page of medical records in an A-Class tertiary hospital in Suzhou,and analyzes the quality of 2 644 medical records discharged during 2023.Results In order to effectively respond to the DRG payment reform,an A-Class tertiary hospital in Suzhou innovatively established a pre-audit man-agement mechanism,and improved the quality of the first page of medical records to a certain extent,but there are still problems such as non-standard filling,inconsistent medical record data and untimely completion of medical record documents.Conclusion The hospital should build consensus,attach importance to the quality management;standardize the filling,ensure the accuracy and completeness;communicate and collaborate,improve the soft and hard power of the hospital;improve the assessment,and optimize the incentive mechanism for the management to improve the quality of the first page of medical records and assist DRG payment.

Myopia is the most common refractive error,which seriously damages the visual health of adolescents.The current research on the pathogenesis of myopia mainly focuses on genetics,visual environment,biochemical mechanism and so on.Neurotransmitters,as important mediators of refractive development,form complex regulatory networks and participate in molecular synthesis and metabolic activities related to myopia.Intraocular neurotransmitters affect scleral re-modeling by regulating the growth of retinal pigment epithelium and the thickness of choroid and play an important role in the occurrence and development of myopia.This paper reviews the role of cholines,amines,amino acids,peptides and other neurotransmitters in the pathogenesis of myopia,providing new ideas for the prevention and control of myopia.

Hypoxia is the common characteristic of almost all solid tumors,which prevents therapeutic drugs from reaching the tumors.Therefore,the development of new targeted agents for the accurate diagnosis of hypoxia tumors is widely concerned.As carbonic anhydrase Ⅸ(CA Ⅸ)is abundantly distributed on the hypoxia tumor cells,it is considered as a potential tumor biomarker.4-(2-Aminoethyl)benzenesulfo-namide(ABS)as a CA Ⅸ inhibitor has inherent inhibitory activity and good targeting effect.In this study,Ag2S quantum dots(QDs)were used as the carrier to prepare a novel diagnostic and therapeutic bio-probe(Ag2S@polyethylene glycol(PEG)-ABS)through ligand exchange and amide condensation reaction.Ag2S@PEG-ABS can selectively target tumors by surface-modified ABS and achieve accurate tumor im-aging by the near infrared-Ⅱ(NIR-Ⅱ)fluorescence characteristics of Ag2S QDs.PEG modification of Ag2S QDs greatly improves its water solubility and stability,and therefore achieves high photothermal sta-bility and high photothermal conversion efficiency(PCE)of 45.17％.Under laser irradiation,Ag2S@PEG-ABS has powerful photothermal and inherent antitumor combinations on colon cancer cells(CT-26)in vitro.It also has been proved that Ag2S@PEG-ABS can realize the effective treatment of hypoxia tumors in vivo and show good biocompatibility.Therefore,it is a new efficient integrated platform for the diagnosis and treatment of hypoxia tumors.

Hepatitis B virus (HBV) DNA integration occurs during the reverse transcription process of HBV replication, which develops in the early stages of HBV infection and accompanies the entire disease course. The integration of HBV DNA is detrimental to the attainment of clinical cure goals and also raises the risk of developing liver cancer. Theoretically, nucleos(t)ide analogs can reduce the synthesis of new double-stranded linear DNA, but there is no clearance function for hepatocytes that have already integrated HBV. Therefore, patients with serum HBV DNA-negative conversions still have the risk of developing liver cancer. As an immunomodulatory drug, interferon can not only inhibit viral replication but also inhibit or even eliminate existing clonally amplified hepatocytes carrying integrated HBV DNA fragments. However, there are currently few studies on the effects of nucleos(t)ide analogues and interferon therapy on HBV DNA integration. Thus, large-scale clinical studies are urgently needed for further clarification.