Hepatic fibrosis is a pathological process of chronic liver injury. Without timely intervention and treatment， liver fibrosis may eventually lead to liver cirrhosis and cancer. Janus kinase （JAK）/signal transducer and activator of transcription （STAT） signaling pathway is closely associated with the occurrence and development of liver fibrosis. Based on this， this paper summarized and analyzed the mechanism and effects of active ingredients and compounds of traditional Chinese medicine improving liver fibrosis based on JAK/STAT signaling pathway. It is found that the active ingredients and compounds of traditional Chinese medicine that promote blood circulation and remove blood stasis （ingredients such as ethanol extract of Euonymus alatus and paclitaxel， as well as compounds such as Ershiwuwei songshi pill and Ganfukang）， clear away heat and toxic material （ingredients such as betulinic acid， total flavonoids from Persicaria perfoliata， as well as compounds such as Pianzaihuang and Kehuang capsules）， and sooth the liver and promote qi circulation （ingredients such as fraxetin and cucurbitacin B， as well as compounds such as Chaihu shugan powder and Xiaochaihu decoction） can all relieve liver fibrosis by inhibiting the activity of the JAK/STAT signaling pathway， reducing inflammatory reactions， and inhibiting the proliferation of hepatic stellate cells.

ObjectiveTo identify the pharmacodynamic material basis of Ruyi Zhenbaowan in relieving neuropathic pain by integrating the calculation of biological network proximity and pharmacokinetic characterization. MethodThe interaction network of "drug candidate target-related gene of disease" was constructed by Cytoscape 3.8.2， and the average shortest path value of each drug putative target acting on neuropathic pain-related genes in this network was calculated by Pesca 3.8.0 tool so as to evaluate the network proximity between them， and screen prescription candidate targets with strong intervention efficiency and their corresponding potential effect components. After that， plasma and cerebrospinal fluid samples were collected from rats after administration of Ruyi Zhenbaowan at set time points， and the contents of potential effect components in samples was quantified by ultra performance liquid chromatography-quadrupole-ion trap mass spectrometry（UPLC-Q-TRAP/MS）， and drug concentration-time curves were plotted， then the pharmacokinetic parameters were calculated by DAS 2.1.1. ResultBy evaluating the network proximity between candidate targets and neuropathic pain-related genes in the interaction network， a total of 40 putative targets of Ruyi Zhenbaowan with strong intervention effects on neuropathic pain-related genes， such as estrogen receptor 1（ESR1）， cyclic adenosine monophosphate（cAMP）-dependent protein kinase catalytic subunit alpha（PRKACA） and protein kinase B1 （Akt1）， and 10 corresponding potential effect components， such as glycyrrhizic acid and betulinic acid， were obtained. Pharmacokinetic characterization showed that among the 10 potential effect components， gallic acid， apigenin-7-O-glucuronide， glycyrrhizic acid and apigenin were well absorbed and metabolized in plasma and cerebrospinal fluid， with long onset time and good bioavailability. ConclusionFrom the perspective of efficacy-target-constituent-pharmacokinetic， this study analyzes the main effective materials of Ruyi Zhenbaowan， such as glycyrrhizic acid， gallic acid， apigenin-7-O-glucuronide and apigenin， which have a high exposure in plasma or cerebrospinal fluid and have a strong intervention effect on neuropathic pain. The related results provide reliable experimental evidences for clarifying the material basis and developing quality standards of Ruyi Zhenbaowan.

The regulation of the cell cycle is essential for maintaining normal cellular function,especially in the development of diseases such as lung cancer.The cell cycle consists of four major phases(G1,S,G2 and M phases),which are characterized by a series of precise molecular events to ensure proper cell proliferation and division.In lung cancer cells,cell cycle dysregulation can lead to disordered proliferation and increased invasiveness of cancer cells.G2 and S-phase expressed 1(GTSE1)is a regulatory protein found in the cytoplasm of the cell,which plays a key role in the cell cycle distribution of a wide range of cancer cells and is involved in life processes such as cell proliferation and apoptosis.GTSE1 affects cell cycle progres-sion by interacting with cyclin-dependent kinase inhibitor 1A(p21)and maintaining the stability of p21,which in turn inhibits the activity of cyclin-dependent kinase 1/2(CDK1/2).In addition,GTSE1 is also involved in the regulation of tumor protein 53(p53)signaling pathway.With the assistance of mouse double minute 2 homolog(MDM2),GTSE1 is able to transport p53 from the nucleus to the cytoplasm and promote its ubiquitination and degradation,thus affecting cell cycle and cell death-related signaling pathways.This paper reviews the expression of GTSE1 in lung cancer cells and its effects on lung cancer,as well as its potential mechanisms involved in cell cycle regulation.

Objective To build a whole-course nursing quality evaluation system for liver transplanta-tion in children,so as to provide a basis for nursing quality evaluation and management.Methods With Donabedian's"structure-process-outcome"model as the theoretical framework,we employed literature analysis,Delphi method,and hierarchical analysis to determine the contents and weights of indexes in the whole-course nursing quality evaluation system for liver transplantation in children.Results The three rounds of survey based on questionnaires showed the questionnaire recovery rate of 100% ,the expert authority coefficients of 0.95,0.96,and 0.98,and the Kendall's coefficients of concordance of 0.165,0.209,and 0.220,respectively(all P<0.001).The established nursing quality evaluation system included 3 first-level indexes,15 second-level inde-xes,and 67 third-level indexes.Conclusion The whole-course nursing quality evaluation system for liver trans-plantation in children that was built in this study can provide a basis for the evaluation of the nursing quality.

Objective To explore heterogeneous subtypes of psychological and behavioral adaptation characteristics of pediatric recipients after liver transplantation and the characteristics differences of different types of children after liver transplantation. Methods Seven hundred and forty-one children who underwent living-related liver transplantation were enrolled. The self-designed general information questionnaire, Chinese version of 5-Item World Health Organization Well-Being Index (WHO-5) and the parent-report version of the Strengths and Difficulties Questionnaire (SDQ) were filled out by their guardians. The scores of five dimensions of SDQ were used as the manifest variables of the model. The classification model of psychological and behavioral adaptation characteristics of pediatric recipients after liver transplantation was constructed by latent profile analysis. The latent categories of psychological and behavioral adaptation characteristics of pediatric recipients after liver transplantation were analyzed. The influencing factors of latent categories were analyzed by univariate analysis and logistic regression model. Results There were three latent categories of psychological and behavioral adaptation characteristics of pediatric recipients after liver transplantation, including peer communication problem group (n=302), psychological and behavioral adaptation group (n=145) and psychological and behavioral adjustment difficulty group (n=294). The first two groups were merged into the psychological and behavioral health group (n=447), which had significant differences in the five dimensions and the total score of difficulties of SDQ compared with the psychological and behavioral adjustment difficulty group (n=294) (all P<0.001). Logistic regression analysis showed that age≤5 years old, primary disease of non-cholestatic liver disease, stem family were the risk factors for psychological and behavioral adjustment difficulties in pediatric recipients after liver transplantation. Female gender, high education levels of parents and high WHO-5 score of guardians were the protective factors for psychological and behavioral adjustment difficulties in pediatric recipients after liver transplantation (all P<0.05). Conclusions The psychological and behavioral adaptation characteristics of pediatric recipients after liver transplantation are heterogeneous. Medical staff should pay extensive attention to different characteristics of pediatric recipients after liver transplantation with different psychological and behavioral adaptation categories and adopt targeted screening and intervention strategies, aiming to improve psychological and behavioral adaptation outcomes of pediatric recipients after liver transplantation.

OBJECTIVES: To investigate the effects and molecular mechanisms of asiatic acid on β-cell function in type 2 diabetes mellitus (T2DM). METHODS: The T2DM model was established by high fat diet and streptozotocin injection in ICR mice, and the effects of asiatic acid on glucose regulation were investigated in model mice. The islets were isolated from palmitic acid-treated diabetic mice. ELISA was used to detect the glucose-stimulated insulin secretion, tumor necrosis factor (TNF)-α and interleukin (IL)-6. ATP assay was applied to measure ATP production, and Western blotting was used to detect protein expression of mature β cell marker urocortin (Ucn) 3 and mitofusin (Mfn) 2. The regulatory effects of asiatic acid on glucose-stimulated insulin secretion (GSIS) and Ucn3 expression were also investigated after siRNA interference with Mfn2 or treatment with TNF-α. RESULTS: Asiatic acid with the dose of 25 mg·kg^－1·d^－1 had the best glycemic control in T2DM mice and improved the homeostasis model assessment β index. Asiatic acid increased the expression of Mfn2 and Ucn3 protein and improved the GSIS function of diabetic β cells in vitro and in vivo (both P<0.05). Moreover, it improved the ATP production of islets of T2DM mice in vitro (P<0.05). Interfering Mfn2 with siRNA blocked the up-regulation of Ucn3 and GSIS induced by asiatic acid. Asiatic acid inhibited islet TNF-α content and increased Mfn2 and Ucn3 protein expression inhibited by TNF-α. CONCLUSIONS Asiatic acid improves β cell insulin secretion function in T2DM mice by maintaining the β cell maturity, which may be related to the TNF-α/Mfn2 pathway.
Mice ; Animals ; Insulin Secretion ; Diabetes Mellitus, Type 2/drug therapy* ; Islets of Langerhans/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Insulin/therapeutic use* ; Diabetes Mellitus, Experimental ; Mice, Inbred ICR ; Glucose/therapeutic use* ; Interleukin-6/metabolism* ; RNA, Small Interfering/pharmacology* ; Adenosine Triphosphate ; GTP Phosphohydrolases/therapeutic use*

OBJECTIVE: To explore the clinical and genetic characteristics of two children with Williams-Beuren syndrome (WBS). METHODS: Two children who had presented at the Department of Pediatrics, General Hospital of Ningxia Medical University respectively on January 26 and March 18, 2021 were selected as the study subjects. Clinical data and results of genetic testing of the two patients were analyzed. RESULTS: Both children had featured developmental delay, characteristic facies and cardiovascular malformation. Child 1 also had subclinical hypothyroidism, whilst child 2 had occurrence of epilepsy. Genetic testing revealed that child 1 has harbored a 1.54 Mb deletion in the 7q11.23 region, whilst child 2 has a 1.53 Mb deletion in the same region, in addition with a c.158G>A variant of the ATP1A1 gene and a c.12181A>G variant of the KMT2C gene. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.158G>A and c.12181A>G variants were rated as variants of unknown significance (PM1+PM2_Supporting+PP2+PP3；PM2_Supporting). CONCLUSION Both children had characteristic features of WBS, for which deletions of the 7q11.23 region may be accountable. For children manifesting developmental delay, facial dysmorphism and cardiovascular malformations, the diagnosis of WBS should be suspected, and genetic testing should be recommended to confirm the diagnosis.
Child ; Humans ; Williams Syndrome/diagnosis* ; Genetic Testing ; Facies ; Epilepsy/genetics* ; Chromosomes, Human, Pair 7/genetics* ; Chromosome Deletion

OBJECTIVE To establish and optimize tablets adding mechanism of automatic tablet dispensing machine in the inpatient pharmacy, realize tablets checking and fine management for tablets inventory and expiration date in process of tablets adding, reduce incidence of errors, improve work efficiency, and ensure the safety of tablets use for patients. METHODS Intelligent software combined with barcode scanning technology was used to carry out intelligent intervention on the error-prone link in the process of tablets adding of automatic drug dispensing machine. The error ratio of tablets adding(%), average of daily tablets adding time(min), error ratio of tablets quantity in monthly inventory check(%) were compared before and after intelligent intervention. RESULTS Compared with before optimization, the error ratio of tablets adding decreased from 0.11 % to 0%, average of daily tablets adding time decreased from (96.50±21.84)min to (64.23±19.59)min(P<0.01), which saved 32.27 min on average, and error ratio of tablets quantity in monthly inventory check decreased from (9.42±1.13)% to (3.42±0.88)%(P<0.01) after optimizing the dosing process of the automatic drug dispensing machine. CONCLUSION The optimized process of tablets adding of automatic drug dispensing machine is simple and rapid to operate, which has high accuracy. The tablets inventory and expiration date can be tracked and managed in real time, which ensures the safety of tablets use for patients, promotes development of digital pharmacy management system, and improves quality of pharmaceutical care.

SIRT6 belongs to the conserved NAD⁺-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD⁺. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC₅₀ of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.

Objective:To systematically evaluate the therapeutic efficacy of enteral nutrition(EN)versus parenteral nutrition(PN)in patients after liver transplantation(LT).Methods:The databases of Cochrane Library, MEDLINE, EmBase, EBSCO, Sinomed, CBM, CNKI and Wanfang Data were systematically searched up to August 2021 for collecting randomized controlled trials(RCT)of comparing EN and PN in patients after LT.In strict accordance with the inclusion and exclusion criteria, two independent researchers carried out literature screening, data extracting and literature methodological quality evaluations.Then RevMan5.3 software was utilized for quantitative synthesis and statistical processing.Results:A total of 13 RCTs involving 571 grade B patients were included.Meta-analysis indicated that, as compared with PN, serum albumin of EN spiked[WMD=2.5(1.33, 3.68), WMD>0, P<0.000 1], prealbumin rose[WMD=59.78(32.22, 87.35), WMD>0, P<0.000 1], total bilirubin dropped[WMD=-27.81(-41.88, -13.74), WMD<0, P=0.000 1]and infection incidence was significantly lower[ OR=0.25(0.16, 0.39), OR<1, P<0.000 01]. Conclusions:After LT, as compared with PN, EN can boost the nutritional level, promote the recovery of liver function and lower the incidence of postoperative infections.It offers some clinical values.