OBJECTIVE To evaluate the therapeutic effects and safety of everolimus combined with letrozole and conventional chemotherapy for metastatic or recurrent endometrial carcinoma （EC）. METHODS The clinical and follow-up data of 156 patients with metastatic or recurrent EC admitted to Nanyang Central Hospital from January 2020 to January 2024 were analyzed retrospectively. They were divided into a control group （77 cases） and an observation group （79 cases） according to different therapeutic regimens. The control group received paclitaxel+carboplatin/cisplatin regimen， and concurrently took Letrozole tablets at a dose of 2.5 mg orally once daily； the observation group took Everolimus tablets 10 mg orally， once a day， in addition to the treatment regimen given to the control group. Each treatment cycle lasted 21 days， and both groups of patients underwent continuous treatment for 6 to 8 cycles. The short-term efficacy indicators （objective response rate and disease control rate）， the levels of serum tumor markers [carbohydrate antigen 125， human epididymis protein 4， vascular endothelial growth factor and matrix metalloproteinase-9] and medium- to long-term efficacy indicators [progression-free survival （PFS） and overall survival （OS）] were compared between the two groups. Additionally， the occurrence of toxic and side effects in both groups of patients was recorded. RESULTS The objective response rate （53.16%）， disease control rate （89.87%）， median PFS （6.47 months） and median OS （10.79 months） of the observation group were significantly higher or longer than those （22.08%， 68.83%， 4.63 months， 8.84 months） of the control group （P＜0.05）. Compared with before treatment， the levels of serum tumor markers in both groups decreased significantly after 6 cycles of treatment； the above indexes of the observation group were significantly lower than those of the control group （P＜0.05）. The proportion of patients with stomatitis in the observation group was significantly higher than that of the control group （P＜0.05）， and there was no statistically significant difference in the proportions of patients experiencing other toxic and side effects， such as leukopenia， between the two groups （P＞0.05）. CONCLUSIONS The everolimus combined with letrozole and conventional chemotherapy can effectively improve the short-term efficacy and prolong the survival period in patients with metastatic or recurrent EC， but attention should be paid to the occurrence of toxic and side effects， especially stomatitis.

BACKGROUND:Traditional treatments for corneal alkali burns are limited,especially in controlling inflammation,preventing neovascularization,and inhibiting corneal scarring.Natural,synthetic,or composite materials provide a wide range of treatment options.However,the mechanism by which biomaterials promote corneal alkali burn repair has not yet been systematically understood. OBJECTIVE:To summarize the current research on biomaterials in promoting corneal alkali burn repair in and outside China,and review the mechanism and application of biomaterials in repairing corneal alkali burn. METHODS:The first author searched"cornea,alkali burn,amniotic membrane,hyaluronic acid,collagen,chitosan,polymer materials"as Chinese keywords and"amniotic membrane,hyaluronic acid,collagen,chitosan,polymer,cornea,alkali burn"as English keywords in PubMed,Web of Science,CNKI,and WanFang databases.According to inclusion and exclusion criteria,76 eligible articles were finally included for review. RESULTS AND CONCLUSION:(1)In the field of corneal alkali burn repair,biomaterials such as amniotic membrane,hyaluronic acid,collagen,chitosan,and degradable polymer materials have been widely studied and applied.Each of these biomaterials has its own characteristics,advantages,and disadvantages,and stands out in different aspects.(2)First and foremost,amniotic membranes are considered one of the most promising biomaterials due to their abundance of bioactive factors.They are biocompatible and can regulate the corneal inflammatory response.However,there are issues with donor shortages and susceptibility to infectious diseases.(3)Hyaluronic acid has good moisturizing properties and biocompatibility,and is able to improve the survival rate of corneal cells and increase corneal transparency.(4)The good biocompatibility and scaffold structure of collagen enable the promotion of corneal cell adhesion and proliferation,as well as the reconstruction of corneal tissue structure.(5)Chitosan is recognized for its good biocompatibility and degradability,making it suitable as a carrier for drug delivery and cell transplantation.(6)Degradable polymer materials have good controllability over degradation and can provide a good support and delivery platform for the repair of corneal alkali burns,but further research is needed on their stability and biocompatibility.(7)Overall,there is currently no single biomaterial that can completely address the repair problem of corneal alkali burns,and each biomaterial has its own specific application scenarios and limitations.(8)Future research directions should focus on further improving the properties and structure of biomaterials,exploring more effective combination applications,and deeply understanding the interaction mechanism between biomaterials and corneal tissue,in order to enhance the therapeutic effect of corneal alkali burns and the quality of life of patients.

ObjectiveTo investigate the clinical features and outcomes of recompensation in patients with autoimmune hepatitis （AIH）-related decompensated cirrhosis， to identify independent predictive factors， and to construct a nomogram prediction model for the probability of recompensation. MethodsA retrospective cohort study was conducted among the adult patients with AIH-related decompensated cirrhosis who were admitted to The Fifth Medical Center of PLA General Hospital from January 2015 to August 2023 （n=211）. The primary endpoint was achievement of recompensation， and the secondary endpoint was liver-related death or liver transplantation. According to the outcome of the patients at the end of the follow-up， the patients were divided into the recompensation group （n=16） and the persistent decompensation group（n=150）.The independent-samples t test was used for comparison of normally distributed continuous data with homogeneity of variance， and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data with heterogeneity of variance； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups； the Kaplan-Meier method was used for survival analysis； the Cox proportional-hazards regression model was used to identify independent predictive factors， and a nomogram model was constructed and validated. ResultsA total of 211 patients were enrolled， with a median age of 55.0 years and a median follow-up time of 44.0 months， and female patients accounted for 87.2%. Among the 211 patients， 61 （with a cumulative proportion of 35.5%） achieved recompensation. Compared with the persistent decompensation group， the recompensation group had significantly higher white blood cell count， platelet count （PLT）， total bilirubin （TBil）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total bile acid， prothrombin time， international normalized ratio （INR）， SMA positive rate， Model for End-Stage Liver Disease （MELD） score， Child-Pugh score， and rate of use of glucocorticoids （all P0.05）， as well as significantly lower age at baseline， number of complications， and death/liver transplantation rate （all P0.05）. At 3 and 12 months after treatment， the recompensation group had continuous improvements in AST， TBil， INR， IgG， MELD score， and Child-Pugh score， which were significantly lower than the values in the persistent decompensation group （all P0.05）， alongside with continuous increases in PLT and albumin， which were significantly higher than the values in the persistent decompensation group （P0.05）. The multivariate Cox regression analysis showed that baseline ALT （hazard ratio ［HR］=1.067， 95% confidence interval ［CI］： 1.010 — 1.127， P=0.021）， IgG （HR=0.463，95%CI：0.258 — 0.833， P=0.010）， SMA positivity （HR=3.122，95%CI：1.768 — 5.515， P0.001）， and glucocorticoid therapy （HR=20.651，95%CI：8.744 — 48.770， P0.001） were independent predictive factors for recompensation， and the nomogram model based on these predictive factors showed excellent predictive performance （C-index=0.87，95%CI：0.84 — 0.90）. ConclusionAchieving recompensation significantly improves clinical outcomes in patients with AIH-related decompensated cirrhosis. Baseline SMA positivity， a high level of ALT， a low level of IgG， and corticosteroid therapy are independent predictive factors for recompensation. The predictive model constructed based on these factors can provide a basis for decision-making in individualized clinical management.

The paper introduces Professor SUN Shentian's experience in clinical practice of Ningshen (tranquilizing the mind) point. This point is an empirical point discovered by Professor SUN on the basis of meridian differentiation, nerve function and anatomic location, and in association with the years of clinical practice. The point is located in the prefrontal area, jointed with the distribution of the governor vessel, and responded to the body surface projection area of the frontal pole. It works on regulating the mind, regaining consciousness, improving cognition, alleviating depression, mutually treating physical and mental disorders, as well as unblocking collaterals, regulating the tendons and relieving spasm. This point is widely used in treatment of mental disorders, stroke and extrapyramidal diseases and obtains the reliable therapeutic effect in clinical practice.
Humans ; Acupuncture Points ; Acupuncture Therapy/history* ; China ; Meridians ; History, 20th Century

OBJECTIVES: To investigate the clinical significance of SLC1A5 overexpression in pan-cancer and its mechanism for promoting hepatocellular carcinoma (HCC) progression. METHODS: We analyzed the correlation of SLC1A5 expression with clinical stage, lymph node metastasis and prognosis in pan-cancer using TCGA and ICGC datasets and explored its association with immune cell infiltration using EPIC, CIBERSORT, and TIMER algorithms. In HCC cell lines, the effects of lentivirus-mediated SLC1A5 overexpression or RNA interference on cell proliferation were examined using CCK-8 assay, and the growth of HCC cell xenografts overexpressing SLC1A5 was observed in nude mice. The effects of SLC1A5 overexpression or silencing in HCC cells on macrophage polarization were evaluated in a cell co-culture system. RESULTS: SLC1A5 was mainly localized on cell membrane and was highly expressed in most cancers in association with clinical stage, lymph node metastasis and poor prognosis. SLC1A5 expression was positively correlated with immunity score in 13 cancer types, especially in low-grade glioma (LGG), LIHC and thyroid cancer. SLC1A5 was positively correlated with macrophage infiltration level in LGG and LIHC but negatively correlated with macrophage infiltration in 5 cancers including lung squamous carcinoma, pancreatic carcinoma, and gastric carcinoma. Patients with SLC1A5 overexpression and high level of M2 macrophage infiltration had the worst survival outcomes. SLC1A5 was correlated with immunosuppression-related genes, cytokines, and cytokine receptors, which was the most obvious in LGG and LIHC. SLC1A5 was highly expressed in different HCC cell lines, and its overexpression promoted HCC cell proliferation both in vitro and in nude mice. In the cell co-culture experiment, SLC1A5 was positively correlated with the molecular markers of M2 polarization of macrophages, and its overexpression strongly promoted M2 polarization of the macrophages and inhibited T cell secretion of IFN-γ. CONCLUSIONS SLC1A5 expression level is correlated with clinical stage, lymph node metastasis, prognosis, and immune cell infiltration in most cancers, and its overexpression promotes HCC progression by inhibiting T-cell function via promoting M2 polarization of macrophages.
Humans ; Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Animals ; Macrophages/cytology* ; Disease Progression ; Cell Line, Tumor ; Mice ; Amino Acid Transport System ASC/genetics* ; Cell Proliferation ; Lymphatic Metastasis ; Mice, Nude ; Prognosis ; Minor Histocompatibility Antigens

The management of surplus drugs is an important part of drug administration. At present, China′s medical institutions are in the initial exploration stage in managing surplus drugs.This study analyzed the causes, safety hazards, management policies, and management problems of surplus drugs in medical institutions, and proposed targeted countermeasures and suggestions, including establishing unified and standardized management methods, consensus or guidelines, optimizing internal management of medical institutions, improving the management awareness of medical staff, and clarifying the benefits of surplus drugs, so as to provide references for medical institutions to manage surplus drugs reasonably.

To standardize the management of surplus drugs, improve the efficiency of medical resource utilization, promote the rational use of medical insurance funds, and reduce the financial burden on patients, a large tertiary hospital implemented a practice for managing surplus drugs starting in May 2023. This practice encompassed multiple aspects, including the establishment of organizational structure, clarification of responsibilities, formulation of billing for fractional doses and a reasonable surplus drugs list, establishment of standardized management processes, and allocation of special funds for surplus drugs. These efforts had initially achieved effective management of surplus drugs. As of November 2023, the management of surplus drugs had benefited 136 908 patients, with an average savings of 873.61 yuan per patient and a cumulative savings of approximately 34.7 million yuan in medical insurance funds. This practice had effectively reduced the wastage of medical resources, and could provide references for promoting standardized management of surplus drugs in medical institutions of China. In the future, the hospital should further expand the coverage of surplus drugs, ensure patients′ rights to informed consent, and establish a comprehensive performance incentive mechanism to promote the sustainable development of surplus drug management.

Objective To investigate the application effects of Waveone Gold,Protaper,MTwo and Reciproc on curved root canals of molar teeth.Methods Collect 100 curved in vitro molars and randomly divide them into 5 groups,Root canal preparation was performed using Waveone Gold,Proteper,Reciproc,MTwo,and stainless steel K-files,respectively.Compare the root canal preparation effects and related complications,root canal offset,and root canal filling effects among five groups.Results After analysis,the five groups of root canal preparation time,the difference was statistically significant,Waveone Gold group the shortest preparation time(P<0.05).There were statistically significant differences in the incidence of step formation among the five groups(P<0.05),but there were no statistically significant differences in the incidence of lateral root canal puncture and instrument fracture among the five groups(P>0.05).The root canal offset of 2mm,4mm and 6mm vertical plane in the five groups was small,the difference was statistically significant,and the root canal offset of Waveone Gold group was the smallest(P<0.05).There was no statistically significant difference in overcharging rates among the five groups(P>0.05).However,there was a statistically significant difference in overcharging and underfilling rates among the five groups(P<0.05),with Waveone Gold and Reciproc groups having higher overcharging rates than the control group and lower underfilling rates than the control group(P<0.05).Conclusion The application of Ni-Ti instruments in curved molar root canals can shorten the preparation time of root canals,reduce the related complications,reduce the deviation of root canals,better root canal filling effect,especially Waveone Gold have obvious advantages.

Objective:The phenotype and genotype of a pedigree with Glanzmann thrombasthenia caused by compound heterozygous mutation in the ITGA2B gene and its molecular pathogenesis were explored.Methods:The platelet aggregation rate of the proband and his family was detected by using a platelet aggregation test with adenosine diphosphate, collagen, epinephrine, arachidonic acid, and ristocetin. The expression levels of CD41 (αⅡb), CD61 (β3), and CD42b (GPⅠb) on the platelet surface was detected by flow cytometry. Gene sequencing technology was used for the genetic identification of the family. RT-PCR was used in the detection of mRNA splicing, and qRT-PCR was used in detecting the relative mRNA level of the ITGA2B gene. Bioinformatics analysis was used to evaluate the pathogenicity of mutation sites and their effects on protein structure and function. The expressions of total αⅡb and β3 in platelets were analyzed by Western blot.Results:Except ristocetin, the other four inducers could not induce platelet aggregation in the proband. Flow cytometry showed that the expression levels of αⅡb and β3 were only 0.25% and 9.76%, respectively, on the platelet surface of the proband, whereas GPⅠb expression was relatively normal. The expression levels of glycoproteins in the other family members were almost normal. c.480C>G and c.2929C>T mutations were detected in the proband through gene sequencing. The c.480C>G mutation was inherited from his mother, and the c.2929C>T mutation was inherited from his father. The RT-PCR and sequencing results showed that the c.480C>G mutation caused mRNA splicing in the proband and his mother, resulting in the deletion of 99 bases in c.476G-574A (p.S160-S192). qRT-PCR showed that the c.2929C>T variant reduced the mRNA level of the ITGA2B gene in the proband and his father. Bioinformatics analysis suggested that the c.480C>G mutation might form a binding sequence with hnRNP A1 protein and generate the 5′SS splice site. The three-dimensional structural model of the αⅡb subunit showed that the β-propeller domain of the p.S160-S192 deletion lost two β-strands and one α-helix in blade 2. The c.2929C>T nonsense mutation caused premature translation termination and produced a truncated protein with the deletion of p.R977-E1039, including the cytoplasmic domain, transmembrane domain, and a β chain of the extracellular Calf-2 domain. The total αⅡb expression of the proband was absent, and the relative expression of β3 was 11.36% of the normal level.Conclusion:The compound heterozygous mutation c.480C>G in exon 4 and c.2929C>T in exon 28 of the ITGA2B gene probably underlies Glanzmann thrombasthenia in this pedigree.

Objective:To analyze the F10 gene mutations in a Chinese pedigree affected with the deficiency of the hereditary coagulation factor X (FX), resulting from a new deletion mutation, and to study the associated molecular pathogenesis.Methods:Next generation sequencing (NGS) was performed to screen the genetic mutations in the proband which were then verified by Sanger sequencing. The FX activity (FX∶C) of probands and their family members was detected using the blood clotting method, and the mutation sites of the family members were analyzed using Sanger sequencing. The pathogenicity of the mutation site was predicted by using the online bioinformatics software, Mutation Taster. The SWISS-MODEL software was used for stimulating the three-dimensional models of the wild-type and mutant proteins for analyzing the influence of the mutation site on the structure and function of the proteins, and for analyzing the difference between the catalytic residues of the wild-type and the mutant proteins. The level of the F10 gene mRNA was quantitatively analyzed by qRT-PCR (quantitative reverse transcription polymerase chain reaction) method by constructing plasmids, transfecting human embryonic kidney 293T cells (HEK 293T), and analyzing the splicing of the mutated site by RT-PCR method. The levels of FⅩ∶Ag in cell lysates and cell culture media (both inside and outside the cells) were detected by the ELISA (enzyme linked immunosorbent assay) method.Results:A medium-grade factor X deficiency with a 36.42% FⅩ∶C ratio was detected in the proband by the coagulation method. NGS analysis demonstrated a heterozygous deletion mutation in exon 8:c.902_919del (p.Ala301_Glu306del) in the proband. Sanger sequencing analysis indicated that some members of the family (mother and grandfather) were also carriers of the corresponding deletion mutation. Online bioinformatics software predicted the pathogenic nature of the c.902_919del mutation, with a pathogenic score of 0.999. The 3D protein structure model analysis indicated that the c.902_919del mutation resulted in the disappearance of a segment of β-fold in the protein structure, thereby shortening the preceding segment of the β-fold and a subsequent loss of hydrogen bonds between adjacent amino acids with no significant difference in the side chain conformation of the key catalytic residues compared to the wild-type. mRNA splicing analysis indicated the absence of alternative splicing changes in the mutation, and qRT-PCR results indicated the absence of a statistically significant difference between the mRNA levels of F10 gene and wild-type mRNA in cells expressing c.902_919del mutant. The ELISA results indicated that there was no statistically significant difference in the FX∶Ag levels of the mutant cell culture medium and the lysate.Conclusions:In this pedigree, the heterozygous mutation in exon 8 of F10 gene (c.902_919del, p.Ala301_Glu306del) caused the hereditary factor Ⅹ deficiency.