Female ; Humans ; Breast Neoplasms ; Testosterone ; Prolactin ; Estradiol ; Testosterone Congeners ; China

Osteosarcoma is a common primary malignant bone tumor in adolescents and children,characterized by a high recurrence rate and metastasis,making its treatment extremely challenging.Traditional treatment modalities,including surgery,radiation therapy,and chemotherapy,can alleviate symptoms to some extent,but improving long-term survival rates remains a pressing issue.With the continuous development of immunotherapy,breakthroughs have been made in the research of tumor immune microenvironment and the application of immunotherapy in recent years,providing new perspectives and strategies for osteosarcoma treatment.Currently,immunotherapy strategies include tumor vaccines,targeted cytokines,immune checkpoint inhibition,adoptive cell therapy,combination therapy,etc.,significantly enhancing patient immune responses from the aspects of boosting immunity,overcoming immune tolerance,and preventing immune evasion,thereby effectively improving the patients'survival rates and prognosis.This review aims to systematically introduce the immune microenvironment of osteosarcoma and discuss the latest advances in immunotherapy in clinical translational research of osteosarcoma.By deeply understanding the immune characteristics of osteosarcoma and corresponding treatment methods,it is hopeful to provide more effective strategies for personalized treatment,contributing to the improvement of the patients' survival rates and prognosis.

Objective:To explore the value of 18F-fibroblast activation protein inhibitor (FAPI) PET/CT in the assessment of early-stage graft fibrosis (S1-S2) after liver transplantation (LT). Methods:From November 2021 to April 2022, 17 adult liver transplant recipients (12 males and 5 females; age (52.6±7.9) years) in the Affiliated Hospital of Qingdao University were enrolled retrospectively in this study. All 17 patients received laboratory examinations, FibroScan, 18F-FAPI PET/CT and liver biopsy. According to the Scheuer scoring system, hepatic tissue was divided into no fibrosis (S0) and early fibrosis (S1-S2). Independent-sample t test was used to compare SUV max between two groups, and Mann-Whitney U test was used to compare liver stiffness measurement (LSM). ROC curve analysis was used to evaluate the diagnostic efficacy of LSM and SUV max in the early fibrosis of liver grafts. Delong test was used to compare the difference of AUCs. Results:Among 17 adult LT recipients, 11 were in stage S0, 5 were in stage S1, and 1 was in stage S2. There were significant differences in LSM and SUV max between no fibrosis group and early fibrosis group (LSM: 5.4(4.7, 6.6) vs 12.9(5.6, 19.9) kPa, z=-2.01, P=0.044; SUV max: 1.7±0.8 vs 3.9±1.6, t=-3.14, P=0.019). The threshold value of LSM in predicting early-stage graft fibrosis was 8.2 kPa and the AUC was 0.80 (95% CI: 0.54-0.95), which was 2.0 and 0.92 (95% CI: 0.78-1.00) for SUV max respectively. There was no significant difference in AUC between the two tools ( z=0.80, P=0.421). Conclusion:18F-FAPI PET/CT can precisely evaluate the early fibrosis of allografts, with the similar diagnostic efficacy with FibroScan (LSM), which is expected to be a new non-invasive diagnostic tool for predicting the early-stage of graft liver fibrosis.

Objective:To analyze the clinical characteristics of patients with de-novo non-alcoholic fatty liver disease (de-novo NAFLD) and patients with de-novo NAFLD combined with metabolic syndrome (MS) after liver transplantation (LT) , and to determine the related risk factors.Methods:Patients who underwent LT at the Organ Transplantation Center, the Affiliated Hospital of Qingdao University, from Jan. 2016 to Oc. 2020 and were monitored until Oct. 2021 were gathered. The recipients were divided into the group with/without de-novo NAFLD, and LT recipients with de-novo NAFLD were divided into the group with/without combined MS. Clinical characteristics of the LT recipients with de-novo NAFLD combined with MS were analyzed. Logistic regression analyses were performed to identify the risk factors for LT recipients with de-novo NAFLD and those with combined MS.Results:A total of 324 LT recipients with a median follow-up of 2.9 years (range: 2.0-4.3 years) were included in the study. De-novo NAFLD was diagnosed in 21.0% (68/324) of the LT recipients, and MS was diagnosed in 44.1% (30/68) of these patients. Compared with LT recipients without de-novo NAFLD, those with de-novo NAFLD had higher preoperative body mass index (BMI) , blood glucose, glycated hemoglobin levels and lower platelet levels, and longer postoperative follow-up, higher BMI, waist circumference, albumin, triglycerides (TG) , low-density lipoprotein (LDL) , blood glucose, glycated hemoglobin levels, and the incidence of MS (all P<0.05) . Preoperative platelets, glucose, postoperative albumin, LDL and BMI were independent risk factors for predicting de-novo NAFLD after LT (all P<0.05) . Preoperative glucose performed well in predicting the occurrence of de-novo NAFLD (threshold: 5.5mmol/L, P<0.001, AUC=0.678) . The differences in Pre-LT blood glucose, post-LT BMI, waist circumference, prevalence of prediabetes or diabetes, fatty liver index (FLI) , and NAFLD fibrosis score (NFS) between de-novo NAFLD LT recipients with and without combined MS were significantly different (all P<0.05) . Conclusions:The incidence of de-novo NAFLD after LT is noteworthy, and LT recipients with de-novo NAFLD are more likely to have a combination with MS. In preoperative treatment, keeping blood glucose to 5.5 mmol/L or below trends helps to lower the risk of de-novo NAFLD following LT. LT recipients’ nutritional state and lipid levels require prompt care. High albumin levels might not be a desirable thing. De-novo NAFLD LT recipients with concomitant prediabetes or diabetes may imply an increased risk of developing comorbid MS during the post-LT follow-up. Controlling FLI levels in LT recipients with de-novo NAFLD may reduce the risk of developing comorbid MS.

Objective To evaluate the impact of hepatobiliary surgery in a tertiary public hospital on its core medical operation indicators after the implementation of subspecialty reform.Methods The Department of Hepatobiliary Sur-gery,which implemented the subspecialty reform,was the experimental group,and six surgical departments with-out subspecialties were the control group.Seven indicators in the dimensions of medical quality,medical efficiency,and rational use of medication were collected from September to December 2022,and the difference between the experimental group and the control group was analyzed by the differences-in-differences method using the Septem-ber data before the implementation of sub-specialty reform as the baseline value.Results After the subspecialty re-form,the changes of the indicators of the percentage of discharged patients for surgery,intensity of antimicrobial drug use and average hospital stay in hepatobiliary surgery were better than those of the control group;the percentage of discharged patients for minimally invasive surgery and the percentage of medical service revenue were inferior to those of the control group;the intergroup differences of the two indicators of the percentage of discharged patients for level IV surgery and the case-mix index were not significant.Conclusion By setting up similar control departments in the same period and excluding the influence of external confounding factors on the study results,overall,the core medical operation indexes of hepatobiliary surgery were slightly better than those of the control group,but the advantage was not obvious,which might be related to the short observation time after the subspecialty reform,and its long-term effects need to be continuously followed up and analyzed.

Objective:To investigate the effects of biologics on psychological status and quality of life in patients with inflammatory bowel disease (IBD).Methods:A cross-sectional survey was conducted in 42 hospitals in 22 provinces (autonomous regions and municipalities directly under the central government) from September 2021 to May 2022. General clinical information and the use of biologics were obtained from adult patients diagnosed with IBD who voluntarily participated in the study. Psychological status was evaluated using the Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), and Inflammatory Bowel Disease Questionnaire (IBDQ) assessment tools. Counts were analyzed via the Chi-square test, and datasets that were not normally distributed were analyzed via nonparametric tests. P<0.05 was considered statistically significant. Results:A total of 2 478 valid questionnaires were collected. The GAD-7 score of the biologics group was significantly lower than that of the non-use group [6 (2, 9) vs. 7 (3, 10), Z=-3.49, P<0.001]. IBDQ scores [183 (158, 204) vs. 178 (152, 198), Z=-4.11, P<0.001], intestinal symptom scores [61 (52, 67) vs. 58 (49, 65), Z=-5.41, P<0.001], systemic symptom scores [28 (24, 32) vs. 27 (23, 31), Z=-2.37, P=0.018], emotional ability scores [69 (58, 77) vs. 67 (56, 75), Z=-3.58, P<0.001] and social ability scores [26 (22, 29) vs. 25 (22, 29), Z=-2.52, P=0.012] in the biologics group were significantly higher than in the non-use group. GAD-7 scores [5 (2, 9) vs. 6 (3, 10), Z=-3.50, P<0.001] and PSQI scores [6 (4, 9) vs. 6 (4, 9), Z=-2.55, P=0.011] were significantly lower in the group using infliximab than in the group not using it. IBDQ scores were significantly higher in patients using vedolizumab than in those not using it [186 (159, 205) vs. 181 (155, 201), Z=-2.32, P=0.021] and were also significantly higher in the group treated with adalimumab than in the group not treated with adalimumab [187 (159, 209) vs. 181 (155, 201), Z=-2.16, P=0.030]. However, ustekinumab had no significant effect on any of the scores. Conclusion:The use of biologics is strongly associated with improvements in anxiety status and quality of life in IBD patients.

Objective:To investigate the efficacy of liposomal doxorubicin intensive preconditioning regimen and allogeneic hematopoietic stem cell transplantation (allo-HSCT) in treatment of leukemia.Methods:The data of 20 patients with intensive preconditioning regimen allo-HSCT who were admitted to Shenzhen Second People's Hospital from January 2016 to June 2017 were retrospectively analyzed. The transplantation effect, occurrence of complications and prognosis of patients were analyzed.Results:The median time of granulocyte engraftment was 17 d (13-23 d); the median time of platelet engraftment was 22.5 d (minimum 13 d, maximum >90 d). The acute graft-versus-host disease (GVHD) and chronic GVHD occurred in 2 cases and 1 case, respectively. Eight cases occurred hemorrhagic cystitis, 15 cases occurred Epstein-Barr viremia, 8 cases occurred cytomegaloviremia, 1 case occurred sepsis, 1 case occurred acute liver injury, and 2 cases occurred fungal pneumonia. The median follow-up time was 31.7 months (0.8-53.8 months). One patient died of intracranial infection on the 25th day after transplantation; 3 patients relapsed during the follow-up period, and 2 of them died; the other 16 patients carried 100% donor genes during the follow-up period.Conclusions:The liposomal doxorubicin intensive preconditioning regimen and allo-HSCT have a good effect on leukemia. Increasing the intensity of pretreatment does not increase the treatment-related adverse reactions. The incidence rates of Epstein-Barr viremia and cytomegaloviremia are high, but they are improved after active treatment.

The oral cavity of each person is home to hundreds of bacterial species.While taxa for oral diseases have been studied using culture-based characterization as well as amplicon sequencing,metagenomic and genomic information remains scarce compared to the fecal microbiome.Here,using metagenomic shotgun data for 3346 oral metagenomic samples together with 808 published samples,we obtain 56,213 metagenome-assembled genomes(MAGs),and more than 64％of the 3589 species-level genome bins(SGBs)contain no publicly available genomes.The resulting genome collection is representative of samples around the world and contains many genomes from candi-date phyla radiation(CPR)that lack monoculture.Also,it enables the discovery of new taxa such as a genus Candidatus Bgiplasma within the family Acholeplasmataceae.Large-scale metagenomic data from massive samples also allow the assembly of strains from important oral taxa such as Por-phyromonas and Neisseria.The oral microbes encode genes that could potentially metabolize drugs.Apart from these findings,a strongly male-enriched Campylobacter species was identified.Oral sam-ples would be more user-friendly collected than fecal samples and have the potential for disease diagnosis.Thus,these data lay down a genomic framework for future inquiries of the human oral microbiome.

OBJECTIVE：To explore refined management mode of outpatient pharmacy ，and to improve the efficiency and quality of outpatient pharmacy service. METHODS ：From the hospital information and big data center of our hospital ，the outpatient pharmacy prescription data under the traditional management mode were collected ；fish bone analysis was used to find out the factors that may affect the waiting time of patients ，the work efficiency and quality of pharmacy ；4M1E method was adopted to improve the related problems and implement refined management. The prescription data of 10 working days before improvement，stage 1 and stage 2 of refined management were selected. The work efficiency of pharmacists ，average waiting time of patients ，dispensing errors and inventory errors before and after the improvement were compared and analyzed to evaluate the effects of refined management. RESULTS ：By fishbone diagram ，the factors influencing the waiting time of patients ，the work efficiency and quality of outpatient pharmacy service in our hospital included personnel factors ，machine factors ，material factors ， method factors ，environmental factors ，such as the number of personel and time alloction was unreasonable ，the machine was aging，etc. After the implementation of refined management ，the outpatient pharmacy of our hospital had taken a variety of measures，such as adjusting the staff working time and refining the performance rew ard scheme ，maintaining the automatic dispensing machine and updating the prescription scanning equipment，setting up temporary drug containers and opti- mizing the location number ，strengthening drug management and relevant personnel training ， openning the window ofcharacteristic single variety dispensing. The statistical results com showed that in the first stage of fine management ，the number of dispensing prescriptions and the number of p rescription items in the outpatient pharmacy of our hospital increased slightly in 10 working days. Due to the decrease of the number of on-the-job staff and the change of the number and time of open windows ，the cumulative working hours of on-the-job staff decreased from 1 680 hours to 1 440 hours；the number of dispensing prescriptions and prescription items per hour per capita increased from 52.0 pieces，58.7 to 65.1 pieces，69.6（P＜0.05）；the number of dispensing errors decreased from 30 to 5；there was no significant change in waiting time of patients and inventory errors. In the second stage of fine management ，when the amount of dispensing prescriptions in outpatient pharmacy of our hospital was similar ，the number of dispensing prescriptions and the number of prescription items per hour per capita increased from 52.0 pieces，58.7 to 59.9 pieces，67.3，respectively（P＜0.05）；the average waiting time of patients decreased from 9.30 min to 7.32 min（P＜0.05）. After further refining the error data collection method and adjusting the performance incentive scheme ，the number of dispensing errors in outpatient pharmacy increased to 75，and the number of inventory errors decreased from 5 to 0. CONCLUSIONS ：By 4M1E method，outpatient pharmacy of our hospital carry out refined management ，to achieve the improvement of work efficiency and quality，shorten the waiting time of patients

Objective To investigate the effects of WNK3 kinase on the regulation of large-conductance calcium-activated potassium channels (Maxi K channels) on African green monkey kidney fibroblast-like cells (Cos-7 cells) and its mechanisms.Methods (1) Cos-7 cells were transfected with 0,0.6,1.2,1.8 μg WNK3 plasmid+0.5 μg Maxi K plasmid.The total protein expression of Maxi K channel and the phosphorylation of mitogen-activated protein kinase (MAPK) extracellular regulated kinase-1 and-2 (ERK1/2) were detected by Western blotting.(2) Cos-7 cells were divided into the control group (2.5 μg Maxi K plasmid) and the experimental group (2.5 μg WNK3 plasmid+2.5 μg Maxi K plasmid).Cell surface biotinylation was used to investigate the cell surface protein expression of Maxi K channel in Cos-7 cells.Immunoprecipitation and Western blotting were used to detect the ubiquitination of Maxi K channel protein.(3) WNK3 kinase was knocked down by WNK3 siRNA.The lysosomal degradation pathway was blocked by the proton pump inhibitor (Baf-A1).Cos-7 cells were divided into Maxi K+negative control siRNA group,Maxi K+WNK3 siRNA group and Maxi K+WNK3 siRNA+Baf-A1 group.The protein expression of Maxi K channel protein was detected by Western blotting.Results (1) Compared with those in 0 μg WNK3 plasmid groups,in 0.6,1.2,1.8 μg WNK3 plasmid groups the total protein expression of the Maxi K channel increased and the phosphorylation level of MAPK ERK1/2 reduced on a dose-dependent manner (all P ＜ 0.01).(2)Compared with those in the control group,the total protein expression and cell surface membrane protein expression of the Maxi K channel increased in the experimental group (P ＜ 0.01),while the ubiquitination of the Maxi K channel protein reduced (P ＜ 0.01).(3) Compared with the Maxi K +negative control siRNA group,the expression of Maxi K protein reduced in the Maxi K+WNK3 siRNA group (P ＜ 0.01),but did not change in the Maxi K+WNK3 siRNA + Bar-A1 group (P ＞ 0.05).The expression of Maxi K protein in Maxi K+WNK3 siRNA+Baf-A1 group was higher than that in Maxi K+WNK3 siRNA group (P ＜ 0.01).Conclusions WNK3 kinase inhibits the lysosomal degradation pathway of Maxi K channel protein by reducing the ubiquitination of Maxi K channel,and promotes the expression of Maxi K channel protein in cells and on cell membrane.These effects may be achieved by suppressing MAPK ERK1/2 signal transduction pathway.