Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.

Objective To investigate the effect of percutaneous balloon mitral valvuloplasty under echocardiographic guidance for patients with moderate to severe mitral stenosis during pregnancy. Methods A retrospective observational study was conducted to include pregnant women who were diagnosed with moderate to severe mitral stenosis and underwent percutaneous balloon mitral valvuloplasty under echocardiographic guidance in Fuwai Hospital from August 2018 to June 2022, and their baseline characteristics, surgical outcomes, echocardiographic results, and follow-up results were analyzed. Results A total of 3 pregnant women aged 30-35 years, with gestational age of 19-26 weeks, and New York Heart Association (NYHA) function class Ⅲ were included. All the procedures were successfully performed. The mitral valve orifice area increased from 0.9 cm2 preoperatively to 2.1 cm2 postoperatively. The mean transvalvular pressure gradient decreased from 15.0 mm Hg preoperatively to 6.7 mm Hg postoperatively. No perioperative adverse events occurred. The follow-up time ranged from 3 to 48 months. All patients delivered uneventfully and returned to normal life, with maternal-fetal safety. Conclusion Percutaneous balloon mitral valvuloplasty under echocardiographic guidance is a feasible and effective procedure for the treatment of patients with moderate to severe mitral stenosis in pregnancy, with satisfactory maternal-fetal outcomes.

Based on the panel data of four waves of the Chinese Longitudinal Healthy Longevity Survey from 2008 to 2018,the paper analyzed the influence of different living arrangements status and their changes on the self-reported quality of life in elderly by using the time-fixed effect model.The study found that compared to the elderly living alone,those living with others report higher living quality,while among the different living situation,the elderly living only with their children report their living quality the highest.Living arrangement change also affect the self-reported quality of life in elderly.Compared with the elderly who always live with others,the elderly who always live alone and live with others before living alone are generally lower in their self-rated living quality,but living alone before living with others does not have a significant impact on their self-reported quality of life.Therefore,in order to further improve the overall living quality of the elderly,the paper argues that we should focus on strengthening the life care of the empty-nester elderly and the elderly living alone,and we should also strive to create comfortable and stable living conditions for the elderly.

This study utilizes balanced panel data from five waves of the Chinese Longitudinal Healthy Longevity Survey(CLHLS)spanning 2005 to 2018 to analyze the impact of urban and rural resident medical insurance participation on moral hazard among older adults.The research findings are as follows:Firstly,participation in urban and rural resident medical insurance does not increase ex-ante moral hazard,such as unhealthy behaviors among older adults.However,it does result in ex-post moral hazard,indicated by a rise in medical expenditures.Secondly,younger seniors and those with deteriorating health conditions are more likely to experience increased medical expenses as an ex-post moral hazard after enrolling in the insurance.Lastly,compared to basic medical insurance for urban residents,older adults are more likely to experience increased medical expenses as an ex-post moral hazard after enrolling in the New Rural Cooperative Medical Scheme,primarily due to a rise in outpatient expenses.First,A comprehensive understanding of the multi-dimensional attributes of public healthcare policy evaluation is needed;Second,We should innovate the development concept of the basic medical insurance system for urban and rural residents.

Objective:To analyze the implementation effect of single disease payment policy for day surgery (hereinafter referred to as the policy), for references for the reform of medical insurance payment.Methods:By collecting the information of inpatients from 2017 to 2019 in a tertiary hospital, the research group took patients with colorectal benign tumor and nodular goitre as the policy implementation group and the control group respectively. 2017-2018 was the pre implementation stage of the policy, and 2019 was the post implementation stage of the policy. The difference-in-differences (DID) model was used to analyze the changes in indicators such as length of stay and hospitalization expenses after policy implementation, under whether the policy is implemented or not, as well as before or after policy implementation.Results:A total of 2 419 patients were included, including 927 patients with nodular goiter in the control group and 1 492 patients with colorectal benign tumors in the policy implementation group (688 patients before the policy implementation and 804 patients after the policy implementation). The results of DID showed that the hospital days for patients with colorectal benign tumor decreased by 56.53%, the hospitalization expenses decreased by 26.51%, the out-of-pocket expenses decreased by 26.66%, the treatment expenses increased by 11.96%, the drug expenses decreased by 50.29% and the consumables expenses decreased by 20.23% after the implementation of the policy.Conclusions:The implementation of the policy could reduce length of stay, hospitalization expenses and out-of-pocket expenses, optimize the structure of hospitalization expenses, improve the efficiency of hospital diagnosis and treatment, and help the hospital realize its transformation from a size expansion to a quality and benefit expansion.

Background/Aims: Data of coronavirus disease 2019 (COVID-19) vaccine immunogenicity among chronic liver disease (CLD) and liver transplant (LT) patients are conflicting. We performed meta-analysis to examine vaccine immunogenicity regarding etiology, cirrhosis status, vaccine platform and type of antibody. Methods: We collected data via three databases from inception to February 16, 2022, and reported pooled seroconversion rate, T cell response and safety data after two vaccine doses. Results: Twenty-eight (CLD only: 5; LT only: 18; both: 2; LT with third dose: 3) observational studies of 3,945 patients were included. For CLD patients, seroconversion rate ranged between 84% (95% confidence interval [CI], 76–90%) and 91% (95% CI, 83–95%), based predominantly on neutralizing antibody and anti-spike antibody, respectively. Seroconversion rate was 81% (95% CI, 76–86%) in chronic hepatitis B, 96% (95% CI, 93–97%) in non-alcoholic fatty liver disease, 85% (95% CI, 75–91%) in cirrhosis and 85% (95% CI, 78–90%) in non-cirrhosis, 86% (95% CI, 78–92%) for inactivated vaccine and 89% (95% CI, 71–96%) for mRNA vaccine. The pooled seroconversion rate of anti-spike antibody was 66% (95% CI, 55–75%) after two doses of mRNA vaccines and 88% (95% CI, 58–98%) after third dose among LT recipients. T cell response rate was 65% (95% CI, 30–89%). Prevalence of adverse events was 27% (95% CI, 18–38%) and 63% (95% CI, 39–82%) among CLD and LT groups, respectively. Conclusions CLD patients had good humoral response to COVID-19 vaccine, while LT recipients had lower response.

The progression of hyperuricemia disease is often accompanied by damage to renal function. However, there are few studies on hyperuricemia nephropathy, especially its association with intestinal flora. This study combines metabolomics and gut microbiota diversity analysis to explore metabolic changes using a rat model as well as the changes in intestinal flora composition. The results showed that amino acid metabolism was disturbed with serine, glutamate and glutamine being downregulated whilst glycine, hydroxyproline and alanine being upregulated. The combined glycine, serine and glutamate could predict hyperuricemia nephropathy with an area under the curve of 1.00. Imbalanced intestinal flora was also observed. , , , , and other conditional pathogens increased significantly in the model group, while and , the short-chain fatty acid producing bacteria, declined greatly. At phylum, family and genus levels, disordered nitrogen circulation in gut microbiota was detected. In the model group, the uric acid decomposition pathway was enhanced with reinforced urea liver-intestine circulation. The results implied that the intestinal flora play a vital role in the pathogenesis of hyperuricemia nephropathy. Hence, modulation of gut microbiota or targeting at metabolic enzymes, , urease, could assist the treatment and prevention of this disease.

BACKGROUNDSome problems have been found in the usually adopted combined approach for the removal of intra-extracranial tumors in skull base. Herein, we described a pure endoscopic transnasal or transoral approach (ETA) for the removal of intra-extracranial tumors in various skull base regions.

METHODSRetrospectively, clinical data, major surgical complications, pre- and postoperative images, and follow-up information of a series of 85 patients with intra-extracranial tumors in various skull base regions who were treated by surgery via ETA in our skull base center during the past 10 years were reviewed and analyzed.

RESULTSGross total tumor removal was achieved in 80/85 cases (94.1%) in this study. All 37 cases with tumors in anterior skull base and all 14 cases with tumors in jugular foramen received total tumor removal. Thirteen and three cases with tumors in clivus received total and subtotal tumor removal, respectively. Total and subtotal tumor removal was performed for 16 cases and 2 cases in lateral skull base, respectively. The complications in this study included: cerebrospinal fluid leakage (n = 3), meningitis (n = 3), and new cranial nerve deficits (n = 3; recovered in 3 months after surgery). In the follow-up period of 40-151 months (median: 77 months), seven patients (8.8%) out of the 80 cases of total tumor removal experienced recurrence.

CONCLUSIONSComplete resection of intra-extracranial growing tumors in various skull base regions can be achieved via the pure ETA in one stage in selected cases. Surgical procedure for radical removal of tumors is feasible and safe.

Objective To explore the effects of cyclophosphamide administered by different routes or in different doses on the embryo-fetal development in pregnant rabbits, and to determine the optimal mode of cyclophosphamide administration to induce fetal malformation.Methods Pregnant rabbits were divided into control group C (saline), group Y1 (intravenous injection of 15 mg/kg cyclophosphamide,), group Y2 (subcutaneous injection of low dose cyclophosphamide, 20 mg/kg), and group Y3 (subcutaneous injection of high dose cyclophosphamide, 30 mg/kg).Each rat was administrated according to the corresponding mode once daily on GD10~13.The day of conception was designated as GD0.The pregnant rabbits were sacrificed and dissected on GD28.Then, the number of corpora lutea and implantation, the weight of uterus with contained fetus, and fetal resorption rate were detected, the fetuses were removed and the fetal sex, body length, tail length, the number of live births and stillbirths were recorded, and the appearance of deformities, visceral deformities and skeletal malformations were detected.Results Pregnant rabbit fetuses in the cyclophosphamide intravenous injection group and subcutaneous injection of low dose cyclophosphamide group showed deformities.The appearance malformation rates in the two groups were 30.77% and 95.65%, the skeletal deformity rates were 7.69% and 73.91%, and the visceral abnormality rates were 20.51% and 47.83%, respectively.The fetal resorption rate in the high dose cyclophosphamide subcutaneous injection group was 100%.Conclusions Subcutaneous injection of 20 mg/kg cyclophosphamide to pregnant rabbits at GD10~13 can be used as a positive administrationmethod for rabbit embryo-fetal developmental toxicity test.Thismethod has the advantages of short administration period, easy operation, few fetus resorption, and high rate of fetal malformation, thus, providing the evidence for selection of appropriate model of rabbit embryo-fetal developmental toxicity.

The chinmedomics method was used to explore the effect of Nanshi capsule on endogenous metabolites of rats with kidney-yang deficiency syndrome, investigate the metabolites and metabolic pathways closely related to kidney-yang deficiency syndrome (KYDS)and identify the therapeutic basis of Nanshi capsule(NPC)as well as its action mechanism for KYDS. The routine biochemical indexes of serum were detected and histomorphology was observed. Based on the chinmedomics technology platform, discriminatory analysis in multivariate modes was conducted for rat blood and urine, thus to investigate the biomarkers of KYDS and the therapeutic effect of NPC against KYDS. Meanwhile, the main constituents of NPC in rat serum were also detected to analyze its correlation between the constituents in vivo and the biomarkers of KYDS, and determine the potential effective compounds for therapeutic effect. Eleven biomarkers of KYDS were identified in the rat models, involving steroid hormone biosynthesis, tryptophan metabolism and tyrosine metabolism. It was found that NPC could regulate steroid hormone biosynthesis, tryptophan metabolism and tyrosine metabolism; PCMS analysis showed that caffeic acid, 2-hydroxy-1-methoxy-anthraquinone, 1-hydroxy-2-methoxyanthraquinone, ferulic acid glucuronide conjugation, deacetylasperulosidic acid, cynaroside, betaine and umbelliferone were the main effective compounds of NPC for KYDS. In this study, cynaroside, betaine, umbelliferone and other compounds in NPC could integrally regulate the disturbance of metabolic profile in KYDS by improving the hormone synthesis, hormone synthesis pathway, hormone synthesis and release pathway in tyrosine metabolism and linoleic acid synthesis pathway in linoleic acid metabolism. These results indicated that the NPC had the characteristics of multi-pathway, multi-target and overall regulation in the treatment of KYDS. Chinmedomics approach can provide methodology support to discover innovative drug from traditional Chinese medicine.