【Objective】 To compare the desalination effects of five desalination methods and their effects on the components for human coagulation factor Ⅷ(FⅧ), and provide reference for selection of protein desalination methods. 【Methods】 Sephadex G-25 Medium gel, Fractogel EMD BioSEC gel, ultrafiltration, room temperature dialysis and 4℃ dialysis were used to desalt human FⅧ. The desalination effect was evaluated by the removal rate of Na +, citrate ion and glycine. FⅧ protein recovery, FⅧ activity (FⅧ∶C), VWF antigen (VWF∶Ag), VWF activity(VWF∶Ac), VWF polymers and SDS-PAGE analysis before and after desalination were compared to evaluate the effect of desalination on FⅧ components. 【Results】 In terms of desalination effect, the removal rate of Na⁺ was the lowest in ultrafiltration desalination, while that of Fractogel EMD BioSEC gel was the highest [(97.90±0.06) % vs (99.82±0.07) %]. Except that there was no statistical significance between Sephadex G-25 Medium gel desalination and Fractogel EMD BioSEC gel desalination (P=0.90), the removal rates of the other four methods were statistically significant. The removal rate of glycine was the lowest in ultrafiltration desalination, wihle that of Fractogel EMD BioSEC gel desalination was the highest [(95.78±0.42) % vs (99.81±0.08) %]. Significant difference in glycine removal was noticed in ultrafiltration desalination, but not among the other four desalination methods. There was no significant difference in the removal rate of citrate ions among the five methods (P=0.85). For the effect of FⅧ components, FⅧ∶C, VWF∶Ag, VWF∶Ac and protein recovery rates of ultrafiltration desalination were the highest, with (18.34±1.99) IU/mL, (11.81±0.33) IU/mL, (12.26±0.58) IU/mL and (97.13±1.37) %, respectively. There was no significant change in VWF∶Ac/VWF∶Ag before and after desalination by the five methods. SDS-PAGE and VWF polymer analysis showed that different desalination methods had no significant impact on protein composition. 【Conclusion】 Although different desalination methods had no significant effect on the composition of FⅧ protein, the desalination effect was different. Moreover, different desalination methods had significant effects on protein recovery, FⅧ∶C, VWF∶Ag and VWF∶Ac. The selection of desalination methods should be more considered during protein processing,

Objective:To analyze the current status and deficiencies of family bed service policies in China, for references for promoting the construction of China′s home health service system.Methods:Key words such as " family bed" and " home health services" were used to search for relevant policies(from January 1, 1984 to May 31, 2023)in Peking University Treasure Database, the State Council′s policy document repository, and official websites of health administrative departments at all levels. NVivo 11.0 software was utilized for a three-level coding process to establish a policy text analysis framework and to identify deficiencies in the construction of policies.Results:A total of 63 policy documents were included, comprising 53 provincial and municipal documents, which were mainly concentrated in economically developed provinces; After three-level coding, 72 third level nodes, 21 second level nodes, and 8 first level nodes(service objects, service providers, service methods, service content, service fees, subsidy policies, hospital bed configuration, and standardized management) were obtained. Among them, the responsibilities of service providers needed to be further clarified, the technical and innovative nature of service content was still insufficient, the charging standards and medical insurance reimbursement policies needed to be improved, the support for subsidy policies was limited, and the use of intelligent devices in bed configuration needed to be strengthened.Conclusions:China′s family bed service policy focused on eight dimensions, covering a comprehensive range of content, but there were still areas that need to be refined and improved. This study suggested that relevant departments should further clarify the responsibilities of service providers, deepen the construction of service connotations, moderately increase government support, promote the intelligent construction of services, and achieve multi-party collaboration to jointly promote the sustainable development of family bed services in China.

Objective To construct luciferase reporter plasmids of truncated fragments of different lengths of human guanylate binding protein 5(GBP5)gene promoter and analyze the transcriptional activity of each fragment to determine the core regulatory region.Methods GBP5promoter sequence was amplified by PCR,truncated into five fragments of different lengths and connected to pGL3-basic plasmid.The constructed recombinant plasmids pGL3-GBP5-11/21/31/41/51were transfected into 293FT cells and detected for luciferase activity.The binding sites of transcription factors in GBP5promoter region were predicted by JASPAR software,and Yin-Yang transcription factor 1(YY1)targeting the core regulatory region was selected and verified for the transcriptional regulatory activity.The CDS sequence of YY1 was amplified by PCR to construct the overexpression plasmid pIRES2-EGFP-YY1,which was then co-transfected to 293FT cells with plasmids pGL3-GBP5-21(-1 623 ～ +47 bp)and internal reference plasmid pRL-CMV,and detected for luciferase activity to analyze the regulation of transcription factor YY1 on GBP5 promoter activity.Results Colony PCR and double enzyme digestion identification proved that the plasmid of human GBP5 promoter reporter gene was correctly constructed;JASPAR software predicted that there were multiple transcription factor binding sites such as STAT1,YY1 and Foxp3 in GBP5promoter region.Double luciferase activity assay showed that pGL3-GBP5-21(-1 623 ～ +47 bp)showed the highest promoter activity,while the promoter activity of pGL3-GBP5-41(-520 ～ +47 bp)decreased significantly,suggesting that the core region of GBP5 promoter was located at upstream-1 623 ～-520 bp of 5 'UTR;Overexpression of YY1 significantly activated the GBP5 promoter activity and regulated the expression of GBP5.Conclusion The core regulatory region of human GBP5 promoter was located in upstream-1 623 ～-520 bp of the 5 'UTR,with a binding site of transcription factor YY1 existing in this region.Meanwhile,overexpression of YY1 significantly effected the activity of GBP5 promoter.

One of the traditional prescriptions for treating lung diseases, Jiegeng decoction (JGT), is still unknown in terms of its chemical makeup and mechanism. In this study, Q-Exactive-Orbitrap MS technology was used to identify the chemical constituents of JGT, and metabolomics was used to examine the effect of JGT on metabolites in the lung tissue of mice with acute lung injury (ALI) model. The potential biomarkers were screened by fold change (FC) > 1.5 or FC < 0.67 and P < 0.05, and enriched for metabolic pathways. A total of 40 compounds, including triterpenoid saponins, flavonoids and glycosides, were identified by mass spectrometry analysis of JGT. All animal experiments were approved by the Experimental Animal Ethics Committee of Tianjin University of Traditional Chinese Medicine (No. TCM-LAEC2021106). The results showed that JGT improved the lung coefficient, and lung tissue morphology of mice with ALI, lowered the levels of malondialdehyde (MDA), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) in bronchoalveolar lavage fluid (BALF), and reduced myeloperoxidase (MPO) content in lung tissue. The metabolomic results showed that JGT could regulate 22 metabolites associated with ALI, among which leukotriene D4, docosapentaenoic acid, hypoxanthine, L-5-oxoproline, and other metabolites were mainly associated with the body′s inflammatory response and oxidative stress, and were enriched in the pathways of glutathione metabolism, purine metabolism, and primary bile acid biosynthesis. This study analyzed the potential mechanism of JGT in the treatment of ALI through metabolomics, providing an important theoretical basis for the clinical application of JGT.

Humans ; Multiple Myeloma/drug therapy* ; Thalidomide/therapeutic use* ; Dexamethasone/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols ; Neoplasm Recurrence, Local/drug therapy*

Autophagy is a process that delivers cytoplasmic components to lysosome for degradation, which plays an important role in intracellular homeostasis and achieving self-renewal.Recent studies have shown a close relation between autophagy and renal cystogenesis in ADPKD.Further studies show that there are two phenomena of autophagy impairment and autophagy enhancement in the ADPKD disease model.Autophagy disorders influence the occurrence and development of ADPKD.Therefore, the regulation of autophagy may be a new strategy for ADPKD treatment.Medicines that regulate autophagy through mTOR-dependent and mTOR-independent pathways also show a positive effect in alleviating ADPKD symptoms.This paper reviews the progress of the role of autophagy in ADPKD and provides reference for further research of autophagy in ADPKD and its medicine regulation.

Objective:To investigate the treatment options for multiple myeloma patients with central nervous system involvement (CNS-MM) , as well as their clinical characteristics and prognostic factors.Methods:Between January 2011 and January 2022 our center diagnosed 18 people with CNS-MM. A retrospective analysis was done on the clinical information from the initial diagnosis and central nervous system involvement, and it was compared to 1∶3 matched newly diagnosed MM from the same period. Analysis was done on the clinical characteristics and survival rates of the two groups.Results:In patients with CNS-MM, the median time of onset was 14.2 (0.9-79.6) months and the median overall survival (OS) was 30.5 months from initial diagnosis and only 3.8 months in patients after CNS involvement. The CNS-MM patients showed more IgD type ( P=0.010) , severer anemia ( P=0.014) , a higher proportion of bone marrow plasma cells ( P=0.013) , more extramedullary lesions ( P=0.001) , and increased lactic dehydrogenase (LDH) ( P=0.009) when compared to the control group. Lenalidomide or pomalidomide-based combinations had higher rates of hematology and CNS remission than bortezomib or daratumumab-based regimens (75.0% vs 16.7% , P=0.019) . Patients who received IMiD-based regimens and had 2 high-risk factors at initial diagnosis (high LDH and extramedullary lesions) had a significantly lower incidence of CNS-MM ( P=0.026) . At the initial diagnosis, LDH ( P=0.008, HR=7.319, 95% CI 1.663-32.219) and extramedullary lesions ( P=0.006, HR=8.054, 95% CI 1.828-35.486) were independent risk factors for the occurrence of CNS-MM. Conclusion:Patients with CNS-MM had a poor prognosis. Patients with high LDH or extramedullary lesions at the time of the initial diagnosis are more likely to have CNS-MM. The prognosis of this patient may be improved by immunoregulator-based therapy.

Breast Neoplasms/metabolism* ; COVID-19/complications* ; China/epidemiology* ; Female ; Humans ; SARS-CoV-2/pathogenicity*

Objective:To investigate the efficacy and safety of daratumumab in relapsed and refractory multiple myeloma (RRMM) .Methods:The clinical characteristics, adverse reactions, efficacy, and prognosis of 46 patients with RRMM treated with daratumumab in Shanghai Changzheng Hospital from September 2017 to March 2020 were retrospectively analyzed.Results:All patients were treated with daratumumab-based regimen: 8 in the Dd group, 35 in the DRd group, and 3 in the DVd group. With a median follow-up of 9.6 months, the overall response rate (ORR) was 75% [complete remission (CR) rate 18.2% ] among the 44 patients available for evaluation. The ORRs of patients resistant to bortezomib, lenalidomide, and both were 70.6% , 69.2% , and 63.6% , respectively. The CR rates of patients resistant to bortezomib, lenalidomide, and both were 17.6% , 11.5% , and 13.6% , respectively. No significant difference was observed in ORR and CR rates among the three groups. The ORRs of the DRd, DVd, and Dd groups were 85.3% , 66.7% , and 28.6% , respectively ( P=0.007) . The median PFS of 46 patients was 8.9 months, the median OS was not reached, and the 1-year OS rate was 74% . The median PFS and OS in the DRd group were longer than those in the Dd group (PFS: 14.4 months vs 2.0 months; OS: not reached vs 5.2 months) . After treatment with daratumumab, neutropenia is the most common hematological adverse reaction above grade 3. Non-hematological adverse reactions are mainly infusion-related adverse reactions and infections. Prognostic analysis showed that patients with extramedullary invasion had shorter PFS and OS compard with patients without extramedullary invasion (PFS: 5.7 vs 14.4 months, P=0.033; OS: 6.3 months vs not reached, P=0.029) . The OS of patients with an ECOG score of 3-4 was significantly shorter than patients with an ECOG score of 1-2 (5.9 months vs not reached, P=0.004) . Conclusion:Daratumumab-based regimens have good efficacy and safety in the treatment of RRMM.

Objective:To discuss the clinical efficacy of Yixinshu capsule for viral myocarditis (VMC) with deficiency of Qi and Yin, and to investigate its antioxidant and anti-inflammatory effect. Method:One hundred and thirty-two patients were randomly divided into control group (66 cases) and observation group (66 cases) by random number table. Patients in two group got comprehensive treatment of Western medicine, i.e. intravenous drip of creatine phosphate injection for 14 days, 1 g/time, 1 time/day. Coenzyme Q10 capsule, 1 grain/time, 3 times/day after meals. Trimetazidine dihydrochloride tablets, 1 tablet/time, 3 times/day during meals. And critically ill patients got intravenous drip of dexamethasone sodium phosphate injection for 14 days, 10-20 mg/time, 1 time/day. The control group took Wenxin granules orally,One bag at a time,3 times/day. Patients in observation group additionally got Yixinshu capsule, 3 grains/time, 3 times/days. The courses of treatment were 8 weeks in both groups. The serum troponin I (cTnI) and creatine phosphokinase (CK-MB) were monitored, and after treatment, the recovery rates of cTnI, CK-MB were recorded. Before and after treatment, the electrocardiogram was observed and the recovery rate after treatment was recorded. Before and after treatment, the scores of deficiency of Qi and Yin were graded, and levels of creatine phosphokinase (CPK), hydroxybutyrate dehydrogenase (HBDH), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), interferon-γ (IFN-γ), interleukin-10 (IL-10), IL-17 and IL-35 were detected. Echocardiography, left ventricular ejection fraction (LVEF), cardiac index (CI), and maximum velocity values between early and late diastolic (E/A) were detected. Result:In the analysis of rank sum test, clinical efficacy in observation group was better than that in control group (Z=2.151, P<0.05). Recovery rates of cTnI, CK-MB and electrocardiogram in observation group were 82.26% (51/62), 90.32% (56/62) and 80.65% (50/62), higher than 65.00% (39/60), 73.33% (44/60) and 63.33% (38/60) in control group (P<0.05). Levels of serum cTnI, CK-MB, CPK, HBDH, LDH, AST, MDA, IFN-γ and IL-17 were lower than those in control group (P<0.01), while levels of LVEF, CI, E/A, SOD, GSH-Px, IL-10 and IL-35 were higher than those in control group (P<0.01). Conclusion:On the basis of comprehensive anti-infection treatment, Yixinshu capsule can additional protect myocardium by anti-inflammatory and antioxidant effect, reduce myocardial enzyme, promote the recovery of ECG and cardiac enzyme, improve cardiac function and improve the effect of clinical treatment.