Sishen Pills and its separated prescriptions are classic prescriptions of traditional Chinese medicine to treat intestinal diseases. In this study, a high-performance liquid chromatography-electrospray ionization tandem mass spectrometry(HPLC-ESI-MS/MS) technology was used to identify the components of Sishen Pills, Ershen Pills, and Wuweizi Powder. The positive and negative ion sources of electrospray ionization were simultaneously collected by mass spectrometry. A total of 11 effective components were detected in Sishen Pills, with four effective components detected in Ershen Pills and eight effective components detected in Wuweizi Powder, respectively. To explore the effects of Sishen Pills and its separated prescriptions on the human intestinal flora, an in vitro anaerobic fermentation model was established, and the human intestinal flora was incubated with Sishen Pills, Ershen Pills, and Wuweizi Powder in vitro. The 16S rDNA sequencing technology was used to analyze the changes in the intestinal flora. The results showed that compared with the control group, Sishen Pills, and its separated prescriptions could decrease the intestinal flora abundance and increase the Shannon index after fermentation. The abundance of Bifidobacterium was significantly increased in the Sishen Pills and Ershen Pills groups. However, the abundance of Lactobacillus, Weissella, and Pediococcus was significantly increased in the Wuweizi Powder group. After fermentation for 12 h, the pH of the fermentation solution of three kinds of liquids with feces gradually decreased and was lower than that of the control group. The decreasing amplitude in the Wuweizi Powder group was the most obvious. The single-bacteria fermentation experiments further confirmed that Sishen Pills and Wuweizi Powder had inhibitory effects on Escherichia coli, Staphylococcus aureus, and Enterococcus faecalis, and the antibacterial activity of Wuweizi Powder was stronger than that of Sishen Pills. Both Sishen Pills and Ershen Pills could promote the growth of Lactobacillus brevis, and Ershen Pills could promote the growth of Bifidobacterium adolescentis. This study provided a more sufficient theoretical basis for the clinical application of Sishen Pills and its separated prescriptions.
Humans ; Gastrointestinal Microbiome/drug effects* ; Drugs, Chinese Herbal/chemistry* ; Fermentation/drug effects* ; Bacteria/drug effects* ; Chromatography, High Pressure Liquid ; Tandem Mass Spectrometry ; Intestines/microbiology*

OBJECTIVE: To precise classify sacral meningeal cysts, effective guide minimally invasive neurosurgery and postoperative personalized rehabilitation by multiple dimensions radiographic reconstruction MRI. METHODS: From March to December 2021, based on the original 3D-fast imaging employing steadystate acquisition (FIESTA) scanning sequence, 92 patients with sacral meningeal cysts were pre-operatively evaluated by multiple dimensional reconstruction MRI. The shape of nerve root and the leakage of cyst were reconstructed according to the direction of nerve root or leakage track showed on original MRI scans. Sacral canal cysts were accurately classified as including nerve root and without nerve root, so as to accurately design the incision of skin and formulate corresponding open range of the posterior wall of the sacral canal. Under the microscope intraoperation, the shape of the nerve roots inside cysts or leakage track of the cysts without nerve roots were verified and explored. After the reinforcement and shaping operation, several reexaminations of multiple dimensional reconstruction MRI were performed to understand the deformation of the nerve root and hydrops in the operation cavity, so as to formulate a persona-lized rehabilitation plan for the patients. RESULTS: Among the 92 patients with sacral mengingeal cyst, 58 (63.0%) cysts with nerve root cyst, 29 (31.5%) cysts without nerve root cyst, and 5 (5.4%) cysts with mixed sacral canal cyst. In 58 patients with nerve root cysts, the accuracy of preoperative clinical classification on MRI image reached 96.6% (56/58) through confirmation by operating microscope. Only 2 cases of large single cyst with nerve root on the head of cyst were mistaken for without nerve root type. In 29 patients with sacral cyst without nerve root, the accuracy of preoperative image reached 100% through confirmation by operating microscope. The accuracy of judging the internal nerve root and leakage of 12 cases with recurrent sacral cyst was also 100%. Two cases of delayed postoperative hydrops were found one month after operation. After rehabilitation treatment by moxibustion and bathing, the hydrops disappeared 4-6 months after operation. CONCLUSION Multiple dimensional reconstruction MRI can precisely make clinical classification of sacral meningeal cysts before operation, guide minimally invasive neurosurgery effectively, and improve the rehabilitation effect.
Humans ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Sacrum/surgery* ; Adult ; Middle Aged ; Imaging, Three-Dimensional/methods* ; Cysts/rehabilitation* ; Aged ; Adolescent ; Young Adult ; Spinal Nerve Roots/diagnostic imaging* ; Minimally Invasive Surgical Procedures ; Neurosurgical Procedures/methods*

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Objective:Induced pluripotent stem cells (iPSCs) cell lines were established using peripheral blood mononuclear cells (PBMCs) from a patient suffering from neonatal respiratory distress syndrome (NRDS) who carried Adenosine triphosphate-binding cassette transporter A3 ( ABCA3) compound heterozygous mutations. Methods:Cell experimental research.Peripheral venous blood was collected and PBMCs were isolated and cultured in vitro. PBMCs were transfected with non-integrated Sendai vector carrying reprogramming factors.The chromosome karyotypes of the established iPSCs were analyzed.Immunofluorescence and flow cytometry were used to detect pluripotency markers of stem cells and verify their differentiation potential.Sanger sequencing was performed to analyze gene mutations.In addition, short tandem repeat (STR) analysis was performed, polymerase chain reaction(PCR) and agarose gel electrophoresis were used to detect virus residual. Results:Karyotype analysis of established iPSCs cell lines showed normal diploid 46, XY karyotype.Immunofluorescence showed positive staining of stem cell pluripotency markers OCT4, SSEA4, Nanog and Sox2.Flow cytometry was used to detected stem cell pluripotency markers and showed expression of TRA-1-60, SSEA-4 and OCT4.After differentiation into all three germ layers, immunofluorescence was performed to detect ectoderm (Pax-6), mesoderm (Brachyury) and endoderm alpha-fetoprotein markers, and the results showed positive staining, which confirmed that the iPSCs had the potential to differentiate.Sanger sequencing showed c. 3997_3998del and c. 3137C>T compound heterozygous mutations.STR analysis showed they originate from PBMCs, and no Sendai virus residual was detected by PCR and agarose gel electrophoresis.Conclusions:In this study, PBMCs from patient carrying ABCA3 compound heterozygous mutations was used to establish iPSCs cell lines.The research lays a foundation for the study of pathogenesis, therapeutic drug screening and cell therapy of NRDS caused by ABCA3 gene mutations.

BACKGROUND:Irreducible femoral neck fracture was difficult to obtain anatomic reduction.As a new type of internal fixation,the femoral neck system is still blank for the treatment of non-anatomical reduced femoral neck fractures. OBJECTIVE:To explore the biomechanical stability of femoral neck system internal fixation under nonanatomical reduction in the treatment of femoral neck fractures based on finite element analysis. METHODS:CT data of the hip joint of a healthy female adult were obtained.Anatomical reduction of femoral neck fracture models with Pauwels angles of 30°,50°,and 70° were established using Mimics 21.0,Geomagic Wrap 2021,and SolidWorks 2020.The fracture proximal ends of the three anatomical reduction models were shifted upward by 2 mm along the fracture line,and three positive buttress models with different Pauwels angles were obtained.In the same way,three negative buttress models were acquired by shifting downward by 2 mm.SolidWorks 2020 was used to make the femoral neck system internal fixation,and the nine femoral neck fracture models were assembled with the femoral neck system.Then Ansys 19.0 was used for finite element analysis.The displacement distribution and maximum displacement,stress distribution and maximum stress of the femur and femoral neck system were recorded under 2100 N stress. RESULTS AND CONCLUSION:(1)When Pauwels angles were 30°,50°,and 70°,the maximum stresses of the femoral neck system appeared to be concentrated at the junction of the sliding hip screw and anti-rotation screw.The maximum femur stresses appeared to be concentrated in the medial cortex of the femur.The maximum displacement was concentrated at the upper of the femoral head and femoral neck system.(2)When Pauwels angles were 30° and 50°,the maximum displacement and maximum stress of the femoral neck system and femur were:negative buttress>anatomical reduction>positive buttress.(3)When Pauwels angle was 70°,the maximum displacement and maximum stress of the femoral neck system were:negative buttress>anatomical reduction>positive buttress;the maximum displacement and maximum stress of the femur were:negative buttress>positive buttress>anatomical reduction.(4)With the increase of Pauwels angle,the biomechanical advantage of the positive buttress was weakening.However,it was better than a negative buttress.When Pauwels angle was 30°,positive buttress was more stable than anatomical reduction.When Pauwels angle was 50°,the biomechanical difference between positive buttress and anatomical reduction became smaller.When Pauwels angle was 70°,the stability of anatomical reduction was slightly better than positive buttress.(5)If it was difficult to achieve anatomical reduction of femoral neck fracture during operation,but the positive buttress had been displaced within 2 mm,the femoral neck system could be used to offer stable mechanical fixation.It is necessary to avoid negative buttress reduction.

Objective To optimize the formulation and preparation process of lenvatinib mixed micelles.Methods Hybrid micelles of lenvatinib were prepared by film hydration method,with Pluronic P123 and F127 as carrier materials.Optimal formulation was selected through single-factor experiments and central composite design-response surface methodology,and preliminary characterization of its physical properties was conducted.Results The optimized formulation and process conditions were identified as follows:P123 mass percentage of 80%,carrier material amount of 90 mg,drug loading of 10 mg,hydration volume of 6 ml,hydration time of 45 min,and rotary evaporation temperature of 55℃.The resulting lenvatinib mixed micelles had an average particle size of(104.0±0.32)nm,a polydispersity index(PDI)of 0.22±1.19,and a Zeta potential of(-2.56±0.81)mV.The average encapsulation efficiency was 83.33%±0.30%and the average drug loading was 8.67%±0.07%.The micelles displayed a uniform spherical morphology with a certain sustained-release capability.Conclusion The preparation process developed in this study was simple and feasible and produced drug-loaded micelles with high drug loading and encapsulation rates,and stable release,which could provide valuable insights for further research and development of lenvatinib mixed micelles.

Objective:To analyze the current status of salary system reform in public hospitals in Mianyang City, Sichuan Province, and provide reference for the deepening of salary system reform in public hospitals.Methods:From April to May 2023, a self-designed survey questionnaire was used to conduct a survey of medical staff in five municipal tertiary public hospitals through the Wenjuanxing platform. The survey questionnaire mainly included the basic information of the survey subjects, the implementation status of the salary system, and employee satisfaction with salary. In May 2023, semi-structured interviews were conducted with relevant personnel from government departments and public hospitals involved in the reform. The interview content included the reform measures taken and their impact, changes in medical staff salaries after the reform, and the current difficulties faced by the reform. Descriptive analysis was conducted on the data, and Chi-square test was used to compare the count data. Kendall′s tau-b test was used to analyze the correlation between salary level and basic information of the survey subjects.Results:In the reform of the salary system in public hospitals in Mianyang City, measures such as system construction, total salary quota determination and dynamic control, and salary management for non-establishment employees have been mainly adopted. 826 valid questionnaires were collected, with an effective response rate of 94.5%. The annual income level was positively correlated with age, education level, years of work experience, and professional title level ( r=0.420, P<0.001; r=0.245, P<0.001; r=0.364, P<0.001; r=0.504, P<0.001). Compared with the personnel in the same positions at the same level of hospitals in other cities and states in Sichuan Province, 274 people (33.2%) were quite satisfied or very satisfied with the current salary level; 350 people (42.3%) were quite satisfied or very satisfied with the salary distribution mechanism, and 441 people (53.4%) were quite satisfied or very satisfied with non-economic salaries. The proportion of survey respondents who believe that the existing salary structure and performance evaluation methods could reflect their actual work value was 464 people (56.2%) and 423 people (51.2%), respectively. A total of 10 people were interviewed, with 4 individuals believing that the salary level has increased after the reform, but the change was not significant compared to before the reform; 8 individuals believed that the current reform does not involve the reform of the salary structure; 6 individuals believed that the internal performance based salary distribution mechanism in hospitals was not sound; 3 individuals believed that there was insufficient attention to the reform of non-economic compensation; 7 individuals believe that the difficulties in the salary system reform were mainly concentrated on the unified understanding of policies, how to determine the increase in the total salary quota, and how to reasonably distribute it internally. Conclusions:Mianyang City has scientifically determined the total salary and implemented dynamic control, enhancing the public welfare nature of public hospitals, while also taking into account the salary management of employees both inside and outside the establishment, promoting equal pay for equal work. However, there were also issues such as disagreements on the dynamic adjustment of the total salary, an imperfect internal distribution mechanism within hospitals, and an incomplete salary system reform. It is necessary to further strengthen top-level design, reasonably increase salary levels, improve the internal distribution mechanism, and optimize the salary structure to continue deepening the reform of the salary system in public hospital.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.
Animals ; Mice ; Antiviral Agents/pharmacology* ; COVID-19 ; Hepatitis B virus ; Interferon Type I/metabolism* ; SARS-CoV-2/drug effects* ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/antagonists & inhibitors*