ObjectiveTo investigate the effect and potential mechanism of caffeic acid （CA） on severe acute pancreatitis （SAP） induced by caerulein combined with lipopolysaccharide （LPS）， and to provide a basis for the research on novel drugs for the treatment of SAP. MethodsC57BL/6J mice， aged 6 weeks， were divided into control group， model group， CA group， and octreotide acetate （OA） group， with 6 mice in each group. The mice in the control group were given injection of normal saline， and those in the other groups were given intraperitoneal injection of caerulein combined with LPS to establish a mouse model of SAP. At 1 hour after the first injection of caerulein， the mice in the CA group and the OA group were given intraperitoneal injection of CA or subcutaneous injection of OA at an interval of 8 hours. The general status of the mice was observed after 24 hours of modeling， and serum， pancreas， lung， and colon samples were collected. HE staining was used to observe the histopathological changes of the pancreas and lungs， and the serum levels of α-amylase， lipase， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， alanine aminotransferase， aspartate aminotransferase， and creatinine were measured. RT-PCR was used to measure the expression of proinflammatory factors in the pancreas and lungs； myeloperoxidase （MPO） immunohistochemistry was used to observe the degree of neutrophil infiltration； Western blot was used to measure the activation of nuclear factor-kappa B （NF-κB） and the level of citrullinated histone H3 （CitH3）， a marker for the formation of neutrophil extracellular traps （NETs）， in the pancreas and lungs， as well as the expression level of ZO-1 in colon tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the Dunnett’s t-test was used for further comparison between two groups. ResultsCompared with the control group， the model group had severe injury in the pancreas and lungs and significant increases in the activity of serum α- amylase and lipase and the levels of the proinflammatory cytokines IL-6， interleukin-1β （IL-1β）， and TNF-α in serum and lung tissue （all P<0.05）， as well as significant increases in NF-κB activation， neutrophil infiltration， and the formation of NETs in the pancreas and lungs （all P<0.05）. Compared with the model group， the CA group had alleviated pathological injury of the pancreas and lungs and significant reductions in the activity of serum α-amylase and the levels of the proinflammatory cytokines IL-6， IL-1β， and TNF-α in serum and lung tissue （all P<0.05）， as well as significant reductions in NF-κB activation， neutrophil infiltration， and the formation of NETs in the pancreas and lungs （all P<0.05）. ConclusionCA can alleviate SAP induced by caerulein combined with LPS in mice， possibly by inhibiting neutrophil recruitment and the formation of NETs.

BACKGROUND: The effects of human umbilical cord-derived mesenchymal stem cell (UC-MSC) treatment on coronavirus disease 2019 (COVID-19) patients have been preliminarily characterized. However, real-world data on the safety and efficacy of intravenous transfusions of MSCs in hospitalized COVID-19 patients at the convalescent stage remain to be reported. METHODS: This was a single-arm, multicenter, real-word study in which a contemporaneous external control was included as the control group. Besides, severe and critical COVID-19 patients were considered together as the severe group, given the small number of critical patients. For a total of 110 patients, 21 moderate patients and 31 severe patients were enrolled in the MSC treatment group, while 26 moderate patients and 32 severe patients were enrolled in the control group. All patients received standard treatment. The MSC treatment patients additionally received intravenous infusions of MSCs at a dose of 4 × 10 7 cells on days 0, 3, and 6, respectively. The clinical outcomes, including adverse events (AEs), lung lesion proportion on chest computed tomography, pulmonary function, 6-min walking distance (6-MWD), clinical symptoms, and laboratory parameters, were measured on days 28, 90, 180, 270, and 360 during the follow-up visits. RESULTS: In patients with moderate COVID-19, MSC treatment improved pulmonary function parameters, including forced expiratory volume in the first second (FEV1) and maximum forced vital capacity (VCmax) on days 28 (FEV1, 2.75 [2.35, 3.23] vs . 2.11 [1.96, 2.35], P  = 0.008; VCmax, 2.92 [2.55, 3.60] vs . 2.47 [2.18, 2.68], P  = 0.041), 90 (FEV1, 2.93 [2.63, 3.27] vs . 2.38 [2.24, 2.63], P  = 0.017; VCmax, 3.52 [3.02, 3.80] vs . 2.59 [2.45, 3.15], P  = 0.017), and 360 (FEV1, 2.91 [2.75, 3.18] vs . 2.30 [2.16, 2.70], P  = 0.019; VCmax,3.61 [3.35, 3.97] vs . 2.69 [2.56, 3.23], P  = 0.036) compared with the controls. In addition, in severe patients, MSC treatment notably reduced the proportion of ground-glass lesions in the whole lung volume on day 90 ( P  = 0.045) compared with the controls. No difference in the incidence of AEs was observed between the two groups. Similarly, no significant differences were found in the 6-MWD, D-dimer levels, or interleukin-6 concentrations between the MSC and control groups. CONCLUSIONS: Our results demonstrate the safety and potential of MSC treatment for improved lung lesions and pulmonary function in convalescent COVID-19 patients. However, comprehensive and long-term studies are required to confirm the efficacy of MSC treatment. TRIAL REGISTRATION Chinese Clinical Trial Registry, ChiCTR2000031430.
Humans ; COVID-19/therapy* ; Female ; Male ; Mesenchymal Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adult ; Umbilical Cord/cytology* ; Mesenchymal Stem Cells/cytology* ; SARS-CoV-2 ; Aged ; Treatment Outcome

Objective : To analyze the current status of anti-PD-1 combined with chemotherapy in advanced gastric cancer. Methods: The clinical data of 120 patients with advanced gastric cancer treated with chemotherapy or anti-PD-1 plus chemotherapy were retrospectively analyzed. The efficacy [measures include objective response rate(ORR), disease control rate(DCR), and progression-free survival(PFS)]and the occurrence of adverse reactions in patients was monitored. Univariate and multivariate Cox were used to analyze the relationship between clinicopathologic data [including age, gender, body mass index(BMI), differentiation degree, and related hematological indexes], specific treatment conditions and PFS, and to analyze the influence of treatment plan and line number on the curative effect. Results : The PFS of chemotherapy plus immunotherapy was significantly better than that of chemotherapy alone(P<0.05), and the median PFS of the two was 7.17 months(95%CI5.85-8.49) and 5.33 months(95%CI3.96-5.70), respectively. In the combination group, the overall ORR was 27.5% and DCR was 94.8%. In the chemotherapy group alone, the overall ORR was 9.7% and DCR was 69.4%.In the chemotherapy plus anti-PD-1 group, a high prognostic nutritional index(PNI) level also provided superior PFS in patients with a 47% reduction in the risk of progression versus a low PNI level [HR0.53(95%CI0.30-0.96);P<0.05]. The median PFS was 7.47 months(95%CI5.83-9.11) with a high PNI level versus 6.00 months(95%CI4.45-7.55) with a low PNI level. The overall incidence of adverse reactions of chemotherapy combined with anti-PD-1 was slightly higher than that of chemotherapy alone, and the incidence of adverse reactions of grade 3-4 was similar, within a controllable range, and could be improved after clinical treatment. Conclusion The efficacy of anti-PD-1 combined with chemotherapy in patients with advanced gastric cancer is better than that of chemotherapy, and the adverse reactions are controllable. In the chemotherapy plus anti-PD-1 group, patients with high PNI levels achieved a higher PFS.

Objective To study the effect of temperature on microleakage of Beautifil Flow Plus F00,FiltekTM Z350 XT,SDR,Tet-ric?N-Flow and Constic,and to provide reference for clinical selection of ideal fluid resins.Methods A total of 60 adult detached premolars removed for orthodontic extraction were divided into 10 groups(n=12),which were divided into F00A group,Z350A group,SDRA group,TetricA group and ConsticA group according to whether they had undergone cold and hot cycle aging test,and F00B group,Z350B group,SDRB group,TetricB group,ConsticB group,a total of 10 groups.The occlusal surface of each isolated tooth was prepared into a type Ⅰhole with the width of 2 mm,length of 4 mm and depth of 2 mm,which was filled with the corresponding fluid resin respectively.Methylene blue staining experiment was performed on specimens in group A,and methylene blue staining experiment was performed on specimens in group B after 5 000 times of cold and hot cycling aging experiment.The crowns of all specimens were dissected longitudinally along the long axis of the tooth body from the direction of buccal tongue(palate).The degree of microleakage in each group was observed under stereomicroscope,and the data were recorded and analyzed statistically.Results ①There was no sig-nificant difference in the degree of microleakage between the F00A group,the Z350A group,the SDRA group,the TetricA group and the ConsticA group(P>0.05).②The degree of microleakage in the SDRB group and TetricB group was significantly higher than that in the F00B group and Z350B group(P<0.05).③Temperature had a significant effect on the microleakage degree of Beautifil Flow Plus F00,FiltekTM Z350 XT,SDR,Tetric? N-Flow and Constic(P<0.05).Conclusion ①There was no significant difference in the de-gree of immediate microleakage of Beautifil Flow Plus F00,FiltekTM Z350 XT,SDR,Tetric?N-Flow,and Constic without cold and hot cycle aging experiments.②After the cold and hot cycle aging experiments,the microleakage degree of SDR fluid resin and Tetric? N-Flow fluid resin was high,and the edge tightness was poor.Beautifil Flow Plus F00 fluid resin and FiltekTM Z350 XT fluid resin had a low degree of microleakage and better edge tightness.③The micro-leakage degree of Beautifil Flow Plus F00，FiltekTM Z350 XT，SDR，Tetric? N-Flow and Constic was aggravated by the cold and hot cycle aging ex-periments.

Improving the construction of new mechanisms for the operation of public hospitals is an important task in promoting the comprehensive reform of public hospitals and the construction of modern hospital management systems.It analyzes the background of constructing new operational mechanisms based on policy evolution,histori-cal evolution,and practical needs,and analyzes the problems of imbalanced management resource allocation struc-ture,one-sided pursuit of economic benefits,low input-output efficiency,and low personnel enthusiasm in hospital operation.It proposes to grasp the key path and main measures to improve the construction of new operating mecha-nisms for public hospitals while respecting industry characteristics,adhering to government leadership,and improving market regulation.

In order to make the shared traditional Chinese medicine （TCM） pharmacy develop more efficiently and normatively at the grass-roots level， using the “shared TCM pharmacy” as the retrieval word， this paper uses the literature research method to retrieve the reports， documents and policies from CNKI， the websites of people’s governments at all levels， the official websites of the State Administration of Traditional Chinese Medicine， people.com， China News Network， Xinhua News and other platforms before May 20， 2022， sort out the development mode and history of two “Internet plus” TCM pharmacies， namely “shared TCM pharmacies” and “smart TCM pharmacies”， and compare them with each other. Combined with the actual work of community hospitals and community service centers （stations）， the necessity and advantages （such as reducing the costs of the intermediate links of drug circulation and standardizing the grass-roots drug use process） of the development of “shared TCM pharmacy” are obtained from the perspective of primary medical care. Combined with the current situation of the promotion and application of shared TCM pharmacy in county medical communities， it is concluded that the shared TCM pharmacy should be further constructed from four aspects： improving the work process of drug centralized procurement under the background of normalization， improving the compatibility and synchronization of the whole process dispensing information system module， unifying pharmaceutical services and personnel training， defining the authority of data query and clarifying the boundaries of patient privacy to further build a shared TCM pharmacy. Finally， it integrates information technology， summarizes the definition of shared TCM pharmacy and its future construction direction， and provides reference for the next development of shared TCM pharmacy at the grass-roots level.

Critical care medicine is the last line of defense for people′s lives and health, and it is necessary to attach great importance to the development of critical care medicine and the construction of treatment capabilities. This study analyzed the development effect of critical care medicine and critical care capacity in China, analyzed the shortcomings of the current shortage of talent and treatment capacity reserves in the field of critical care medicine, combed the experience of foreign countries in attaching importance to the reserve of critical care resources, the mechanism of combining peacetime and wartime, and the construction of critical care database. Targeted suggestions were proposed to strengthen development planning, optimize investment mechanism, improve talent cultivation and growth, and build critical care database, so as to provide reference for promoting the development of critical care medicine and improving the ability of critical care in China.

Objective:To analyze the patterns of intercellular communication in facioscapulohumeral muscular dystrophy (FSHD) by single-cell nuclear transcriptome sequencing.Methods:Bilateral asymmetrical lesions mouth orbicular muscle of two patients with FSHD and mouth orbicular muscle of two healthy patients were selected. Six samples were obtained, and were divided into control group, mild group and severe group. The normal orbicularis muscle sample was collected from 2 healthy individuals (the control group). The muscle samples in the mild group were from two patients with relatively normal muscle sides, and the samples in the severe group were from two patients with more severe muscle damage sides. Single-cell nuclear transcriptome sequencing was performed on all cells of the three groups. Reduced dimension clustering and cell definition were performed to identify differentially expressed genes and enrichment pathways. Intercellular communication patterns among major cell types and key signaling pathways were explored by cellular communication analysis.Results:Differential gene expression analysis of FSHD bilateral muscle samples identified 46 functionally differentially expressed genes associated with the disease in different cell types, related to apoptosis, oxidative stress, immune inflammation, and muscle function. Intercellular communication was generally increased in the severe group. Fibro-adipogenic progenitors (FAPs) and macrophages are important signaling sources in the abnormal muscle microenvironment of FSHD and are closely associated with disease progression. There are six unique signaling pathways in the mild group, including bone morphogenetic proteins (BMP), transforming growth factor-β (TGF-β), CXC motif chemokine ligand (CXCL), adhesion G protein-coupled receptor E5 (ADGRE5), interleukin-16 (IL-16), and wingless-type MMTV integration site family (WNT) signaling pathways. These signaling pathways are mainly involved in the interaction between macrophages, FAPs, and adipocytes and may be involved in the regulation of fat deposition and fibrosis changes in the diseased muscle.Conclusions:Single-cell nuclear transcriptome sequencing provides a relatively comprehensive pattern of intercellular communication between key cell types in FSHD, providing an appropriate reference for understanding the intercellular regulatory mechanisms of the FSHD muscle microenvironment.

We report on two cases of type C insulin resistance syndrome(TCIRS) admitted to the Department of Endocrinology, Peking Union Medical College Hospital from January 2000 to December 2020. Both patients presented with persistent hyperglycemia, low immunoreactive insulin, extreme insulin resistance, high insulin autoantibodies, high total insulin, and large insulin antibody pool. TCIRS is marked by extreme insulin resistance with ketoacidosis and respond to medium to high doses glucocorticoids rather than plasmapheresis.