Acid-switchable nanoparticles induce self-adaptive aggregation for enhancing antitumor immunity of natural killer cells

Deficiency of natural killer (NK) cells shows a significant impact on tumor progression and failure of immunotherapy. It is highly desirable to boost NK cell immunity by upregulating active receptors and relieving the immunosuppressive tumor microenvironment. Unfortunately, mobilization of NK cells is hampered by poor accumulation and short retention of drugs in tumors, thus declining antitumor efficiency. Herein, we develop an acid-switchable nanoparticle with self-adaptive aggregation property for co-delivering galunisertib and interleukin 15 (IL-15). The nanoparticles induce morphology switch by a decomposition-metal coordination cascade reaction, which provides a new methodology to trigger aggregation. It shows self-adaptive size-enlargement upon acidity, thus improving drug retention in tumor to over 120 h. The diameter of agglomerates is increased and drug release is effectively promoted following reduced pH values. The nanoparticles activate both NK cell and CD8+ T cell immunity in vivo. It significantly suppresses CT26 tumor in immune-deficient BALB/c mice, and the efficiency is further improved in immunocompetent mice, indicating that the nanoparticles can not only boost innate NK cell immunity but also adaptive T cell immunity. The approach reported here provides an innovative strategy to improve drug retention in tumors, which will enhance cancer immunotherapy by boosting NK cells.

Expression level and clinical significance of SOCS1 in the serum of patients with chronic HBV-related liver disease / 西安交通大学学报(医学版)

【Objective】 To study the expression levels of suppressor of cytokine signaling 1 (SOCS1) and its clinical significance in hepatitis B virus (HBV)-related liver diseases. 【Methods】 For this study we enrolled 25 patients with chronic hepatitis B (CHB), hepatitis B cirrhosis, or HBV-associated chronic acute liver failure (HBV-ACLF), and 25 healthy controls. The expression levels of SOCS1 mRNA in peripheral blood mononuclear cells (PBMCs) were determined using the RT-PCR method. The levels of SOCS1 and interleukin-6 (IL-6) in the plasma of patients with chronic liver diseases and healthy controls were measured using the ELISA method. The relative expression levels of SOCS1, SOCS1 mRNA, and other laboratory test indicators such as HBV-DNA, alanine aminotransferase (ALT), aspartate aminotransferase (AST), prothrombin activity (PTA) and total bilirubin (TBil) were compared among the groups. Additionally, the correlation between the expression levels of SOCS1 mRNA and the aforementioned laboratory indicators was assessed. 【Results】 The expression levels of SOCS1 mRNA and serum SOCS1 were highest in the HBV-ACLF group, followed by the cirrhosis group, and lowest in the healthy control group, with statistically significant differences (F=109.65, P<0.001). The relative expression of SOCS1 mRNA was positively correlated with TBil (r=0.89, P<0.001), ALT (r=0.89, P<0.001), AST (r=0.84, P<0.001) and IL-6 (r=0.93, P<0.001), but negatively correlated with PTA (r=-0.89, P<0.001) and was not significantly correlated with HBV-DNA (P=0.28). 【Conclusion】 The expression levels of SOCS1 in patients with HBV-related chronic liver diseases can reflect the severity of the disease and show a significant correlation with indicators used to assess the severity of liver diseases.

Analysis of DRG grouping effect and influential factors of hospitalization cost of diabetic patients / 中国药房

OBJECTIVE To explore the grouping efficacy of diagnosis related group （DRG） and the influential factors of hospitalization cost in diabetes cases， and to provide theoretical support for improving DRG payment system， reducing medical cost and enhancing the efficiency of medical insurance funds. METHODS The information of 4 368 diabetic patients who were hospitalized in a 3A hospital in Xi’an from January 1， 2021 to June 30， 2023 was retrospectively analyzed， and DRG grouping of them was summarized； the hospitalization costs of patients in different DRG groups were analyzed by using one way ANOVA and Bonferroni multiple comparison. Coefficient of variation （CV） was used for evaluation within the group， and the influential factors of hospitalization costs were analyzed by one-way linear regression analysis and multi-factor linear regression analysis. RESULTS & CONCLUSIONS The CV values of the four DRG groups were all lower than 0.8， indicating good grouping results and good consistency within the group； the difference of hospitalization cost among the four groups was statistically significant （P＜0.05）， and the hospitalization cost of China Healthcare Security-DRG version 1.1 FW11 group was significantly higher than those of other three groups （P＜0.05）. Length of stay， drug cost， the number of other diagnoses， test cost and payment method have significant positive effects on the hospitalization cost of diabetic patients. Whether there is pharmacist intervention has a significant negative influence on the hospitalization cost of patients. Under the DRG payment method， medical institutions can consider multidisciplinary linkage and incorporate a variety of management and service tools， including pharmacist’s intervention， to develop refined management measures， to reduce the economic burden of patients’ families and society.

Prevention and caring of children's tic disorders based on incubative evil theory / 国际中医中药杂志

Tic disorder (TD) is a common neuro-developmental disorders in children during school age. The cause is complex and it can be induced or aggravated by varies of factors such as genetics, exogenous pathogens, and emotions. TD affects children's self-cognition, academic level, and social function, and causes parents to have unhealthy psychological states such as anxiety and depression, and affects family harmony. Therefore, clinical attention should not only be paid to the treatment of this disease, but also to prevention and nursing care. Incubative evil theory is one of the important theories of Traditional Chinese Medicine. This theory can help to treat and prevent diseases. Incubative evil is characterized by no symptoms with spontaneous attack by latent pathogen, but symptoms appearance induced by the pathogen. The pathological process of TD is similar to incubative evil characteristics. This paper discusses the prevention and nursing care of children's tic disorder based on the theory of incubative evil.

Influencing factors of surgical site infection after abdominal surgery / 中华消化外科杂志

Objective:To investigate the influencing factors of surgical site infection (SSI) after abdominal surgery.Methods:The retrospective cross-sectional study was conducted. The clinical data of 567 patients undergoing abdominal surgery in 6 medical centers, including 445 cases in the Zhengzhou Central Hospital Affiliated to Zhengzhou University, 54 cases in the the First Affiliated Hospital of Zhengzhou University, 49 cases in the Shangqiu First People's Hospital, 10 cases in the Luoyang Central Hospital, 5 cases in the First Affiliated Hospital of Henan University of Science and Technology and 4 cases in the Henan Provincial People's Hospital, from June 1 to June 30, 2020 were collected. There were 284 males and 283 females, aged (51±18)years. Observation indicators: (1) incidence of SSI after surgery; (2) influencing factors of SSI. Follow-up was conducted using outpatient examination and telephone interview to detect the incidence of SSI. Patients without implant were followed up within postoperative 30 days, and patients with implant were followed up within postoperative 1 year. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measure-ment data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was performed using the chi-square test or Fisher exact probability. Univariate analysis was performed using the corresponding statistical methods. Multivariate analysis was performed using the Logistic stepwise regression model advance method. Results:(1) Incidence of SSI after surgery. All the 567 patients were followed up after surgery as planned. There were 27 cases with SSI after surgery including 9 cases with superficial incision infection, 9 cases with deep incision infection, 9 cases with organ/gap infection. Of the 27 cases with SSI after surgery, 18 cases with positive results of incisional microbial culture including 8 cases with positive results of Escherichia coli, 6 cases with positive results of Klebsiella pneumonia, 3 cases with positive results of Enterococcus faecium and 1 case with positive result of Pseudomonas aeruginosa. (2) Influencing factors of SSI. Results of univariate analysis showed that age, preoperative hemoglo-bin, preoperative albumin, preoperative fasting blood glucose, preoperative intestinal preparation, surgical type, surgical site, surgical incision type, duration of intensive cure unite, duration of post-operative hospital stay, duration of total hospital stay, operation time, hospital expense were related factors affecting the incidence of SSI of patients undergoing abdominal surgery ( χ2=40.12, Z=?4.22, ?2.21, ?4.75, χ2=7.07, 16.43, 38.06, 17.50, Z=?4.43, ?4.42, ?7.14, ?7.15, ?5.90, P<0.05) and the American Association of Anesthesiologists Classification, preoperative oral antibiotics, surgical methods and postoperative intensive care unit stay were related factors affecting the incidence of SSI of patients undergoing abdominal surgery ( P<0.05). Results of multivariate analysis showed that age, preopera-tive fasting blood glucose, preoperative intestinal preparation, surgical type, surgical site as appendix and rectum, surgical methods, surgical incision type as infective incision and polluted incision, operation time were independent factors affecting the incidence of SSI of patients undergoing abdo-minal surgery ( odds ratio=7.69, 1.21, 0.27, 5.82, 5.19, 19.08, 0.23, 27.76, 4.97, 1.01, 95% confidence intervals as 2.04?28.95, 1.04?1.41, 0.08?0.94, 1.36?24.85, 1.10?24.43, 4.48?81.25, 0.06?0.87, 2.54?303.53, 1.12?22.14, 1.01?1.02, P<0.05). Conclusion:Age, preoperative fasting blood glucose, preoperative intestinal preparation, surgical type, surgical site as appendix and rectum, surgical methods, surgical incision type as infective incision and polluted incision, operation time are independent factors affecting the incidence of SSI of patients undergoing abdominal surgery.

Levels of base excision repair proteins in CD4+ T cells in patients with systemic lupus erythematosus / 中南大学学报(医学版)

OBJECTIVES@#Systemic lupus erythematosus (SLE) is a multi-systemic disease with the unknown pathogenic mechanism. DNA demethylation is involved in SLE pathogenesis. Growth arrest and DNA damage inducible 45 alpha (Gadd45a) takes part in the process of DNA demethylation. Gadd45a is a DNA repair-related protein. This study aims to investigate the expressions of some proteins [including activation-induced cytidine deaminase (AID), thymine DNA glycosylase (TDG), and methyl-CpG-binding domain protein 4 (MBD4)] involving in base excision repair (BER) process in CD4+ T cells in patients with SLE, and to analyze the correlations between the above BER proteins and lupus disease.@*METHODS@#From January 2019 to September 2020, 12 SLE patients and 12 healthy controls were recruited from Second Xiangya Hospital of Central South University. Peripheral blood mononuclear cells (PBMCs) were separated by Ficoll-Hypaque density gradient centrifugation and then CD4+ T cells were isolated via positive selection using Miltenyi beads. We measured the messenger RNA (mRNA) and protein expressions of AID, TDG, and MBD4 by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blotting, respectively.@*RESULTS@#In contrast to controls, in SLE CD4+ T cells, the mRNA and protein expressions of AID were elevated (P=0.003, P=0.022, respectively); TDG protein expression was increased (P=0.017); and MBD4 protein level was reduced (P<0.001). No visible distinctions was found in the mRNA expressions of either TDG or MBD4 between the 2 groups (both P>0.05). The mRNA and protein expressions of AID and the protein levels of TDG were positively correlated with SLE disease activity index (SLEDAI). And the mRNA and protein expressions of MBD4 were negatively correlated with SLEDAI.@*CONCLUSIONS@#In SLE CD4+ T cells, the increased expressions of AID and TDG and the decreased MBD4 expression may participate in SLE pathogenic mechanism.

Efficacy and safety of dupilumab in the treatment of 123 cases of atopic dermatitis / 中华皮肤科杂志

Objective:To investigate clinical efficacy and safety of dupilumab in the treatment of atopic dermatitis (AD) .Methods:An ambispective study was conducted on 123 AD patients treated with dupilumab in Department of Dermatology, the Second Xiangya Hospital of Central South University from July 2020 to March 2022, clinical data were collected, and efficacy and safety of dupilumab were evaluated. Primary outcomes included scores of eczema area and severity index (EASI) , patient-oriented eczema measure (POEM) , peak pruritus numerical rating scale (NRS) and dermatology life quality index (DLQI) before and after 4-, 8-, 12- and 16-week treatment, and adverse reactions and events were recorded. Comparison of scores before and after treatment was performed using paired t test or repeated measures analysis of variance, Mann-Whitney U test was used for the comparison of efficacy among patients with different types of skin lesions or different IgE levels, and multiple regression model based on robust standard errors was used to analyze factors influencing the efficacy. Results:Among the 123 AD patients, 107 were enolled into the efficacy analysis, and 85 (79.44%) completed at least 4 weeks of treatment, including 6 (7.06%) achieving EASI75 and 23 (27.06%) achieving EASI50, and the EASI, NRS, POEM, DLQI scores (10.41 ± 6.72, 4.12 ± 1.74, 8.60 ± 4.29, 7.81 ± 4.38, respectively) significantly decreased compared with those before treatment (18.08 ± 10.69, 7.21 ± 2.01, 16.88 ± 5.74, 12.95 ± 5.95, respectively; all P < 0.001) in the 85 patients. Among the 107 patients, 47 (43.93%) completed at least 16 weeks of treatment. Among the 47 patients, 23 (82.14%) of 28 adults and 17 (89.47%) of 19 adolescents and children achieved 75% or greater improvement in EASI score; the EASI, NRS, POEM and DLQI scores before the treatment all significantly differred from those 4, 8, 12, 16 weeks after the treatment (all P < 0.001) , and all the scores were significantly lower at weeks 4, 8, 12 and 16 than at the previous adjacent time points (all P < 0.05) . At week 4 during the treatment, the EASI improvement rate was significantly lower in the AD patients with prurigo nodularis than in those without ( U = 151.00, P = 0.006) , while there was no significant difference in the EASI improvement rate between the AD patients with xeroderma and those without ( P > 0.05) ; at week 16 during the treatment, there was no significant difference in the EASI improvement rate between patients with prurigo nodularis or xeroderma and those without (both P > 0.05) . Multiple regression analysis based on robust standard errors at week 16 showed that the improvement degree in the EASI score was not correlated with the type of skin lesions ( β = 3.20, P = 0.075) , but correlated with age ( β = -0.22, P = 0.030) , whether patients were in adulthood ( β = 9.54, P = 0.049) , immediate family history ( β = 7.46, P = 0.017) ; the improvement degree in the NRS score was correlated with the type of skin lesions ( β = 0.55, P = 0.032) , age ( β = -0.04, P = 0.033) , weight ( β = -0.05, P = 0.020) , whether patients were in adulthood ( β = 2.06, P = 0.003) and whether patients received combined treatment with antihistamines ( β = -1.91, P = 0.001) . Adverse reactions: among the 123 patients, 6 (4.88%) developed conjunctivitis, and 2 (1.63%) developed facial erythema. Adverse events: vitiligo-like changes occurred on the right forehead of 1 patient, and 3 patients discontinued the treatment with dupilumab due to Henoch-Sch?nlein purpura, distal axonal damage in peripheral nerves in both upper limbs, and epilepsy, respectively. The causal relationship between these adverse events and dupilumab was unclear. Conclusion:Dupilumab is effective in the treatment of AD with high overall safety, and can serve as a new treatment option for AD patients with an unsatisfactory response to traditional treatment.

Expression and clinical significance of vitamin D receptor in children with hand, foot and mouth disease / 中国小儿急救医学

Objective:To detect the expression level of vitamin D receptor(VDR) in children with hand, foot, and mouth disease(HFMD), and explore its potential value in the diagnosis and treatment of children with HFMD.Methods:A total of 82 children with HFMD hospitalized in the Second Affiliated Hospital of Xi′an Jiaotong University and Xi′an Children′s Hospital from May 2017 to May 2019 were selected as the case group.At the same time, 42 healthy children who underwent physical examination in the Child Health Department during the same period were randomly selected as the control group.Peripheral blood of two groups of children was extracted to detect and compare the expression levels of VDR mRNA in mononuclear cells, and the correlation between the expression level of VDR and HFMD and the correlation with various clinical characteristics were analyzed.Results:The relative expression of VDR in children with EV71 HFMD was 2.03%±0.38%, which was lower than that in children of control group(3.11%±1.29%), and the difference was statistically significant( t=-3.586, P=0.001). However, the relative expression of VDR in children with CA16 HFMD was 3.69%±1.79%, which was higher than that in children of control group, and the difference was not statistically significant( t=1.043, P=0.305). Among children with EV71 HFMD, the relative expression level of VDR was significantly different between the mild group and the severe group(2.18%±0.44% vs. 1.84%±0.17%, t=2.199, P= 0.041). There was no statistical difference regarding the relative expression level of VDR between mild and severe CA16 HFMD(4.16%±1.73% vs. 2.93%±1.73%, t=1.587, P=0.129). Conclusion:Compared with healthy children, the expression level of VDR is significantly lower in children with EV71 HFMD, and may be related to the severity of EV71 HFMD.

Current approaches of nanomedicines in the market and various stage of clinical translation

Compared with traditional drug therapy, nanomedicines exhibit intriguing biological features to increase therapeutic efficiency, reduce toxicity and achieve targeting delivery. This review provides a snapshot of nanomedicines that have been currently launched or in the clinical trials, which manifests a diversified trend in carrier types, applied indications and mechanisms of action. From the perspective of indications, this article presents an overview of the applications of nanomedicines involving the prevention, diagnosis and treatment of various diseases, which include cancer, infections, blood disorders, cardiovascular diseases, immuno-associated diseases and nervous system diseases, etc. Moreover, the review provides some considerations and perspectives in the research and development of nanomedicines to facilitate their translations in clinic.

Light-controllable charge-reversal nanoparticles with polyinosinic-polycytidylic acid for enhancing immunotherapy of triple negative breast cancer

Nucleic acid drugs are highly applicable for cancer immunotherapy with promising therapeutic effects, while targeting delivery of these drugs to disease lesions remains challenging. Cationic polymeric nanoparticles have paved the way for efficient delivery of nucleic acid drugs, and achieved stimuli-responsive disassembly in tumor microenvironment (TME). However, TME is highly heterogeneous between individuals, and most nanocarriers lack active-control over the release of loaded nucleic acid drugs, which will definitely reduce the therapeutic efficacy. Herein, we have developed a light-controllable charge-reversal nanoparticle (LCCN) with controlled release of polyinosinic-polycytidylic acid [Poly(I:C)] to treat triple negative breast cancer (TNBC) by enhanced photodynamic immunotherapy. The nanoparticles keep suitably positive charge for stable loading of Poly(I:C), while rapidly reverse to negative charge after near-infrared light irradiation to release Poly(I:C). LCCN-Poly(I:C) nanoparticles trigger effective phototoxicity and immunogenic cell death on 4T1 tumor cells, elevate antitumor immune responses and inhibit the growth of primary and abscopal 4T1 tumors in mice. The approach provides a promising strategy for controlled release of various nucleic acid-based immune modulators, which may enhance the efficacy of photodynamic immunotherapy against TNBC.

Research advance in androgenetic alopecia in 2020 / 中华皮肤科杂志

Androgenetic alopecia is a distinctive condition associated with genetic factors and effect of androgens, usually adversely affects the appearance and mental health of patients. This review summarizes research progress in the pathogenesis, diagnosis, evaluation and clinical treatment of androgenetic alopecia in 2020.

Clinical analysis of 1 057 patients with critical illnesses in a dermatological ward / 中华皮肤科杂志

Objective:To summarize clinical characteristics of and treatment experience with patients with critical illnesses in a dermatological ward.Methods:All patients with serious or life-threatening conditions, who were hospitalized at the dermatological ward of the Second Xiangya Hospital of Central South University from July 9, 2011 to December 31, 2020, were collected, and their clinical data were retrospectively analyzed. Demographic characteristics, disease types and proportions, main complications, causes of serious or life-threatening conditions, important treatment measures and outcomes were summarized, and causes of death were also analyzed and discussed.Results:A total of 1 057 patients with critical illnesses were collected, with a male-to-female ratio of 1∶1.11, and 64.81% of them aged 18 to 65 years. The types of diseases mainly included drug eruptions (332 cases) , connective tissue diseases (226 cases) , bullous skin diseases (104 cases) , psoriasis (57 cases) , erythroderma (45 cases) , infectious skin diseases (67 cases) , etc. Among them, psoriasis (39 cases) and erythroderma (32 cases) mostly occurred in males, and connective tissue diseases (168 cases) mostly occurred in females. Common complications mainly involved infections, important organ damage or dysfunction, hypoalbuminemia, and fluid, electrolyte and acid-base imbalances. A total of 94 patients were diagnosed with life-threatening conditions, which were found to be mainly caused by primary skin diseases, hematologic abnormalities, respiratory failure, nervous system abnormalities, renal failure, sepsis, fluid, electrolyte and acid-base imbalances, etc. During the management of critical illnesses, 43 patients were treated with high-dose glucocorticoid pulse therapy, 264 were treated with gamma-globulin pulse therapy, 355 were transfused with other blood products, and 34 received special therapies such as hemoperfusion/immunoadsorption therapy, plasma exchange, dialysis, artificial liver support therapy; 42 patients were transferred to the intensive care unit (ICU) , 12 were transferred to the department of surgery for operations, and 12 were transferred to the department of obstetrics and gynecology for delivery or induction of labor. After treatment, 989 patients (93.57%) achieved improvement and were discharged. A total of 14 patients (1.32%) died, of whom 7 died of secondary sepsis, 2 died of severe pulmonary infections, 2 died of asphyxia caused by respiratory mucosa shedding-induced airway obstruction, the other 3 died of gastrointestinal hemorrhage, cerebral hemorrhage and neuropsychiatric systemic lupus erythematosus, respectively.Conclusions:Critical cases in the dermatological ward mainly suffered from serious skin diseases such as severe drug eruptions, connective tissue diseases and bullous skin diseases, as well as complications such as severe underlying diseases, severe organ dysfunction, sepsis or severe fluid, electrolyte and acid-base imbalances. In terms of treatment, it is of critical significance to make a clear diagnosis and assess the severity of disease as early as possible, monitor and prevent possible complications, and to consult with specialists in relevant disciplines in time.

A case of atypical late-onset Netherton syndrome without bamboo hair / 中华皮肤科杂志

A 24-year-old female patient presented with recurrent itchy annular erythema and scales on the trunk and extremities for 9 years. Histopathological study revealed hyperkeratosis with focal parakeratosis, neutrophil aggregation in the stratum corneum, blisters below the stratum corneum, and perivascular infiltration with lymphocytes, a small number of eosinophils and neutrophils in the superficial and middle dermis. Direct immunofluorescence assay showed negative staining for IgG, IgM, IgA and C3. Whole-exome sequencing of the SPINK5 gene showed a missense mutation c.2423C>T (p.T808I) in exon 25, and a splicing site mutation c.2965-1G>A in exon 31. The compound heterozygosity for the two mutations may be the cause of Netherton syndrome in the patient. Based on the clinical manifestations and genetic testing results, the patient was diagnosed with Netherton syndrome.

Influencing factors for the short-term prognosis of patients with HBV-related acute-on-chronic liver failure / 临床肝胆病杂志

ObjectiveTo investigate the influencing factors for the short-term prognosis of patients with HBV-related acute-on-chronic liver failure (HBV-ACLF). MethodsClinical data were collected from 240 HBV-ACLF patients without liver transplantation who were admitted To The Second Affiliated Hospital of Xi’an Jiaotong University from January 2009 to December 2019, and the patients were divided into groups according to survival on days 28 and 90 after admission (28-day survival group with 164 patients and 28-day death group with 76 patients; 90-day survival group with 140 patients and 90-day death group with 100 patients). The data collected included predisposing factors, liver function parameters, Model for End-Stage Liver Disease (MELD) score, MELD combined with serum sodium concentration (MELD-Na) score, and complications. The Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The receiver operating characteristic (ROC) curve was plotted to calculate the area under the ROC curve (AUC), and a multivariate logistic regression analysis was used to investigate the risk factors for the short-term prognosis of HBV-ACLF. ResultsThe main predisposing factors of HBV-ACLF included spontaneous activation of HBV (55.6%) and HBV activation caused by the withdrawal of or resistance to nucleoside analogues (25.2%). There were significant differences in age, prothrombin time activity (PTA), neutrophil-lymphocyte ratio (NLR), serum sodium, MELD score, MELD-Na score, and total bilirubin (TBil) at baseline between the 28-day survival group and the 28-day death group (Z=-2.400,-6.015, -5.070, -5.103, -5.044, -7.430, and -6.637, all P＜0.05), and there were also significant differences in age, PTA, NLR, serum sodium, MELD score, MELD-Na, TBil, and cholesterol at baseline between the 90-day survival group and the 90-day death group (Z=-2.205, -7.728, -3.335, -4.015, -6.053, -7.908, -6.655, and -3.607, all P＜0.05). The multivariate logistic regression analysis showed that TBil ＞260.20 mmol/L (odds ratio ［OR］=4.572, 95% confidence interval ［CI］: 1.321-15823, P＜0.05), PTA ＜24.8% (OR=8.934, 95%CI: 3.026-26.374, P＜0.05), NLR＞5.63 (OR=2.632, 95%CI: 1.126-6.152, P＜0.05), serum sodium ＜130.8 mmol/L (OR=27.467, 95%CI: 6.113-123.423, P＜0.05), MELD score ＞17.84 (OR=4.303, 95%CI: 1.048-17.663, P＜0.05), and MELD-Na score ＞25.1 (OR=3.453, 95%CI: 1.614-7.387, P＜0.05) were independent risk factors for 28-day survival; TBil＞260.20 mmol/L (OR=5.148, 95%CI: 1.918-13.822, P＜0.05), PTA ＜25.5% (OR=15.718, 95%CI: 5.161-47.866, P＜0.05), serum sodium ＜135.3 mmol/L (OR=10.080, 95%CI: 3.244-31.323, P＜005), MELD score ＞17.84 (OR=11.157, 95%CI: 2.580-48.254, P＜0.05), MELD-Na score ＞25.1 (OR=4.391, 95%CI: 2057-9.372, P＜0.05) were independent risk factors for 90-day survival. Among the 240 patients, 160 (66.7%) experienced infection within 90 days, among whom 140 had bacterial infection, 12 had viral infection, and 8 had fungal infection. The 160 patients with infection had a significantly higher 90-day mortality rate than the patients without infection (46.3% vs 32.5%, χ2=6.720, P=0.010). Of all 240 patients, 176 had ascites, 44 had pleural effusion, 36 had acute renal injury, 60 had hepatic encephalopathy, and 12 had gastrointestinal bleeding within 28 days, and there were significant differences in the proportion of patients with acute renal injury, grade Ⅲ-Ⅳ hepatic encephalopathy, or gastrointestinal bleeding between the 28-day survival group and the 28-day death group (χ2=64.088，29811，7.797，all P＜0.05). ConclusionTBil, PTA, serum sodium, MELD score, and MELD-Na score at baseline are independent risk factors for the 28- and 90-day prognosis of HBV-ACLF. Liver inflammation and necrosis caused by HBV activation may be the initiating factor for ACLF, and infection, acute renal injury, hepatic encephalopathy, and gastrointestinal bleeding are the main complications affecting the prognosis of patients.

Exploration and practice of applying discussion-based film and television appreciation to the cultivation of medical professionalism / 中华医学教育探索杂志

In view of the lack of teaching methods in the cultivation of medical professionalism, this paper puts forward some important strategies for improving medical students' professionalism through discussion-based film and television appreciation. High-quality discussion-based film and television appreciation can be designed according to the four links of film selection, concentrated viewing, independent discussion and summary feedback. At the same time, in practice, attention should be paid to three key issues: selecting appropriate films, ensuring the quality and depth of discussion, and paying attention to feedback and evaluation. Practice has proved that discussion-based film and television appreciation makes the cultivation of professionalism more attractive, and can promote the professional knowledge and professional spirit, enhance students' professional enthusiasm, promote the understanding of the connotation of professionalism and reflection on related issues. Medical colleges should continue to improve the design of film viewing in practice, so as to help students better absorb humanistic nutrients from the discussion and enhance the teaching effect of professionalism.

SWOT analysis of medical online teaching in X hospital during COVID-19 epidemic / 中华医学教育探索杂志

SWOT theory can be used to analyze the internal and external competitive environment and conditions of online teaching in teaching hospitals during the epidemic prevention and control. Conducting online education of clinical medicine courses in a hospital affiliated toa hospital affiliated to a comprehensive university has advantages in resources, administrations and platforms. However, disadvantages of online medical education lie in the professionalism, specificity of doctors as teacher and request of special teaching tools, all of which may not be available online. Online education meets the need of constructing top level courses national wide, carrying out the dominant role of ideological work in medical education field, and promoting the autonomous learning. Meanwhile, online education also challenges the future reform of teaching mode, management, and space. Based on this, it's proposed to promote the informatization construction of hospital medical education, improve IT literacy of all teachers, build an educational informatization platform matching the hospital management, construct a multiple evaluation system based on intelligent teaching space, build an online and offline mixed curriculum system based on multi-disciplinary, and take it as a breakthrough to promote the construction of "new medicine".

Analysis and reflection on the current construction of massive open online course of medical humanities under the epidemic situation / 中华医学教育探索杂志

This study aims to analyze the current construction of massive open online course (MOOC) of medical humanities in China, promote the sharing of high-quality curriculum resources, and provide information reference for curriculum design and planning. Mathematical statistics and mind map analysis were used to analyze 42 medical humanities MOOCs on 17 online course platforms during the epidemic, and the results showed that: ①the scale and quantity of medical humanities MOOCs need to be expanded; ②there is regional imbalance in MOOCs construction, with the largest number in East China; ③most of the courses are taught by teachers in a team, teachers with senior professional titles are the main force of the team, and some teams have multidisciplinary backgrounds; ④there are rich teaching contents related to humanistic knowledge and ability, but the content related to medical humanistic spirit cognition needs to be added appropriately. According to the above analysis, it's suggested that the construction of MOOC should focus on systematism and standardization, equip a team of teachers with multidisciplinary backgrounds, value curriculum design and planning, and pay full attention to the feedback and evaluation of learners to find out deficiencies.

Targeting peptide-decorated biomimetic lipoproteins improve deep penetration and cancer cells accessibility in solid tumor

The limited penetration of nanoparticles and their poor accessibility to cancer cell fractions in tumor remain essential challenges for effective anticancer therapy. Herein, we designed a targeting peptide-decorated biomimetic lipoprotein (termed as BL-RD) to enable their deep penetration and efficient accessibility to cancer cell fractions in a tumor, thereby improving the combinational chemo-photodynamic therapy of triple negative breast cancer. BL-RD was composed of phospholipids, apolipoprotein A1 mimetic peptide (PK22), targeting peptide-conjugated cytotoxic mertansine (RM) and photodynamic agents of DiIC18(5) (DiD). The counterpart biomimetic lipoprotein system without RM (termed as BL-D) was fabricated as control. Both BL-D and BL-RD were nanometer-sized particles with a mean diameter of less than 30 nm and could be efficiently internalized by cancer cells. After intravenous injection, they can be specifically accumulated at tumor sites. When comparing to the counterpart BL-D, BL-RD displayed superior capability to permeate across the tumor mass, extravasate from tumor vasculature to distant regions and efficiently access the cancer cell fractions in a solid tumor, thus producing noticeable depression of the tumor growth. Taken together, BL-RD can be a promising delivery nanoplatform with prominent tumor-penetrating and cancer cells-accessing capability for effective tumor therapy.

Phospholipid membrane-decorated deep-penetrated nanocatalase relieve tumor hypoxia to enhance chemo-photodynamic therapy

Hypoxia is a serious impediment to current treatments of many malignant tumors. Catalase, an antioxidant enzyme, is capable of decomposing endogenous hydrogen peroxide (H

Characterization of Mycobacterium tuberculosis dihydrofolate reductase immobilized on magnetic nanoparticles / 生物工程学报

To explore the immobilization of target proteins for screening libraries of ligand mixtures, magnetic submicron particles (MSP) functionalized with Ni²⁺-NTA and carboxyl were compared for the immobilization of Mycobacterium tuberculosis dihydrofolate reductase (MtDHFR). MtDHFR fused with 6×His was expressed, purified and characterized for kinetics. MtDHFR was immobilized on Ni²⁺-NTA-functionalized MSP directly and carboxyl-functionalized MSP upon activation. The immobilization capacity, residual activity, thermostability and affinities for putative inhibitors were characterized. MtDHFR immobilized on Ni²⁺-NTA-functionalized MSP retained about 32% activity of the free one with the immobilization capacity of (93±12) mg/g of MSP (n=3). Ni²⁺ and EDTA synergistically inhibited MtDHFR activity, while Fe³⁺ had no obvious interference. MtDHFR immobilized on carboxyl-functionalized MSP retained (87±4)% activity of the free one with the immobilization capacity of (8.6±0.6) mg/g MSP (n=3). In 100 mmol/L HEPES (pH 7.0) containing 50 mmol/L KCl, there was no significant loss of the activities of the free and immobilized MtDHFR after storage at 0 °C for 16 h, but nearly 60% and 35% loss of their activities after storage at 25 °C for 16 h, respectively. The inhibition effects of methotrexate on the immobilized and free MtDHFR were consistent (P>0.05). The immobilization of MtDHFR on carboxyl-functionalized MSP was thus favorable for higher retained activity and better thermostability, with promise for rapid screening of its ligand mixtures.