Characteristic and prognosis of patients with non-EBV infection-associated hemophagocytic lymphohistiocytosis / 中华血液学杂志

Objective: To explore the clinical characteristics and outcomes of patients with non-Epstein-Barr virus (EBV) infection-associated hemophagocytic lymphohistiocytosis (IAHLH) . Methods: Clinical data of 48 patients diagnosed with non-EBV IAHLH in Beijing Friendship Hospital from January 2015 to March 2021 were collected, and the clinical characteristics, treatment, curative effect and prognosis of the patients were analyzed retrospectively. Results: This study included 48 patients, 28 males and 20 females, with a median (range) age of 34.5 (2-74) years. Pathogens that cause IAHLH were as follows: virus (16 cases, 33.3%) , bacteria (17 cases, 35.4%) , parasitic agents (13 cases, 27.1%) , and fungi (2 cases, 4.2%) . The median time from onset to diagnosis of hemophagocytic syndrome (HLH) was 40 (10-160) days. The median (range) time duration from prodrome to the definite diagnosis of IAHLH was 67 (23-270) days. The clinical characteristics were fever (48 cases, 100%) , splenomegaly (34 cases, 70.8%) , cytopenia (38 cases, 79.1%) , elevated ferritin (45 cases, 93.8%) , elevated fasting triglyceride levels (7 cases, 14.6%) , hypofibrinogenemia (17 cases, 35.4%) , decrease natural killer cell activity (26 in 44 cases, 59.1%) , and elevated sCD25 (35 cases, 74.5%) . Twenty-five patients (52.1%) had adenopathy. Once a certain pathogen was identified as the causative factor of hemophagocytic lymphohistiocytosis (HLH) , cytotoxic agents and glucocorticoids were withdrawn, and specific pathogen-directed treatment was initiated. After treatment, 36 cases (75.0%) achieved complete response, and 14 of 15 patients (93.3%) with parasitic and fungal HLH got a response; however, the response rate of patient with bacterial and viral HLH was only 66.7% (22 of 33 patients) . The estimated 5-year overall survival rate was 72.3% (95%CI 50.3%-69.8%) . The adverse prognostic factors were total bilirubin over the upper limit of normal (OR=20.0, 95%CI 1.1-378.3, P=0.046) and pathogenic infection not fully controlled (OR=19.9, 95%CI 2.9-134.5, P=0.002) . Conclusion: Non-EBV IAHLH has a good prognosis. When diagnosed, cytotoxic agents and glucocorticoids should be tapered off, and pathogen-targeted therapy should be critically administered to clear the triggering infection.

Cloning, induction pattern and prokaryotic expression of a small heat shock protein SmHSP21.8 gene from Salvia miltiorrhiza / 药学学报

In order to reveal the molecular mechanism of the small heat shock proteins (sHSPs) involved in stress resistance and active ingredients accumulation in Salvia miltiorrhiza, a small heat shock protein gene was cloned from Salvia miltiorrhiza by reverse transcription PCR according to the transcriptome data of orange root Salvia miltiorrhiza. The gene is named SmHSP21.8 based on the molecular weight of the protein, and it contains an open reading frame of 585 bp, which encodes 194 amino acids. The results of phylogenetic analysis and amino acid sequence alignment showed that SmHSP21.8 protein belongs to the endoplasmic reticulum (ER) subfamily, and contains a conserved endoplasmic reticulum-specific DPFR-I/V-LE-H/Q-x-P motif at N-terminus. The prokaryotic expression vector pMAL-c2X-SmHSP21.8 was constructed and transformed into E. coli BL21 competent cells. The recombinant protein was successfully expressed after inducted. Temporal and spatial expression analysis showed that SmHSP21.8 gene was the highest expressed in flowers and had significant tissue specificity. The relative expression of the gene was significantly increased in seedlings after induction by 38 ℃, PEG6000, abscisic acid(ABA), and indole-3-acetic acid (IAA), indicating that SmHSP21.8 gene may be involved in abiotic stress such as high temperature and drought, as well as the response to exogenous hormones ABA and IAA. These results lay the foundation for further research on the molecular mechanism of small heat shock proteins involved in adversity stress.

Targeting glutamine utilization to block metabolic adaptation of tumor cells under the stress of carboxyamidotriazole-induced nutrients unavailability

Tumor cells have unique metabolic programming that is biologically distinct from that of corresponding normal cells. Resetting tumor metabolic programming is a promising strategy to ameliorate drug resistance and improve the tumor microenvironment. Here, we show that carboxyamidotriazole (CAI), an anticancer drug, can function as a metabolic modulator that decreases glucose and lipid metabolism and increases the dependency of colon cancer cells on glutamine metabolism. CAI suppressed glucose and lipid metabolism utilization, causing inhibition of mitochondrial respiratory chain complex I, thus producing reactive oxygen species (ROS). In parallel, activation of the aryl hydrocarbon receptor (AhR) increased glutamine uptake via the transporter SLC1A5, which could activate the ROS-scavenging enzyme glutathione peroxidase. As a result, combined use of inhibitors of GLS/GDH1, CAI could effectively restrict colorectal cancer (CRC) energy metabolism. These data illuminate a new antitumor mechanism of CAI, suggesting a new strategy for CRC metabolic reprogramming treatment.

Clinical effects of free hallux-nail flap combined with the second toe composite tissue flap in the reconstruction of damaged thumb after electrical burns / 中华烧伤杂志

Objective: To explore the clinical effects of free hallux-nail flap combined with the second toe composite tissue flap in the reconstruction of damaged thumb after electrical burns. Methods: A retrospective observational study was conducted. From May 2018 to April 2021, 12 male patients with thumb destructive defects caused by electrical burns who met the inclusion criteria were admitted to Zhengzhou First People's Hospital, aged 27 to 58 years, including 10 cases with degree Ⅲ thumb defect and 2 cases with degree Ⅳ thumb defect after thorough debridement. The thumb was reconstructed with free hallux-nail flap combined with composite tissue flap of the second phalangeal bone, joint, and tendon with skin island. The donor site of hallux-nail flap was covered with artificial dermis in the first stage and performed with continuous vacuum sealing drainage, and covered with medium-thickness skin graft from the groin site in the second stage. The donor site in the second toe was filled and fixed with iliac bone strips. The survival of reconstructed thumb was observed 1 week after the reconstruction surgery, the survival of skin graft in the donor site of hallux-nail flap was observed 2 weeks after skin grafting, and the callus formation of the reconstructed thumb phalanx and the second toe of the donor foot was observed by X-ray 6 weeks after the reconstruction surgery. During the follow-up, the shape of reconstructed thumb was observed and the sensory function was evaluated; the function of reconstructed thumb was evaluated with trial standard for the evaluation of the functions of the upper limbs of the Hand Surgery Society of the Chinese Medical Association; whether the interphalangeal joints of the hallux and the second toe were stiff, the scar hyperplasia of the foot donor site, and whether the walking and standing functions of the donor feet were limited were observed. Results: One week after the reconstruction surgery, all the reconstructed thumbs of the patients survived. Two weeks after skin grafting, the skin grafts in the donor site of hallux-nail flap of 11 patients survived, while the skin graft in the donor site of hallux-nail flap of 1 patient was partially necrotic, which was healed completely after 10 days' dressing change. Six weeks after the reconstruction surgery, callus formation was observed in the reconstructed thumb and the second toe of the donor foot of 10 patients, the Kirschner wires were removed; while callus formation of the reconstructed thumb was poor in 2 patients, and the Kirschner wires were removed after 2 weeks of delay. During the follow-up of 6 to 24 months, the shape of reconstructed thumb was similar to that of the healthy thumb, the discrimination distance between the two points of the reconstructed thumb was 7 to 11 mm, and the functional evaluation results were excellent in 4 cases, good in 6 cases, and fair in 2 cases. The interphalangeal joints of the hallux and the second toe of the donor foot were stiff, mild scar hyperplasia was left in the donor site of foot, and the standing and walking functions of the donor foot were not significantly limited. Conclusions: The application of free hallux-nail flap combined with the second toe composite tissue flap in the reconstruction of damaged thumb after electrical burns adopts the concept of reconstruction instead of repair to close the wound. It can restore the shape and function of the damaged thumb without causing great damage to the donor foot.

Research progress on related factors of occult myopia / 国际眼科杂志(Guoji Yanke Zazhi)

Occult myopia refers to a special type of myopia, which is caused by the axial length beyond the normal range of children's normal age, and the corneal curvature is lower than the normal range of children with the normal age range of the vision. Because the vision of occult myopia children is within the normal range, it is easy to be ignored in myopia screening. Without timely myopia prevention and control, occult myopia is very easy to develop into dominant myopia, not only the visual development is seriously affected, but visual function will also produce irreversible changes. It is found that the axial length, corneal curvature, retina and chorioid of occult myopia are different from those of ordinary myopia. The change of these indicators can be used to assist the diagnosis and observe their development process. The purpose of this paper is to summarize the research progress at home and abroad on ocular axis length, corneal curvature, macular retinal thickness, macular choroidal thickness and other related factors in children with occult myopia, in order to provide references for related clinical research.

Multiple Mild Stimulations Reduce Membrane Distribution of CX3CR1 Promoted by Annexin a1 in Microglia to Attenuate Excessive Dendritic Spine Pruning and Cognitive Deficits Caused by a Transient Ischemic Attack in Mice / 神经科学通报·英文版

A transient ischemic attack (TIA) can cause reversible and delayed impairment of cognition, but the specific mechanisms are still unclear. Annexin a1 (ANXA1) is a phospholipid-binding protein. Here, we confirmed that cognition and hippocampal synapses were impaired in TIA-treated mice, and this could be rescued by multiple mild stimulations (MMS). TIA promoted the interaction of ANXA1 and CX3CR1, increased the membrane distribution of CX3CR1 in microglia, and thus enhanced the CX3CR1 and CX3CL1 interaction. These phenomena induced by TIA could be reversed by MMS. Meanwhile, the CX3CR1 membrane distribution and CX3CR1-CX3CL1 interaction were upregulated in primary cultured microglia overexpressing ANXA1, and the spine density was significantly reduced in co-cultured microglia overexpressing ANXA1 and neurons. Moreover, ANXA1 overexpression in microglia abolished the protection of MMS after TIA. Collectively, our study provides a potential strategy for treating the delayed synaptic injury caused by TIA.

Non/hypo-response to hepatitis B vaccination and influencing factors in HIV-infected patients in the context of different immunization schedules / 中华流行病学杂志

Objective: To study the non/hypo-response to hepatitis B vaccination in HIV-infected patients, identify the influencing factors and provide evidence for the development of hepatitis B prevention and control strategies and measures for special population. Methods: On the basis of the randomized controlled trial of 20 µg hepatitis B vaccine immunization at 0-1-6 month, 0-1-2-6 month and 60 µg hepatitis B vaccine immunization at 0-1-2-6 month, the HIV-infected patients who completed one-month follow-up after the full course vaccination were selected as study subjects. Quantification of antibody to hepatitis B surface antigen (anti-HBs) in serum samples was performed by using chemiluminescent microparticle immunoassay (CMIA) and demographic characteristics, disease history, HIV infection and treatment status of the study subjects were collected. Statistical analysis was conducted by χ2 test, t test, unconditional logistic regression and interaction analyses. Results: The non/hypo-response rates to hepatitis B vaccination were 34.65% (35/101), 24.49% (24/98) and 10.99% (10/91) in 20 µg group at 0-1-6 month or 0-1-2-6 month and 60 µg group at 0-1-2-6 month (P<0.001), respectively. Logistic regression analysis showed that after controlling for confounding factors, the risk for non/hypo-response was 0.22 times higher in HIV-infected patients receiving 60 µg hepatitis B vaccine at 0-1-2-6 month than in patients receiving 20 µg hepatitis B vaccine at 0-1-6 month (95%CI: 0.10-0.50), the risk for non/hypo-response was higher in men than in women (OR=3.65, 95%CI: 1.88-7.07), and the risk for non/hypo-response was 2.64 times higher in those without hepatitis B vaccination history than in those with hepatitis B vaccination history (95%CI: 1.10-6.32). Moreover, there were multiplicative interactions between immunization schedule and gender (OR=2.49, 95%CI: 1.24-5.00). Conclusion: The non/hypo-response rate to hepatitis B vaccination was significantly lower in HIV-infected patients receiving 60 µg hepatitis B vaccine at 0-1-2-6 month than in those receiving 20 µg hepatitis B vaccine at 0-1-6 month and 0-1-2-6 month. Gender, vaccination schedule and history of hepatitis B vaccination were the influencing factors of the non/hypo-response to hepatitis B vaccination. There was a multiplicative interaction between vaccination schedule and gender, and men receiving 20 µg hepatitis B vaccines had a higher risk for non/hypo-response to hepatitis B vaccination.

The Relationship between MicroRNA Expression Profiling in Imatinib-Resistant Cell Line K562/G and Potential Mechanism through FOXO3/Bcl-6 Signaling Pathway / 中国实验血液学杂志

OBJECTIVE@#To investigate the drug resistant related FOXO3/Bcl-6 signaling pathway in K562/G cell line and its related microRNA(miRNA) mechanisms.@*METHODS@#The drug resistance potency of imatinib on K562/G was detected by MTT assay. The expression of FOXO3 and Bcl-6 proteins in K562 and K562/G cells was detected by Western blot. Real-time PCR (RT-PCR) was used to detect the expression of FOXO3 and Bcl-6 mRNA. The miRNA expression profiling in K562 and K562/G cells was analyzed by microarray technique, and the miRNA targeted to FOXO/Bcl-6 signaling pathway was identified.@*RESULTS@#The expression of FOXO3 and Bcl-6 protein was significantly increased in K562/G cells as compared with that in K562 cells (P<0.01), the expression level of Bcl-6 mRNA showed no increase in K562/G cells. However, FOXO3 mRNA was up-regulated in K562/G cells (P<0.05). MiRNA microarray results showed that 109 miRNAs were expressed differentially in K562 and K562/G cells. The expression of 81 miRNAs were up-regulated while 28 miRNAs were down-regulated. Through reverse prediction by bioinformatics, miR-6718-5p, miR-5195-5p, miR-4711-3p, miR-4763-5p, miR-4664-5p and miR-3176 were related to FOXO/Bcl-6 signaling pathway.@*CONCLUSION@#The FOXO3/Bcl-6 signaling pathway contributes to imatinib resistance in K562/G cell line, and the miRNA expression profiles showed significant differences between K562/G and K562 cells.

Effects of Angong Niuhuang Pills against heart failure based on cross-scale polypharmacological study / 中国中药杂志

Angong Niuhuang Pills(AGNHP) are effective in clearing heat, removing the toxin, and eliminating phlegm for resuscitation. Clinically, it is widely used to treat various diseases such as febrile convulsion due to heat attacking pericardium, but its therapeutic effects on heart failure(HF) have not been well recognized. In this study, the profiles of differential metabolites regulated by AGNHP were identified by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS). The underlying mechanism of AGNHP against HF was illustrated based on the integrated analysis of pharmacological data and metabolic molecular network. The HF model was induced by isoproterenol in mice. After oral administration of AGNHP for one week, cardiac functions in HF mice were evaluated by echocardiography, and serum samples of mice were collected for metabolomics analysis. Eight differential metabolites of AGNHP against HF were screened out through partial least square discriminant analysis(PLS-DA) and input into MetaboAnalyst for the analysis of metabolic pathways. Moreover, the critical metabolic pathways regulated by AGNHP were enriched according to the potential targets of major compounds in AGNHP. After AGNHP treatment, the recovered index of relative content of some metabolites underwent cross-scale fusion analysis with therapeutic efficacy data, followed by "compound-reaction-enzyme-gene" network analysis. It is inferred that the anti-HF effects of AGNHP may be attributed to the metabolism of arachidonic acid, amino acid, glycerophospholipid, and linoleic acid. The cross-scale polypharmacological analysis method developed in this study provides a new method to interpret scientific principles of AGNHP against HF with modern technologies.

Awareness of HPV and willingness to HPV vaccination among male university students in Tongzhou District / 预防医学

Objective@#To investigate the awareness of knowledge about HPV infections and the willingness to HPV vaccination among male university students in Tongzhou District, Beijing Municipality, so as to provide insights into the formulation of the HPV vaccination strategy among males.@*Methods@#A total of 997 male university students in Tongzhou District were selected as the study subjects using a multi-stage stratified cluster random sampling method, and a self-designed questionnaire was used to investigate the awareness of HPV infections and HPV vaccine, and willingness to HPV vaccination. In addition, the factors affecting the willingness to HPV vaccination were identified. @*Results@#A total of 935 subjects were enrolled, with a mean age of (19.08±1.38) years, and there were 570 subjects with a Beijing household registration (60.96%). Among the 313 male university students that had heard of HPV, the awareness of HPV and HPV-related diseases was 59.42%, and among the 300 male university students that had heard of HPV vaccines, the awareness of HPV vaccines was 75.33%. The willingness to HPV vaccination was 38.50%, and the willingness was high among male university students with a non-Beijing household registration ( χ2=3.971, P=0.046 ), high household annual income ( χ2trend=6.219, P=0.013 ), short distance to vaccination clinics ( χ2=19.238, P<0.001 ), having heard of HPV ( χ2=11.188, P=0.001 ), having heard of HPV vaccine ( χ2=14.548, P<0.001 ), awareness of HPV and related diseases ( χ2=16.855, P<0.001 ) and awareness of HPV vaccine ( χ2=19.299, P<0.001 ).@*Conclusions@#The awareness of HPV and HPV vaccines and the willingness to HPV vaccination are low among male university students in Tongzhou District. Improving the correct recognition of HPV and HPV vaccines and the access to vaccination services are helpful to improve the willingness to HPV vaccination among male university students.

Special topic on sarcopenia in the elderly Interpretation of core information on sarcopenia prevention in the elderly / 中华老年医学杂志

The elderly are the main body of people with sarcopenia which not only seriously affects the quality of life of the elderly, but also brings a heavy burden to the family and society.Maintaining and improving the function of the elderly and preventing the occurrence of sarcopenia in the elderly are the important measures in the health management of the elderly.In order to effectively carry out health education on sarcopenia in the elderly and to popularize relevant health care knowledge, the National Center of Gerontology and the Chinese Geriatrics Society have formulated the "Chinese expert consensus on the core information for the prevention of sarcopenia in the elderly(2021)" , relying on the expert team after several rounds of expert discussions.It provides scientific basis for the management and early intervention of sarcopenia.Let us now try to interpret the consensus on the key knowledge points of the core information sequence.

Application of the Delphi method in developing a core information index systen for prevention of sarcopenia in the elderly / 中华老年医学杂志

Objective:To analyze the process of Chinese expert consensus on the core information on prevention of sarcopenia in the elderly(2021)in China, so as to realize the early diagnosis and treatment of sarcopenia and to improve the quality of life in the elderly.Methods:The index system framework was established by literature review and expert questionnaire discussion, and Delphi expert consultation method was adopted to construct the index system.Results:A total of 109 experts(128 person-times)in Geriatrics from various fields participated in Delphi expert consultation.Positive coefficient for four rounds of expert consultation were 88.9%, 100.0%, 100.0% and 100.0% respectively, with expert authority factors being concentrated on 0.78~0.90.Through 4 rounds of Delphi expert surveys, the core information index system for sarcopenia prevention in the elderly has been definitive: Chinese Expert Consensus(2021)consists of nine indicators including "enhancing public scientific awareness of myosis, and so on."Conclusions:The core information index system for sarcopenia prevention in the elderly has high levels of overall convergence, comprehensive coverage, strong authority, stability, comprehensiveness and popularity.

The correlation between frailty and cardiac autonomic nervous function in elderly patients / 中华老年医学杂志

Objective:To assess the correlation between frailty and cardiac autonomic nervous system function in elderly patients.Methods:Elderly hospitalized patients aged 65 years and over were enrolled and assessed for frailty by using the clinical frailty scale.Cardiac autonomic modulation was evaluated by heart rate variability analysis through 24 h electrocardiogram recording.Results:A total of 180 elderly patients were enrolled in this study, including 66 patients with frailty and 114 patients without frailty.The mean age of the frailty group was higher than that of the non-frailty group(79.8±6.0 vs.75.0±6.3, t=5.030, P<0.001). The proportions of patients with hypertension, stroke/transient cerebral ischemia attack(TIA), heart failure and osteoarthritis were higher in the frailty group than in the non-frailty group(all P<0.05). Compared with the non-frailty group, the standard deviation of normal-to-normal intervals(SDNN)[103.0(76.0, 121.2) vs.107.5(92.0, 136.0), Z=-2.108, P=0.035], the standard deviation of the averages of NN intervals in all 5-min segments(SDANN)[86.0(67.7, 106.5) vs.97.5(78.0, 126.0), Z=-2.694, P=0.007], normalized low frequency(LFnorm)(53.1±13.0 vs.59.3±13.9, t=-3.024, P=0.003)and low frequency/high frequency(LF/HF)ratio[1.2(1.0, 1.4) vs.1.4(1.1, 1.7), Z=-3.041, P=0.002]were decreased and normalized high frequency(HFnorm)(36.8±9.2 vs.32.2±10.7, t=3.033, P=0.003)was increased in the frailty group.HFnorm in the frailty group was significantly higher than that in the non-frailty group.The incidents of SDANN<92 ms, LFnorm<50 nU, HFnorm>32 nU and LF/HF ratio<1.5 were higher in the frailty group than in the non-frailty group(59.1% or 39/66 vs.41.2% or 47/114, 42.4% or 28/66 vs.22.8% or 26/114, 72.7% or 48/66 vs.49.1% or 56/114, 84.8% or 56/66 vs.65.8% or 75/114, χ2=5.346, 7.660, 9.547, 7.664, P=0.021, 0.006, 0.002, 0.006). Logistic multivariate regression analysis showed that LFnorm, HFnorm and LF/HF ratio were correlated with frailty( OR=0.971, 1.039 and 0.333, all P<0.05), and HFnorm>32 nU and LF/HF ratio<1.5 were risk factors for frailty( OR=2.401 and 2.773, both P<0.05). Conclusions:Cardiac autonomic nerve system function is impaired in elderly frail patients, with the imbalance between the sympathetic and vagus nerves.Therefore particular attention should be paid to heart rate variability in elderly patients with frailty.

Influencing factors of proteinuria in patients with hypertension in Qinghai-Tibet Plateau / 中华地方病学杂志

Objective:To investigate the risk factors of proteinuria in patients with hypertension in Qinghai-Tibet Plateau.Methods:From March 2019 to June 2020, prospective design was used to collect data of Qinghai-Tibet Plateau hypertension patients who were eligible for continuous enrollment in the Department of Cardiovascular Medicine in Hospital of Chengdu Office of People's Government of Tibet Autonomous Region. Questionnaire survey, physical examination and blood pressure measurement were performed on the selected patients. Fasting venous blood samples were collected for liver function test, blood lipid test, blood glucose test, and hemoglobin test, etc. Three times of morning urine samples were taken on different days, and urine protein creatinine ratio (UACR) was measured, UACR < 30 mg/g was negative for urinary protein, and UACR≥30 mg/g was positive for urinary protein. At the same time, the selected patients were examined by carotid artery color ultrasound and heart color ultrasound. The risk factors of proteinuria were analyzed.Results:A total of 588 patients with hypertension met the inclusion criteria, including 472 patients (80.3%) who received antihypertensive drug therapy, 239 patients (40.6%) had antihypertensive treatment compliance, and 252 patients (42.9%) reached the standard blood pressure after theropy. Hypertension was associated with diabetes mellitus in 150 patients (25.5%), and urinary protein was positive in 126 patients (21.4%). In univariate analysis, ethnic composition, systolic blood pressure [(138.19 ± 19.65) vs (133.16 ± 18.45) mmHg, 1 mmHg = 0.133 kPa], diastolic blood pressure [(85.80 ± 13.51) vs (83.17 ± 12.19) mmHg], uric acid [(411.79 ± 101.54) vs (379.96 ± 102.18) μmol/L], hemoglobin [(152.86 ± 30.70) vs (143.49 ± 21.15) g/L], pulmonary artery trunk width [(21.76 ± 3.94) vs (20.98 ± 3.34) mm], and ventricular septal thickness [(9.90 ± 1.70) vs (9.47 ± 1.60) mm] in the positive group ( n = 126) were significantly higher than those in the negative group ( n = 462, P < 0.01 or < 0.05). In multivariate logistic regression analysis, increased systolic blood pressure [odds ratio ( OR) = 1.015, 95% confidence interval (95% CI): 1.005 - 1.026], uric acid ( OR = 1.003, 95% CI: 1.001 - 1.005), and pulmonary artery trunk width ( OR = 1.058, 95% CI: 1.001 - 1.118) were risk factors for proteinuria; Tibetans had a decreased risk of proteinuria compared with Han ( OR = 0.505, 95% CI: 0.317 - 0.805), but increased hemoglobin had an increased risk of proteinuria compared with normal hemoglobin ( OR = 1.890, 95% CI: 1.231 - 2.903). Conclusion:In patients with hypertension at high altitude, increased hemoglobin, systolic blood pressure, uric acid, pulmonary artery trunk width, and Han nationality are risk factors for proteinuria.

Clinical diagnosis and treatment of neonatal enterovirus infections / 中华实用儿科临床杂志

Enterovirus infections are common virus infections during the neonatal period.Different from older children, neonatal enterovirus infections are often more severe, with clinical manifestations indistinguishable from bacterial sepsis, and can be complicated by necrotizing hepatitis, meningitis and myocarditis, with rapid progression and high mortality.Early intravenous immunoglobulin treatment might contribute to reducing the mortality of neonatal severe enterovirus infection and the morbidity of complications.Further research is needed to evaluate the safety and efficacy of new antiviral drugs for neonatal enterovirus infections.

Evaluation Effectiveness of in Vitro Cultivation of Bezoar on Mouse Model Combining Disease with Syndrome of Coronavirus Pneumonia with Yidu Xifei Syndrome / 中国实验方剂学杂志

Objective:To determine the therapeutic effect of <italic>in vitro</italic> cultivation of bezoar on a mouse model adding disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome. Method:BALB/c mice were randomly divided into six groups according to their weight grade： normal group， HCoV-229E infection group， cold and damp group， a mouse model combining disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome， and high and low dose group of <italic>in vitro</italic> cultivation of bezoar. The combination model of human coronavirus pneumonia with Yidu Xifei syndrome mice was established by the method of cold dampness condition stimulation+coronavirus HCoV-229E infection. <italic>In vitro</italic> cultivation of bezoar （0.128，0.064 g·kg^-1） was administrated by gavage for 3 days from the day of infection. The observation indexes included： general state observation of mice， inhibition rate of lung index and lung index of mice. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the viral load in the lung tissues of mice. Serum levels of motilin（MTL）， gastrin （GAS）， and cytokines interleukin（IL）-10，IL-6， tumor necrosis factor-<italic>α</italic>（TNF-<italic>α</italic>）and interferon-<italic>γ</italic>（IFN-<italic>γ</italic>） in lung tissue of mice were determined by enzyme-linked immunosorbent assay（ELISA）. The percentages of CD4⁺ T lymphocytes，CD8⁺ T lymphocytes and B lymphocytes in the blood of mice were determined by flow cytometry. Result:The high and low dose group of <italic>in vitro</italic> cultivation of bezoar can significantly improve the general condition of model mice. Compared with blank group， model group mice lung index increased significantly （<italic>P</italic><0.01）， nucleic acids significantly increased expression of lung tissue in mice （<italic>P</italic><0.01）， significantly higher serum MTL content in mice， GAS content significantly decreased （<italic>P</italic><0.05，<italic>P</italic><0.01）， lung tissue cells in the immune factor TNF-<italic>α</italic>， IL-10 and IL-6 were significantly increased （<italic>P</italic><0.01）， peripheral blood lymphocyte CD4⁺ T cells in mice， The percentages of CD8⁺ T cells and B cells were significantly decreased （<italic>P</italic><0.01）. Compared with model group， <italic>in vitro</italic> cultivation bezoar mice lung index of high and low dose group were significantly lower （<italic>P</italic><0.01）， the lung tissue of mice express nucleic acid decreased significantly （<italic>P</italic><0.01）， MTL content decreased significantly （<italic>P</italic><0.01）， the lung tissue of mice in the IL-6， IL-10， the TNF-<italic>α</italic>， IFN-<italic>γ</italic> levels were significantly lower （<italic>P</italic><0.01）， <italic>in vitro</italic> cultivation bezoar high dose group can significantly increase the CD4⁺ T cell percentage （<italic>P</italic><0.05）， <italic>in vitro</italic> cultivation bezoar can to a certain extent reduce model mice lung inflammatory exudation， pulmonary interstitial edema， as well as blood stasis symptoms. Conclusion:<italic>In vitro</italic> cultivation of bezoar has a significant therapeutic effect on a mice model adding disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome. It can be treated by reducing the lung index of the model mice， improving the pathological damage of the lung tissue， adjusting the immune effective and inhibiting the clearing of inflammatory factors， and to provide a laboratory basis for clinical medication.

Effect of Shuangyu Tiaozhi Decoction on HNF1α/PCSK9/LDLR Signaling Pathway in Liver of Hypercholesterolemic Rats / 中国实验方剂学杂志

Objective:To observe the expression of hepatocyte nuclear factor 1<italic>α</italic> （HNF1<italic>α</italic>）， proprotein convertase subtilisin/kexin type 9 （PCSK9） and low-density lipoprotein cholesterol （LDLR） in hypercholesterolemia rat liver， and investigate the mechanism of Shuangyu Tiaozhi Decoction regulating cholesterol metabolism and attenuating hypercholesterolemia. Method:After providing a high-fat diet for 4 weeks， 40 SD rats were selected， 8 of which were randomly selected as normal group and fed a normal diet， and the remaining 32 rats were fed a high-fat diet. The rats successfully established as hypercholesterolemic model， were randomized into 4 groups： model group， low dose of Shuangyu Tiaozhi decoction group （7.8 g·kg^-1）， high dose of Shuangyu Tiaozhi decoction group （15.6 g·kg^-1）， and simvastatin group （4 mg·kg^-1）， with 8 rats in each group. The drugs were continuously given for 8 weeks. Serum total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C） were measured. The pathomorphological changes in liver were observed by hematoxylin and eosin （HE） staining. The immunohistochemistry was used to detect PCSK9 and LDLR expression in liver. The mRNA and protein expression levels of HNF1<italic>α</italic>， PCSK9 and LDLR were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. Result:Compared with normal group， the TC， TG， LDL-C levels in model group were significantly increased （<italic>P</italic><0.01）， the morphology showed obvious liver steatosis. The mRNA and protein expression of HNF1<italic>α</italic> and PCSK9 were increased （<italic>P</italic><0.05）， the mRNA and protein expression of LDLR was decreased （<italic>P</italic><0.05）. Compared with model group， the serum TC， TG， LDL-C levels were significantly lowered in the Shuangyu Tiaozhi decoction high-dose group （<italic>P</italic><0.01）， the serum TC， LDL-C levels were significantly lowered in the Shuangyu Tiaozhi decoction low-dose group and simvastatin group （<italic>P</italic><0.05，<italic>P</italic><0.01）， while no significant effect was observed on the serum HDL-C levels in each treatment group. The liver steatosis decreased in each treatment group. The mRNA and protein expression of HNF1<italic>α</italic> was obviously decreased in each treatment group （<italic>P</italic><0.05，<italic>P</italic><0.01）， the mRNA and protein expression of PCSK9 was obviously decreased in Shuangyu Tiaozhi decoction low and high-dose groups （<italic>P</italic><0.05，<italic>P</italic><0.01）， the mRNA expression of PCSK9 was significantly increased in the simvastatin group （<italic>P</italic><0.01）， while the protein expression showed a downward trend. The LDLR mRNA levels were significantly increased in each treatment group （<italic>P</italic><0.01）， the LDLR protein expression was significantly increased in Shuangyu Tiaozhi high-dose group （<italic>P</italic><0.01）， and showed an upward trend in Shuangyu Tiaozhi low-dose group and simvastatin group. Results of immunohistochemistry showed PCSK9 expression was weakly positive， the expression of LDLR was strongly positive in each treatment group. The therapeutic effect of Shuangyu Tiaozhi decoction high-dose group was more remarkable than simvastatin group， while there was no obvious difference between the Shuangyu Tiaozhi decoction low-dose group and simvastatin group. Conclusion:Shuangyu Tiaozhi decoction may reduce the blood lipid levels through HNF1<italic>α</italic>/PCSK9/LDLR signaling pathway， play an active role on regulating cholesterol metabolism and alleviating high-fat diet-induced hypercholesterolemia.

Screening of Active Components and Analysis of Mechanism of Dipsaci Radix in Treating Rheumatoid Arthritis Based on UPLC-QTOF-MS/MS and TCMIP / 中国实验方剂学杂志

Objective:To explore active components and mechanism of Dipsaci Radix in treating rheumatoid arthritis （RA） based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry （UPLC-QTOF-MS/MS） and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP）. Method:UPLC-QTOF-MS/MS with electrospray ionization （ESI） was used to qualitatively analyze the chemical components in methanol extract of Dipsaci Radix under positive and negative ion scanning modes. The mobile phase consisted of 0.1% formic acid aqueous solution （A）-acetonitrile （B） for gradient elution （0-10 min， 0.2%-20%B； 10-20 min， 20%-40%B； 20-25 min， 40%-50%B； 25-33 min， 50%-98%B； 33-35 min， 98%-0.2%B）， and the scanning range was <italic>m</italic>/<italic>z</italic> 50-2 000. Based on TCMIP， candidate target groups of Dipsaci Radix， RA and syndrome with Yin deficiency of liver and kidney were obtained， and correlation analysis on "disease-syndrome-prescription" was used to enrich the main active components and key targets. Cytoscape 3.8.0 and STRING 11.0 database were used to construct protein-protein interaction （PPI） network diagram. Metascape platform was used to analysis gene ontology biological progress and Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathways. Result:A total of 81 ingredients were identified by UPLC-QTOF-MS/MS. Based on TCMIP， 283 candidate targets corresponding to 81 ingredients， 7 RA related targets and 215 genes corresponding to syndrome with Yin deficiency of liver and kidney were collected. With further correlation analysis on "disease-syndrome-prescription"， 17 key active ingredients were predicted， mainly including saponins and fatty acids of Dipsaci Radix. It mainly involved 7 hub targets， namely tumor necrosis factor （TNF）， nuclear factor-<italic>κ</italic>B subunit 1 （NF-<italic>κ</italic>B₁）， hepatocyte nuclear factor 4 alpha （HNF4A）， nuclear receptor subfamily 3 group C member 1 （NR3C1）， peroxisome proliferator activated receptor gamma （PPARG）， nuclear receptor subfamily 1 group H member 4 （NR1H4） and nuclear receptor coactivator 1 （NCOA1）. All of them were related to inflammation， and two of them were related to bile acid pathway. The 7 hub targets and 7 pathways played an important role in RA were screen out， including 4 bile acid related pathways and 3 inflammatory related pathways. Conclusion:UPLC-QTOF-MS/MS combined with TCMIP preliminarily elucidates the regulatory effect of multi-components in Dipsaci Radix on several pathways related to the inflammatory response and bile acid synthesis and metabolism， which lays a foundation for further study on the mechanism of Dipsaci Radix against RA.

Cost accounting of hospital pharmaceutical service based on job analysis / 中华医院管理杂志

With the full implementation of the separation policy of medicine in China, the circulation of drugs in hospitals no longer produces direct economic value, but turns into the operating cost in the process of providing medical services. The research on the cost calculation of hospital pharmaceutical service can not only help the hospital to strengthen the internal cost management, but also provide the basis for the government policy compensation. This paper constructed a model of pharmaceutical service cost calculation based on job analysis, and produced basic pharmaceutical and advanced pharmaceutical service cost based on the data of a sample hospital.

Optimization of polysaccharide extraction from Hippocampus by deep neural network and Box-Behnken design-response surface methodology / 中国中药杂志

In this paper, the extraction rate of crude polysaccharides and the yield of polysaccharides from Hippocampus served as test indicators. The comprehensive evaluation indicators were assigned by the R language combined with the entropy weight method. The Box-Behnken design-response surface methodology(BBD-RSM) and the deep neural network(DNN) were employed to screen the optimal parameters for the polysaccharide extraction from Hippocampus. These two modeling methods were compared and verified experimentally for the process optimization. This study provides a reference for the industrialization of effective component extraction from Chinese medicinals and achieves the effective combination of modern technology and traditional Chinese medicine.