Based on the concept of quality by design(QbD), the Box-Behnken design-response surface methodology combined with standard relation(SR) and analytic hierarchy process(AHP)-entropy weight method(EWM) was applied to optimize the extraction process of the classic prescription Yihuang Decoction. The content of geniposidic acid, phellodendrine hydrochloride, and berberine hydrochloride in Yihuang Decoction, the extract yield, and fingerprint similarity were used as the critical quality attributes(CQAs) of the extraction process. The extraction time, water addition, and extraction times were used as the critical process parameters(CPPs). After determining the levels of each factor and level through single-factor experiments, response surface experiments were designed according to the Box-Behnken principle, and the experimental results were analyzed. The SR between each sample and the reference sample under various evaluation indicators of different extraction parameters was calculated. The weights of the five evaluation indicators were determined using AHP-EWM, followed by comprehensive evaluation. A function model between CPPs and CQAs characterized by comprehensive scores was established to predict the optimal extraction process parameters. In the final comprehensive weight coefficients, the yield rate accounted for 43.1%, and the content of berberine hydrochloride, phellodendrine hydrochloride, and geniposidic acid accounted for 35.1%, 6.3%, and 15.5%, respectively. After comprehensive score analysis with SR, the established second-order polynomial model was statistically significant(P<0.01, and the lack of fit was not significant). The predicted optimal extraction conditions for Yihuang Decoction were determined as follows: 8-fold volume of water, extraction time of 1.5 h, and extraction once. The mean comprehensive score of the validation experiment was 85.77, with an RSD of 0.99%, and it met the quality control stan-dards for the reference sample of Yihuang Decoction. The results indicate that the optimized extraction process for Yihuang Decoction is stable and reliable, and the water extract is close in quality attributes to the reference sample. This can serve as a foundation for the research and development of granules in the future. Box-Behnken design-response surface methodology combined with SR and AHP-EWM can provide references for the modern extraction process research of other classic prescriptions.
Drugs, Chinese Herbal ; Analytic Hierarchy Process ; Berberine ; Entropy ; Water

AIM:To explore the correlation and consistency of three tear assessment methods in the diagnosis of dry eye, which include the Schirmer Ⅰ test(SⅠt), tear meniscus height(TMH)measurement and a new generation of tear detection technology-Strip meniscometry tube(SMTube).METHODS: A diagnostic test study. A total of 183 dry eye outpatients(183 right eyes)in the Dry Eye Center of Henan Eye Hospital were enrolled from May to June 2021. The SⅠt, TMH and SMTube were performed on all patients, and the correlation and consistency of the measurement results were analyzed.RESULTS:The ocular surface disease index(OSDI)of all included patients was 43.75(31.25, 58.33), noninvasive breakup time(NIBUT)was 7.26(4.97, 9.37)s, and the results of SⅠt, TMH and SMTube were 6(2, 12)mm/5min, 0.18(0.14, 0.22)mm and 5(3,8)mm/5s, respectively; The results of correlation analysis: TMH was positively correlated with SMTube(rs=0.751, P<0.001), however, SⅠt had no correlation with TMH(rs=0.139, P=0.060)and SMTube(rs=0.019, P=0.799). The results of consistency analysis: TMH showed good consistency with SMTube(Kappa=0.794, P=0.044), however, SⅠt showed poor consistency with TMH(Kappa=0.271, P=0.074)and SMTube(Kappa=0.193, P=0.070)respectively.CONCLUSION:SMTube is a new, simple and convenient tool for evaluating tear volume. It has a good correlation and consistency with TMH measurement results. Therefore, it can replace TMH measurement, but cannot replace SⅠt in clinical application.

OBJECTIVE: To explore the characteristics of infection in patients with myelodysplastic syndromes (MDS), risk factors of serious infection, and their correlation with curative effect. METHODS: The clinical data of 92 newly diagnosed MDS patients with nosocomial infection from January 2016 to June 2020 in our hospital were retrospectively analyzed. RESULTS: A total of 306 courses of treatment were completed in 92 newly diagnosed MDS patients. The infection rate was the highest in the first course of treatment (84.8%, 78/92), and then decreased gradually. The top three infection sites were lung, upper respiratory tract, and gastrointestinal tract. A total of 90 strains of pathogenic bacteria were detected, of which 33.4% (30/90) were gram-negative bacilli, 23.3% (21/90) were gram-positive cocci, 23.3% (21/90) were fungi, and 20.0% (18/90) were viruses. The serious infection rate among 92 patients with MDS was 22.8% (21/92). Multivariate analysis showed that neutrophil deficiency>7 days (OR=10.875, 95%CI: 2.747-43.051, P=0.001) was an independent risk factor for serious infection in MDS patients. Compared with non-severe infection group, the total effective rate of severe infection group was lower (90.9% vs 63.6%, χ²=4.393, P<0.05). CONCLUSION The infection rate of MDS patients is high in the first course of treatment, and the most common infection site is the lung. Gram-negative bacteria is the most common pathogen. MDS patients with neutrophil deficiency>7 days have a high risk of serious infection and poor efficacy.
Cross Infection ; Gram-Negative Bacteria ; Humans ; Myelodysplastic Syndromes ; Retrospective Studies ; Risk Factors

Objective:To observe the clinical efficacy of the modified Buzhong Yiqitang combined with Erxian decoction in treating stress urinary incontinence （SUI） of perimenopausal women due to spleen and kidney Qi deficiency. Method:One hundred and six patients were randomly divided into a control group （52 cases） and an observation group（54 cases）. Patients in both groups received lifestyle intervention and pelvic floor muscle training （PFMT）. On this basis， patients in the observation group were further treated with the modified Buzhong Yiqitang combined with Erxian decoction， 1 bag/day， while those in the control group were provided with Suoquan pills， 6 g/time， 2 times/day， for eight weeks. Following the international consultation on incontinence questionnaire-short form （ICIQ-SF） scoring before and after treatment， the urodynamic parameters such as maximum urinary flow rate （Q_max）， maximum urethral closure pressure （MUCP）， residual urine volume （RUV）， abdominal pressure leakage point pressure （ALPP）， and bladder capacity （BC） were measured. The number of incontinence episodes per 24 h， the degree of urinary incontinence， the amount of 1 h urine leakage， and the spleen and kidney Qi deficiency syndrome score were recorded before and after treatment. The levels of estradiol （E₂）， follicle stimulating hormone （FSH）， pituitary adenylate cyclase activating peptide （PACAP）， and vasoactive intestinal peptide （VIP） were measured before and after treatment. Result:The ICIQ-SF sub-scores of the urinary incontinence frequency， severity， and impact on quality of life as well as the total score in the observation group were all lower than those in the control group （P<0.01）. Q_max， MUCP， ALPP and BC in the observation group were elevated in contrast to those in control group （P<0.01）， while the RUV declined （P<0.01）. Compared with the control group， the observation group exhibited a decreased number of incontinence episodes per 24 h， milder degree of urinary incontinence， reduced amount of 1 h urine leakage， and lower spleen and kidney Qi deficiency syndrome score （P<0.01）. The E₂， PACAP， and VIP in the observation group were up-regulated as compared with those in the control group （P<0.01）， whereas the FSH was down-regulated （P<0.01）. The cure and effective rates of the observation group were （29/50） 58.00% and （47/50）94.00%， respectively， significantly better than （18/48）37.50% and （38/48）79.17% of the control group （χ²=4.124， χ²=4.683， P<0.05）. Conclusion:On the basis of the lifestyle intervention and PFMT， the modified Buzhong Yiqitang combined with Erxian decoction obviously alleviates urinary incontinence， adjusts sex hormones， PACAP and VIP， ameliorates urodynamic parameters， and enhances the quality of life of patients with SUI due to spleen and kidney Qi deficiency. The resulting cure and effective rates are superior to those of the positive control.

Dengue virus (DENV) is the most rapidly transmitted mosquito-borne pathogen, which is the main cause of seasonal outbreaks of dengue fever and dengue hemorrhagic fever in tropical and subtropical regions, and may cause serious life-threatening diseases. There is an urgent need to develop effective vaccines or antiviral therapies. In this paper, we found that a podocarpane-type diterpenoid, (3α,5β,10α)-13-methoxypodocarpa-8,11,13-triene-3,12-diol (MPTD), isolated from the stems and leaves of Aleurites moluccana, showed good effect against DENV. The anti-DENV activity of MPTD against four different DENV serotypes was studied by plaque assay. The cytotoxicity of MPTD in Vero and Huh7 cells was tested by MTT assay. qRT-PCR and Western blot assays were used to investigate the anti-DENV activity of MPTD at RNA and protein levels, respectively. The results showed that MPTD greatly reduced the virus titer in DENV infected Vero cells, and its 50% effective concentration (EC₅₀) for DENV (1–4) were 2.72 ± 0.39, 10.99 ± 5.18, 18.72 ± 0.21, and 0.48 ± 0.28 μmol·L^-1, respectively. The results showed that MPTD inhibits DENV RNA level and the expression of E protein. In addition, MPTD may inhibit the early stage of DENV replication and exert antiviral activity. Further studies showed that the inhibitory effect of MPTD against DENV infection is not targeting the viral entry stage. Therefore, MPTD has a significant anti-dengue virus effect, and is an anti-DENV compound with potential application value.

This study integrates metabolomics and network pharmacology techniques to systematically analyze the possible mechanism of Pudilan Xiaoyan oral liquid (PDL) in the treatment of acute respiratory infections. GC-MS metabolomics analysis found 8 endogenous metabolites, 3-phosphoglycerate, α-aminoadipate, D-ribulose-5-phosphate, β-mannosylglyceric acid, D-fructose, urea, D-maltose and ornithine in the serum of mice with acute respiratory infection induced by LPS; these substances can be used as biomarkers for PDL use in the treatment of acute respiratory infections. Biological network studies revealed 10 potential targets for intervention by PDL in the glycolysis and pentose phosphate pathways, including GPI, G6PD, H6PD, PFKM, TALDO1, TKT, GAPDH, HK1, PKLR and TPI1. All animal experiments were carried out with approval of the Animal Ethics Committee of Nanjing University of Chinese Medicine. Our findings indicate that the strategy of combining metabolomics and network analysis can provide information on the possible mechanism of PDL in acute respiratory infections, and reveal that PDL may ameliorate the pathological process of acute respiratory infections by regulating disordered metabolic pathways.

In this study, we used molecular docking technology and validation experiments in vitro to screen the active ingredients of Erzhi pill for treating osteoporosis. Firstly, the compound in Erzhi pill was docked with ten osteoporosis-related targets by molecular docking technology, and the five active compounds, salidroside, specnuezhenide, tyrosol, quercetin, and wedelolactone, were initially selected. Then, MC3T3-E1 osteoblasts were cultured in α-Mem medium containing different concentrations of compounds, and the cell proliferation rate and mineralized nodules were tested. The verification results showed that the proliferation of MC3T3-E1 cells with salidroside, specnuezhenide and quercetin were more obvious, and salidroside has a better effect on the mineralization of MC3T3-E1 cells than those of specnuezhenide and tyrosol. The molecular docking technology coupled with validation experiment in vitro can be used for the screening of anti-osteoporotic active ingredients of Erzhi pill, and it can also provide a method for the study of effective ingredients of traditional Chinese medicine.

OBJECTIVE: To study the efficacy and safety of vitamin D as an adjuvant therapy for childhood pneumonia through a systematic review. METHODS: Cochrane Library, PubMed, EMbase, CNKI, Wanfang Data, and Weipu Data were searched for randomized controlled trials (RCTs) of vitamin D as the adjuvant therapy for childhood pneumonia published up to August 2019. Literature screening, quality assessment, and data extraction were performed based on inclusion and exclusion criteria. Revman 5.3 was used to perform the Meta analysis of outcome indicators. RESULTS: A total of 7 RCTs with 1 527 children were included, with 762 children in the vitamin D adjuvant therapy group and 765 children in the control group. The results of the Meta analysis showed that vitamin D adjuvant therapy had no effect on recovery time (P=0.67), length of hospital stay (P=0.73), and time to relief of fever (P=0.43). Furthermore, it did not reduce the recurrence rate (P=0.14), rate of adverse events (P=0.20), and mortality rate (P=0.98) of childhood pneumonia. CONCLUSIONS Current evidence shows that vitamin D adjuvant therapy has no marked efficacy in the treatment of childhood pneumonia.

Natural indigo, as one of the oldest dyes, is also a pivotal dye utilized in cotton fabrics today. A diversity of plants rich in indigo compounds belong to traditional Chinese herbal medicines. Indigo compounds have a variety of biological and pharmacological activities, including anticonvulsant, antibacterial, antifungal, antiviral and anticancer activities. A substantial progress in indigo biosynthesis has been made lately. This paper summarizes the value of indigo from the aspects of cultural history, biosynthetic pathways and the medicinal activities of its related derivatives involved in the pathways. In addition, the latest research advancements in indigo biosynthetic pathways is demonstrated in this paper, which would lay the theoretical foundation for the exploration and utilization of natural indigo.
Biosynthetic Pathways ; Coloring Agents ; Indigo Carmine/metabolism* ; Indigofera/metabolism*

Prostate cancer (PCa) exhibits epidemiological and molecular heterogeneity. Despite extensive studies of its phenotypic and genetic properties in Western populations, its molecular basis is not clear in Chinese patients. To determine critical molecular characteristics and explore correlations between genomic markers and clinical parameters in Chinese populations, we applied an integrative genetic/transcriptomic assay that combines targeted next-generation sequencing and quantitative real-time PCR (qRT-PCR) on samples from 46 Chinese patients with PCa. Lysine (K)-specific methyltransferase 2D (KMT2D), zinc finger homeobox 3 (ZFHX3), A-kinase anchoring protein 9 (AKAP9), and GLI family zinc finger 1 (GLI1) were frequently mutated in our cohort. Moreover, a clinicopathological analysis showed that RB transcriptional corepressor 1 (RB1) deletion was common in patients with a high risk of disease progression. Remarkably, four genomic events, MYC proto-oncogene (MYC) amplification, RB1 deletion, APC regulator of WNT signaling pathway (APC) mutation or deletion, and cyclin-dependent kinase 12 (CDK12) mutation, were correlated with poor disease-free survival. In addition, a close link between KMT2D expression and the androgen receptor (AR) signaling pathway was observed both in our cohort and in The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) data. In summary, our results demonstrate the feasibility and benefits of integrative molecular characterization of PCa samples in disease pathology research and personalized medicine.
A Kinase Anchor Proteins/genetics* ; Adult ; Aged ; Biomarkers, Tumor/genetics* ; China ; Cytoskeletal Proteins/genetics* ; DNA-Binding Proteins/genetics* ; Gene Amplification ; High-Throughput Nucleotide Sequencing ; Homeodomain Proteins/genetics* ; Humans ; Male ; Middle Aged ; Mutation ; Neoplasm Proteins/genetics* ; Prostatic Neoplasms/pathology* ; Proto-Oncogene Mas ; Receptors, Androgen/genetics* ; Signal Transduction/genetics* ; Zinc Finger Protein GLI1/genetics*