Harmonizing international quality standards for Andrographis paniculata: A comparative analysis of content determination methods across pharmacopeias.

The quality standards for Andrographis paniculata, a widely used medicinal herb, exhibited significant variations across different pharmacopeias. In this study, we compared the HPLC content determination methods and total lactone content of A. paniculata samples from different regions, as specified in the Chinese (CP), United States (USP), European (EP), Thai (TP), and Indian pharmacopeias (IP), as well as the Hong Kong Chinese Materia Medica Standards (HK). We aimed to assess the differences and similarities among these pharmacopeias and harmonized international quality standards for A. paniculata. The analysis revealed variations in sample preparation, liquid chromatographic conditions, fingerprint profiles, and total lactone content among the different pharmacopeias. Specifically, the CP and HK methods exhibited superior sample preparation and chromatographic separation. Further comparing the content of 20 A. paniculata samples with the CP, USP, EP and HK methods showed consistent determinations for the same components, indicating similar detection capabilities. The discrepancies in total lactone content primarily stemmed from differences in the number and types of detected compounds. Moreover, the acceptance criteria exhibited a stringency in the order CP > HK > EP > USP. In conclusion, this comparison analysis of content determination in CP, USP, HK, EP, TP and IP provided a scientific foundation for the international standardization and trade regulations of A. paniculata. It also served as a valuable reference for the development of international quality standards for other medicinal herbs, facilitating the harmonization of global pharmaceutical standards.

Progress on evaluation of dysphagia in patients with Parkinson′s disease / 中华神经科杂志

Parkinson′s disease (PD) is a common neurodegenerative disease. The prevalence of dysphagia in patients with PD is 16%-87%. Dysphagic patients show abnormalities in the oral, pharyngeal and esophageal phases of swallowing. The evaluation tools of dysphagia in patients with PD include instrumental assessment tools, non-instrumental objective assessment tools and subjective assessment tools. Videofluoroscopic study of swallowing and flexible endoscopic examination of swallowing are the gold standards for swallowing assessment in patients with PD; high-resolution manometry, tongue pressure measurement, surface electromyography and ultrasonography can be used as supplementary tests; the Swallowing Disturbance Questionnaire Scale, which is sensitive, specific, reliable and valid, is recommended as a screening tool.

Synthesis, evaluation and proteomic analysis of PROTAC based on parthenolide / 药学学报

As a natural product with a long history of medicinal use, parthenolide has aroused great interest of chemists and biologists. Existing studies have shown that it has anti-inflammatory, antitumor and other pharmacological activities, and also revealed its action on NF-κB signaling pathway, DNMT1 enzyme and Wnt/β-catenin signaling pathway. But its biological targets remain to be elucidated systematically. Proteolysis Targeting Chimeras (PROTAC) provides a new strategy for target discovery of natural products, which can be used to explore the panorama of protein changes in cells through proteomic investigation, so as to analyze their potential targets. Based on this idea, current study designed and synthesized 20 parthenolide-derived degraders. After measured their antitumor activity in vitro, selected compounds were carried out the proteomic experiment. Finally, 139 down-regulated differentially expressed proteins were identified and the discovery of parthenolide interacting protein was preliminarily explored.

Research advances of small molecule inhibitors in the treatment of mixed lineage leukemia / 药学学报

Acute leukemia (AL) is a kind of malignant clonal disease of hematopoietic stem cells. Rearrangement of mixed lineage leukemia (MLL) gene can be observed in about 5%-10% of AL patients. Currently, AL patients with MLL-rearrangements (MLL-r) lack effective treatment and are usually associated with poor prognoses. Recent studies have shown that many epigenetic regulators are directly or indirectly involved in the occurrence and development of AL carrying MLL-r (MLL), which provides a biological basis for the use of epigenetic regulation strategies to treat MLL. In this review, we start from the epigenetic regulation mechanism of MLL, and select representative drug targets to briefly analyze the relationship between each target and MLL and summarize the development progress of their inhibitors, hoping to provide reference for the subsequent research and development of drugs for the treatment of MLL.

Efficacy and safety of a modified method for blind bedside placement of post-pyloric feeding tube: a prospective preliminary clinical trial.

OBJECTIVE: To compare the efficacy and safety of a new modified method of bedside post-pyloric feeding tube catheterization with the Corpak protocol versus electromagnetic-guided catheterization. MATERIALS AND METHODS: We conducted a single-center, single-blinded, prospective clinical trial. Sixty-three patients were treated with a non-gravity type gastrointestinal feeding tube using different procedures: modified bedside post-pyloric feeding tube placement (M group), the conventional Corpak protocol (C group), and standard electromagnetic-guided tube placement (EM group). RESULTS: The success rate in the M group, C group, and EM group was 82.9% (34/41), 70.7% (29/41), and 88.2% (15/17), respectively, with significant differences among the groups. The time required to pass the pylorus was significantly shorter in the M group (26.9 minutes) than in the C group (31.9 minutes) and EM group (42.1 minutes). The proportion of pylorus-passing operations completed within 30 minutes was significantly higher in the M group than in the C group and EM group. No severe complications occurred. CONCLUSION: This modified method of bedside post-pyloric feeding tube catheterization significantly shortened the time required to pass the pylorus with no severe adverse reactions. This method is effective and safe for enteral nutrition catheterization of patients with dysphagia and a high risk of aspiration pneumonia.

Research progress of cyclic peptides derived from phage display technology / 药学学报

Cyclic peptide drugs have gradually become an emerging research direction due to their some favorable properties such as high-efficiency binding affinity, high selectivity, lower toxicity, and stable metabolism. In recent years, the number of cyclic peptide drugs under clinical research has continued to increase. Unlike the previous cyclic peptide drugs, which were mostly derived from natural products and their derivatives, these cyclic peptide drugs are designed by genetically encoded display technologies which are based on rational design and in vitro evolution (such as BT1718, PTG-300, POL6326, etc). Among them, phage display technology has some advantages such as mature research system, low cost, and simpler operation that make it well recognized and praised by the majority of researchers in this field. Here, we reviewed the recent progress of applying phage display technology to explore diverse cyclic peptide libraries, which, we believe, will contribute more valuable candidate cyclic peptide drugs in clinical research.

Analysis on the diagnosis and treatment of necrotizing fasciitis complicated with sepsis / 中华危重病急救医学

Objective:To recognize the characteristics of necrotizing fasciitis patients complicated with sepsis and summarize the experience the treatment.Methods:A retrospective study was conducted. The clinical data of 57 patients with necrotizing fasciitis complicated with sepsis admitted to Guangdong Provincial People's Hospital from July 2009 to December 2019 was analyzed by collecting such factors as gender, age, complications, infection sites, pathogens, surgery information, treatment options and outcome. The patients were divided into debridement group ( n = 14) and control group ( n = 43) according to whether the debridement was completed within 48 hours of admission, and the mortality during hospitalization between the two groups was compared. A telephone follow-up had been done to record the long-term outcome of these patients. Results:Among 57 patients with necrotizing fasciitis complicated with sepsis, there were 43 males and 14 females with the average age of (57.9±12.1) years old. Most of the underlying diseases were diabetes mellitus (70.17%), other diseases included hypertension (8.77%), tumor chemotherapy (7.02%), liver disease (hepatitis, cirrhosis, 7.02%), coronary artery heart disease (3.51%), systemic lupus erythematosus (3.51%), etc. Most of the infection site was lower limbs (71.93%). There were 78 pathogens cultured in 57 patients, in which 52 were non-drug resistant bacteria (66.67%), and 26 were drug resistant bacteria (33.33%). There were 40 Gram positive (G +) bacteria (51.28%), 29 Gram negative (G -) bacteria (37.18%), 8 fungi (10.26%) and 1 mixed bacteria (1.28%). Finally, of 57 patients, 46 patients were cured, and 11 patients died with hospital mortality of 19.30%. Among 57 patients, the hospital mortality in the debridement group was significantly lower than that in the control group [0% (0/14) vs. 25.58% (11/43), P < 0.05]. Among the 46 cured patients, 11 had accepted amputations, accounting for 23.91%. In December 2020, 43 patients who were cured (3 patients were lost to follow-up) were followed up by telephone. Twenty-three patients were completely self-care, 9 patients were partly self-care, 8 patients were completely unable to take care of themselves, and 3 patients died. Conclusions:Necrotizing fasciitis with sepsis mostly occurs in people with weakened immunity, and has a high mortality and disability rate. Early identification and active surgical debridement may be the key to improve the treatment effect.

Effects of three kinds of active ingredients of traditional Chinese medicine on dre-miR-723-5p expression in morphine-induced zebrafish brain / 中国药理学通报

Aim To study the effect of three kinds of active ingredients of traditional Chinese medicine (sinomenine, rhynchophylline and isorhynchophylline) on dre-miR-723-5p expression in morphine-induced zebrafish brain. Methods Morphine was injected intraperitoneally to zebrafish, conditional position preference (CPP) was trained and then the behavioral of animals were observed; the miRNA expression profiles of morphine-additive zebrafish were determined by small RNA sequencing; qRT-PCR was used to verify the expression of dre-miR-723-5p, three target gene databases (miRanda, miRDB, andRNAhybrid) were used to predict the target genes of dre-miR-723-5p; Kobas 3.0 was used to perform Gene Ontology (GO) and KEGG pathway analysis of these target genes. Results Morphine-induced CPP model was established successfully. Compared with control group, the resident time and movement map in drug-pair box of zebrafish in model group significantly increased. After drug administration, the resident time and movement map in drug-pair box of zebrafish decreased. The verification results of qRT-PCR were consistent with the results of small RNA sequencing. Ninety-nine putative target genes of dremiR-723-5p that were common to all three target gene databases, which were mainly enriched in biological process, cell composition and molecular function, involved in the positive regulation of MAPK signaling pathway, lysosome, cytokine-cytokine receptor interaction, and apoptosis. Conclusion Morphine can increase the expression of dre-miR-723-5p in the zebrafish brain, which can be reversed by sinomenine, isorhynchophylline, and rhynchophylline treatment, and dre-miR-723-5p may participate in the mechanism underlying morphine-induced damage of brain.

Structure of SARS-CoV-2 main protease in the apo state reveals the inactive conformation

Mpro is of considerable interest as a drug target in the treatment of COVID-19 since the proteolytic activity of this viral protease is essential for viral replication. Here we report the first insight of the structure Mpro for SARS-CoV-2 in the inactive conformation under conditions close to the physiological state (pH 7.5) to an overall resolution of 1.9 [A]. The comparisons of Mpro in different states reveal that substrate binding site and the active site are more flexible in the inactive conformation than that in the active conformations. Notably, compared with the active conformation of the apo state structure in pH7.6 of SARS, the SARS-CoV-2 apo state is in the inactive conformation under condition close to physiological state (pH7.5). Two water molecules are present in the oxyanion hole in our apo state structure, whereas in the ligand-bound structure, water molecular is absence in the same region. This structure provides novel and important insights that have broad implications for understanding the structural basis underlying enzyme activity, and can facilitate rational, structure-based, approaches for the design of specific SARS-CoV-2 ligands as new therapeutic agents.

[Current quality standards of Andrographis Herba of different countries and regions].

Andrographis Herba is a commonly used plant medicine, and has been recorded in pharmacopeias of different countries. However, there are some differences in the quality standards. Based on this, this paper compare the quality standards of Andrographis Herba between Chinese Pharmacopoeia, Hong Kong Chinese Materia Medica Standards, United States Pharmacopoeia, European Pharmacopoeia and Indian Pharmacopoeia, including origin, botanical characteristics, identification(microscopic identification and chromatographic identification), content determination, specific test(such as impurities, loss on drying, extractives, pesticides, heavy metals, mycotoxins, and other items) and storage requirements, so as to provide a reference for studying international quality standards of Andrographis.

A case report of extramedullary plasmacytoma of the right epididymis / 中华泌尿外科杂志

Extramedullary plasmacytoma is a localized plasmacytoma originating from tissues other than bone marrow, and epididymal affecting is rare. This paper summarizes a case of this tumor admitted to our hospital in recent years, with the purpose of improving the further understanding and treatment of this tumor and avoiding misdiagnosis.

Urine turbulent shear stress system of bionic human bladder based on bacterial biofilm reactor: In vitro construction / 中国组织工程研究

BACKGROUND: The formation of bacterial biofilm on the material surface is the core problem of catheter-related urinary tract infection. Many researches have focused on the mechanism and prevention of such category of infection under static or simple hydrodynamic stimulation. The construction of dynamic model of bacterial biofilm of bladder urine flow close to real human diseases is the key to study the pathological mechanism and develop new technology of anti-biofilm infection. OBJECTIVE: To put forward the concept of turbulent flow shear stress of human bladder urine flow, construct this turbulent shear stress system based on the bacterial biofilm reactor of in vitro bionic human bladder, and explore the formation of E. coli biofilm stimulated by different stresses. METHODS: An in vitro dynamic bionic bladder urine flow model was designed. E. coli standard strain ATCC25922 was used as research object, and the medical silica gel was used as bacterial biofilm forming carrier. Four artificial urine flow stresses were simulated: hydrostatic pressure, constant turbulent flow shear stress, physiological turbulent flow shear stress and pathological turbulent flow shear stress (simulated urine retention environment). A bacterial biofilm reactor loaded with turbulent flow shear stress was established. Optical density value, colony count, and biofilm surface area of bacterial biofilm suspension were detected 24, 72, 120, and 168 hours. RESULTS AND CONCLUSION: (1) Optical density value of bacterial membrane suspension: there was significant difference between different urinary stress groups and different test time points (F=110.84, 187.96, all P < 0.000 1), and there was interaction effect between time and stress (F=50.05, P < 0.000 1). From hydrostatic pressure, constant turbulent flow shear stress, physiological turbulent flow shear stress, to pathological turbulent flow shear stress, the number of biofilm bacterial colonies increased. (2) Colony count of biofilm bacterial suspension smear: there was significant difference between different time (F=6.30, P=0.002 9); no difference was found between different urinary stress groups (F=1.11, P=0.400 1); and there was no interaction effect between time and stress (F=0.85, P=0.581 4). However, with the time extension of stress action, the colony count of complex stress group showed an increasing tendency, especially in the pathological turbulent shear stress. (3) Scanning electron microscopic characterization of biofilm bacteria: qualitative comparison between each group and different time points showed that the formation of bacterial biofilm was different from sparse fragments, lumps to large lumps. There were significant differences in the bacterial biofilm surface area between different urinary stress groups and at different times (F=505.72, 1 201.84, all P < 0.000 1), and there was interaction effect between time and stress (F=78.14, P < 0.000 1). From hydrostatic pressure, constant turbulent flow shear stress, physiological turbulent flow shear stress, to pathological turbulent flow shear stress, the biofilm formation increased significantly. (4) The results showed that this turbulent flow shear stress of human bladder urine flow can obviously stimulate E. coli biofilm formation in vitro. Its functional changes and pathogenic mechanism need to be further explored.

Current quality standards of Andrographis Herba of different countries and regions / 中国中药杂志

Andrographis Herba is a commonly used plant medicine, and has been recorded in pharmacopeias of different countries. However, there are some differences in the quality standards. Based on this, this paper compare the quality standards of Andrographis Herba between Chinese Pharmacopoeia, Hong Kong Chinese Materia Medica Standards, United States Pharmacopoeia, European Pharmacopoeia and Indian Pharmacopoeia, including origin, botanical characteristics, identification(microscopic identification and chromatographic identification), content determination, specific test(such as impurities, loss on drying, extractives, pesticides, heavy metals, mycotoxins, and other items) and storage requirements, so as to provide a reference for studying international quality standards of Andrographis.

Cytotoxic Prenylated Xanthones from the Leaves of Garcinia bracteata.

Six new prenylated xanthones (1: -6: ) and seventeen known xanthones were isolated from extracts of Garcinia bracteata leaves. Their structures were determined by extensive NMR and MS spectroscopic data analysis. The inhibitory activities of the isolates were assayed on HeLa, A549, PC-3, HT-29, and WPMY-1 cell lines. Compounds 1: and 15: -17: showed moderate inhibitory effects on tumor cell growth, with IC50s ranging from 3.7 to 14.7 µM.

Bioactive scalemic caged xanthones from the leaves of Garcinia bracteata.

Four pairs of previously undescribed caged xanthones (1-4) and twelve known caged xanthones (5-16) were isolated from the leaf extract of Garcinia bracteata. Their structures were unambiguously elucidated on the basis of spectroscopic methods. The planar structure and relative configuration of 1 was confirmed by X-ray crystallographic analysis. The enantiomers of compounds 1, 2, 4 were further resolved by semi-preparative chiral HPLC, and the absolute configurations of enantiomers of compounds 1 and 4 were determined by measurement and calculation of electronic circular dichroism (ECD) spectra and specific rotations. The inhibitory activities of the isolated compounds against human HeLa, A549, PC-3, HT-29, and WPMY-1 cell lines were assayed, and garcibractatin A (4) showed the most potent inhibitory activities in vitro with IC50 values from 1.11 to 2.93 µM. A preliminary structure-activity relationship has been discussed, and some helpful conclusions have been drawn.

Analysis of late diagnosis and its influencing factors of newly reported HIV/AIDS in Guizhou Province from 2014 to 2018 / 中华疾病控制杂志

Objective To find late diagnosis and its influencing factors of newly reported HIV/AIDS in Guizhou Province from 2014 to 2018. Methods Through the Chinese National Comprehensive HIV/AIDS Prevention and Care Information System,all newly reported HIV/AIDS cases from 2014 to 2018 in Guizhou Province were analyzed and related factors of late diagnosis were analyzed using binary Logistic regression model. Results From 2014 to 2018, there were 33 611 newly reported HIV/AIDS cases in Guizhou Province, and the late diagnosis rates of newly reported cases were 35.46%, 34.49%, 38.35%, 39.74% and 38.80% respectively. The analysis showed that the proportion of late diagnosis cases from medical institutions increased year by year ( 2=64.603,P<0.001). By analyzing the late diagnosis rate of cases from different sample sources, medical institutions was significantly higher than that reported by voluntary counseling and testing, positive spouses or sexual partners( 2=276.033,P<0.001). Multivariate analysis showed that gender, marital status, route of transmission, occupation, ethnicity and source of samples were associated with the late diagnosis of newly reported cases (all P<0.05). Conclusions It shows a slow upward trend of late diagnosis rate among HIV/AIDS reported in Guizhou Province from 2014 to 2018.On the one hand, it is of great significance to continue to strengthen the publicity and education of the whole population in Guizhou , in order to improve the awareness of HIV active detection. On the other hand, we should continue to expand HIV testing in Guizhou Province to improve the early detection level of HIV/AIDS.

Discovery of a series of dimethoxybenzene FGFR inhibitors with 5pyrrolo2,3-pyrazine scaffold: structure-activity relationship, crystal structural characterization and study

Genomic alterations are commonly found in the signaling pathways of fibroblast growth factor receptors (FGFRs). Although there is no selective FGFR inhibitors in market, several promising inhibitors have been investigated in clinical trials, and showed encouraging efficacies in patients. By designing a hybrid between the FGFR-selectivity-enhancing motif dimethoxybenzene group and our previously identified novel scaffold, we discovered a new series of potent FGFR inhibitors, with the best one showing sub-nanomolar enzymatic activity. After several round of optimization and with the solved crystal structure, detailed structure-activity relationship was elaborated. Together with metabolic stability tests and pharmacokinetic profiling, a representative compound () was selected and tested in xenograft mouse model, and the result demonstrated that inhibitor was effective against tumors with FGFR genetic alterations, exhibiting potential for further development.

Application of venous super drainage technique in free flaps transfer / 中华显微外科杂志

To investigate the effect of venous super drainage applying in free flaps. Methods From June, 2017 to December, 2018, 7 cases who had severe soft tissue injuries were treated with free flap. Cause of injury: 1 electric injuries, 2 tumor-related wounds, 1 deep burns, 2 mechanical trauma, and 1 necrotizing fasciitis. All patients were underwent free flap transplantation. There were 5 cases of anterolateral thigh artery perforator flap, 1 case of superficial circumflex iliac artery perforator flap, and 1 case of first dorsal metatarsal artery perforator flap.The application of venous super-drainage technology was carried out according to needs and specific conditions. Two sets of venous passages were prepared in both recipient and donor site to form a double set of venous reflux super-drainage mode. Blood supply, swelling, exudation, secondary exploration and survival rate of the flap were observed after operation, and regularly followed-up. Results All 7 flaps survived. Venous super drainage technique was ap-plied in 7 cases. No arteriovenous crisis occurred after the operation. The flaps had good blood circulation, slight swelling, less exudation, rapid edema regression and no secondary surgical exploration. Followed-up for 2-18 (average 10.5) months, there was no infection recurred. Flaps survived well, and the donor sites healed well without sensory loss.The flexion and extension function of joint was normal. Conclusion The technique of venous super-drainage prepares 2 sets of venous systems for the free flap in the treatment of vascular pedicle in the free flap repair operation, which is conducive to reducing the venous crisis after flap surgery, reducing flap edema, reducing exudation, reducing secondary surgical exploration and improving the survival rate of the flap.

Mortality and influencing factors on injecting drug users with HIV/AIDS in Guizhou province, 1996-2015 / 中华流行病学杂志

Objective@#To understand the mortality and influencing factors on injecting drug users (IDUs) with HIV/AIDS, in Guizhou province, 1996-2015.@*Methods@#A retrospective cohort study was conducted on IDUs with HIV/AIDS that were reported through national comprehensive HIV/AIDS information system, in Guizhou province during 1996-2015. Cox proportional hazard regression model was used to analyze the influencing factors on the mortality of HIV/AIDS.@*Results@#A total of 3 958 cases of IDUs with HIV/AIDS were recruited in this study, with all-cause mortality rate of 44.01% (1 742/3 958) and total mortality rate of 7.80/100 person-years, respectively. The median survival time between diagnosis and death was 8.08 years. Mortality rate was 3.57/100 person-years in the group receiving antiretroviral therapy (ART). The mortality appeared to be 4.08/100 person-years in the group who were on methadone maintenance treatment (MMT). Data from the multiple regression analysis indicated that factors of gender, ethnicity, age when HIV/AIDS diagnosis was made, CD4+T lymphocyte (CD4) count at the first testing, ART and MMT were significantly associated with deaths among these people. The risk of death in females was 0.82 times (95%CI: 0.69-0.98) higher than that in males. The risk of deaths among the ethnic minority subjects was 1.39 times (95%CI: 1.21-1.60) higher than that of the Hans. The risk of death appeared to be 2.44 times higher (95%CI: 1.07-5.56) in the over-50-year of age group than in the <20 year-old group, when HIV/AIDS was diagnosed for the first time. The risk of death in CD4 ≥500/μl group in the first time was 0.27 times (95%CI: 0.22-0.32) more than CD4 <200/μl group in the firs time. The risk of death in cases who were treated with ART or MMT was 2.83 times (95%CI: 2.45-3.26) and 1.35 times (95%CI: 1.15-1.59) higher than those who did not receive any treatment, respectively.@*Conclusion@#Higher risks on death seemed to be related to the following factors: being male, older age at the time of diagnosis, lower CD4 at diagnosis, not on ART or MMT among the IDUs with HIV/AIDS in Guizhou province, between 1996-2015.

Modified posterior occipital fusion for treatment of atlantooccipital and atlantoaxial dislocation in children and adolescents / 中华神经医学杂志

Objective To study the clinical efficacy of modified posterior occipital fusion in atlantooccipital and atlantoaxial dislocation in children and adolescents. Methods The clinical data of 11 children or adolescents with atlantooccipital and atlantoaxial dislocation, admitted to and accepted modified posterior occipital fusion in our hospital from November 2013 to March 2018, were retrospectively analyzed. Before and after the surgery, Japanese orthopedic association (JOA) scale was used to evaluate the cervical vertebral function of the patients, the atlanto-dens interval (ADI) was measured by CT images to evaluate the dislocation and reduction of joints, and the medulla bulbar cervical medulla angle (CMA) of the patients was measured by MR imaging to evaluate the degrees of spinal cord compression. Results The clinical symptoms of 11 patients improved in different degrees. No postoperative complications occurred. JOA scale scores after operation were significantly higher than those before operation (15.0±1.0 vs. 12.2±1.6). Significantly decreased of ADI and significantly increased CMA after operation were noted as compared with those before operation (P<0.05). Conclusion Modified posterior occipital fusion is safe and effective for treatment of atlantooccipital and atlantoaxial dislocation in children and adolescents.