Noninvasive identificational diagnosis of diabetic nephropathy and non-diabetic renal disease based on clinical characteristics of Traditional Chinese Medicine symptom pattern and conventional medicine.

OBJECTIVE: To study the clinical characteristics relating to differential diagnosis of diabetic nephropathy (DN) and non-diabetic renal disease (NDRD). METHODS: The subjects were patients with type 2 diabetes mellitus (T2DM) complicated with chronic kidney disease (CKD). Western medical history data and Traditional Chinese Medicine (TCM) symptom pattern were collected, and logistic regression was used to analyze. RESULTS: Blood deficiency pattern [odds ratio () = 2.269, 0.017] and stagnation pattern ( = 1.999, 0.041) are independently related to DN. CONCLUSIONS: TCM factors blood deficiency pattern and stagnation pattern are relating to differential diagnosis of DN and NDRD.

Matrine suppresses NLRP3 inflammasome activation via regulating PTPN2/JNK/SREBP2 pathway in sepsis.

BACKGROUND: Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Abnormal activation of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome plays a vital role in the pathogenesis of sepsis. Matrine is proved to show good anti-inflammatory properties, whereas its effect and the underlying molecular machinery on sepsis remains unclear. PURPOSE: The aim of this study is to evaluate the effect and mechanism of Matrine on sepsis. STUDY DESIGN: THP-1 cells and J774A.1 cells were stimulated by lipopolysaccharide (LPS) with nigericin or adenosine triphosphate (ATP) to establish an in vitro model. Cecal ligation and puncture (CLP)-induced sepsis mouse model was used. Matrine was given by gavage. METHODS: To investigate the NLRP3 inflammasome activation, phorbol myristate acetate (PMA)-induced THP-1 cells were first primed with LPS and then stimulated by matrine, followed by treatment with nigericin or ATP. The concentration of interleukin 1ß (IL-1ß) and interleukin 18 (IL-18) in the cell culture supernatant was detected. The mechanism was explored by cell death assay, immunoblots and immunofluorescence in vitro. C57BL/6 mice were intragastrically administered with matrine for 5 days before CLP. The therapeutic effect of matrine was evaluated by symptoms, pathological analysis, ELISA and RT-qPCR. RESULTS: Our results revealed that matrine inhibited IL-1ß and IL-18 secretion, suppressed caspase-1 activation, reduced cell death, and blocked ASC speck formation upon NLRP3 inflammasome activation. Furthermore, matrine restrains NLRP3 inflammasome activation as well as pyroptosis through regulating the protein tyrosine phosphatase non-receptor type 2 (PTPN2)/JNK/SREBP2 signaling. Matrine also prominently improved the symptoms and pathological changes with reduced levels of TNF-α, IL-1ß, and IL-6 in the lung tissues and serum in a dose-dependent manner. CONCLUSION: Matrine effectively alleviates the symptoms of CLP-induced sepsis in mice, restrains NLRP3 inflammasome activation by regulating PTPN2/JNK/SREBP2 signaling pathway, and may become a promising therapeutic agent for sepsis treatment.

Traditional Chinese Medicine Intervention in Membranous Nephropathy Based on Podocyte Injury： A Review / 中国实验方剂学杂志

Membranous nephropathy， an autoimmune kidney disease with glomerular podocyte injury as the core mechanism， is a common pathological type of adult nephrotic syndrome and has become the main cause of end-stage renal disease in China. Podocytes are terminally differentiated cells that play an important role in maintaining the structural and functional stability of glomeruli and are molecular barriers for protein filtration. Glomerular filtration membrane injury induced by podocyte injury is an important cause of massive proteinuria. Persistent or aggravated proteinuria may prolong the course of membranous nephropathy. It is believed that podocyte destruction in membranous nephropathy is mainly related to oxidative stress， autophagy dysregulation， abnormal expression of podocyte marker proteins， chronic inflammation， epithelial-mesenchymal cell transdifferentiation， and so on. At present， western medicine mostly uses immunosuppressants and hormones for treatment according to its pathological stage， but there are certain adverse reactions. Traditional Chinese medicine （TCM） has made some achievements in the prevention and treatment of membranous nephropathy. In recent years， studies have found that many Chinese medicines can affect the occurrence and development of membranous nephropathy in different links by acting on multiple targets in the human body， with manifest advantages. This paper overviewed the podocyte injury mechanism in membranous nephropathy and summarized the treatment of membranous nephropathy with Chinese medicine monomers， compounds， and Chinese patent medicines in intervening related target pathways， aiming to provide a basis for the clinical treatment， basic research， and targeted drug development of TCM against membranous nephropathy.

Research status on efficacy enhancement and toxicity reduction of Chinese medicine in treatment of malignant tumors: a review of projects supported by National Natural Science Foundation of China / 中国中药杂志

Through a retrospective analysis of the projects supported by the National Natural Science Foundation of China in the past ten years in the field of Chinese medicine for the treatment of malignant tumors, this article systematically summarized the main research contents and hotspots of Chinese medicine in efficacy enhancement and toxicity reduction. The efficacy enhancement of Chinese medicine mainly included the mitigation of molecule-targeted drug resistance, multidrug resistance, and chemotherapy resistance, synergistic efficacy enhancement, and radiotherapy sensitization. The toxicity reduction is mainly reflected in the alleviation of the side effects of radiotherapy and chemotherapy. In addition, Chinese medicine has advantages in reducing serious adverse reactions of malignant tumors, providing more options for the adjuvant treatment of tumors.

Epidemiological and clinical characteristics of COVID-19 patients in Hengyang, Hunan Province, China.

BACKGROUND: In December 2019, an ongoing outbreak of coronavirus disease 2019 (COVID-19) was first identified in Wuhan, China. The characteristics of COVID-19 patients treated in local hospitals in Wuhan are not fully representative of patients outside Wuhan. Therefore, it is highly essential to analyze the epidemiological and clinical characteristics of COVID-19 in areas outside Wuhan or Hubei Province. To date, a limited number of studies have concentrated on the epidemiological and clinical characteristics of COVID-19 patients with different genders, clinical classification, and with or without basic diseases. AIM: To study the epidemiological and clinical characteristics of COVID-19 patients in Hengyang (China) and provide a reliable reference for the prevention and control of COVID-19. METHODS: From January 16 to March 2, 2020, a total of 48 confirmed cases of COVID-19 were reported in Hengyang, and those cases were included in this study. The diagnostic criteria, clinical classification, and discharge standard related to COVID-19 were in line with the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7) released by National Health Commission and National Administration of Traditional Chinese Medicine. The presence of SARS-CoV-2 in pharyngeal swab specimens was detected by quantitative reverse transcription polymerase chain reaction. All the data were imported into the excel worksheet and statistically analyzed by using SPSS 25.0 software. RESULTS: A total of 48 cases of COVID-19 were collected, of which 1 was mild, 38 were moderate, and 9 were severe. It was unveiled that there were 31 (64.6%) male patients and 17 (35.4%) female patients, with a female-to-male ratio of 1.82:1. The range of age of patients with COVID-19 was dominantly 30-49 years old [25 (52.1%) of 48], followed by those aged over 60 years old [11 (22.9%)]. Besides, 29.2% (14 of 48) of patients had basic diseases, and 57.2% (8 of 14) of patients with basic diseases were aged over 60 years old. The occupations of 48 COVID-19 patients were mainly farmers working in agricultural production [15 (31.5%) of 48], rural migrant workers from Hengyang to Wuhan [15 (31.5%)], and service workers operating in the service sector [8 (16.7%)]. The mean latent period was 6.86 ± 3.57 d, and the median was 7 [interquartile range (IQR): 4-9] d. The mean time from onset of symptoms to the first physician visit was 3.38 ± 2.98 (95%CI: 2.58-9.18) d, with a median of 2 (IQR: 1-5) d, and the mean time from hospital admission to confirmed diagnosis was 2.29 ± 2.11 (95%CI: 1.18-6.42) d, with a median of 2 (IQR: 1-3) d. The main symptoms were fever [43 (89.6%) of 48], cough and expectoration [41 (85.4%)], fatigue [22 (45.8%)], and chills [22 (45.8%)]. Other symptoms included poor appetite [13 (27.1%)], sore throat [9 (18.8%)], dyspnea [9 (18.8%)], diarrhea [7 (14.6%)], dizziness [5 (10.4%)], headache [5 (10.4%)], muscle pain [5 (10.4%)], nausea and vomiting [4 (8.3%)], hemoptysis [4 (8.3%)], and runny nose [1 (2.1%)]. The numbers of peripheral blood leukocytes, lymphocytes, and eosinophils were significantly reduced in the majority of the patients. The levels of C-reactive protein, fibrinogen, blood glucose, lactate dehydrogenase, D-dimer, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (γ-GT), myoglobin (MB), and creatine kinase (CK) were increased in 64.6%, 44.7%, 43.2%, 37.0%, 29.5%, 22.9%,20.8%, 21.6%, 13.6%, and 12.8% of patients, respectively. The incidence of ALT elevation in male patients was remarkably higher than that in females (P < 0.01), while the incidences of AST, CK, and blood glucose elevations in severe patients were remarkably higher than those in moderate patients (P < 0.05, respectively). Except for the mild patients, chest computed tomography showed characteristic pulmonary lesions. All the patients received antiviral drugs, 38 (79.2%) accepted traditional Chinese medicine, and 2 (4.2%) received treatment of human umbilical-cord mesenchymal stem cells. On March 2, 2020, 48 patients with COVID-19 were all cured and discharged. CONCLUSION: Based on our results, patients with COVID-19 often have multiple organ dysfunction or damage. The incidences of ALT elevation in males, and AST, CK, and blood glucose elevations in severe patients are remarkably higher.

Prevention and treatment of biotoxin-induced acute renal injury / 解放军医学杂志

With the increase of human activities, biotoxin poisoning has gradually become a serious health problem. Biotoxins are usually classified into bacterial toxins, mycotoxins, marine toxins, animal venoms, enterotoxins, exotoxins, etc. A variety of toxins can cause impaired renal function and even lead to acute renal failure. The biotoxin-induced kidney injury is a dangerous clinical condition involving a variety of pathophysiological mechanisms. Failure to treat properly in time often leads to higher mortality. Blood purification therapy plays a central role in the treatment of patients with biotoxin-induced renal injury. The present paper reviews the current status of prevention and treatment of acute renal injury caused by common biotoxins in China, including poisonous mushrooms, fish gall, snake venom and bee stings. The purpose of this review is to make Chinese nephrologists and specialists clear the prevention and treatment of biotoxin-induced renal injury, and standardize the prevention and treatment strategy of biotoxin-induced kidney injury.

Electroacupuncture improves neurovascular unit reconstruction by promoting collateral circulation and angiogenesis.

Acupuncture at Shuigou (GV26) shows good clinical efficacy for treating stroke, but its mechanism remains poorly understood. In this study, a cerebral infarction model of ischemia/reperfusion injury received electroacupuncture at GV26 (15 Hz and 1 mA, continuous wave [biphasic pulses], for 5 minutes). Electroacupuncture effectively promoted regional cerebral blood flow on the infarct and non-infarct sides, increased infarct lesions, lectin, and number of blood vessels, upregulated von Willebrand factor and cell proliferation marker Ki67 expression, and diminished neurological severity score. These findings confirm that electroacupuncture at GV26 promotes establishment of collateral circulation and angiogenesis, and improves neurological function.

Large doses of uterotonic drugs caused type II second degree sinoatrial block during cesarean section.

In China, it is a routine procedure to inject 250 µg of hemabate (sterile solution, an oxytocic, contains the tromethamine salt of the (I5S)-15 methyl analogue of naturally occurring prostaglandin F2α in a solution suitable for intramuscular injection) into the myometrium of patients experiencing uterine inertia after delivery, with an additional dose given in the event that the efficacy is not obvious. Although hemabate is prohibited from being used in patients with active liver disease, there are no restrictions regarding the application of hemabate in positive hepatitis B surface antigen (HbsAg)-positive subjects with normal liver function. Here we report adverse effects of hemabate in 1 HbsAg-positive subject with normal liver function. This subject experienced increased blood pressure, chest tightness, and type II second degree sinoatrial block 25 minutes after an additional injection of hemabate. Thus, special attention should be paid when applying hemabate in HbsAgpositive subjects with normal liver function.

Metabolomics analysis of Tripterygium wilfordii formulation based on theory of detoxicity compatibility / 中国中药杂志

Tripterygium wilfordii Hook. f. induced-hepatotoxicity was the main limitation for its usage in clinic. Qingluo Tongbi formulation showed obvious attenuation for hepatotoxicity in clinic and fundamental research in vivo. To explore the potential mechanism of the attenuation, we conducted a study on the plasma metabolomic profiles of T. wilfordii and Qingluo Tongbi formulation in rats by a sensitive gas chromatography-mass spectrometry (GC-MS/MS) method. In plasma samples, a total of 72 compounds were analyzed by EI source MS, and were successfully identified by matching NIST database. The semi-quantification results were then calculated by OPLS-DA model with SIMCA-P 13.0 software. The three groups were clearly distinguished in OPLS-DA score plot. In addition, the observation values of Qingluo Tongbi formulation showed the obvious trend towards the control levels, suggesting the detoxicity effect of the formulation. Variation metabolites were further analyzed by VIP and One Way ANOVAs, and the results showed a significant increase in compounds of glycogenic amino acids, such as alanine, proline, serine and glutamine after the administration of T. wilfordii, indicated that the tissue proteins were decomposed and amino acids were leakage into blood. Qingluo Tongbi formulation could reverse the amino acids into normal level. On the contrary, the levels of glucose, lactic acid and hydroxy butyrate decrease, and the formulation can relieve the disorder in the levels of lactic acid, suggesting the regulation of the energy metabolism. Additionally, the level of branched chain amino acid was decreased, suggested the toxicity was induced, but the formulation cannot increase it into the normal levels. Nevertheless, all the above results suggested that the classical Qingluo Tongbi formulation displayed the liver protection effect by adjusting the amino acid levels and regulating the energy metabolism. Qingluo Tongbi formulation was developed based on traditional Chinese medicine theory "detoxicity compatibility", and contained Panax notoginseng (Burk.) F. H. Chen to nourish blood and absorb clots. Modern pharmacology suggested that its liver protection effect was correlated with the promotion of protein synthesis. Another important herb is Rehmannia glutinosa Libosch., which can regulate the energy metabolism. Both were consistent with the metabolomic results in this study, which explained the potential mechanism of "detoxicity compatibility" theory. Therefore, the currently developed metabolomic approach and the obtained results would be highly useful for the comprehensive toxicity studies for other herbal medicines and various complex deoxicity formulations.

Guidelines and strategy of the International Conference of Harmonization (ICH) and its member states to overcome existing impurity control problems for antibiotics in China.

In the present report, we review the technical guidelines and principles on impurity research and control for antibiotics established by various agencies, including the International Conference of Harmonization (ICH), the US Food and Drug Administration (FDA), the European Medicines Agency (EMA) and the China Food and Drug Administration (CFDA). Progresses with the US Pharmacopoeia (USP), the European Pharmacopoeia (EP) and the Chinese Pharmacopoeia (ChP) to control impurities in antibiotics are also presented. Next, our discussion is focused on analyzing the CFDA's requirements on impurity research and control for antibiotics, and the implementation of ICH, FDA and other technical guidelines for generic drugs impurity control in China. Existing problems are further reviewed, in order to improve the overall process for the control of antibiotic purity.

Inhibition mechanism of Qingluo Tongbi Granule () on osteoclast differentiation induced by synovial fibroblast and monocytes co-culture in adjuvant-induced arthritic rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the mechanism underlying the inhibitory effect of Qingluo Tongbi Granule (, QTG) on osteoclast differentiation in rheumatoid arthritis in rats.</p><p><b>METHODS</b>Fibroblast and monocyte co-culture were used to induce osteoclast differentiation in adjuvant-induced arthritic (AIA) rats. Serum containing QTG was prepared and added to the osteoclasts, and activation of the tumor necrosis factor receptor-associated factor 6/mitogen-activated protein kinase/nuclear factor of activated T cells, cytoplasmic1 (TRAF6/MAPK/NFATc1) pathways was examined.</p><p><b>RESULTS</b>The induced osteoclasts were multinucleated and stained positive for tartrate-resistant acid phosphatase (TRAP) staining. Serum containing QTG at 14.4, 7.2 or 3.6 g/kg inhibited the activation of TRAF6, extracellular regulated protein kinase (ERK)1/2, c-Jun N-terminal kinase (JNK) and p38 and decreased the percentage of cells with nuclear NFATc1 in a dose-dependent manner, the high and middle doses exhibited clear inhibitory activity (P<0.01 and P<0.05, respectively). After the addition of MAPK inhibitors, the NFATc1 expression showed no significant difference compared with the control group (P>0.05).</p><p><b>CONCLUSIONS</b>Serum containing QTG could generally inhibit the TRAF6/MAPK pathways and possibly inhibit the NFATc1 pathway. In addition, QTG may regulate other signaling pathways that are related to osteoclast differentiation and maturation.</p>

Curcumin suppresses malignant glioma cells growth and induces apoptosis by inhibition of SHH/GLI1 signaling pathway in vitro and vivo.

AIMS: To study the role of curcumin on glioma cells via the SHH/GLI1 pathway in vitro and vivo. METHODS: The effects of curcumin on proliferation, migration, apoptosis, SHH/GLI1 signaling, and GLI1 target genes expression were evaluated in multiple glioma cell lines in vitro. A U87-implanted nude mice model was used to study the role of curcumin on tumor volume and the suppression efficacy of GLI1. RESULTS: Curcumin showed cytotoxic effects on glioma cell lines in vitro. Both mRNA and protein levels of SHH/GLI1 signaling (Shh, Smo, GLI1) were downregulated in a dose- and time-dependent manner. Several GLI1-dependent target genes (CyclinD1, Bcl-2, Foxm1) were also downregulated. Curcumin treatment prevented GLI1 translocating into the cell nucleus and reduced the concentration of its reporter. Curcumin suppressed cell proliferation, colony formation, migration, and induced apoptosis which was mediated partly through the mitochondrial pathway after an increase in the ratio of Bax to Bcl2. Intraperitoneal injection of curcumin in vivo reduced tumor volume, GLI1 expression, the number of positively stained cells, and prolonged the survival period compared with the control group. CONCLUSION: This study shows that curcumin holds a great promise for SHH/GLI1 targeted therapy against gliomas.

Protective effects of compound tianpupian against oxidative damage in mouse erythrocytes / 中国实验血液学杂志

The aim of this study was to investigate the protective effects of compound tianpupian (TPP) and its compositions against oxidative damage in mouse erythrocytes. The protective effect of TPP and its compositions against the red cell hemolysis induced by (2)O(2) or auto-oxidation were observed by scanning electron microscopy and spectrophotomety. The result indicated that compound TPP and all of its four components including extract of Rhodiola sachalinensis, Grape Seed Extract proanthocyanidins, Acanthopanax senticosus extract, and tea polyphenols had significant inhibitory activities for the oxidative damage of mouse erythrocytes, out of which the Grape seed extract proanthocyanidins showed the maximal protective effect. It is concluded that compound TPP can protect erythrocytes against oxidative stress and can be used as a valuable Chinese traditional medicine.

[Experimental study on the prevention and treatment of radiation lung injury by blood-activating and stasis-dissipating drugs].

OBJECTIVE: To observe the pathological changes and the expression of tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta) in lung tissue of rats with radiation injury for exploring the mechanism of blood-activating and stasis-dissipating drugs in radiation injury prevention and treatment. METHODS: One hundred and thirty SD female rats were randomly allocated into the simple irradiation group (n=60), the TCM herbs treatment group (n=60) and the blank control group (n=10). The right lung of all rats except those in the blank control group were irradiated by linear accelerator, 3 Gy each time, twice weekly, the maximum accumulated dose being 30 Gy. Ten rats in the two groups were randomly sacrificed at each of the 6 time points (1, 3, 5, 8, 12 and 26 weeks after repeated irradiation), their lung was harvested out, sliced and dyed with HE stain. The histological changes, levels of TNF-alpha and TGF-beta expression in the lung tissue were then observed by immunohistochemical technique. RESULTS: The most serious acute radiation pneumonia was seen in the 5th week and pulmonary fibrosis was remarkable in the 26th week in the simple irradiation group, with the expressions of TNF-alpha and TGF-beta at different time phases enhanced significantly (P < 0.01). While in the TCM herbs treatment group, the pneumonia was milder, pulmonary fibrosis in late stage was not so obvious, and the expressions of TNF-alpha and TGF-beta significantly lower than those in the simple irradiation group (P < 0.01). CONCLUSION: Blood-activating and stasis-dissipating drugs can inhibit expression of inflammation-inducing factors and fibrosis-inducing factors to lessen the inflammatory reaction of early radiation pneumonia, prolong the progression of radiation lung fibrosis, showing preventive and treating action on radiation lung injury.

Experimental study on the prevention and treatment of radiation lung injury by blood-activating and stasis-dissipating drugs / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the pathological changes and the expression of tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta) in lung tissue of rats with radiation injury for exploring the mechanism of blood-activating and stasis-dissipating drugs in radiation injury prevention and treatment.</p><p><b>METHODS</b>One hundred and thirty SD female rats were randomly allocated into the simple irradiation group (n=60), the TCM herbs treatment group (n=60) and the blank control group (n=10). The right lung of all rats except those in the blank control group were irradiated by linear accelerator, 3 Gy each time, twice weekly, the maximum accumulated dose being 30 Gy. Ten rats in the two groups were randomly sacrificed at each of the 6 time points (1, 3, 5, 8, 12 and 26 weeks after repeated irradiation), their lung was harvested out, sliced and dyed with HE stain. The histological changes, levels of TNF-alpha and TGF-beta expression in the lung tissue were then observed by immunohistochemical technique.</p><p><b>RESULTS</b>The most serious acute radiation pneumonia was seen in the 5th week and pulmonary fibrosis was remarkable in the 26th week in the simple irradiation group, with the expressions of TNF-alpha and TGF-beta at different time phases enhanced significantly (P < 0.01). While in the TCM herbs treatment group, the pneumonia was milder, pulmonary fibrosis in late stage was not so obvious, and the expressions of TNF-alpha and TGF-beta significantly lower than those in the simple irradiation group (P < 0.01).</p><p><b>CONCLUSION</b>Blood-activating and stasis-dissipating drugs can inhibit expression of inflammation-inducing factors and fibrosis-inducing factors to lessen the inflammatory reaction of early radiation pneumonia, prolong the progression of radiation lung fibrosis, showing preventive and treating action on radiation lung injury.</p>

[Determination of trace platinum, palladium, gold and rhodium in geological samples by ICP-AES after preconcentration by diphenlthiourea immobilized on aluminum oxide].

A method for the determination of Au, Pt, Pd and Rh by ICP-AES after preconcentration on a column containing diphenylthiourea immobilized on aluminum oxide was developed. The optimum acidity of solution, amount of adsorbent, elution solution, flow rate and volume of the samples were obtained for the elements studied. The effect of interfering ions on the recovery of the analytes was also investigated. Under the optimum measuring conditions, the recoveries were found to be between 95%-105%. The detection limits of Au, Pd, Pt and Rh was 0.0085, 0.022, 0.015 and 0.022 microgram.g-1, respectively, and the relative standard deviation was lower than 5%. This procedure was applied to the determination of Au, Pd, Pt and Rh in geological samples.