[Characteristics of Water Environment and Its Influencing Factors in Zhari Namco Basin, Xizang].

Zhari Namco is situated in the alpine grassland belt of northwestern Xizang with a fragile ecological environment. As the third-largest lake in Xizang, there has been a long-term lack of research data concerning its basin water environment. In an effort to elucidate the surface water environment characteristics of the basin and the factors influencing them, an extensive investigation was conducted from August 2021 to June 2022, encompassing periods of high flow, low flow, and base flow. Further, the study also involved comprehensive assessments of the water chemistry characteristics and spatial-temporal variation in lake sampling sites of the basin that were not significant by using mathematical statistics, hydrochemical analysis, correlation analysis, and principal component analysis. The findings revealed the following： ① The water in the Zhari Namco Basin exhibited an alkaline nature, with dominant ionic compositions in the lake comprising Na+, SO42-, and Cl-, whereas the rivers were primarily characterized by Ca2+, HCO3-, and SO42-. ② The main pollutants exceeding established standards included sulfates, arsenic, chlorides, and total phosphorus. The study identified significant spatiotemporal variations in water quality. Temporally, the exceedance of sulfates, arsenic, and total phosphorus was most pronounced during high-flow periods, followed by that during low-flow and base flow periods, with chloride levels showing less temporal variation. Spatially, river water quality surpassed that of the lakes, with arsenic, total phosphorus, TDS, sulfate, chloride, K+, and Na+ concentrations in lakes 1 to 2 orders of magnitude higher than those in rivers. Water qualities exceeding the established standard were primarily found in the lake, with less spatial variations within the lake itself. ③ Hydrochemical processes within the basin were found to be primarily influenced by natural phenomena, including evaporation-concentration and rock weathering. Various elements entered the lakes via surface runoff, where they continuously accumulated under the influence of evaporation-concentration processes, ultimately leading to exceedances. ④ Temporal variations in water quality were primarily attributed to increased elemental loss and intensified evaporation during high-flow periods. The spatial discrepancies in water quality were predominantly a consequence of the differing hydrodynamic conditions between flowing water bodies and enclosed water bodies.

Hypoxic stress caused apoptosis of MDBK cells by p53/BCL6-mitochondrial apoptosis pathway.

Hypoxia is an important characteristic of Tibetan plateau environment. It can lead to apoptosis, but the mechanism of apoptosis caused by hypoxic stress needs further clarification. Here, cattle kidney cell MDBK were used as cell model. The effect of hypoxic stress on apoptosis and its molecular mechanism were explored. MDBK cells were treated with hypoxic stress, apoptosis and mitochondrial apoptotic pathway were significantly increased, and the expression of B-cell lymphoma 6 (BCL6) was significantly decreased. Overexpressing or inhibiting BCL6 demonstrated that BCL6 inhibited the apoptosis. And the increase of apoptosis controlled by hypoxic stress was blocked by BCL6 overexpressing. MDBK cells were treated with hypoxic stress, the expression and the nuclear localization of p53 were significantly increased. Overexpressing or inhibiting p53 demonstrated that hypoxic stress suppressed the expression of BCL6 through p53. Together, these results indicated that hypoxic stress induced the apoptosis of MDBK cells, and BCL6 was an important negative factor for this regulation process. In MDBK cells, hypoxic stress suppressed the expression of BCL6 through p53/BCL6-mitochondrial apoptotic pathway. This study enhanced current understanding of the molecular mechanisms underlying the regulation of apoptosis by hypoxic stress in MDBK cells.

The effect of high altitude on ephedrine content and metabolic variations in two species of Ephedra.

Ephedra is an important plant in Chinese medicine; however, there are few reports on two species of Ephedra which are distributed at high altitudes from 3000 to 5200 meters. We collected a total of 84 individuals representing five Ephedra gerardiana and nine Ephedra saxatilis populations respectively located from 3158 to 5200 meters altitude, and determined the relative content of 213 metabolites using UHPLC-MS/MS (Ultra-High-Performance Liquid Chromatography-tandem mass spectrometry). 37 Chemical compositions were annotated using the KEGG (Kyoto Encyclopaedia of Genes and Genomes) database. From the top five significant enrichments in metabolic KEGG pathway analysis, we found a total of 166 compounds belonging to phenylpropanoids, 123 flavonoids, 67 metabolites carried by ABC transporters, and 61 in purine metabolism. We identified the top 8 altitude-related compounds in two species. Ephedrine and pseudoephedrine were found to be associated with altitude in both E. saxatilis and E. gerardiana. To verify which environmental factors influenced the metabolic content, the soil moisture and temperature of each population site were collected, and quantitative analysis of ephedrine and pseudoephedrine was performed using UHPLC-MS (Ultra-High-Performance liquid chromatography-tandem mass spectrometry). After detection, soil moisture ranged from 0.074 to 0.177 mm3/mm3, and temperature ranged from 9.7°C to 23.9°C. The content of ephedrine ranged from (0.84 ± 0.49)% to (2.01 ± 0.41)% in E. saxatilis, which was positively correlated with soil moisture; the content of pseudoephedrine ranged from (0.72 ± 0.45)% to (1.11 ± 0.57)% and was negatively correlated with soil moisture. In contrast to these results, in E. gerardiana, the content of ephedrine and pseudoephedrine was negatively correlated with soil moisture. Furthermore, the trends of alkaloid contents in two kinds of Ephedra were similar when the temperature was lower than 17°C even if the sum was various. With the increase in soil moisture and temperature, the total alkaloid content of E. saxatilis was higher than that of E. gerardiana. When the soil moisture was lower, the alkaloid content of the two Ephedra species was higher. These results provide useful data for the future separation of new compounds, and for seed homogeneous growth to determine artificial breeding of Ephedra located at high altitudes.

Ephedrine and pseudoephedrine in Ephedra saxatilis on the vertical altitude gradient changed in southern Tibet Plateau, China.

Ephedra is one of the world's most important plants, used in medicine, plants and ecology. Most Ephedra grows in plain areas and is stable. But the plateau environment is special, with the change of altitude, the variety difference of plateau Ephedra saxatilis is very obvious. E. saxatilis metabolism on the Tibetan Plateau is not only affected by altitude, but also environmental conditions such as climate conditions and different soil components. However, the change mechanism of E. saxatilis alkaloids in special ecological environment is still unclear. Therefore, we analyzed the metabolic and altitude of E. saxatilis species in the Tibetan Plateau. Through the functional analysis of Kyoto Metabolism and Metabolomic Encyclopedia (KEGG), we can determine that the number of E. saxatilis metabolites decreases with the increase of altitude, and there are differences in metabolism among the three mountains. This was confirmed by univariate analysis of the top five metabolic pathways. Based on the analysis of soil and metabolomics, it was found that soil water content was also a factor affecting E. saxatilis metabolism. According to the difference of vertical height gradient, ephedrine and pseudephedrine showed the same change in vertical altitude under different mountains. Ephedrine increased as the altitude gradient increased, and pseudoephedrine decreased as the altitude gradient decreased. Our results provide valuable information for further study of metabolic mechanism and efficacy stability. It provides useful reference for the research of E. saxatilis planting in special area.

Polymorphisms Analysis of BMP15, GDF9 and BMPR1B in Tibetan Cashmere Goat (Capra hircus).

The Tibetan cashmere goat is a prolific goat breed in China. In sheep breeds, natural mutations have demonstrated that the transforming growth factor beta (TGF-ß) super family ligands, such as growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15) and their type I receptor (bone morphogenetic protein receptor (BMPR1B), are essential for ovulation and increasing litter size. In this study, 216 female Tibetan cashmere goats were sampled, and candidate genes with fecundity traits were detected via restriction fragment length polymorphism (RFLP) and sequenced. Four polymorphic loci were found in specific amplification fragments of BMP15 and GDF9. Two SNP sites of the BMP15 gene were discovered, namely G732A and C805G. The G732A mutation did not cause the change in amino acids, and the frequencies of each genotype were 0.695 for the GG type, 0.282 for the GA type and 0.023 for the AA type. The C805G mutation caused amino acids to change from glutamine to glutamate. The genotype frequencies were 0.620 for the CC type, 0.320 for the CG type and 0.320 for the CG type. For the GG type 0.060, the G3 and G4 mutations of the GDF9 gene were all homozygous mutations. Two known SNP sites, C719T and G1189A, were detected in the Tibetan cashmere goat GDF9 gene, of which the C719T mutation caused a change of alanine to valine, with a genotype frequency of 0.944 for the CC type and 0.056 for the CT type, whereas no TT type was found. The G1189A mutation caused valine to become isoleucine, and the frequencies of each genotype were 0.579 for the GG type, 0.305 for the GA type and 0.116 for the AA type; G1, B2, B3, B4, FecXH, FecXI, FecXL, G2, G5, G6, G7, G8, FecGE, FecTT and FecB mutations were not found in Tibetan cashmere goats. The results of this study provide a data basis for future studies of BMP15, GDF9 and BMPR1B gene mutations in goats.

Obesity and risk of fracture in postmenopausal women: a meta-analysis of cohort studies.

BACKGROUND: Obesity is associated with an increased risk of fracture in adults, but is unclear in postmenopausal women. We aim to determine the association of obesity with the risk of fracture in postmenopausal women. METHODS: PubMed, EMBASE, Cochrane Library and Web of Science were searched up to 11 April 2022 for cohort studies. And the included studies regarding the relationship between obesity with all cause of fracture in postmenopausal women were included in our meta-analysis. Data were screened and extracted independently by two reviewers. The relative risks (RR) were estimated using a random-effects model. Between-study heterogeneity was assessed using Cochran's Q and I2 statistics. RESULTS: Eight cohort studies comprising 671,532 postmenopausal women and 40,172 fractures were included. Overall, the pooling analysis shows that obesity in postmenopausal women is associated with an increased risk of all-cause fracture (relative ratio (RR) = 1.18; 95% confidence interval (CI):1.09-1.28, I2 = 86.3%, p = .000). Sub-analyses for each site of fracture indicate that obesity was associated with an increased risk of vertebral fracture in postmenopausal women (RR = 1.154, 95% CI: 1.020-1.305, I2 = 94.5%, p = .023), but reduced the risk of pelvic fracture (RR = 0.575, 95% CI:0.470-0.702, I2 = 0.0%, p = .000). There is no statistically significant difference in the risk of hip and humerus fractures associated with obesity in postmenopausal women. CONCLUSION: Obesity is associated with an increased risk of all-cause and vertebral fractures in postmenopausal women, but is a protective factor for pelvic fractures. Our findings suggest that postmenopausal women who regulate their weight might lower their risk of fractures.Registration: (PROSPERO: CRD42022324973)KEY MESSAGESObesity is associated with an increased risk of all-cause and vertebral fractures in postmenopausal women.Obesity maybe a protective factor for pelvic fractures in postmenopausal women.Postmenopausal women should regulate their weight to prevent fractures.

Knowledge and awareness of nicotine, nicotine replacement therapy, and electronic cigarettes among general practitioners with a special interest in respiratory medicine in China.

Objectives: This study aimed to assess the knowledge and awareness of nicotine, nicotine replacement therapy (NRT), and electronic cigarettes (e-cigarettes) among general practitioners with a special interest (GPwSIs) in respiratory medicine. Methods: A cross-sectional study was conducted from October 2021 to February 2022. Knowledge and awareness were compared among smokers and non-smokers, as well as different age and gender groups. Results: The study consisted of 102 GPwSIs from 21 cities in Sichuan Province, China. Most respondents would recommend NRT for long-term use. Only a few believed that e-cigarettes are an effective means of smoking cessation and 71.6% would not recommend e-cigarettes as a substitute for cigarettes to their patients. Additionally, the majority did not regularly provide extensive help to assist patients in quitting smoking and needed smoking cessation counseling training. Conclusion: GPwSIs in respiratory medicine in China could have a relatively low level of knowledge and awareness regarding nicotine, NRT, and e-cigarettes. The study highlights the need for smoking cessation training among GPwSIs to improve their knowledge and provide better assistance to patients who want to quit smoking.

Discrimination of different processing degrees and quantitative study of processing end point of vinegar-processing Cyperi Rhizoma pieces based on electronic sensory technology / 中国中药杂志

In this study, CM-5 spectrophotometer and Heracles NEO ultra-fast gas-phase electronic nose were used to analyze the changes in color and odor of vinegar-processed Cyperi Rhizoma(VPCR) pieces. Various analysis methods such as DFA and partial least squares discriminant analysis(PLS-DA) were combined to identify different processing degrees and quantify the end point of processing. The results showed that with the increase in vinegar processing, the brightness parameter L~* of VPCR pieces decreased gradua-lly, while the red-green value a~* and yellow-blue value b~* initially increased and reached their maximum at 8 min of processing, followed by a gradual decrease. A discriminant model based on the color parameters L~*, a~*, and b~* was established(with a discrimination accuracy of 98.5%), which effectively differentiated different degrees of VPCR pieces. Using the electronic nose, 26 odor components were identified from VPCR samples at different degrees of vinegar processing. DFA and PLS-DA models were established for different degrees of VPCR pieces. The results showed that the 8-min processed samples were significantly distinct from other samples. Based on variable importance in projection(VIP) value greater than 1, 10 odor components, including 3-methylfuran, 2-methylbuty-raldehyde, 2-methylpropionic acid, furfural, and α-pinene, were selected as odor markers for differentiating the degrees of vinegar processing in VPCR. By combining the changes in color and the characteristic odor components, the optimal processing time for VPCR was determined to be 8 min. This study provided a scientific basis for the standardization of vinegar processing techniques for VPCR and the improvement of its quality standards and also offered new methods and ideas for the rapid identification and quality control of the end point of processing for other traditional Chinese medicine.

Cone beam computed tomography study on the root and root canal morphology of mandibular first permanent molars in a Tibetan population / 口腔疾病防治

Objective @#To investigate and analyze the root and root canal morphology of mandibular first molars (MFMs) in the Tibetan population using cone-beam computed tomography (CBCT) and to provide references for clinical root canal treatment in the Tibetan population. @*Methods@#This study was reviewed and approved by the Ethics Committee, and informed consent was obtained from the patients. CBCT imaging data of 300 mandibular first molars from 300 Tibetan patients were included. Patient age, the number of roots in mandibular first molars were recorded. The morphology and incidence of mesial root and mesial root canals and the morphology and incidence of distal root and distal root canals were statistically analyzed by Vertucci classification. @*Results @#There were 198 double-root teeth and 102 three-root teeth in the 300 mandibular first permanent molars. Among the three-rooted molars, 1 case had mesiolingual roots, and the rest had distolingual roots. The incidence rate of the distolingual root was 33.7%(101/300). The most common root canal configuration was Vertucci Ⅳ 65.7% (197/300), followed by Vertucci Ⅱ 20.3% (61/300) in the mesial roots. The overall incidence of middle mesial canals (MMCs) was 6% (18/300), with the highest incidence of MMCs in the 20-40 year-old group at 9% (9/100). The distal roots canals of single-distal-rooted mandibular first molars were mainly Vertucci Ⅰ 66.8% (133/199), followed by Vertucci Ⅱ 14.6% (29/199) and Vertucci Ⅳ 11.6% (23/199). For the mandibular first permanent molars with two distal roots, 96% (97/101) of the distal buccal roots and 100% (101/101) of the distal lingual roots were Vertucci Ⅰ root canals. @*Conclusion@# The root and root canal morphology of mandibular first permanent molars in a Tibetan population is complex and variable. Approximately one-third of patients have distolingual roots, and clinicians should carefully explore the root canals under the guidance of CBCT.

Epidemiological survey of hepatitis B and analysis of hepatitis B vaccine coverage rate among children aged 1-14 years in Lhasa in 2006, 2014 and 2020 / 中华预防医学杂志

In 2006, 2014 and 2020, the positive rates of HBsAg in 560, 384 and 402 children aged 1 to 14 years were 4.5%, 2.6% and 2.5%, respectively, with no statistically significant differences (P>0.05). The positive rate of anti-HBs was highest in 2014 (57.8%) and lowest in 2006 (34.1%) (P<0.05). The positive rate of anti-HBc was highest in 2006 (15.7%), and decreased in 2014 (7.8%) and 2020 (5.7%) (P<0.001). The timely rate of the first dose of hepatitis B vaccine for children in Lhasa in 2006, 2014 and 2020 was 7.7% (43/560), 50.3% (193/384) and 94.8% (381/402), respectively. The overall vaccination rates were 15.4% (86/560), 35.2% (135/384) and 96.0% (386/402), respectively, showing a trend of gradual increases (χtrend values were 718.63 and 589.59, both P values<0.001).

Rapid identification and differential markers of Curcumae Radix decoction pieces of different sources based on Heracles Neo ultra-fast gas phase electronic nose / 中国中药杂志

Since Curcumae Radix decoction pieces have multiple sources, it is difficult to distinguish depending on traditional cha-racters, and the mixed use of multi-source Curcumae Radix will affect its clinical efficacy. Heracles Neo ultra-fast gas phase electronic nose was used in this study to quickly identify and analyze the odor components of 40 batches of Curcumae Radix samples from Sichuan, Zhejiang, and Guangxi. Based on the odor fingerprints established for Curcumae Radix decoction pieces of multiple sources, the odor components was identified and analyzed, and the chromatographic peaks were processed and analyzed to establish a rapid identification method. Principal component analysis(PCA), discriminant factor analysis(DFA), and soft independent modeling cluster analysis(SIMCA) were constructed for verification. At the same time, one-way analysis of variance(ANOVA) combined with variable importance in projection(VIP) was employed to screen out the odor components with P<0.05 and VIP>1, and 13 odor components such as β-caryophyllene and limonene were hypothesized as the odor differential markers of Curcumae Radix decoction pieces of diffe-rent sources. The results showed that Heracles Neo ultra-fast gas phase electronic nose can well analyze the odor characteristics and rapidly and accurately discriminate Curcumae Radix decoction pieces of different sources. It can be applied to the quality control(e.g., online detection) in the production of Curcumae Radix decoction pieces. This study provides a new method and idea for the rapid identification and quality control of Curcumae Radix decoction pieces.

Deciphering the core seed endo-bacteriome of the highland barley in Tibet plateau.

Highland barley (Hordeum vulgare var. nudum (L.) Hook.f., qingke) has unique physical and chemical properties and good potential for industrial applications. As the only crop that can be grown at high altitudes of 4200-4500 m, qingke is well adapted to extreme habitats at high altitudes. In this study, we analysed the seed bacterial community of 58 genotypes of qingke grown in different regions of Tibet, including qingke landraces, modern cultivars, and winter barley varieties, and characterised endophytic bacterial communities in seeds from different sources and the core endo-bacteriome of qingke. This study aim to provide a reference for the application of seed endophytes as biological inoculants for sustainable agricultural production and for considering microbe-plant interactions in breeding strategies. A total of 174 qingke seed samples from five main agricultural regions in Tibet were collected and subjected to investigation of endophytic endo-bacteriome using high-throughput sequencing and bioinformatics approaches. The phyla of endophytic bacteria in qingke seeds from different sources were similar; however, the relative proportions of each phylum were different. Different environmental conditions, growth strategies, and modern breeding processes have significantly changed the community structure of endophytic bacteria in seeds, among which the growth strategy has a greater impact on the diversity of endophytic bacteria in seeds. Seeds from different sources have conserved beneficial core endo-bacteriome. The core endo-bacteriome of qingke seeds dominated by Enterobacteriaceae may maintain qingke growth by promoting plant growth and assisting plants in resisting pests and diseases. This study reveals the core endo-bacteriome of qingke seeds and provides a basis for exploiting the endophytic endo-bacteriome of qingke seeds.

Radiography, CT, and MRI Diagnosis of Enzootic Nasal Tumor in Goats Infected With Enzootic Nasal Tumor Virus.

The aim of this study was to describe radiography, computed tomography (CT), and magnetic resonance imaging (MRI) findings of enzootic nasal tumors in goats infected with enzootic nasal tumor viruses. Five of six goats with a mean age of 2 years, showed clinical signs of respiratory disease. Head radiographs showed increased density of the unilateral or bilateral nasal cavity in four goats, and a CT scan showed that the space-occupying lesion of the nasal cavity originated from the ethmoid bone and was enhanced homogeneously postcontrast in all goats. The nasal concha was destroyed and the paranasal sinus mucosa was thickened and filled with fluid in some goats. On MRI, the mass exhibited equal or slightly higher signal intensity on T2 weighted images, equal signal intensity on T1 weighted images, a high signal on fluid-attenuated inversion recovery images and heterogeneous enhancement postcontrast. After dissection, histopathological examination of the mass and virus genome detection of the nasal secretions confirmed that the intranasal mass was a low-grade adenocarcinoma and that the goats were infected with enzootic nasal tumor virus type 2. In conclusion, CT and MRI have high diagnostic values for enzootic nasal tumors because they match the postmortem findings and are more accurate than radiography.

Comparison of lipid metabolism between broodstock and hybrid offspring in the hepatopancreas of juvenile shrimp (Macrobrachium nipponense): Response to chronic ammonia stress.

Ammonia nitrogen is a major pollutant that causes great physiological harm to crustaceans in culture. In this study, we conducted a 28 day chronic ammonia nitrogen stress experiment with broodstock populations (Dianshan, DS) and hybrid offspring populations (DS ♀ × CD (Changjiang ♂ × Dongting ♀), SCD) exposed to 0, 1 and 10 mg/L of ammonia concentrations. A 28 day feeding trial and chronic ammonia nitrogen stress were used to investigate the effects on the growth performance, histological structure and lipid metabolism of juvenile shrimp, Macrobrachium nipponense. Our results indicated that survival rates in the SCD groups were significantly higher than those in the DS groups, whereas weight and length gain rates were not significantly different between the groups (p > 0.05). Histological structure results showed that the number of vacuoles in the DS group was significantly higher than that in the SCD group and hepatopancreas cell structures were disrupted in the ammonia treatment groups. The results of oil red staining showed that the number of lipid droplets increased significantly with the increase in ammonia concentration. As the ammonia concentration increased, fatty acid contents, lipid enzyme activities and lipid metabolism-related gene expression all tended to rise. In conclusion, ammonia nitrogen exposure caused damage to the hepatopancreas structure of juvenile shrimp and disturbed the lipid metabolism of the hepatopancreas. In addition, the SCD population had stronger stress resistance than the DS population when subjected to the same concentration of ammonia nitrogen stress.

Risk Factors, Prognosis, and a New Nomogram for Predicting Cancer-Specific Survival Among Lung Cancer Patients with Brain Metastasis: A Retrospective Study Based on SEER.

PURPOSE: To make a comprehensive population-based study on risk and prognostic factors of brain metastasis from lung cancer. METHODS: A total of 91,643 patients diagnosed with lung cancer from 2010 to 2018 were collected from the Surveillance, Epidemiology and End results (SEER) database. To analyze the risk and prognostic factors of brain metastasis among lung cancer patients, both Logistic and Cox regression methods were applied, respectively. Also, the competing risk regression model was performed to establish a new nomogram to predict cancer-specific survival (CSS). RESULTS: Among the 91,643 lung cancer patients, 10,855 were found to have brain metastasis, with the incidence of 11.84%. The residence, age, race, income, primary site, histological type, extracranial metastasis, T stage, and N stage were all found to be independent risk factors of brain metastasis. The median overall survival (OS) of brain metastasis patients was limited to 6.08 months. By dividing patients randomly into a primary cohort with 7237 patients and a validation cohort with 3618 patients, a conclusion that the income, race, gender, age, histological type, extracranial metastasis, T stage, and N stage were all associated with the prognosis of brain metastasis was drawn. Our established primary-cohort-based new nomogram showed a good discriminative ability in predicting the probability of CSS among patients with brain metastasis, and the C-index was 0.62. Besides, the calibration curves for CSS also showed that the predicted survival by nomogram was consistent with the actual survival in the validation cohort. CONCLUSION: Our study shall provide a deeper insight into the risk factors and prognosis of brain metastasis among lung cancer patients.

Efficacy-related substances of blood-activating and stasis-resolving medicinals derived from Curcuma plants: a review / 中国中药杂志

Derived from Curcuma plants, Curcumae Longae Rhizoma, Curcumae Rhizoma, Wenyujin Rhizoma Concisum, and Curcumae Radix are common blood-activating and stasis-resolving medicinals in clinical practice, which are mainly used to treat amenorrhea, dysmenorrhea, chest impediment and heart pain, and rheumatic arthralgia caused by blood stasis block. According to modern research, the typical components in medicinals derived from Curcuma plants, like curcumin, demethoxycurcumin, bisdemethoxycurcumin, curdione, germacrone, curcumol, and β-elemene, have the activities of hemorheology improvement, anti-platelet aggregation, anti-thrombosis, anti-inflammation, anti-tumor, and anti-fibrosis, thereby activating blood and resolving stasis. However, due to the difference in origin, medicinal part, processing, and other aspects, the efficacy and clinical application are different. The efficacy-related substances behind the difference have not yet been systematically studied. Thus, focusing on the efficacy-related substances, this study reviewed the background, efficacy and clinical application, efficacy-related substances, and "prediction-identification-verification" research method of blood-activating and stasis-resolving medicinals derived from Curcuma plants, which is expected to lay a theoretical basis for the future research on the "similarities and differences" of such medicinals based on integrated evidence chain and to guide the scientific and rational application of them in clinical practice.

Effective substance and mechanism of Ziziphi Spinosae Semen extract in treatment of insomnia based on serum metabolomics and network pharmacology / 中国中药杂志

This study aims to study the effective substance and mechanism of Ziziphi Spinosae Semen extract in the treatment of insomnia based on serum metabolomics and network pharmacology. The rat insomnia model induced by p-chlorophenylalanine(PCPA) was established. After oral administration of Ziziphi Spinosae Semen extract, the general morphological observation, pentobarbital sodium-induced sleep test, and histopathological evaluation were carried out. The potential biomarkers of the extract in the treatment of insomnia were screened by ultra-high performance liquid chromatography-mass spectrometry(UHPLC-MS) combined with multivariate analysis, and the related metabolic pathways were further analyzed. The "component-target-pathway" network was constructed by ultra-high performance liquid chromatography coupled with quadrupole-Exactive mass spectrometry(UHPLC-Q-Exactive-MS/MS) combined with network pharmacology to explore the effective substances and mechanism of Ziziphi Spinosae Semen in the treatment of insomnia. The results of pentobarbital sodium-induced sleep test and histopathological evaluation(hematoxylin and eosin staining) showed that Ziziphi Spinosae Semen extract had good theraputic effect on insomnia. A total of 21 endogenous biomarkers of Ziziphi Spinosae Semen extract in the treatment of insomnia were screened out by serum metabolomics, and the metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, and nicotinate and nicotinamide metabolism were obtained. A total of 34 chemical constituents were identified by UHPLC-Q-Exactive-MS/MS, including 24 flavonoids, 2 triterpenoid saponins, 4 alkaloids, 2 triterpenoid acids, and 2 fatty acids. The network pharmacological analysis showed that Ziziphi Spinosae Semen mainly acted on target proteins such as dopamine D2 receptor(DRD2), 5-hydroxytryptamine receptor 1 A(HTR1 A), and alpha-2 A adrenergic receptor(ADRA2 A) in the treatment of insomnia. It was closely related to neuroactive ligand-receptor interaction, serotonergic synapse, and calcium signaling pathway. Magnoflorine, N-nornuciferine, caaverine, oleic acid, palmitic acid, coclaurine, betulinic acid, and ceanothic acid in Ziziphi Spinosae Semen may be potential effective compounds in the treatment of insomnia. This study revealed that Ziziphi Spinosae Semen extract treated insomnia through multiple metabolic pathways and the overall correction of metabolic disorder profile in a multi-component, multi-target, and multi-channel manner. Briefly, this study lays a foundation for further research on the mechanism of Ziziphi Spinosae Semen in treating insomnia and provides support for the development of innovative Chinese drugs for the treatment of insomnia.

Factors Affecting the Risk of Postpartum Hemorrhage in Pregnant Women in Tibet Health Facilities.

BACKGROUND Postpartum hemorrhage (PPH), the leading cause of maternal death, is defined as a blood loss >500 mL within 24 h after vaginal delivery or >1000 mL within 24 h after cesarean section. This study aimed to investigate the incidence of PPH and assess its risk factors in pregnant women in Tibet to provide a reference for clinicians in this region. MATERIAL AND METHODS A total of 4796 pregnant women with gestational age ≥28 weeks who were admitted to hospitals in Tibet between December 2010 and December 2016 were involved in this study. Patient sociological and clinical data and pregnancy outcomes were collected. The related risk factors of PPH were analyzed by univariate and multivariable logistic regression. The area under the curve of the receiver operating characteristic curves was used to evaluate the effect of the PPH prediction model. RESULTS PPH occurred in 95 women, with an incidence of 1.98%. The following factors were associated with higher risk for PPH: maternal age ≥35 (odds ratio [OR]=1.96; 95% confidence interval [CI], 1.18-3.27; P=0.010), history of preterm birth (OR=2.66; 95% CI, 1.60-4.42; P<0.001), cesarean section (OR=6.69; 95% CI, 4.30-10.40; P<0.001), neonatal weight >4 kg (OR=3.92; 95% CI, 1.75-8.81; P<0.001) and occurrence of neonatal asphyxia (OR=5.52; 95% CI, 2.22-13.74; P<0.001). CONCLUSIONS Maternal age ≥35, history of preterm birth, cesarean section, newborn weight >4 kg, and neonatal asphyxia were risk factors of PPH, which can help evaluate PPH in Tibet.

ABCC9 Is Downregulated and Prone to Microsatellite Instability on ABCC9tetra in Canine Breast Cancer.

Tumorigenesis is associated with metabolic abnormalities and genomic instability. Microsatellite mutations, including microsatellite instability (MSI) and loss of heterozygosity (LOH), are associated with the functional impairment of some tumor-related genes. To investigate the role of MSI and LOH in sporadic breast tumors in canines, 22 tumors DNA samples and their adjacent normal tissues were evaluated using polyacrylamide gel electrophoresis and silver staining for 58 microsatellites. Quantitative real-time polymerase chain reaction, promoter methylation analysis and immunohistochemical staining were used to quantify gene expression. The results revealed that a total of 14 tumors (6 benign tumors and 8 breast cancers) exhibited instability as MSI-Low tumors. Most of the microsatellite loci possessed a single occurrence of mutations. The maximum number of MSI mutations on loci was observed in tumors with a lower degree of differentiation. Among the unstable markers, FH2060 (4/22), ABCC9tetra (4/22) and SCN11A (6/22) were high-frequency mutation sites, whereas FH2060 was a high-frequency LOH site (4/22). The ABCC9tetra locus was mutated only in cancerous tissue, although it was excluded by transcription. The corresponding genes and proteins were significantly downregulated in malignant tissues, particularly in tumors with MSI. Furthermore, the promoter methylation results of the adenosine triphosphate binding cassette subfamily C member 9 (ABCC9) showed that there was a high level of methylation in breast tissues, but only one case showed a significant elevation compared with the control. In conclusion, MSI-Low or MSI-Stable is characteristic of most sporadic mammary tumors. Genes associated with tumorigenesis are more likely to develop MSI. ABCC9 protein and transcription abnormalities may be associated with ABCC9tetra instability.

Historical evolution and research advance in processing adjuvant--vinegar / 中国中药杂志

Processing of Chinese medicinals with vinegar is one of the characteristic processing techniques. Vinegar is vital for the quality of vinegar-processed decoction pieces. However, there have been no specified standards for adjuvants. Through consulting relevant literature and monographs, we comprehensively reviewed the historical evolution of processing with vinegar in records, selection and application of vinegar, and summarized the relevant standards and current status of vinegar as an adjuvant in China. According to the records in literature, vinegar is effective in activating blood, moving qi, dispersing blood stasis, removing toxin, promoting appetite, and nourishing the liver. Traditionally, rice vinegar is chosen in processing. Nowadays, the vinegar made from rice under solid-state fermentation should be chosen. At present, only food standards can be taken for reference for vinegar in the processing. Integrative and specific inspection indicators are lacking, so the standards for adjuvants need to be improved urgently. In addition, the inadequacy in quality control and management is also a major problem to be solved. Through literature research, we reviewed the historical evolution and research advance in vinegar to provide a reference for the standardization and further research of vinegar used in the Chinese medicinal processing.