Cognitive impairment （CI） is a clinical syndrome characterized by progressive decline in advanced cognitive functions such as memory， thinking， and judgment. Its etiology and pathogenesis are complex， and there is currently a lack of specific drug interventions. Metformin， as a first-line hypoglycemic drug for type 2 diabetes， not only lowers blood glucose levels but also improves CI. This article reviews and summarizes the pharmacological effects and mechanisms of metformin in improving Alzheimer’s disease， diabetes cognitive impairment， cognitive impairment after chemotherapy， in order to provide novel insights and approaches for the treatment of CI-related diseases. Studies have shown that the mechanism by which MET intervenes in CI mainly includes regulating β-amyloid protein and tau protein metabolism， reducing insulin resistance， inhibiting neuroinflammation， improving synaptic plasticity， improving mitochondrial dysfunction， regulating gut microbiota and lipid metabolism， etc. Future research needs to be conducted through interdisciplinary collaboration， fully integrating multiple omics data， and combining advanced technologies to further reveal their mechanisms of effect.

Cognitive impairment is a major public health challenge facing global aging societies， and currently lacks effective treatment measures. Herb pair， characterized by their rigorous compatibility and synergistic effects， demonstrate unique advantages in clinical practice. Acorus tatarinowii-Polygala tenuifolia is a classic herbal pair for treating cognitive impairment， widely utilized in various traditional Chinese medicine formulations， such as Kaixin san， Shenghui tang， and Yuanzhi san. This article summarizes the pharmacological mechanisms of A. tatarinowii， P. tenuifolia and their compatible compound prescriptions in ameliorating cognitive impairment. It is found that they can exert effects in ameliorating cognitive impairment through mechanisms such as reducing amyloid β-protein deposition and inhibiting excessive phosphorylation of Tau protein， suppressing inflammatory responses， alleviating oxidative stress， protecting neurons and regulating neurotransmitters， modulating the structure and function of the blood- brain barrier， and regulating autophagy. Subsequently， in-depth analysis can be conducted on the active ingredients of A. tatarinowii- P. tenuifolia herb pair that ameliorate cognitive impairment， along with the addition of relevant clinical trials for verification. This will provide theoretical foundations and research approaches for the treatment of cognitive impairment using traditional Chinese medicine.

Objective:To explore the characteristics and evolution trend of renal disease spectrum in Ningxia.Methods:The demographic, clinical manifestations and renal pathological examination results of patients who underwent renal biopsies in the General Hospital of Ningxia Medical University from August 1, 2008 to December 31, 2019 were collected and analyzed retrospectively. According to the time period of receiving renal biopsy, the patients were divided into 2008—2013 group and 2014—2019 group. The age and sex constituent, clinical manifestation, renal disease type, pathological types of primary and secondary glomerular disease and the main clinical manifestations of patients with diabetic nephropathy were compared between the two groups. The changing trend of renal disease spectrum in Ningxia from 2008 to 2019 was analyzed.Results:A total of 3 867 patients who underwent renal biopsies were enrolled in this study, with more males (53.71%, 2 077/3 867), and age of (39.59±14.05) years old. The most common clinical manifestation of patients receiving renal biopsies was nephrotic syndrome (36.33%, 1 405/3 867). Among them, primary glomerular diseases accounted for 78.79% (3047/3 867), followed by secondary glomerular diseases (18.57%, 718/3 867), renal tubulointerstitial diseases (1.45%, 56/3 867) and hereditary nephropathy (1.19%, 46/3 867). The most common primary glomerular disease was IgA nephropathy (44.60%, 1 359/3 047), followed by membranous nephropathy (30.75%, 937/3 047). The most common secondary glomerular disease was Henoch-Sch?nlein purpura nephritis (27.44%, 197/718), followed by lupus nephritis (25.07%, 180/718). Compared with the 2008—2013 group, the proportion of membranous nephropathy increased, the proportion of mesangial proliferative glomerulonephritis (non-IgA deposition) decreased (both P<0.001), the proportions of diabetic nephropathy and hypertensive renal damage increased, and the proportions of Henoch-Sch?nlein purpura nephritis and hepatitis B virus-associated glomerulonephritis decreased in 2014—2019 group (all P<0.01). Compared with the 2008—2013 group, the proportions of acute kidney injury, chronic renal failure, simple hematuria and urinary protein≤1.0 g/24 h increased in kidney biopsy patients in 2014—2019 group, while the proportion of nephrotic syndrome decreased (all P<0.05). Compared with the 2008—2013 group, the proportion of chronic renal failure in diabetic nephropathy patients increased during renal biopsy, and the proportion of albuminuria with hematuria decreased in 2014—2019 group (all P<0.05). Conclusions:Primary glomerular disease is the most common kidney disease in Ningxia. IgA nephropathy is the most common cause, and the proportion of membranous nephropathy is increasing year by year. Henoch-Sch?nlein purpura nephritis is the most common secondary glomerular disease, and the proportions of diabetic nephropathy and hypertensive renal damage are increasing year by year, suggesting that the screening of renal complications of metabolic diseases in Ningxia should be strengthened and pay more attention to the patients with mild abnormal urine test.

Totally 21 batches of Gastrodiae Rhizoma pieces from various habitats with different appearance characteristics were analyzed. Five active components( gastrodin,4-hydroxybenzyl alcohol,parishin B,parishin C,and parishin A) were determined by UPLC. Polysaccharide content was determined by phenol sulfuric acid method. And the content of alcohol extracts was determined. The correlation between appearance characteristics and active components,polysaccharide content and amount of alcohol extracts of Gastrodiae Rhizoma pieces was statistically analyzed by SPSS 19. 0 software. And the five active components in the 21 Gastrodiae Rhizoma pieces were clustered by using the Ward' s method in SPSS 19. 0 software. The study found that inconspicuous keratinous Gastrodiae Rhizoma had a low content of each component,and the degree of keratin was positively correlated with the content of each component and the extract,with no significant correlation with the polysaccharide content. In the cluster analysis,the 21 batches were divided into three groups,except the second group whose gastrodin content was significantly higher than the special conditions of other groups. According to the content of the five active components,19 batches of Gastrodiae Rhizoma pieces were classified into two groups with obvious keratin and no obvious keratin. In terms of color,with the deepening of brown color,the content of each component showed a downward trend. The grading of decoction pieces of Gastrodiae Rhizoma shall give full consideration to the color and texture. And the combination of chemical composition and appearance characteristics is an indicator to evaluate the product specification standards.
Drugs, Chinese Herbal ; Gastrodia ; Rhizome

An analysis method was established by UPLC fingerprint and then applied to simultaneous determination of multiple compounds in Gardeniae Fructus from different areas in China. Samples were separated on a Waters Acquity UPLC BEH C₁₈( 2. 1 mm×50 mm,1. 7 μm) column with 0. 1% formic acid-water and acetonitrile solution as gradient mobile phase at a flow rate of 0. 4 m L·min-1 at various wavelengths. The similarity of samples was over 0. 95 with ″Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine( 2012 edition) ″. The UPLC common fingerprints for 32 batches were established with 19 common peaks identified. The samples were divided into 3 groups analyzed by HCA and PCA. Five components were identified as the main compositions which caused the differences of chemical constituents in the samples from different areas with partial least squares discriminant analysis( PLS-DA). The content of the total components in each area was Zhejiang > Fujian > Jiangxi > Sichuan. This method was accurate and viable,could be used to evaluate the quality of Gardeniae Fructus.
China ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/standards* ; Fruit/chemistry* ; Gardenia/chemistry* ; Phytochemicals/analysis*

To optimize the technology of Gardeniae Fructus processed with ginger juice,establish fingerprints and simultaneously determine seven compounds( geniposidic acid,chlorogenic acid,genipin-1-β-D-gentiobioside,geniposide,rutin,crocin Ⅰ,and crocin Ⅱ) by using ultra high performance liquid chromatography( UPLC). Waters ACQUITY UPLC BEH C18( 2. 1 mm×50 mm,1. 7μm) column was used with acetonitrile and 0. 1% formic acid solution as mobile phase for gradient elution at the flow rate of 0. 4 m L·min-1. The data was comprehensively processed and analyzed with similarity evaluation,principal component analysis( PCA) and partial least squares discriminant analysis( PLS-DA) methods. Twenty common peaks were identified in this study,and the similarity of samples was over 0. 97. The results of PCA and PLS-DA showed that there were differences in chemical compositions and contents between the raw Gardeniae Fructus and those processed with ginger juice,with 9 potential differentiated chromatographic peaks. After being processed with ginger juice,the contents of chlorogenic acid,crocin Ⅰ and crocin Ⅱ were less than before and the contents of other four compositions were higher than before. The optimized preparation for Gardeniae Fructus processed with ginger juice was stable and feasible. The methods of UPLC fingerprints and simultaneous determination of seven components can be effectively carried out to distinguish Gardeniae Fructus and Gardeniae Fructus processed with ginger juice.
Carotenoids/analysis* ; Chlorogenic Acid/analysis* ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/chemistry* ; Fruit/chemistry* ; Gardenia/chemistry* ; Zingiber officinale ; Technology, Pharmaceutical/methods*

In this experiment,the gradation analysis method was used to evaluate the quality of different pieces of Gardeniae Fructus through the extraction rate difference and the difference analysis of the main components in the extract. In this experiment cold-dip and hot-dip methods were used to compare the yield of Gardeniae Fructus extract and the content of chemical constituents with water,25%,50%,75% and 95% ethanol fractions. By weighted calculation,the optimal extraction method of Gardeniae Fructus was determined,and this was verified by practical application. RESULTS:: showed that for the water-soluble extract,cold dip method was better than the hot dip method; and for alcohol-soluble extract,75% ethanol under cold dip method was best. The verification results showed that water-soluble extracts under cold dip methods could be used to significantly distinguish the raw Gardeniae Fructus( GF) and processed( stir-baked) GF( GFP) collected from the market. Meanwhile,this method could be also used to distinguish the same batch of GF,GFP and carbonized GF( GFC) with significant differences,respectively( P<0. 05). Ethanol-soluble extract can be used to clearly distinguish GFP and GFC pieces in the same batch( P<0. 05). The results of content determination showed that the variation coefficient of components in GF processed products was higher than that in extracts,and the content of hydroxygeniposide was the most significant component between GF and its processed products. It is suggested that the method of water-soluble extract of GF and the determination of the content of gardoside should be combined together to evaluate the quality of GF and its heat processed products.
Drugs, Chinese Herbal ; analysis ; Fruit ; chemistry ; Gardenia ; chemistry ; Plant Extracts ; analysis

Objective: To construct and identify a mouse model with conditional knockout (cKO) of p75 neurotrophin receptor (p75NTR-cKO) gene in epidermis cells by Cre-loxP system. Methods: Five p75NTR^flox/flox transgenic C57BL/6J mice (aged 6-8 weeks, male and female unlimited, the age and sex of mice used for reproduction were the same below) and five keratin 14 promotor-driven (KRT14-) Cre^{+ /-} transgenic C57BL/6J mice were bred and hybridized via Cre-loxP system. Five p75NTR^flox/+ ·KRT14-Cre^{+ /-} mice selected from the first generation of mice were mated with five p75NTR^flox/flox mice to obtain the second generation hybrids. After the second generation mice were born 20-25 days, the parts of the mice tail were cut off to identify the genotype by polymerase chain reaction method. Four p75NTR gene complete cKO mice (6 weeks old) and 4 wild-type mice (6 weeks old) were selected and sacrificed respectively. The abdominal skin tissue and brain tissue were excised to observe the expression of p75NTR in the two tissue of two types of mice by immunohistochemical staining. The abdominal skin tissue of two types of mice was obtained to observe the histomorphological changes by hematoxylin and eosin staining. Results: (1) Twenty second generation mice were bred. The genotype of 4 mice was p75NTR^flox/flox·KRT14-Cre^{+ /-}(p75NTR^-/-), i. e. p75NTR gene complete cKO mice; the genotype of 5 mice was p75NTR^flox/+ ·KRT14-Cre^{+ /-}, i. e. p75NTR gene partial cKO mice; the genotype of 5 mice was p75NTR^flox/flox·KRT14-Cre^-/-, and that of 6 mice was p75NTR^flox/+ ·KRT14-Cre^-/-, all of which were wild-type mice. (2) The expression of p75NTR was negative in skin epidermis tissue of p75NTR gene complete cKO mice, while numerous p75NTR positive expression was observed in skin epidermis tissue of wild-type mice. Abundant p75NTR positive expression was observed in brain tissue of both wild-type mice and p75NTR gene complete cKO mice. (3) There was no abnormal growth of skin epidermis tissue in both wild-type mice and p75NTR gene complete cKO mice, with intact hair follicle structure. Conclusions Applying Cre-loxP system can successfully construct a p75NTR-cKO mice model in epidermis cells without obvious changes in skin histomorphology.

Objective To evaluate the application value of absorbable hemostat textile as submucosal injection of endoscopic submucosal dissection(ESD). Methods Twelve New Zealand rabbits were injected with absorbable hemostat textile solution,glycerol fructose and normal saline. The uplift effect was measured after injection. Simulated ESD was performed in the rabbit stomach and bleeding amount was measured. The injection site was pathologically examined at 30 minutes after the soluble hemostat textile and normal saline were injected. Fifteen pigs were injected with absorbable hemostat textile at two locations of 20-30 cm from the anus,and injected normal saline at another two locations of 20-30 cm from the anus.One site was performed simulated ESD and the other was not. Fifteen simulated ESD were performed in the soluble hemostatic group and the normal saline group, respectively. Operation time was recorded and difference in wound healing was compared between the two groups. Results In the uplift experiment, the absorbable hemostat textile group had higher uplift height(4.3±1.4 mm,4.1±1.9 mm,3.8±0.7 mm, 3.3±0.9 mm, respectively)at 0 min,10 min,20 min,30 min than that of the glycerol fructose group(4.3±2.2 mm,4.1± 2.0 mm,3.6±1.4 mm, 3.2±0.8 mm, respectively, P<0.05), and the glycerol fructose group was higher than that of the normal saline group(3.8±1.6 mm,2.6±1.4 mm,1.9±1.9 mm,1.1±0.7 mm, P<0.05). There was no significant difference in uplift height between the absorbable hemostat textile group and the glycerol fructose group(P>0.05). In the bleeding experiment, the bleeding amount of absorbable hemostat textile group was significantly less than that of the glycerol fructose group(0.36±0.07 mL VS 0.42±0.06 mL, P<0.05);the bleeding amount of glycerol fructose group was significantly lower than that of the normal saline group(0.42±0.06 mL VS 0.55±0.07 mL,P<0.05). There was no obvious tissue necrosis and other adverse complications in the absorbable hemostat textile group and the normal saline group. In simulated ESD experiment,complete resection rate of the absorbable hemostat textile group was higher than that of the normal saline group[86.7%(13/15)VS 46.7%(7/15), P<0.05], and mean operation time of the absorbable hemostat textile group was less than that of the normal saline group(3.2± 0.3 min VS 3.8± 0.5 min, P<0.05). No hemorrhage, perforations or other related adverse events occurred in non-ESD lesions. Conclusion Absorbable hemostat textile is safe and effective as submucosal injection of ESD.

To compare the effects of Curcumae Rhizoma/vinegar-processed Curcumae Rhizomaon immune hepatic fibrosis, proliferation of HSC-T6, and expressions of α-SMA and Procollagen I. The immunological liver fibrosis model was prepared through intraperitoneal injection with porcine serum 0.5 mL in each rat, twice a week, for 14 weeks. Expressions of serum ALT, AST, PC-Ⅲ, IV-C, LN, HA and HYP, MDA in liver tissues were observed after administration of Curcumae Rhizoma/vinegar-processed Curcumae Rhizoma (0.95, 1.90 g•kg⁻¹). The pathological changes in liver tissues were observed by HE staining. Masson staining and Sirius red staining were used to observe the expression of collagen in rat liver. HSC-T6 was cultured, and the proliferation of HSC-T6 was determined by MTT assay at different concentrations in 12, 24, 36, 48 h. The expressions of α-SMA and Procollagen I were detected by Real-time PCR. The results showed that expressions of serum ALT, AST, PC-Ⅲ, IV-C, LN and HA in Curcumae Rhizoma/vinegar-processed Curcumae Rhizoma groups (0.95, 1.90 g•kg⁻¹) were significantly lower than model group; in terms of effect, vinegar-processed Curcumae Rhizoma group was superior to Curcumae Rhizoma group. Curcumae Rhizoma/vinegar-processed Curcumae Rhizoma containing serum could inhibit the proliferation of HSC-T6 in a dose-effect and time-effect manner. Expressions of α-SMA and Procollagen I in HSC-T6 were decreased after 24 h, especially in 20% vinegar-processed Curcumae Rhizoma containing serum group (P<0.01). Both Curcumae Rhizoma/vinegar-processed Curcumae Rhizoma could reduce immune hepatic fibrosis to varying extent. Their anti-hepatic fibrosis mechanism may be correlated with inhibition of the proliferation of HSC-T6, and reduction of the formation of extracellular matrix and promotion of its degradation.