Determining the Stir-Frying Degree of Gardeniae Fructus Praeparatus Based on Deep Learning and Transfer Learning.

Gardeniae Fructus (GF) is one of the most widely used traditional Chinese medicines (TCMs). Its processed product, Gardeniae Fructus Praeparatus (GFP), is often used as medicine; hence, there is an urgent need to determine the stir-frying degree of GFP. In this paper, we propose a deep learning method based on transfer learning to determine the stir-frying degree of GFP. We collected images of GFP samples with different stir-frying degrees and constructed a dataset containing 9224 images. Five neural networks were trained, including VGG16, GoogLeNet, Resnet34, MobileNetV2, and MobileNetV3. While the model weights from ImageNet were used as initial parameters of the network, fine-tuning was used for four neural networks other than MobileNetV3. In the training of MobileNetV3, both feature transfer and fine-tuning were adopted. The accuracy of all five models reached more than 95.82% in the test dataset, among which MobileNetV3 performed the best with an accuracy of 98.77%. In addition, the results also showed that fine-tuning was better than feature transfer in the training of MobileNetV3. Therefore, we conclude that deep learning can effectively recognize the stir-frying degree of GFP.

The Chinese medicine Fufang Zhenzhu Tiaozhi capsule protects against renal injury and inflammation in mice with diabetic kidney disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Zhenzhu Tiaozhi capsule (FTZ) is a patented preparation of Chinese herbal medicine that has been used to treat hyperlipidemia, nonalcoholic fatty liver disease, atherosclerosis, and other glucolipid metabolic diseases (GLMDs) in the clinic for almost 10 years. However, how FTZ reduces albuminuria and attenuates diabetic kidney disease (DKD) progression is unknown. AIM OF THE STUDY: To clarify the effects of FTZ on DKD mice model and to explore the underlying mechanisms. MATERIALS AND METHODS: We used streptozotocin (STZ) (40 mg/kg/d, i.p. for 5 days, consecutively) combined with a high-fat diet (HFD) to induce a DKD mouse model, followed by FTZ (1, 2 g/kg/d, i.g.) treatment for 12 weeks. Losartan (30 mg/kg/d, i.g.) was used as a positive control. Measurements of 24 h proteinuria, serum creatinine (SCr), fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), and low density lipoprotein cholesterol (LDL-C) levels and expression levels of fibronectin (FN), collagen IV, inflammatory cytokines, inflammatory cells, interleukin-17A (IL-17A) and the nuclear transcription factor-κB (NF-κB) signaling pathway in the kidney were examined. RESULTS: FTZ effectively decreased 24 h proteinuria, Scr, FBG, TC, TG, and LDL-C levels, inhibited mesangial cell expansion, reduced FN and collagen IV accumulation, and F4/80+ macrophage cell infiltration and Ly-6G+ neutrophil infiltration in glomerulus and tubulointerstitium. Furthermore, IL-17A production and the NF-κB signaling pathway were also downregulated after the administration of FTZ. CONCLUSION: FTZ might attenuate DKD progression, and inhibited kidney inflammation and fibrosis by inhibiting the expression of RORγT and IL-17A in vivo, offering novel insights for the clinical application of FTZ.

Efficacy and safety of acupuncture therapy for psoriasis: an overview of systematic reviews.

BACKGROUND: Acupuncture therapy is a method of piercing needles into acupoints to treat diseases with/without corresponding manipulations, which could serve as a useful supplementary therapy for psoriasis. The present study aimed to outline and sum up current evidence from systematic reviews (SRs)/meta-analyses (MAs) that investigate the clinical efficacy of acupuncture on psoriasis. METHODS: A comprehensive search involving eight electronic databases was conducted from the date of inception to July 2021, and grey literatures were manually searched. The research was selected according to prespecified inclusion criteria and relevant data were obtained. The methodological quality of the included SRs was scrutinized using the Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2) tool. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was used to appraise the reporting quality of the included SRs. Risk of Bias in Systematic Reviews (ROBIS) was selected for the evaluation of bias risk of the included SRs. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was applied to determine the quality of evidence from primary outcome measures. RESULTS: After screening, seven SRs/MAs met the inclusion criteria, including two English and five Chinese articles. All of the SRs were published between 2015 and 2020. Based on AMSTAR-2, the quality of all SRs was rated as dangerously low. Using the PRISMA-A checklist, major reporting flaws were observed in the financial statements, protocols, and registrations of the included literature. According to the ROBIS tool, two SRs/MAs were classed as low bias risk. Using the GRADE tool, this review contained 27 outcomes, with only one being classified as high-quality evidence, seven moderate-quality evidences, and 19 as low-quality evidence. The present research results advocated acupuncture therapy as a supplementary treatment for psoriasis patients; however, the evidence should still be treated with caution due to certain limitations. CONCLUSIONS: Our overview suggests that acupuncture could be used as a complementary therapy to produce effective clinical result for psoriasis. Nonetheless, considering the poor quality of SRs/Mas that advocate these findings, studies with more rigorous design, larger populations samples and of higher quality are called for to provide stronger evidence for definitive conclusions.

FTZ attenuates liver steatosis and fibrosis in the minipigs with type 2 diabetes by regulating the AMPK signaling pathway.

Fufang Zhenzhu Tiaozhi formula (FTZ), a preparation of Chinese herbal medicine, has various pharmacological properties, such as hypoglycemic, hypolipidemic, anticoagulant, and anti-inflammatory activities. Hepatocyte apoptosis is a marker of nonalcoholic steatohepatitis (NASH) and contributes to liver injury, fibrosis, and inflammation. Given the multiple effects of FTZ, we investigated whether FTZ can be a therapeutic agent for NASH and its mechanism. In the present study, we observed that FTZ treatment had an obviously favorable influence on hepatic steatosis and fibrosis in the histopathologic features of type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD) with NASH minipigs. In addition, immunohistochemical analysis showed increased expression of the fibrotic marker α-smooth muscle actin (α-SMA), and a TUNEL assay revealed increased apoptotic positive hepatic cells in the liver tissues of the model group. Furthermore, FTZ administration reduced the increased expression of α-SMA, and FTZ inhibited apoptosis by affecting Bcl-2/Bax and cleaved caspase-3 expression. Mechanistically, our data suggested that FTZ treatment attenuated hepatic steatosis and fibrosis via the adenosine monophosphate-activated protein kinase (AMPK) pathway. In vitro studies showed that FTZ also attenuated intracellular lipid accumulation in HepG2 cells exposed to palmitic acid (PA) and oleic acid (OA). FTZ upregulated the expression levels of P-AMPK and BCL-2 and downregulated BAX. The changes induced by FTZ were reversed by Compound C, an inhibitor of AMPK. In conclusion, FTZ attenuated NASH by ameliorating steatosis and hepatocyte apoptosis, which is attributable to the regulation of the AMPK pathway.

Study on the related factors of post-herpetic neuralgia in hospitalized patients with herpes zoster in Sichuan Hospital of Traditional Chinese Medicine based on big data analysis.

Although various factors were reported to be related to post-herpetic neuralgia (PHN), studies based on adequate and comprehensive data were absent. Data was extracted from cases of hospitalized patients with herpes zoster in dermatology department, Sichuan hospital of traditional Chinese medicine range from December, 2011 to February, 2018, and then cleaned to build prediction model with TREENET algorithms. Following evaluated the prediction model by ROC and confusion matrix, variables importance ranking and variables dependency analysis were performed, resulting in the importance ranking of factors for PHN and the dependency between factors and PHN. Based on strict inclusion and exclusion criteria, 1303 (571 PHN and 732 normal controls) cases and 2958 indicators were selected. Model evaluation showed high ROC value (training sample = 0.985, test samples = 0.752) and high accuracy value (70.27%), which indicated that the model was predictive. After variables importance ranking and variables dependency analysis, 62 variables in the model were associated with the occurrence of PHN. Our study identified 62 variables related to PHN and revealed that various variables were the important risk factors for PHN, including age, MCHC, sodium and UA.

Low doses of folic acid can reduce hyperhomocysteinemia-induced glomerular injury in spontaneously hypertensive rats.

Hypertension associated with hyperhomocysteinemia (HHcy) is associated with a high risk of vascular diseases. However, the mechanisms of HHcy-associated hypertensive renal damage and the efficacy of folic acid (FA) as a treatment have not been fully elucidated. The aim of the present study was to evaluate whether lowering the plasma homocysteine (Hcy) level using different doses of FA can reduce HHcy-associated glomerular injury in spontaneously hypertensive rats (SHRs) and to clarify the potential mechanisms of such effects. SHRs were randomized into a control group, HHcy group, HHcy + low-dose FA (LFA) group, and HHcy + high-dose FA (HFA) group. Compared with the control group, the HHcy group had reduced serum superoxide dismutase and GFR levels and elevated serum malondialdehyde and urinary albumin creatinine ratio levels. Increased extracellular matrix of the glomerulus and an increased glomerular sclerosis index, podocyte foot process effacement and fusion, as well as increased podocyte apoptosis, were observed in the HHcy group compared with the control group; these effects were associated with increased expression of NOX2 and NOX4 and decreased nephrin expression in renal tissue from SHRs with HHcy. HHcy-induced changes were counteracted by LFA and HFA treatment. Apart from lower levels of NOX2 in the HHcy + HFA group, there were no significant differences in other indicators between the HHcy + LFA and HHcy + HFA groups. These results suggest that even at a low dose, FA can reduce plasma Hcy and attenuate HHcy-induced glomerular injury by inhibiting oxidative stress and apoptosis.

An Ensemble Model With Clustering Assumption for Warfarin Dose Prediction in Chinese Patients.

The prediction of daily stable warfarin dosage for a specific patient is difficult. To improve the predictive accuracy and to build a highly accurate predictive model, we developed an ensemble learning method, called evolutionary fuzzy c-mean (EFCM) clustering algorithm with support vector regression (SVR). A dataset of 517 Han Chinese patients was collected from the data of The First Affiliated Hospital of Soochow University and dataset of International Warfarin Pharmacogenetics Consortium for training and testing. In EFCM+SVR, we adopted SVR to build a generalized base model (SVR model). To achieve an accurate prediction on patients with large dosage, we proposed an EFCM clustering algorithm that can be used to cluster the training set and designed a clustering model on clusters and centroids. The SVR and clustering models were integrated into an ensemble model by stepwise functions. In the experiment, three artificial neural networks, SVR, two ensemble models, and three regression models were used as comparators to the EFCM+SVR model, which obtained the smallest mean absolute error (0.67 mg/d) in warfarin dose prediction and the largest R-squared (43.9%). The model achieved satisfactory prediction in terms of the percentage of patients whose predicted dose of warfarin was within 15% and 20% of the actual stable therapeutic dose (15%-p of 36% and 20%-p of 46.6%).

Quality assessment of Penthorum chinense Pursh through multicomponent qualification and fingerprint, chemometric, and antihepatocarcinoma analyses.

An efficient method combined with fingerprint and chemometric analyses was developed to evaluate the quality of the traditional Chinese medicine plant Penthorum chinense Pursh. Nine samples were collected from different regions during different harvest periods, and 17 components in the form of extracts were simultaneously examined to assess quality by using high-performance liquid chromatography. The hepatoprotective effects of components were investigated by assessing the inhibition of SMMC-7721 cell growth. The results indicated that the quality control method was accurate, stable, and reliable, and the hierarchical heat-map cluster and the principle component analyses confirmed that the classification of all nine samples was consistent. Quercetin and ellagitannins including pinocembrin-7-O-[3''-O-galloyl-4'',6''-hexahydroxydiphenoyl]-ß-glucose (PGHG), thonningianin A, thonningianin B, and other flavonoids were abundant in the extracts, and significantly contributed to the hepatoprotective effects.

Epigallocatechin-3-gallate Prevents Triptolide-Induced Hepatic Injury by Restoring the Th17/Treg Balance in Mice.

Drug-induced liver injury (DILI) is the most common cause of acute liver failure. Disruption of the Th17/Treg balance can lead to hepatic inflammation, which causes the main symptoms of DILI. Here we investigate the protective mechanisms of (-)-Epigallocatechin-3-gallate (EGCG) on triptolide (TP)-induced DILI that shows the Th17/Treg imbalance. Pretreatment with EGCG (5[Formula: see text]mg/kg) for 10 days before TP (0.5[Formula: see text]mg/kg) administration in mice significantly reduced the increased alanine aminotransferase (ALT) level ([Formula: see text]) induced by TP treatment. The hepatic histology analysis further proved that EGCG protected mice from TP-induced liver injury. The imbalance of Th17/Treg was induced by TP treatment, as shown by the upregulation of TLR4 and downregulation of Tim3 expression. EGCG pretreatment can maintain the expression of TLR4 and Tim3 at normal levels to restore the Th17/Treg imbalance. In addition, EGCG can block the TP-induced expression of the downstream targets of TLR4, including MyD88, NF[Formula: see text]B, and retinoid related orphan receptor (ROR-[Formula: see text]t), while EGCG can restore the TP inhibition of forkhead/winged-helix family transcriptional repressor p3 (FoxP3) that is the downstream target of Tim3. Consequently, EGCG pretreatment can effectively inhibit the Th17-related pro-inflammatory cytokine (e.g. IL-17 and IL-6) upregulation induced by TP treatment. However, TP inhibition of Treg-related anti-inflammatory cytokine IL-10 production was restored by EGCG pretreatment. Taken together, these results suggest that EGCG possesses significant protective properties against TP-induced hepatic inflammatory injury, and that these properties are carried out via the restoration of the Th17/Treg imbalance by the inhibition of the TLR4 signaling pathway and the enhanced activation of the Tim3 signaling pathway.

Effects of caffeic acid on learning deficits in a model of Alzheimer's disease.

Caffeic acid is a type of phenolic acid and organic acid. It is found in food (such as tomatoes, carrots, strawberries, blueberries and wheat), beverages (such as wine, tea, coffee and apple juice) as well as Chinese herbal medicines. In the present study, we examined the effects of caffeic acid on learning deficits in a rat model of Alzheimer's disease (AD). The rats were randomly divided into three groups: i) control group, ii) AD model group and iii) caffeic acid group. Caffeic acid significantly rescued learning deficits and increased cognitive function in the rats with AD as demonstrated by the Morris water maze task. Furthermore, caffeic acid administration resulted in a significant decrease in acetylcholinesterase activity and nitrite generation in the rats with AD compared with the AD model group. Furthermore, caffeic acid suppressed oxidative stress, inflammation, nuclear factor­κB­p65 protein expression and caspase­3 activity as well as regulating the protein expression of p53 and phosphorylated (p-)p38 MAPK expression in the rats with AD. These experimental results indicate that the beneficial effects of caffeic acid on learning deficits in a model of AD were due to the suppression of oxidative stress and inflammation through the p38 MAPK signaling pathway.

A Phosphorus Phthalocyanine Formulation with Intense Absorbance at 1000 nm for Deep Optical Imaging.

Although photoacoustic computed tomography (PACT) operates with high spatial resolution in biological tissues deeper than other optical modalities, light scattering is a limiting factor. The use of longer near infrared wavelengths reduces scattering. Recently, the rational design of a stable phosphorus phthalocyanine (P-Pc) with a long wavelength absorption band beyond 1000 nm has been reported. Here, we show that when dissolved in liquid surfactants, P-Pc can give rise to formulations with absorbance of greater than 1000 (calculated for a 1 cm path length) at wavelengths beyond 1000 nm. Using the broadly accessible Nd:YAG pulse laser emission output of 1064 nm, P-Pc could be imaged through 11.6 cm of chicken breast with PACT. P-Pc accumulated passively in tumors following intravenous injection in mice as observed by PACT. Following oral administration, P-Pc passed through the intestine harmlessly, and PACT could be used to non-invasively observe intestine function. When the contrast agent placed under the arm of a healthy adult human, a PACT transducer on the top of the arm could readily detect P-Pc through the entire 5 cm limb. Thus, the approach of using contrast media with extreme absorption at 1064 nm readily enables high quality optical imaging in vitro and in vivo in humans at exceptional depths.

Ursodeoxycholic acid induces apoptosis in hepatocellular carcinoma xenografts in mice.

AIM: To evaluate the efficacy of ursodeoxycholic acid (UDCA) as a chemotherapeutic agent for the treatment of hepatocellular carcinoma (HCC). METHODS: BALB/c nude mice were randomized into four groups 24 h before subcutaneous injection of hepatocarcinoma BEL7402 cells suspended in phosphate buffered saline (PBS) into the right flank. The control group (n = 10) was fed a standard diet while treatment groups (n = 10 each) were fed a standard daily diet supplemented with different concentrations of UDCA (30, 50 and 70 mg/kg per day) for 21 d. Tumor growth was measured once each week, and tumor volume (V) was calculated with the following equation: V = (L × W(2)) × 0.52, where L is the length and W is the width of the xenograft. After 21 d, mice were killed under ether anesthesia, and tumors were excised and weighed. Apoptosis was evaluated through detection of DNA fragmentation with gel electrophoresis and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. Western blot analysis was performed to determine the expression of apoptosis-related proteins BAX, BCL2, APAF1, cleaved caspase-9, and cleaved caspase-3. RESULTS: UDCA suppressed tumor growth relative to controls. The mean tumor volumes were the following: control, 1090 ± 89 mm(3); 30 mg/kg per day, 612 ± 46 mm(3); 50 mg/kg per day, 563 ± 38 mm(3); and 70 mg/kg per day, 221 ± 26 mm(3). Decreased tumor volumes reached statistical significance relative to control xenografts (30 mg/kg per day, P < 0.05; 50 mg/kg per day, P < 0.05; 70 mg/kg per day, P < 0.01). Increasing concentrations of UDCA led to increased DNA fragmentation observed on gel electrophoresis and in the TUNEL assay (control, 1.6% ± 0.3%; 30 mg/kg per day, 2.9% ± 0.5%; 50 mg/kg per day, 3.15% ± 0.7%, and 70 mg/kg per day, 4.86% ± 0.9%). Western blot analysis revealed increased expression of BAX, APAF1, cleaved-caspase-9 and cleaved-caspase-3 proteins, which induce apoptosis, but decreased expression of BCL2 protein, which is an inhibitor of apoptosis, following administration of UDCA. CONCLUSION: UDCA suppresses growth of BEL7402 hepatocellular carcinoma cells in vivo, in part through apoptosis induction, and is thus a candidate for therapeutic treatment of HCC.

A simple and rapid method for the determination of pennogenin diglycoside in rat plasma by HPLC-MS: application to the pharmacokinetics of the extract in Gongxuening capsules.

A sensitive, selective, and reproducible reversed-phase high-performance liquid chromatography method coupled with electrospray ionization-ion trap mass spectrometry (LC-ESI-ITMS) was developed for the simultaneous quantification of pennogenin diglycoside (PD) in a small volume (100 microL) of rat plasma. PD was extracted from rat plasma samples using liquid-liquid extraction with methanol, digoxin as internal standard. The chromatographic separation was performed on a reversed-phase Agilent C(18) (250 mm x 4.6 mm i.d., 5 mum particle size) analytical column using a mobile phase of 0.1% formic acid solution-acetonitrile (75:25, v/v) at a flow-rate of 1.0 mL/min. The mass spectrometer was operated in the negative ion mode at the deprotonated-molecular ions [M-H]- of parent drug. Calibration curve in spiked plasma was linear (correlation coefficient r = 0.999) from 0.5 to 50.0 mg/mL. For the different samples with concentration of 0.50, 5.00, and 50.0 microg/mL, recoveries of PD were (86.45 +/- 4.39)%, (91.40 +/- 4.40)%, and (93.79 +/- 3.29)%, respectively (n = 3). The intra-day assay relative standard deviation at 0.50, 5.00, and 50.0 mg/mL of PD were 4.29%, 5.66%, and 4.03% (n = 3), respectively. The inter-day assay %RSD at the previously mentioned concentrations were 5.53%, 4.99%, and 4.31% (n = 3), respectively. The method was successfully applied to the pharmacokinetic study of PD in rats following either intravenous administration of PD solution or oral administration of the extract in Gongxuening capsules, a famous patent Chinese botanic drug.

Validation of an agricultural non-point source (AGNPS) pollution model for a catchment in the Jiulong River watershed, China.

This study tested and evaluated the agricultural non-point source (AGNPS) model for the Wuchuan catchment, a typical agricultural area in the Jiulong River watershed, Fujian Province, China. The AGNPS model was calibrated and validated for the study area with observed data on ten storms. The data on eight storms in 2002 were used for calibration while data on two storms were used for validation of the model. Considering the lack of water quality data over a long-term series, a novel method, comparing an internal nested catchment with its surrounding catchment, was used to supplement the less long-term series data. Dual calibration and validation of the AGNPS model was obtained by this comparison. The results indicate that the correlation coefficients were 0.99 and 0.98 for runoff, 0.94 and 0.95 for the peak runoff rate of the large catchment and the small catchment, respectively, and 0.76 for the sediment of the small catchment only. Each pair of correlation coefficients is homogeneous for the same event for the two catchments. With the exception of the sediment yield and particulate phosphorus, the peak runoff rate and other nutrients were well predicted. Sensitivity analysis showed that the Soil Conservation Service curve number and rainfall quantity were the most sensitive parameters, which resulted in high output variations. Erosivity and other parameters had little influence on the hydrological and quality outputs.

[Effects of modified longdan xiegan decoction on hyperandrogenism in patients with polycystic ovary syndrome of stagnant fire in Gan channel type].

OBJECTIVE: To observe the therapeutic effect of modified Longdan Xiegan Decoction (LXD) on hyperandrogenism in patients with polycystic ovary syndrome (POS) of stagnant fire in Gan channel type. METHODS: Forty-eight patients were divided into two groups: the LXD group (25 cases) treated with LXI) for 3 months, and the Diane-35 group (23 cases) with Diane-35. Condition of menstruation, acne, hairiness were observed, basal body temperature (BBT) was measured, and the serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), free testosterone (FT), and androstenedione (A) were detected before and after 3 months' treatment. Meanwhile, adverse reaction was observed. RESULTS: After treatment, the condition of menstrual disorder, acne and single-phase BBT were improved significantly, and serum levels of LH, LH/FSH, FT and A decreased in both groups (P < 0.05), showed insignificant difference between them (P > 0.05). The PRL level dropped in the LXD group (P < 0.05), which significantly lower than that in the Diane-35 group (P < 0.05). There were 3 cases with adverse reaction of irregular colporrhagia and 5 cases with nausea and vomiting in the Diane-35 group, while no adverse reaction in the LXD group occurred. CONCLUSION: Modified LXD could significantly improve the condition in hyperandrogenism patients with POS of stagnant fire in Gan channel type.