ObjectiveTo simulate the microstructure and mechanical properties of tendon tissue and promote its regeneration and repair, electrospinning technology was used to prepare L-polylactic acid (PLLA) fiber membranes loaded with different nano zinc oxide contents and with oriented structures. Physical and chemical characterization and biological performance evaluation were carried out to explore their effects on tendon cell proliferation and differentiation. MethodsPreparation of PLLA fiber scaffolds and PLLA/ZnO fiber scaffolds containing different mass fractions of nano ZnO was performed using electrospinning technology. The physicochemical properties of the scaffold were characterized by scanning electron microscopy, mechanical stretching, and EDS spectroscopy. The scaffold was co-cultured with mouse tendon cells to detect its biocompatibility and regulatory effects on cell differentiation behavior. ResultsThe fiber scaffolds were arranged in an oriented manner, and zinc elements were uniformly distributed in the fibers. The tensile strength and Young’s modulus of PLLA/0.1%ZnO fiber scaffolds were significantly higher than PLLA fiber scaffolds. The number of cells on the surface of PLLA/0.1%ZnO fiber scaffold was significantly higher than that of the PLLA group, and the activity was better; mouse tendon cells exhibit directional adhesion and growth along the fiber arrangement direction. ConclusionThe oriented PLLA/0.1%ZnO fiber scaffold had excellent physicochemical properties, which can significantly promote the oriented growth, proliferation and differentiation of tendon cells. It is expected to be used for tendon tissue regeneration and repair in the future.

Celastrol and wilforlide A are the main active triterpenoids of the traditional Chinese medicine Lei Gong Teng, which have anti-tumour, anti-inflammatory and immunosuppressive activities, and are the material basis for the clinical efficacy of Lei Gong Teng-related Chinese medicinal preparations. By analysing the biosynthetic pathway of active ingredients, optimizing genetic elements and utilizing "cell factory" to produce triterpenoids heterologously will be an effective way to obtain from Tripterygium wilfordii in the future in a "low-cost and high-efficient" manner. CYP712Ks are the first cytochrome P450s involved in the skeleton modification of friedelane-type and oleanane-type triterpenoids in T. wilfordii, and they can catalyse the generation of polpunonic acid from friedelin and 3-epi-katonic acid from β-amyrin by carboxylation at C-29 position. In this study, four multifunctional TwCYP712K1/2/3/5 were used to clarify the catalytic function and substrate selection preference using in vivo functional characterization in Saccharomyces cerevisiae. The spatial structure of the protein-substrate binding was clarified through homology modeling and molecular docking, and then the differential amino acids in the active pocket of the protein were mutated to clarify the crucial amino acids determining the catalytic function and the selection of substrate structure. A total of 63 mutant elements were constructed, and the amino acid sites affecting the carboxylation function of TwCYP712Ks were analyzed. In particular, the key amino acids affecting the substrate selectivity of TwCYP712K2 towards oleanane-type and friedelane-type triterpenoids were revealed and the TwCYP712K2^F127I and TwCYP712K2^A227T mutants would result in a reversal of the product ratio. In conclusion, four proteins of TwCYP712Ks were semi-rationally designed by homologous protein alignment and mutual mutation to elucidate multiple amino acid sites determining the catalytic function of the proteins, and a series of activity-enhancing or altering mutants were obtained, which provide abundant catalytic elements for the biosynthesis of active triterpenoids from T. wilfordii, and the mechanism of carboxylation in the C-29 position was initially elucidated.

Eighteen compounds were isolated from the methanol extract of the fruits of Litsea cubeba by silica gel, ODS, Sephadex LH-20 column chromatography, semi-preparative RP-HPLC, chiral HPLC and recrystallization. Their structures were elucidated by spectroscopic analyses and by comparison with reported spectroscopic data and physicochemical properties, and the absolute configurations of the enantiomers were established by experimental and calculated electronic circular dichroism spectra. These compounds were identified as (+)-(R)-4-hydroxypiperitenone (1a), (-)-(S)-4-hydroxypiperitenone (1b), (3S,4S,6R)-3,6-dihydroxy-1-menthene (2), (4S,5R)-4-hydroxy-5-isopropyl-2-methylcyclohex-2-en-1-one (3), (R)-6-hydroxy-3-(2-hydroxypropan-2-yl)-6-methylcyclohex-2-enone (4), (4S,6R)-4-hydroxy-6-isopropyl-3-methylcyclohex-2-enone (5), (1R,3S,4R)-3-hydroxy isopulegol (6), subamone (7), (6S)-3,7-dimethyl-7-hydroxy-2(Z)-octen-6-olide (8), (6S)-6,7-dihydroxy-3,7-dimethyloct-2(Z)-enoate (9), holostylactone (10), sesamin (11), dimethylmatairesinol (12), p-hydroxybenzoylcarbinol (13), syringaldehyde (14), p-hydroxybenzaldehyde (15), 4-hydroxy-3-methoxybenzaldehyde (16), 5,4ʹ-dihydroxy-7-methoxyflavone (17). Among them, compounds 1a and 1b were a pair of new monoterpenoid enantiomers, 8 and 9 were new natural products, 2-7, 10, 11 and 17 were isolated from Litsea genus for the first time. The in vitro anti-inflammatory effects of compounds 1-17 were evaluated using lipopolysaccharide-stimulated RAW264.7 cells, the results showed that compound 14 exhibited significant anti-inflammatory activity with NO inhibitory rate of 66.27% at a concentration of 40 μmol·L^-1.

Two new labdane diterpenoids were isolated from 95% ethanol extract of the leaves of Callicarpa formosana Rolfe by using silica gel column, MCI column, ODS column and HPLC. Their structures were elucidated by HR-ESI-MS, NMR and ECD spectral data. All of them are new compounds, named 13E-6β-hydroxylabda-8(17),13-dien-15-oic acid (1) and 13E-7α-hydroxylabda-8(17),13-dien-15-oic acid (2). Compounds 1 and 2 were tested for antioxidant activity, and none of them had obvious activity.

The aim of this study was to explore the regulating effects of hyperoside (Hyp) on lipid metabolism in high-fat diet mice. The high-fat diet mouse model was established by high-fat diet induction. After 5 weeks of Hyp intragastric administration in high-fat diet mice, the serum lipid levels before and after Hyp administration were measured by the corresponding kits. The tissue structure of mouse liver was observed by HE staining before and after Hyp administration. The changes of intestinal flora and transcriptome were measured by Illumina platforms. Liquid chromatography-mass spectrometry (LC-MS) was used to determine non-targeted metabolites. The results showed that Hyp significantly reduced lipid levels in the high-fat diet mice and effectively restored the external morphology and internal structure of liver tissue. Hyp changed the species composition of the intestinal flora in high-fat diet mice, increased the abundance of beneficial flora such as Ruminococcus, and decreased the abundance of harmful flora such as Sutterella. Combined multi-omics analysis revealed that the effect of retinoic acid on lipid metabolism was significant in the high-fat diet mice treated with Hyp, while the increase of retinoic acid content was significantly negatively correlated with the expression of genes such as cyp1a2 and ugt1a6b, positively correlated with AF12 abundance, and significantly negatively correlated with unidentified_Desulfovibrionaceae abundance. These results suggest that Hyp may modulate the abundance of AF12, unidentified_Desulfovibrionaceae and inhibit the expression of genes such as cyp1a2 and ugt1a6b, thus increasing the content of retinoic acid and regulating lipid metabolism in the high-fat diet mice.
Animals ; Mice ; Diet, High-Fat/adverse effects* ; Lipid Metabolism ; Cytochrome P-450 CYP1A2/pharmacology* ; Multiomics ; Liver ; Lipids/pharmacology* ; Tretinoin/pharmacology* ; Mice, Inbred C57BL

Objective: To evaluate the clinical outcomes of computer aided design and computer aided manufacturing (CAD/CAM) ceramic endocrowns in endodontically treated posterior teeth after five years by a retrospective study. Methods: Patients who received CAD/CAM ceramic endocrowns after endodontically treatment in Department of Endodontics, School of Stomatology, The Fourth Military Medical University between January 2016 and June 2017 were invited for this clinical study. Clinical performance was evaluated in the aspect of color match, anatomic form,marginal adaptation, restoration integrity and secondary caries. Survival rate of the restorations was calculated by the use of Kaplan-Meier method. Log-rank test was applied as well for the sake of analyzing the effect of tooth position, sex and materials to the survival rate of the restorations. Results: Seventy-four patients, 25 men and 49 women with age of (38.8±10.2) years, participated in this study for a total of 101 CAD/CAM ceramic endocrowns after observation period of (62.8±12.0) months. There were 8 failed cases among 101 restorations, 5 were loss of retention, 2 were ceramic fracture and 1 was secondary caries respectively. In particular, 93% (89/96) restorations got score A on anatomic form and 95% (91/96) restorations got score A on marginal adaptation, while 38% (36/96) restorations showed the good color match compared with the abutment teeth. The estimated cumulative survival rate of CAD/CAM ceramic endocrowns in endodontically treated posterior teeth after 5 years was 93.0% (95%CI: 87.9%-98.1%). The single-factor Log-rank analysis demonstrated that there was no statistically significant difference in the survival rate of CAD/CAM ceramic endocrowns among men and women, premolars and molars, position in the dental arch, or different materials (χ²<0.01, P=0.957; χ²=0.64, P=0.422; χ²=0.69, P=0.407; χ²=0.88, P=0.349). Conclusions: Based on this clinical study, the clinical performance of CAD/CAM ceramic endocrowns in endodontically treated posterior teeth after five years is reliable, which could be a general option to restore nonvital teeth.
Humans ; Male ; Female ; Adult ; Middle Aged ; Crowns ; Dental Porcelain/therapeutic use* ; Retrospective Studies ; Dental Prosthesis Design ; Dental Stress Analysis ; Materials Testing ; Computer-Aided Design ; Ceramics

OBJECTIVE: To evaluate pharmacokinetics (PK), efficacy, and safety of atezolizumab (anti-PD-L1) in high interest cancers in China, including esophageal cancer (EC), gastric cancer (GC), hepatocellular carcinoma (HCC), nasopharyngeal cancer (NPC), and non-small cell lung can-cer (NSCLC). METHODS: This phase I, open-label study was conducted at 6 Chinese sites from August 4, 2016 to April 15, 2019. The patients were ≥18 years old with a histologically documented incurable or metastatic solid tumor that was advanced or recurrent and had progressed since the last anti-tumor the-rapy. The PK phase characterized PK and safety of atezolizumab following multiple-dose administration when atezolizumab was administered as a single agent. The extension phase studied safety and efficacy of atezolizumab, as monotherapy (EC, GC, HCC, NPC) and with chemotherapy (NSCLC). RESULTS: This study enrolled 120 patients (PK phase: n=20; extension phase: n=20/cohort). Fourty-two patients (42.0%) were PD-L1 positive in atezolizumab monotherapy group (100 patients), of the 9 patients (9.0%) with microsatellite instability-high (MSI-H) tumors. Atezolizumab clearance was 0.219 L/d, and steady state was reached after 6 to 9 weeks (2-3 cycles) of repeated dosing. Objective response rates (ORRs) in EC, GC, HCC, NPC, and NSCLC were 10.0%, 15.0%, 10.0%, 5.0%, and 40.0%, respectively. In the patients with PD-L1 positive tumors, ORR was 11.9% with atezolizumab and 46.2% with atezolizumab plus gemcitabine and cisplatin. Two GC patients achieved durable response after pseudo-progression. The most common treatment-related adverse events in the atezolizumab monotherapy group were fatigue, anemia, fever, and decreased white blood cell count. The most common treatment-related adverse events in the combination group were anemia, decreased white blood cell count, and decreased appetite. No new safety signals were identified. CONCLUSION Atezolizumab's PK, efficacy, and safety were similar in Chinese patients vs. global patients in previous studies.
Adolescent ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carcinoma, Hepatocellular/drug therapy* ; Cisplatin/therapeutic use* ; Humans ; Liver Neoplasms/drug therapy* ; Lung Neoplasms/pathology* ; Nasopharyngeal Neoplasms/drug therapy*

Objective To study the distribution of sleep duration in mid－pregnancy women and examine its association with prehypertension ( PHT) ． Methods In the baseline survey of a prospective cohort study，943 women in mid－pregnancy were recruited in Guangzhou，China in 2017－2018． A standardized questionnaire was used to assess demographic characteristics，sleep duration and other lifestyles． We obtained maternal blood pressure values，weights，heights，and medical histories from medical records． Multivariate logistic regression was conducted to examine the association between sleep duration and PHT． Ｒesults The average daily sleep duration of women in mid －pregnancy was ( 10. 41 ± 1. 67 ) hours，and it was negatively related to age and educational level． Overall，98. 33% of pregnant women had a daily sleep duration ≥ 7 h and the distribution was related to passive smoking． The average night time sleep duration was ( 9. 48±1. 21 ) hours，and it was negatively related to age and educational level． The daytime sleep duration was ( 0. 93 ± 0. 69 ) hours，and it was positively associated with physical activity． The average bedtime was( 22 ∶ 42 ± 1．24) ，and it was positively associated with passive smoking． The prevalence of PHT was 9. 61%． We did not observe any significant association between sleep duration and PHT． Conclusions The mid－pregnancy women in Guangzhou had relatively long sleep duration， and it differed by maternal age，educational level，physical activity，and passive smoking． There was no significant association between sleep duration and PHT．

The application of special acupoints for different primary symptoms of chronic gastritis in ancient literature of acupuncture and moxibustion was analyzed and summarized. With keywords, electronic and manual retrieval of ancient literature being performed to establish a database, the association rules were performed with SPSS Modeler 18. As a result, ① among all the 2243 items included, 109 items mentioned special acupoints (excluding those only mentioned crossing acupoint). The frequency of special acupoints was 2554 (71.7%), and the special acupoints on the spleen meridian, the stomach meridian, the conception vessel were frequently used. The frequency of five- point was highest, followed by front- points. ② The special acupoints for four main primary symptoms of chronic gastritis, "stomachache" "vomiting and regurgitation" "belching and acid regurgitation" and "epigastric fullness", included Zusanli (ST 36), Neiguan (PC 6), Zhongwan (CV 12), Gongsun (SP 4), Taibai (SP 3). In addition, the back- points were also selected to treat the primary symptoms other than "epigastric fullness". Zhangmen (LR 13) was added to treat "belching and acid regurgitation". The combination of Neiguan (PC 6) and Gongsun (SP 4) showed the strongest correlation; due to different primary symptoms, the combination had different emphasis.

Objective:To investigate the relationship between NOD-like receptor pyrin domain containing 3(NLRP3)/cysteine aspartate-specific protease(Caspase)-1 signaling pathway and esophageal inflammation by observing the effect of Xuanfu Daizhe Tang on the composition of inflammatory body and the expression of relevant inflammatory factors in rats with reflux esophagitis (RE), so as to explain the mechanism of Xuanfu Daizhe Tang in treating RE. Method:Sixty healthy male Wistar rats were randomly divided into four groups:the normal control group, the model control group, the Xuanfu Daizhe Tang group (9.89 g·kg^-1) and the positive control group (omeprazole enteric-coated tablets+mosapride, 2.58 mg·kg^-1), with 15 rats in each group. Except for the blank control group, the remaining rats were operated by " 4.2 mm pyloric clip+2/3 gastric fundus ligation" to establish models. Since the 8^th day after the operation, the rats were given corresponding drugs twice a day for 14 days. The arterial blood and esophageal tissues were taken out at the 15^th day after the intervention. The pathological morphology of esophagus was observed by naked eyes and under light microscopy. The secretion of cytokines Caspase-1 and interleukin(IL)-1β in serum was detected by enzyme linked immunosorbent assay(ELISA). The expressions of NLRP3, Caspase-1 and IL-1β in esophagus were detected by Western blot. Result:Compared with the normal group, the injury of esophageal mucosa in the model group was the most serious. Compared with the normal group, the levels of Caspase-1 and IL-1β in serum and the expression of NLRP3 protein in esophageal tissue of the model group were significantly increased (P<0.05, P<0.01). Compared with the model group, Xuanfu Daizhe Tang could significantly reduce the contents of Caspase-1 and IL-1β in serum of rats, and down-regulate the expressions of NLRP3, Caspase-1 and IL-1β protein in esophageal tissue (P<0.05, P<0.01). Conclusion:Xuanfu Daizhe Tang can regulate the expressions of NLRP3 and Caspase-1, and reduce the content of IL-1β, suggesting that it may antagonize esophageal inflammatory response, reduce esophageal inflammatory injury and treat RE by inhibiting the activation of NLRP3/Caspase-1 signaling pathway.