Based on mass spectrometry(MS)-guided separation strategy, compound 1 was obtained from the roots of Rhus chinensis. By comprehensive analysis of high resolution-electrospray ionization-mass spectrometry(HR-ESI-MS), nuclear magnetic resonance(NMR) data, and quantum chemical calculation of NMR(qcc-NMR) parameters, compound 1 was elucidated as rhuslactone, a 17-epi-dammarane triterpenoid with a rare 17α-side chain. An HPLC-ELSD method for its quantification in R. chinensis was established and adopted for the quantification of rhuslactone in different batches of R. chinensis. Rhuslactone displayed a good linear relationship within the range of 0.021 3-1.07 μmol·mL~(-1 )(r=0.997 6), and the average recovery was 99.34% [relative standard deviation(RSD) 2.9%). Moreover, the results of the evaluation test of the preventive effects of rhusalctone on coronary heart disease(CHD) and thrombosis showed that rhuslactone(0.11 nmol·mL~(-1)) significantly alleviated heart enlargement and venous congestion and increased cardiac output(CO), blood flow velocity(BFV), and heart rate, thereby reducing thrombus formation in zebrafish with CHD. The effects of rhuslactone on CO and BFV were superior to that of digoxin(1.02 nmol·mL~(-1)), and its effect on improving heart rate was comparable to that of digoxin. This study provides experimental references for the isolation, identification, quality control, and application of rhuslactone from R. chinensis against CHD. It is worth mentioning that this study has discussed some omissions in the determination of the stereochemistry of C-17 in dammarane triterpenoids in the present coursebook Chemistry of Chinese Medicine and some research papers, that is, the compound may be 17-epi-dammarane triterpenoid. This paper has also proposed steps for the establishment of C-17 stereochemistry.
Animals ; Zebrafish ; Rhus/chemistry* ; Triterpenes/analysis* ; Coronary Disease ; Thrombosis

Diabetic nephropathy (DN) is one of the most common and serious microvascular complications in patients with diabetes mellitus. Diabetic renal fibrosis ( DRF) is a major pathological change in the development of DN. In recent years the incidence of renal fibrosis (RF) has remained high. For diabetic patients, RF may expose them to kidney transplantation or even death, which brings a great burden to themselves and their families. Therefore, learning the pathogenesis and the current treat ment status of DRF is crucial for the treatment of the disease and the development of new drugs. Here we review the general situa¬tion of DN, the general situation, molecular mechanism, and the treatment of DRF,looking forward to providing a reference for the research and treatment of DRF.

Acephalic spermatozoa syndrome is a rare type of teratozoospermia that severely impairs the reproductive ability of male patients, and genetic defects have been recognized as the main cause of acephalic spermatozoa syndrome. Spermatogenesis and centriole-associated 1 like (SPATC1L) is indispensable for maintaining the integrity of sperm head-to-tail connections in mice, but its roles in human sperm and early embryonic development remain largely unknown. Herein, we conducted whole-exome sequencing (WES) of 22 infertile men with acephalic spermatozoa syndrome. An in silico analysis of the candidate variants was conducted, and WES data analysis was performed using another cohort consisting of 34 patients with acephalic spermatozoa syndrome and 25 control subjects with proven fertility. We identified biallelic mutations in SPATC1L (c.910C>T:p.Arg304Cys and c.994G>T:p.Glu332X) from a patient whose sperm displayed complete acephalia. Both SPATC1L variants are rare and deleterious. SPATC1L is mainly expressed at the head-tail junction of elongating spermatids. Plasmids containing pathogenic variants decreased the level of SPATC1L in vitro. Moreover, none of the patient's four attempts at intracytoplasmic sperm injection (ICSI) resulted in a transplantable embryo, which suggests that SPATC1L defects might affect early embryonic development. In conclusion, this study provides the first identification of SPATC1L as a novel gene for human acephalic spermatozoa syndrome. Furthermore, WES might be applied for patients with acephalic spermatozoa syndrome who exhibit reiterative ICSI failures.
Centrioles/genetics* ; Homozygote ; Humans ; Infertility, Male/genetics* ; Male ; Mutation ; Spermatogenesis/genetics* ; Spermatozoa

BACKGROUND: After radical hysterectomy for cervical cancer, the most common complication is lower urinary tract symptoms. Post-operatively, bladder capacity can alter bladder function for a prolonged period. This study aimed to identify factors affecting bladder storage function. METHODS: A multicenter, retrospective cohort study was conducted. Information of patients with stages IA2 to IIB cervical cancer with urodynamic study results were retrospectively collected from nine hospitals between June 2013 and June 2018 according to the inclusion criteria. Demographic, surgical, and oncological data were collected. The univariate and multivariate logistic regression was used to identify clinical factors associated with bladder storage function. RESULTS: Two hundred and three patients with cervical cancer had urodynamic testing post-operatively. Ninety-five (46.8%) patients were diagnosed with stress urinary incontinence (SUI). The incidence of low bladder compliance (LBC) was 23.2%. Twenty-seven (13.3%) patients showed detrusor overactivity (DO). Fifty-seven patients (28.1%) presented with a decreased maximum cystometric capacity (DMCC). The probability of composite bladder storage dysfunction was 68.0%. Multivariate analysis confirmed that laparoscopy represents a protective factor for SUI with an odds ratio of 0.498 (P = 0.034). Patients who underwent a nerve-sparing procedure were less odds to experience SUI (P = 0.014). A significant positive correlation between LBC and DO was observed (P < 0.001). A greater length of the resected vagina and chemoradiotherapy were common risk factors for LBC and DO, while radiotherapy exerted a stronger effect than chemotherapy. Additionally, patients who received chemoradiotherapy frequently developed a DMCC. The follow-up time was not correlated with bladder storage function. CONCLUSION A nerve-sparing procedure without longer resected vagina is recommended for protecting the bladder storage function.

OBJECTIVE: To compare the effect of acupoint injection and intramuscular injection with mouse nerve growth factor (mNGF) on gross motor function development of children with cerebral palsy (CP), and explore the treatment mechanism. METHODS: A total of 63 children with CP were randomly divided into an observation group (32 cases, 4 cases dropped off ) and a control group (31 cases, 3 cases dropped off). Based on the routine rehabilitation therapy, the control group received intramuscular injection of mNGF(18 µg/2 mL), and the observation group received acupoint injection of mNGF at Xinshu (BL 15), Ganshu (BL 18), Pishu (BL 20), Shenshu (BL 23), Sanjiaoshu (BL 22), Shenting (GV 24), Baihui (GV 20), Fengfu (GV 16), Dazhui (GV 14), etc. Of them, 5-6 acupoints alternately were selected each time, and each acupoint was given 0.3-0.5 mL, totally 18 µg/2 mL. Both treatment were carried out once every other day for six months. Before and after treatment, the children's development of brain function was assessed using gross motor function classification system (GMFCS). Before treatment (T), after 2 (T), 4 (T) and 6 (T) months of treatment, the motor function was evaluated by gross motor function measure (GMFM-88). The systolic peak velocity (Vs), mean velocity (Vm) and vascular resistance index (RI) of anterior cerebral artery (ACA) and middle cerebral artery (MCA) were measured, and the level of N-acetyl aspartate acid (NAA), choline (Cho), lactate (Lac) and creatine (Cr) from the basal ganglia, thalamus and periventricular white mater were detected by magnetic resonance spectroscopy (MRS) technology with MAGNETOM Skyra3.0T magnetic resonance imaging system before and after treatment. RESULTS: Compared with before treatment, the GMFCS classification of the observation group after treatment was significantly improved (<0.05); after treatment, the difference of GMFCS classification between the two groups was not significant (>0.05), however, the observation group had a 3.142 times of feasibility for good gross motor function development by more than level 1 compared to the control group (<0.05). After 2, 4, and 6 months of treatment, the GMFM-88 scores of the two groups showed an upward trend (<0.01), and the increase of the observation group was greater than that of the control group (<0.05). Compared with before treatment, in the ACA and MCA, the Vs and Vm increased, RI decreased in both groups after treatment (<0.01), and in the brain, NAA/Cr increased, Cho/Cr and Lac/Cr decreased (<0.01), and after treatment, the Vs, Vm of ACA and MCA and NAA/Cr of brain in the observation group were higher than those in the control group (<0.05), and the RI of ACA and MCA and Cho/Cr and Lac/Cr of brain in the observation group were lower than those in the control group (<0.05). CONCLUSION The mNGF acupoint injection has a better effect on the gross motor function in the children with cerebral palsy compared with the intramuscular injection, and the mechanism may be associated with exhibiting the double effects of acupoint effect and the targeting therapy of drug, which can effectively improve the cerebral hemodynamics and the metabolism of cerebral nervous substances.

Objctive To investigate the protective effect of resveratrol on oxidative stress damage of follicular granulosa cells induced by hydrogen peroxide. Methods Granulosa cells were collected from the follicular fluid of in vitro fertilization(IVF) patients after oocyte retrieval and cultured. The cultured granulosa cells were divided into four groups: control group, injury model group, 10 μmol / L resveratrol group and 50 μmol / L resveratrol group. Cell viability was determined by CCK-8 assay, malondialdehyde(MDA) content by thiobarbituric(TBA) assay, superoxide dismutase(SOD) level by water soluble tetrazdium-1(WST-1) assay, apoptosis by AnnexinV-FITC / PI double-staining flow cytometry, Bcl-2 and Caspase-3 protein expression by Western blotting, and progesterone secretion by competitive ELISA. Resutls Compared with the control group, the cell viability, SOD level, Bcl-2 protein expression and progesterone secretion were significantly decreased in the injury model group, while MDA content, apoptosis rate and Caspase-3 apoptotic protein expression were significantly increased (P<0. 05) . Compared with the injury model group, the 10 μmol / L resveratrol group showed no statistically significant differences in various parameters; however, the cell viability, SOD level, progesterone secretion, and Bcl-2 and silent information regulator factor 2 related enzyme 1(SIRT1) protein expression were significantly increased, and the MDA content, apoptosis rate, and Caspase-3 apoptotic protein expression were significantly decreased in the 50 μmol / L resveratrol group (P < 0. 05) . Conclusion 50 μmol / L resveratrol can increase the activity of SIRT1, enhance the anti-oxidation and anti-apoptosis ability of granulosa cells and improve the function of granulosa cells.

The peeled root,stem or twig of Syringa pinnatifolia is a representative Mongolian folk medicine with the effects of antidepression and pain relief. It has been used for the treatments of heart tingling,heart palpitations,upset,insomnia and other symptoms. Inspired by Mongolian medical theory and clinical practices,this study evaluated the analgesic effect of S. pinnatifolia ethanol extract( T) through three analgesic models including acetic acid writhing test,formalin test,and hot plate test,and the sedative effect of T was evaluated by locomotor activity and synergistic sleeping experiments,and furthermore the effects of T on the GABAergic nervous system were investigated by ELISA,immunohistochemistry,Western blot,and PCR methods. The results showed that T can significantly reduce the number of writhing,the time of paw licking and extend the thermal threshold of mice,suggesting the analgesic effect of T.T also can indicate its sedative effect by reducing the number of activities,decreasing latency of sleeping and extending sleeping time of mice. ELISA results showed that T can increase the content of GABA/Glu in rat cortex,hippocampus,and hypothalamus,and the most significant increase in hypothalamus. The immunohistochemistry and Western blot results showed that T can up-regulate the expression of GAD67 protein in hypothalamus,and the PCR results showed that T can up-regulate the expression of GABAA Rα1,α2,α3,α5,β1-3,γ1-3 genes,suggesting a sedative effect through the GABAergic nervous system. In conclusion,this study shed insight into the theoretical basis and clinical application of S. pinnatifolia,and also provides inspiration for subsequent development and application.
Analgesics ; pharmacology ; Animals ; Hypnotics and Sedatives ; pharmacology ; Medicine, Mongolian Traditional ; Mice ; Pain ; Plant Extracts ; pharmacology ; Rats ; Syringa ; chemistry

Syringa pinnatifolia Hemsl.( SP) is a representative Mongolian folk medicine with the effects of inhibiting Heyi related diseases,clearing heat and relieving pain. It has been used for the treatment of Heyi-induced heart tingling,heart palpitations,upset,insomnia and other symptoms. Total ethanol extract( T) and major fraction( M) of SP have been evaluated its anti-ischemic effects,and the mechanism was related to the regulation of cyclooxygenase( COX)-mediated inflammatory pathway and p53-mediated apoptosis pathway in our previous studies. This study reports the chemical fractionation on M by which to obtain subfractions( I and M_3),and the pharmacological evaluation of M,I,and M_3 against myocardial ischemia in mice. The result showed that I and M reduced the values of LVEDd and LVEDs,significantly increased EF and FS values,increased serum CK-MB and LDH levels in mice,and reduced in inflammatory cells infiltration and collagen deposition in the infarcted myocardial tissue,suggesting that M and I possess the same degree anti-myocardial is chemia equally whereas M_3 has no this effect. Related mechanism studies suggested that I can reduce the expression of COX-1,COX-2 and p53 protein in myocardial tissue in a dose-dependent manner. This study lays the foundation for further chemical segmentation and clarification of pharmacological substance groups,paving the way for the full use and benefits to be use of systematic biological methods to analyze the pharmacological basis of SP against myocardial ischemia.
Animals ; Cyclooxygenase 1/metabolism* ; Cyclooxygenase 2/metabolism* ; Heart/drug effects* ; Medicine, Mongolian Traditional ; Membrane Proteins/metabolism* ; Mice ; Myocardial Ischemia/drug therapy* ; Myocardium/metabolism* ; Plant Extracts/therapeutic use* ; Syringa/chemistry* ; Tumor Suppressor Protein p53/metabolism*

To investigate the effects of isovitexin Ⅳ on transient outward potassium current in rat ventricular myocytes. In this study, MTT assay was used to investigate the safe range of isovitexin. The results showed that the IC₅₀ of the drug was in the range of 10-30 μmol•L⁻¹, and the drug concentration of 1-3 μmol•L⁻¹ for the patch clamp test was within the safe range. In addition, the single ventricular myocytes were obtained by single-enzymatic hydrolysis through aortic retrograde perfusion. The transient outward potassium current (Ito) of rat ventricular myocytes was guided and measured by whole-cell patch-clamp technique and the changes of current characteristics were recorded after isovite was applied. When the concentration of IV was less than 0.1 μmol•L⁻¹, there was no significant effect on Ito. However, with the increase in the concentration of IV (≥0.3 μmol•L⁻¹), the peak of Ito was decreased gradually, from (32.32±2.9) pA/pF to （25.83±4.3） pA/pF, 1 μmol•L⁻¹ IV and (19.51±3.5) pA/pF, 3 μmol•L⁻¹ IV respectively, with an inhibition effect in a concentration-dependent manner. In the range of 1-3 μmol•L⁻¹, IV down-regulated the I-V curve of Ito significantly. The activation curve showed that IV can enable the maximum half activation potential (V1/2) to move to the positive direction, and the V1/2 was increased from (19.59±1.6) mV to (22.81±1.7) mV and (28.86±1.4) mV at concentration of 1, 3 μmol•L⁻¹, meanwhile the activation curve moved to the right. However, the maximum half inactivating potential (V1/2) of the steady-state inactivation curve of Ito was significantly decreased from (－51.43±0.99) mV to (－61.81±1.3) mV with concentration of 1 μmol•L⁻¹ and (－71.50±1.4) mV with concentration of 3 μmol•L⁻¹. The inactivation time constant of recovery from inactivation (τ) was up-regulated significantly from (94.89±0.73) ms to (118.5±1.5) ms and (162.4±1.4) ms at concentration of 1, 3 μmol•L⁻¹ respectively. Meanwhile IV could enable the inactivation recovery curve to move to the right, which suggested that it can prolong the recovery time from inactivation of the transient outward potassium channel. In conclusion, isovitexin had a high inhibitory effect on Ito in rat ventricular myocytes.