Preliminary investigation on the analysis of the whole components of Pogejiuxin decoction and its formulation pattern based on ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry.

RATIONAL: Pogejiuxin decoction (PGJXD) is one of the most important formulas for the treatment of heart failure. However, there is a great lack of research on the material basis of this formula, especially research on its compatibility laws, which restricts its clinical use. Studying the complete ingredients and compatibility rules of PGJXD has great significance for guiding clinical medication. METHODS: The entire formula, the major single herbs, the drug pairs and the disassembled formula were analyzed by ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UHPLC/QTOFMS/MS), matching the chemical composition database and global natural product social molecular networking to explain the chemical composition as well as the combination pattern of PGJXD. RESULTS: A total of 1048 chemical constituents were fully analyzed from the major single herbs, the drug pairs and the disassembled formula and 188 chemical constituents, including 13 potential novel compounds, were firstly identified from the whole formula. We found that the chemical compositions were reduced after the single herbs were matched to the other herbs, especially the significant reduction of highly toxic diester alkaloids after compatibility, indicating that the medicines of PGJXD were interdependent and controlled by each other. CONCLUSION: This study innovatively researches and compares the compositional differences between the entire formula of PGJXD, the single, paired and separated formulas, greatly extending our understanding of the chemical substance basis of these compounds, and preliminarily explores the compatibility laws of PGJXD, providing some theoretical guidance for clinical medication.

Biochemical Pathways of Salicylic Acid Derived from l-Phenylalanine in Plants with Different Basal SA Levels.

As a plant hormone, salicylic acid (SA) has diverse regulatory roles in plant growth and stress resistance. Although SA is widely found in plants, there is substantial variation in basal SA among species. Tea plant is an economically important crop containing high contents of SA whose synthesis pathway remains unidentified. The phenylalanine ammonia-lyase (PAL) pathway is responsible for basal SA synthesis in plants. In this study, isotopic tracing and enzymatic assay experiments were used to verify the SA synthesis pathway in tea plants and evaluate the variation in phenylalanine-derived SA formation among 11 plant species with different levels of SA. The results indicated that SA could be synthesized via PAL in tea plants and conversion efficiency from benzoic acid to SA might account for variation in basal SA among plant species. This research lays the foundation for an improved understanding of the molecular regulatory mechanism for SA biosynthesis.

AI/ML to Relationship Between Circadian Rhythm of Blood Pressure and Left Ventricular Hypertrophy in Patients with Hypertension.

Objective: The objective of this experiment was to investigate the relationship between the circadian rhythm of blood pressure and left ventricular hypertrophy (LVH) in patients with hypertension. Methods: A total of 500 hypertension patients with documented circadian rhythm of blood pressure were selected for this study. The researchers collected general patient data and fasting blood samples. The following parameters were measured within subgroups of hypertensive patients: age, sex ratio, BMI, fasting blood glucose, total cholesterol, triacylglycerol, HDL-C, LDL-C, duration of hypertension, antihypertensive drug usage, and statin intake. Results: The results of the study showed that LVH hypertension had a significantly higher proportion of grade 3 hypertension compared to non-LVH hypertension (P < .001). Additionally, LVH hypertension displayed higher mean systolic blood pressure levels over a 24-hour period (P = .002), during daytime (P = .029), and during nighttime (P < .001). The 24-hour pulse pressure (P < .001) and pulse pressure index (P = 0.001) were also significantly higher in patients with LVH hypertension. Furthermore, the rate of blood pressure decline at night was significantly lower in the LVH hypertension group compared to the control group (P < .001). B-type natriuretic peptide (BNP) levels (P = .034) and left ventricular mass index (LVMI) (P < .001) were significantly higher in patients with LVH hypertension compared to non-LVH patients. Conclusions: The findings of this study suggest a close association between hypertensive LVH and the weakening or disappearance of the circadian rhythm of blood pressure. It was also observed that the level of blood pressure classification and plasma BNP levels were increased in patients with LVH hypertension.

Optimized electroacupuncture treatment for female stress urinary incontinence: study protocol for a multi-center randomized controlled trial.

Background: Stress urinary incontinence (SUI) is a common condition that can severely affect women's life quality. Electroacupuncture (EA) has been proved to be an optional treatment for SUI, but the tolerance of EA becomes a factor affecting efficiency, which should not be ignored and needs to be solved urgently. The purpose of this study is to find out whether the use of alternating acupoints combination can solve this problem or not and provide an optimization of EA treatment for female SUI. Methods: This multi-center randomized controlled trial will enroll 360 patients with SUI. They will be randomly assigned to one of the three groups-sacral acupoints group (sacral group), abdominal acupoints group (abdominal group), or alternating acupoints group (alternating group)-at a 1:1:1 ratio. The patients will receive 18 sessions of EA treatment and will be followed up for 48 weeks after the treatment. The primary outcome measure of the study is the change of urine leakage at week 6. The secondary outcomes include the incontinence episode frequency (IEF), International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), severity of SUI, patient self-evaluation of therapeutic effects, weekly usage of urine pads, ultrasonography of pelvic floor, specialty therapies for SUI, evaluation of discomfort during EA treatment, patient acceptability evaluation and adverse events related to intervention. Discussion: This trial is specifically designed to offer an optimized EA treatment for female SUI, aiming to enhance their quality of life.Clinical trial registration: ClinicalTrials.gov, identifier ID:NCT05635669.

Mechanistic exploration of Yiqi Liangxue Shengji prescription on restenosis after balloon injury by integrating metabolomics with network pharmacology.

CONTEXT: Yiqi Liangxue Shengji prescription (YQLXSJ) is a traditional Chinese medicine (TCM) formula that has long been used for treatment after percutaneous coronary intervention (PCI). OBJECTIVE: To investigate the putative pharmacological mechanism of YQLXSJ on restenosis through an integrated approach utilizing metabolomics and network pharmacology. MATERIALS AND METHODS: Forty male Sprague-Dawley rats were divided into sham, model, YQLXSJ, and positive groups. YQLXSJ group received the treatment of YQLXSJ (6 g/kg/d, i.g.) and the positive group was treated with atorvastatin (2 mg/kg/d, i.g.). After 4 weeks, the improvement in intimal hyperplasia was evaluated by ultrasound, H&E staining, and immunofluorescence. UPLC-MS/MS technology was utilized to screen the differential metabolites. Network pharmacology was conducted using TCMSP, GeneCards, and Metascape, etc., in combination with metabolomics. Eventually, the core targets were acquired and validated. RESULTS: Compared to models, YQLXSJ exhibited decreased intima-media thickness on ultrasound (0.23 ± 0.02 mm vs. 0.20 ± 0.01 mm, p < 0.01) and reduced intima thickness by H&E (30.12 ± 6.05 µm vs. 14.32 ± 1.37 µm, p < 0.01). We identified 18 differential metabolites and 5 core targets such as inducible nitric oxide synthase (NOS2), endothelial nitric oxide synthase (NOS3), vascular endothelial growth factor-A (VEGFA), ornithine decarboxylase-1 (ODC1) and group IIA secretory phospholipase A2 (PLA2G2A). These targets were further confirmed by molecular docking and ELISA. DISCUSSION AND CONCLUSIONS: This study confirms the effects of YQLXSJ on restenosis and reveals some biomarkers. TCM has great potential in the prevention and treatment of restenosis by improving metabolic disorders.

Neurological mechanism and efficacy of acupuncture for breast cancer-related insomnia: a study protocol for randomized clinical trial.

Background: Breast cancer survivors (BCSs) are at a higher risk of developing insomnia. The negative effects of cancer-related insomnia (CRI) include depression, anxiety, fatigue, aggressive pain, impaired immune functioning, decreased quality of life, and even increased cancer mortality. Although preliminary progress has been made in the treatment of CRI with acupuncture, the evidence is insufficient and the neurological mechanism underlying the effect of acupuncture is still unclear. Methods: The study employs a single-blinded, randomized, controlled trial design. A total of 80 participants will be randomly allocated in a 1:1 ratio to either the treatment group (n = 40) or the control group (n = 40). The former will receive acupuncture treatment, while the latter will receive sham acupuncture treatment. Both groups will receive 12 sessions over a 4-week period, three times per week (every other day), and each session will last for 30 min. Follow-up assessments will be conducted in week 8. The primary outcome will be the treatment response rate. Secondary outcomes include the change in Insomnia Severity Index (ISI), the treatment remission rate, actigraphy sleep assessment, Generalized Anxiety Disorder Scale (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Quality of Life Core Scale (QLQ-C30), the weekly usage of remedial drugs, and functional magnetic resonance imaging (fMRI) analysis. Data for the outcomes will be collected at week 0 (the baseline), week 1 (the intervention period), week 4 (the post-treatment period), and week 8 (the follow-up period). Discussion: The objective of this study is to assess the efficacy of acupuncture for patients with CRI in comparison with sham acupuncture. Additionally, the research aims to explore the neuropathological mechanisms of CRI and provide the first evidence on the characteristics of acupuncture treatment using fMRI. We expect that the results of this study will provide valuable scientific evidence of acupuncture treatment for CRI.Clinical trial registration: Chinese Clinical Trial Registry, identifier ChiCTR2300070349: https://www.chictr.org.cn/showproj.html?proj=188677.

Component analysis using UPLC-Q-Exactive Orbitrap-HRMS and quality control of Kudingcha (Ligustrum robustum (Roxb.) Blume).

Although Kudingcha (Ligustrum robustum (Roxb.) Blume) has been widely used as both traditional medicine and food, systematic studies on their basic active components and quality control are lacking. In this study, a rapid method of identifying the general chemical components of Ligustrum robustum (Roxb.) Blume was established for the first time using UPLC-Q-Exactive Orbitrap-HRMS, and its major basic components were specified as phenylpropanoid, monoterpene, and flavonoid glycosides. The characteristic cleavage pathways of the phenylpropanoid, monoterpene, and flavonoid glycosides were further investigated and elaborated, which could assist in identifying the structures of similar components of other Chinese herbal medicines. A breakthrough was achieved in establishing a chemical fingerprinting profile of Ligustrum robustum (Roxb.) Blume from its original growing areas in China, and chemometric measures were applied to investigate the causes for the variations in its quality stability. The results indicated significant differences in the characteristic compositions of phenylpropanoid and monoterpene glycosides between mature and young leaves of Ligustrum robustum (Roxb.) Blume; however, no significant variation was observed owing to different production areas. Graded harvesting criteria should be established, and harvest period should be specified according to the target active components while considering agricultural metrics, such as leaf shape index, leaf length, and leaf width, to ensure the consistency in quality of active components during their production. From the perspective of overall quality control, an unprecedented quantitative analysis of multi-components by single marker was set up to analyze the signature components of phenylpropanoid glycosides (acteoside, isoacteoside, ligurobustoside N, and ligupurpuroside B) to increase the analytical efficiency and reduce research costs. This study created a scientific basis for the standardized operation, elucidation of the pharmacological materials, and quality control of food and supplements production with Ligustrum robustum (Roxb.) Blume as a raw material.

Reliability of Evidence to Guide Decision-Making in the Use of Acupuncture for Postpartum Depression.

Background: There is conflicting evidence on the effectiveness of acupuncture in the treatment of postpartum depression (PPD). This study aimed to assess previous systematic reviews/meta-analyses (SRs/MAs) on the effectiveness of acupuncture to treat PPD. Method: SRs/MAs regarding the use of acupuncture for PPD were identified from the establishment of digital databases to November 2021. The Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2) was applied to evaluate the methodological quality of included SRs/MAs. The Grades of Recommendations, Assessment, Development and Evaluation (GRADE) was utilized to evaluate the evidence quality for outcomes of interest. Results: Six studies that conducted quantitative syntheses were included. According to AMSTAR-2, the methodological quality of these SRs/MAs was critically low owing to limitations of items 2, 4, and 7. According to GRADE, no study included high-quality evidence and most studies included low-quality evidence. Conclusions: Acupuncture m be beneficial for PPD, however, due to limitations of current evidence and inconsistent findings, further studies are needed to provide stronger evidence to draw definitive conclusions.

Prophylactic Moxibustion in Preventing Postoperative Urinary Retention of Hemorrhoidectomy: A Study Protocol for a Randomized Controlled Trial.

Backgrounds: Postoperative urinary retention (POUR) is one of the most common complications after hemorrhoidectomy. The best treatment for POUR is prevention and should be involved in the whole perioperative period. Moxibustion has been used to treat urinary retention for thousands of years, and clinical studies have also proved its effects. We try to carry out a randomized, controlled, prospective study to observe whether prophylactic moxibustion could effectively reduce the incidence of POUR of hemorrhoidectomy in 24 h. Methods: This study is a single-center, evaluator-blinded, randomized, and controlled trial. Participants who meet the inclusion and exclusion criteria in this RCT will be randomly assigned to either the treatment group (moxibustion) or the control group (tamsulosin hydrochloride) in a 1:1 ratio according to a computer-generated randomization list. Both moxibustion and tamsulosin will be used 1, 10, and 24 h after operation, respectively. The outcomes of occurrence of POUR, time to first urination, catheterization rate, urinary tract infection, length of hospitalization, and adverse effects will be recorded. Discussion: The findings of the study will help to explore the preventive efficacy of prophylactic moxibustion against POUR of hemorrhoidectomy in 24 h. Trial Registration: CHiCTR, CHiCTR2000039350, registered 24 October, 2020, http://www.chictr.org.cn/showproj.aspx?proj = 63204.

[Efficacy of Jujing Decoction combined with lipoic acid in the treatment of asthenospermia and teratospermia].

OBJECTIVE: To observe the clinical efficacy of Jujing Decoction combined with lipoic acid in the treatment of asthenospermia and teratospermia. METHODS: Fifty patients with asthenospermia and teratospermia meeting the inclusion criteria were randomly divided into a blank control (n = 10) and a medication group (n = 40), the former provided with fertility guidance and the latter treated with Jujing Decoction combined with lipoic acid. After 12 weeks of treatment, the clinical therapeutic effects were evaluated by comparing the semen volume, sperm concentration, percentages of progressively motile sperm (PMS) and morphologically abnormal sperm (MAS), rate of acrosome integrity, sperm DNA fragment index (DFI) and pregnancy rate between the two groups. RESULTS: Compared with the control group, the medication group achieved a significantly higher overall effectiveness rate (10% ï¼»1/10ï¼½ vs 88.89% ï¼»32/36ï¼½, P < 0.05) and pregnancy rate (0% ï¼»0/10ï¼½ vs 8.33% ï¼»3/36ï¼½, P < 0.05) after treatment. The medication group also showed remarkably increased PMS from (21.04 ± 6.49)% to (32.66 ± 7.05)%, decreased MAS from (98.31 ± 1.28)% to (96.52 ± 1.11)%, elevated acrosome integrity from (42.18 ± 16.67)% to (60.42 ± 11.61)%, and reduced sperm DFI from (21.92 ± 6.96)% to (12.37 ± 3.79)%, all with statistically significant differences compared with the blank control group. CONCLUSION: Jujing Decoction combined with lipoic acid can significantly improve sperm motility, reduce MAS and DFI and increase the pregnancy rate through antioxidant stress, and has a high clinical safety.

The effectiveness of acupuncture and moxibustion for treating tenosynovitis: A systematic review and meta-analysis protocol.

BACKGROUND: De Quervain's tenosynovitis is an overuse disease that involves a thickening of the abductor pollicis longus and extensor pollicis brevis tendons. Evidence shows that acupuncture and moxibustion (AM) could remarkably relieve the pain of De Quervain's tenosynovitis patients. The aim of this protocol is to determine the efficacy and safety of AM for treating De Quervain's tenosynovitis. METHODS: Several online databases including PubMed, Cochrane Library, Embase, Chinese Biomedical Literatures Database, China National Knowledge Infrastructure, WangFang Database, Chinese Scientific Journal Database will be searched from their establishment to July 1, 2020. We will include all randomized controlled trials using AM as the method for treating De Quervain's tenosynovitis, regardless of blinding or publication types. The selection of studies, data extraction and the assessment of the studies quality will be conducted by 2 reviewers separately. When there is sufficient available data for meta-analysis, we will use the RevMan V.5.3 statistical software for data synthesis. The total effective rate, range of motion of wrist ulnar deviation will be the primary outcomes, and the secondary outcomes contain Visual Analog Scale, Coney Wrist Score and side effects. We will express the result by using Risk ratio for dichotomous data and mean differences with a 95% confidence interval for continuous data. RESULTS: The results of this study be presented in corresponding journal or conferences. CONCLUSIONS: This study is designed to provide sufficient evidence to assess the exact effectiveness of AM on De Quervain's tenosynovitis. PROSPERO REGISTRATION NUMBER: CRD42020158764.

Stuck-moving needle acupuncture myofascial trigger point to treat idiopathic frozen shoulder: study protocol for a randomized controlled trial.

BACKGROUND: There are evidence for the efficacy of acupuncture treatment for chronic shoulder pain, however, it remains unclear the best acupuncture modes for effective treatment. We compared the effect of the myofascial trigger point (MTrp) stuck-moving needle acupuncture with that of common acupuncture treatments. Further, we evaluated the efficacy and safety of stuck-moving needle acupuncture for the MTrp in improving pain and range of motions in patients with idiopathic frozen shoulder. The aim of present study is to select an effective therapy for patients with idiopathic frozen shoulder. METHODS: Randomized controlled trial will be conducted in the three clinical centers of Qingyang Traditional Chinese Medicine Hospital, Qingyang Xifeng district People's Hospital, and Qingyang Second People's Hospital in China from February 2020 to January 2021. One hundred and eight frozen shoulder patients will be recruited and randomized into one of three groups in a 1:1:1 ratio of the stuck-moving needle acupuncture group, common acupuncture control group, and physical exercise control group. This trial will include a 1-week baseline period, a 3-week treatment period, and a 12-week follow-up period. During the 3 weeks of the treatment period, patients will receive nine sessions of acupuncture. The primary outcome will be related to change in the Visual Analogue Scale (VAS) and measurement of range of joint motion (ROM) from the baseline period to the 12-week follow-up period. Secondary outcome measures will include measurement of pressure pain threshold (PPT), pressure pain tolerance (PTT), Oxford Shoulder Score (OSS), 36-item short form survey, and patient satisfaction evaluation. Adverse events also will be recorded for safety assessment. DISCUSSION: The results of this trial will allow us to compare the difference in efficacy between stuck-moving needle acupuncture MTrP with that of common acupuncture treatments. The findings from this trial will be published in the peer-reviewed journals. TRIAL REGISTRATION: Acupuncture-Moxibustion Clinical Trial Registry (ChiMCTR1900002862) and Chinese Clinical Trial Registry (ChiCTR1900028452). Registered on 22 December 2019. http://www.chictr.org.cn/showproj.aspx?proj=47354.

Plum-blossom needle plus Chinese herbal medicine for alopecia areata: A protocol for systematic review and meta analysis.

BACKGROUND: Alopecia areata (AA) is a common, inflammatory, nonscarring type of hair loss that is characterized by depression, anxiety and social isolation. In recent years, Plum-blossom needle plus Chinese herbal medicine has gradually shown its clinical advantages and been more and more widely used in China. Whereas, there has been no systematic review and meta-analysis. The purpose of this study is to estimate the safety and effectiveness of Plum-blossom needle plus Chinese herbal medicine in AA treatment. METHODS: Seven databases as following: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), and Chinese Biomedical Literatures Database (CBM) will be searched from their inception to August 2020. Two reviewers (LBL and ZYZ) will respectively regulate research selection, data extraction, and risk of bias assessment. A third reviewer will be settled to consulting, if necessary. Review Manager Software 5.4 will be implemented for this study. RESULTS: The results will be published in a peer-reviewed medical journal. This meta-analysis will provide a synthetic review of the credible evidence for the treatment of Plum-blossom needle plus Chinese herbal medicine with AA. CONCLUSIONS: This systematic review and meta-analysis expects to provide high-quality evidence regarding the synergistic effect of Plum-blossom needle plus Chinese herbal medicine treatment for AA.

Structural characterization and discrimination of Paris polyphylla var. yunnanensis by a molecular networking strategy coupled with ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry.

RATIONALE: Paris polyphylla var. yunnanensis (Franch) Hand Mazz (PPY) is a traditional Chinese medicine with antitumor, antibacterial, hemostatic, and anthelmintic activities. Identification of the chemical composition in PPY is helpful to discover its active ingredients and can be used to establish its quality control protocols. METHODS: The composition of PPY was identified using ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UHPLC/QTOF-MS/MS) coupled with a molecular networking strategy. First, the UHPLC/QTOF-MS/MS approach was optimized for chemical compound profiling. Then, the MS data were processed using PeakView™ combined with an in-house database to quickly characterize the secondary metabolites. Finally, molecular networking excavated new molecular weights to discover unknown or trace natural products based on the characteristics of each cluster. RESULTS: A total of 222 compounds, including 77 isospirostanols, 2 spirostanols, 19 furostanols, 10 pseudospirostanols, 6 cholesterols, 10 C21 steroids, 5 insect metamorphosis hormones, 3 plant sterols, 6 five-ring triterpenoids, 4 flavonoids, 8 fatty acids, 2 phenylpropanoids, and 8 other compounds, were characterized in PPY by comparing their main fragmentation characteristics and pathways with the literature data, and 62 of them, 54 steroidals and 8 phenylpropanoids, were discovered or tentatively identified for the first time. CONCLUSIONS: This study extended the application of a molecular networking strategy to traditional herbal medicines and developed a molecular networking based screening approach with a significant increase in efficiency for the discovery and identification of trace novel natural products.

New glycosylsphingolipids from Psychotria serpens L.

In clinical, Psychotria serpens L. was often substitute for Caulis trachelospermi to treat cancer in China. Meanwhile, EtOAc and n-BuOH fractions of MeOH extract of P. serpens L. show power activity against H460, HepG2, Hela, and PC9/GR cell lines, and no toxic effects against normal 16HBE cell lines. In our ongoing search for bioactive novel compounds from Chinese material medica, one new type of glycosylsphingolipids Psychotramide (1a-1c) were isolated from P. serpens L., and their structures were identified through spectroscopic techniques including NMR (1D and 2D) and MS (LC-MS, and GC-MS).

[Effect of different fertilization treatments on growth,secondary metabolites,and seed yield and quality of Perilla frutescens].

Perilla frutescens,an annual plant in Labiatae family,is grown throughout China and can be used for medicine purposes and as food additives. The present field experiment was carried out to study the effects of different fertilizer treatments on the concentrations and accumulations of antioxidant components,including flavonoids and polyphenols,growth,seed yields and qualities of this plant.The main aim of this study is to provide farmers some advice for improving the yields and qualities of P. frutescens in theory and practice.Five treatments were set up,including a no fertilizer control(CK),chemical fertilizers(CF),organic fertilizers(M),organic fertilizers plus chemical fertilizers at the rates of 1 ∶1 and 1 ∶3 in terms of nitrogen(50 M,25 M). Plant growth parameters were recorded and total flavonoids and polyphenols were determined in three key growth stages of P. frutescens. At the fast growth period,samples of roots,leaves,and stems were collected for determining a total of flavonoids and polyphenols as well as DPPH removal rate of ethanol extracts. Seed yields and qualities were also recorded at harvest. The results showed fertilization enhanced growth and seed yields although no significant difference was observed in growth and seed yields in inorganic-organic fertilizer treatments. The total flavonoids,polyphenols,and DPPH removal rate of ethanol extracts followed the sequence leaves>stems>roots,indicating synthesis of these metabolites in the leaves. DPPH removal rate showed a positive linear correlation with total flavonoid and polyphenol concentrations. In addition,organic-inorganic fertilization significantly increased the numbers of both effective panicles and paniclegrains. Fertilizer treatments had no effect on seed qualities of P. frutescens,while 50 M achieved the highest yield,which increased by 14. 73% compared to CF alone. In general,50 M increased antioxidant components,biomass,and seed yield of P. frutescens,meriting advocate in cultivation.

The "target + activity" method for rapid discovery of active compounds targeting Hsp90 in pancreatic cancer cells from Physalis angulata L / 药学学报

The purpose of this study was to select the active compounds targeting Hsp90 protein in pancreatic cancer cells through a new dual "target + activity" rapid discovery technique. We combined an in vitro anti-cancer activity screening method with a dual-luciferase reporter gene and multi-chromatography separation technology, for rapid discovery of potential Hsp90 inhibitors from the Chinese herbal medicine Physalis angulata L. The anti-proliferation activity of those compounds was assessed in pancreatic cancer cell line BxPC-3 by MTT assays. The molecular mechanisms of Hsp90 inhibition were explored by Western blot and shRNA knockdown assays. As a result, two withanolides, withanolide E (WE) and 4β-hydroxywithanolide E (HWE), were identified from Physalis angulata L. The half maximal inhibitory concentration (IC50) of WE and HWE were 0.71±0.03 and 1.23±0.10 μmol·L-1 for the growth of BxPC-3 cells in 48 h. Luciferase reporter assay demonstrated that WE and HWE significantly induced heat shock element (HSE) activity in a dose- and time-dependent manner. The molecular mechanism study showed that after exposing to 5 μmol·L-1 WE or HWE for 48 h, the aggregation of Hsp90 dimer was upregulated to 6.5±1.3 and 11.8±2.0 fold, while the expression of Hsp90 client protein Akt was downregulated to 21.7%±2.8% and 9.8%±1.4% of the control group. Moreover, the Hsp90 inhibitory activity of WE or HWE was canceled by shRNA mediated Hsp90 knockdown. Overall, based on the dual "target + active" rapid discovery technique, two new Hsp90 inhibitors WE and HWE were found from Physalis angulata L. The Hsp90 inhibitory mechanism of WE and HWE may be mediated by induction of Hsp90 aggregate dimer and inhibition of Hsp90 client protein Akt expression.

[Modified Jujing No.2 Decoction for varicocele-induced male infertility].

Objective: To investigate the clinical effect of Jujing No.2 Decoction on male infertility induced by varicocele. METHODS: We equally randomized 70 male patients with varicocele-induced infertility into a treatment group and a control group, the former treated with modified Jujing No.2 Decoction (1 dose a day, bid) and the latter given Danshen Tablets (4 tablets once, tid) plus Liu Wei Di Huang Wan (8 pills once, tid), both for 3 months. We examined the spermatic veins of the patients by ultrasonography and performed seminal analysis before and after medication. RESULTS: Compared with the controls, the patients in the treatment group showed significant improvement after medication in sperm concentration (ï¼»12.35±2.12ï¼½ vs ï¼»18.56±4.16ï¼½ ×106/ml, P<0.05), progressively motile sperm (ï¼»16.18±6.34ï¼½ vs ï¼»24.63±8.51ï¼½ %, P<0.05), and morphologically normal sperm (ï¼»11.59±5.31ï¼½ vs ï¼»14.17±6.02ï¼½ %, P<0.05). In the control group, sperm concentration was increased from (12.29±2.07) ×106/ml at the baseline to (13.13±3.13) ×106/ml after medication, progressively motile sperm from (16.13±6.45) % to (20.55±7.30) % (P<0.05), and morphologically normal sperm from (11.62±5.35) % to (12.69±5.77) %. The total effectiveness rate was significantly higher in the treatment than in the control group (71.88% vs 46.67%, P<0.05). The inner diameter of the left spermatic vein was decreased from (0.32±0.05) mm at the baseline to ï¼»0.26±0.05ï¼½ mm after medication in the treatment group (P<0.05) and from (0.32±0.03) mm to (0.29±0.04) mm in the control (P<0.05), with statistically significant difference between the two groups after medication (P<0.05). CONCLUSIONS: Jujing No.2 Decoction is effective in the treatment of varicocele-induced male infertility.

[Distribution, combination, and evolution of syndromic etiologies of erectile dysfunction].

OBJECTIVE: To explore the distribution, combination and evolution of various syndromic etiologies of erectile dysfunction (ED) based on the syndrome etiology theory. METHODS: Using the ED Syndromic Etiology Scale, we collected the clinical data on the Chinese medicine diagnoses of 297 cases of ED, extracted the core syndromic etiologies by analysis of principal components and factors, and analyzed the patterns of distribution, combination, and evolution of ED syndromic etiologies according to the general information of the patients. RESULTS: Through analysis of principal components and factors, 9 core syndromic etiologies were extracted, i. e. , liver constraint with qi stagnation, kidney yin deficiency, damp-heat, liver constraint transforming into liver-fire, blood stasis, kidney yang deficiency, heart-spleen paired deficiency, qi-yin paired deficiency, and phlegm-damp. Each of these syndrome etiologies exhibited its own specific distribution patterns. Of the total number of cases studied, 51.52% had 2 or 3 core syndromic etiologies and 36.03% had only one. CONCLUSION: In the early stage of ED, its syndromic etiologies are usually liver constraint with qi stagnation, kidney yin deficiency, damp-heat, liver constraint transforming into liver-fire, and blood stasis. With the natural progres- sion of the disease, its syndromic etiologies gradually evolve into kidney yang deficiency, heart-spleen paired deficiency, qi-yin paired deficiency, phlegm-damp, and blood stasis, and finally into yin-yang deficiency of the heart, spleen and kidneys, combined with phlegm-damp and blood stasis.

Gypenosides might have neuroprotective and immunomodulatory effects on optic neuritis.

Optic neuritis is a common disease in young adults, inducing apoptosis of retinal ganglion cells, which leads to varying degree of visual function damages, even blindness. As the standard treatment, methylprednisolone pulse therapy can only promote the recovery of visual acuity but not prevent retinal ganglion cell degeneration. It cannot help improve the ultimate visual outcome. Both inflammatory response and endogenous oxidative stress play crucial roles in the progression of optic neuritis. The combination of immunomodulatory and antioxidant is expected to improve the prognosis of the disease by preventing the apoptosis of retinal ganglion cells. Triterpenoids (oleanolic acid derived) were reported to have the dual capacity of simultaneously repressing production of pro-inflammatory mediators and exerting neuroprotective effects through induction of anti-oxidant genes in experimental optic neuritis. Gypenosides with an aglycone mainly of dammarane-type tetracyclic triterpenoids, also has the dual capacity of immune regulation and antioxidation. Both gypenosides and oleanolic acid were reported to have similar roles in hepatoprotection. Beside, gypenosides were reported to have the capacity of modulating the activation of immune cells and the expression of cytokines. In addition, gypenosides showed neuroprotective effect against oxidative injury in dopaminergic neurons and mouse model of Parkinson's disease. Accordingly, we propose that gypenosides have potential neuroprotective and immunomodulatory effects on optic neuritis through antioxidation and immune regulation. The application of gypenosides might prevent the apoptosis of retinal ganglion cells and improve the ultimate visual outcome in patients with optic neuritis.