Du Huo Ji Sheng Tang inhibits Notch1 signaling and subsequent NLRP3 activation to alleviate cartilage degradation in KOA mice.

BACKGROUND: Knee osteoarthritis (KOA) has a complex pathological mechanism and is difficult to cure. The traditional medicine Du Huo Ji Sheng Tang (DHJST) has been used for the treatment of KOA for more than one thousand years, but its mechanism for treating KOA has not been revealed. In our previous study, we confirmed that DHJST inhibited the activation of NLRP3 signaling in rats and humans. In the current study, we aimed to determine how DHJST inhibits NLRP3 to alleviate knee cartilage damage. METHODS: Mice were injected with NLRP3 shRNA or Notch1-overexpressing adenovirus into the tail vein to construct systemic NLRP3 low-expressing or Notch1 high-expressing mice. Mice were injected with papain into the knee joint to replicate the KOA model. DHJST was used to treat KOA model mice with different backgrounds. The thickness of the right paw was measured to evaluate toe swelling. The pathohistological changes and the levels of IL-1ß, MMP2, NLRP3, Notch1, collagen 2, collagen 4, HES1, HEY1, and Caspase3 were detected by HE staining, ELISA, immunohistochemical staining, western blotting, or real-time qPCR. RESULTS: DHJST reduced tissue swelling and serum and knee cartilage IL-1ß levels, inhibited cartilage MMP2 expression, increased collagen 2 and collagen 4 levels, decreased Notch1 and NLRP3 positive expression rates in cartilage, and decreased HES1 and HEY1 mRNA levels in KOA model mice. In addition, NLRP3 interference decreased cartilage MMP2 expression and increased collagen 2 and collagen 4 levels without affecting the expression levels of notch1, HES1 and HEY1 mRNA levels in the synovium of KOA mice. In KOA mice with NLRP interference, DHJST further reduced tissue swelling and knee cartilage damage in mice. Finally, Notch1-overexpressing mice not only showed more severe tissue swelling and knee cartilage degradation but also abolished the therapeutic effect of DHJST on KOA mice. Importantly, the inhibitory effects of DHJST on the mRNA expression of NLRP3, Caspase3 and IL-1ß in the knee joint of KOA mice were completely limited after Notch1 overexpression. CONCLUSION: DHJST significantly reduced inflammation and cartilage degradation in KOA mice by inhibiting Ntoch1 signaling and its subsequent NLRP3 activation in the knee joint.

[Clinical anatomical study on the treatment of tarsal tunnel syndrome with four-point vertical acupotomy].

OBJECTIVE: To explore safety and accuracy of four-point acupotomy for the treatment of tarsal tunnel syndrome regarding release of ankle tunnel flexor retinaculum to provide an anatomical basis of clinical treatment. METHODS: Twenty-nine adult specimens (15 males and 14 females) fixed with 10% formalin, aged from 47 to 98 years old with an average age of (81.10±11.14) years old, 29 on the right side and 29 on the left side, which were selected for the study from September 2020 to October 2020. Simulate the operation of loosening flexor retinaculumt with a needle knife on the human specimen, and place the specimen on the frog position of lower limbs with medial malleolus upward to determine the center of medial malleolus. Choose 4 different positions near the flexor retinaculum to insert the needle so that the needle body was perpendicular to skin and cutting edge direction was perpendicular to the running direction of the flexor retinaculum. The needle knife penetrates the skin and explores slowly. When the flexor retinaculum was reached, the needle tip may touch the tough tissue. At this time, the cutting is loosened for 4 times. After acupotomy release operation was completed, make a lateral incision on the skin surface along acupotomy direction, open the area of the exposed flexor retinaculum, dissecting layer by layer, observe and record the needle knife and its surrounding anatomical structure. The length of acupotomy cutting marks of flexor retinaculum was measured by electronic vernier caliper. The safety and accuracy of acupotomy loosening of ankle canal flexor retinaculum were evaluated by observing the number and degree of ankle canal contents such as tendons and nerves injured by needle knife. The safety is to count the number of cases of acupotomy injury to the contents of the ankle canal, and to calculate the injury rate, that is, the number of injury cases/total cases × 100%. The effective release was defined as the release length L ≥ W/2(W is the width of the flexor retinaculum, defined as 20 mm). RESULTS: For safety, there were no acupotomy injuries to nerves or blood vessels in 58 cases, 26 cases injuried to posterior tibial tendon which 17 of these tendon injury cases, the tendon was penetrated and severely injured, and flexor digitorum longus tendon was injured in 12 cases. Among these cases, tendon was penetrated and severely injured in 4 cases, and total injury rate was 32.14%. No nerve and vessel injury on c3 and c4 point. For accuracy, 58 specimens were successfully released. The length Lc of releasing trace for acupotomy was (10.40±1.36) cm, and length range 6.38 to 12.88 cm. Among all cases, the length of releasing trace was ≥10 mm in 37 cases. The overall success rate of release was 100.00%. Layered structure of ankle tube flexor retinaculumt:fiber diaphragm from flexor retinaculum divides contents of ankle tube into different chambers inward, and fiber diaphragm meets here to synthesize a complete flexor retinaculum at the midpoint of the line between the medial malleolus tip and calcaneal tubercle(above the neurovascular course). CONCLUSION: Four-point needle-knife method of releasing flexor retinaculum for the treatment of tarsal tunnel syndrome is performed at the attachment of the two ends of flexor retinaculum;the tendon, but not the nerves and blood vessels, is easily damaged. It is safe to insert needle on the side of calcaneus. The extent of release is relatively complete, but due to the "layered" structure of the flexor retinaculum, classic surgical technique could only release one layer of flexor retinaculum when a needle is inserted at the edge of the bone and cannot achieve complete release of the full thickness of the flexor. Therefore, it remains to be determined whether the desired effect can be achieved clinically.

Spectrum-Effect Relationships Between High-Performance Liquid Chromatography Fingerprints and Hepatoprotective Activities of Cuscutae Semen.

BACKGROUND: Cuscutae Semen (CS) is a commonly used hepatoprotective traditional Chinese medicine, but the chemical components responsible for its hepatoprotective activity are unclear. OBJECTIVE: The purpose of this study was to evaluate the spectrum-effect relationships between HPLC fingerprints and hepatoprotective effects of CS, and to identify its bioactive components. METHODS: Phytochemical isolation of CS extracts was first carried out and 14 potential bioactive compounds were obtained. Chemical fingerprinting was performed on 27 batches of CS from different sources by HPLC, and further analyzed by similarity analysis (SA) and hierarchical clustering analysis (HCA). Pharmacodynamic testing was performed in a CCl4-induced, acute liver injury cell model to assess the hepatoprotective activity of CS by measuring the cell viability and levels of alanine transaminase (ALT) and aspartate aminotransferase (AST). Bivariate correlations analysis (BCA) and orthogonal projections to latent structures (OPLS) were used to analyze the spectrum-effect relationships of CS. RESULTS: The results showed that the chemical fingerprints of CS were closely correlated with its hepatoprotective activity. Peaks 1, 10, 18, 19, 21, 22, and 24 might be potential hepatoprotective compounds in CS, and the validation experiments of isolated compounds indicated that chlorogenic acid (P10), hyperoside (P21), isoquercitrin (P22), and astragalin (P24) were the main hepatoprotective components. CONCLUSION: By combining chemical fingerprints with hepatoprotective evaluation, the present study provides important guidance for QC and clinical use of CS. HIGHLIGHTS: (1) Ten potential bioactive compounds were isolated from CS; (2) The spectrum-effect relationship of CS was molded by HPLC and analysed by OPLS and BCA. (3) Four compounds including chlorogenic acid were the main hepatoprotective components.

[6-Gingerol ameliorates adipose tissue insulin resistance in aging rats].

This study investigated the effects and mechanisms of 6-gingerol on adipose tissue insulin resistance in naturally aging rats with glycolipid metabolism disorders. Twenty-seven aging male SD rats were randomly divided into a model group(aged, n=9) and two groups treated with 6-gingerol at 0.05 mg·kg~(-1)(G-L, n=9) and 0.2 mg·kg~(-1)(G-H, n=9). Six young rats were randomly assigned to a normal control group(NC). Rats were treated for seven weeks by gavage. Non-esterified fatty acid(NEFA) and insulin content was determined by enzyme-linked immunosorbent assay(ELISA), and adipose tissue insulin resistance index(Adipo-IR) was calculated. HE staining was used to observe the size of adipocytes in epididymal white adipose tissue(eWAT). The gene and protein expression levels of adiponectin receptor 1(AdipoR1), AMP-activated protein kinase α(AMPKα), phosphorylated AMPK(p-AMPKα~(Thr172)), peroxisome proliferator-activated receptor-γ coactivator-1α(PGC-1α), phosphatidylinositol 3-kinase(PI3 K), protein kinase B(Akt), phosphorylated Akt(p-Akt~(Ser473)), tumor necrosis factor-α(TNF-α), c-Jun N-terminal kinase 1/2(JNK1/2), phosphorylated JNK1/2(p-JNK~(Thr183/Tyr185)), interleukin-1ß(IL-1ß), and interleukin-6(IL-6) in adiponectin(APN), insulin, and inflammatory factor signaling pathways were detected by Western blot and real-time RCR, respectively. The results showed that 6-gingerol at a high dose could significantly decrease the fasting plasma content of NEFA and insulin and reduce Adipo-IR. Additionally, 6-gingerol at a high dose significantly increased the protein and mRNA expression of APN, AdipoR1, PGC-1α, and PI3 K in eWAT, elevated the relative expression of p-AMPK~(Thr172) and p-Akt~(Ser 473), reduced the protein and mRNA expression of TNF-α, IL-1, and IL-6 in eWAT, and decreased the relative expression of p-JNK1 and p-JNK2. This study reveals that 6-gingerol can improve insulin sensitivity of adipose tissues in aging rats with glycolipid metabolism disorders, and this effect is presumedly achieved by enhancing the PI3 K/Akt signaling pathway, inhibiting adipose tissue inflammation, increasing APN synthesis, enhancing AdipoR1 expression, and activating its downstream AMPK/PGC-1α signaling pathway.

Dibenzocyclooctadiene lignans from the stems of Schisandra sphaerandra.

Chemical investigation into the stems of the medicinal plant Schisandra sphaerandra led to the isolation and identification of a new dibenzocyclooctadiene lignan sphaerandrin A (1) and 11 known ones gomisin B (2), schirubrisin B (3), kadsuphilin B (4), schizandrin (5), benzoylgomisin Q (6), angeloylgomisin Q (7), gomisin G (8), schisanwilsonin O (9), isogomisin O (10), schisantherin D (11), and wuweizisu C (12). The structure of the new compound was elucidated by comprehensive spectroscopic methods including 1 D/2D NMR, HRESIMS, and CD spectrometry. To the best of our knowledge, compounds 2 - 11 were obtained from this species for the first time. All the compounds were evaluated for the cytotoxic activity against the triple-negative breast cancer cell lines MDA-MB-231 and HCC-1937.

Enhancing the Physiochemical Properties of Puerarin via L-Proline Co-Crystallization: Synthesis, Characterization, and Dissolution Studies of Two Phases of Pharmaceutical Co-Crystals.

Puerarin (PUE) is a Chinese traditional medicine known to enhance glucose uptake into the insulin cells to downregulate the blood glucose levels in the treatment of type II diabetes. Nevertheless, the bioavailability of pristine PUE is limited due to its poor solubility and low intestinal permeability. In this work, we demonstrate that the solubility of PUE can be significantly enhanced via its co-crystallization with L-Proline (PRO). Two crystalline phases, namely, the solvate-free form [PUE][PRO] (I) and the solvated form [PUE]2[PRO]∙EtOH∙(H2O)2 (II) are isolated. These two phases are characterized by single-crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), Fourier-transformed infrared (FT-IR) spectra, nuclear magnetic resonance (NMR), and thermogravimetric analysis in association with differential scanning calorimetry (TGA-DSC). The solubility and dissolution rate of both I and II in water, gastrointestinal tract at pH 1.2, and phosphate buffer at pH 6.8 indicates a nearly doubled increase as compared to the pristine PUE. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay of pristine PUE, I and II against murine colon cancer cell lines CT-26 and human kidney cell lines HEK-293 indicated that neither compound exhibits obvious cytotoxicity after 24 h. This work showcases that the readily available and biocompatible PRO can be a promising adjuvant to enhance the physicochemical properties of PUE toward orally administered drug formulation with improved pharmacokinetics.

Transurethral resection of the prostate stricture management.

For more than nine decades, transurethral resection of the prostate remains the gold standard for the surgical treatment of lower urinary tract symptoms due to benign prostatic obstruction. The occurrence of urethral strictures after transurethral resection of the prostate is one of the major late complications and has been reported as the leading cause of iatrogenic urethral strictures in patients older than 45 years who underwent urethroplasty. Although several postulations have been proposed to explain the urethral stricture after transurethral resection of the prostate, the exact etiology of urethral stricture after TURP is still controversial. Suggested etiological factors of urethral stricture formation after transurethral resection of the prostate include infection, mechanical trauma, prolonged indwelling catheter time, use of local anesthesia, and electrical injury by a stray current. One single treatment option is not appropriate for all stricture types. The management of urethral stricture following transurethral resection of the prostate includes minimally invasive endoscopic methods, including urethral dilation and direct visual incision, or open surgical procedures with varying urethroplasty techniques. Although scientific studies focusing on urethral strictures after transurethral resection of the prostate are relatively limited and sparse, we can apply the principles of urethral stricture management before making decisions on individual stricture treatment.

Extracorporeal Shockwave Therapy for Chronic Knee Pain: A Multicenter, Randomized Controlled Trial.

CONTEXT: Osteoarthritis is the leading cause of chronic knee pain (CKP) in older adults. Medical practitioners often manage CKP using both pharmacological and nonpharmacological therapies. However, no studies have specifically focused on extracorporeal shockwave therapy (ESWT) for treatment of CKP. OBJECTIVE: The research team intended to explore the effectiveness and safety of ESWT for treatment of CKP. DESIGN: The study was a multicenter, randomized controlled trial. SETTING: The study took place at the Affiliated Hongqi Hospital of Mudanjiang Medical University (Mudanjiang, China) and at the People's Hospital of Yan'an (Yan'an, China). PARTICIPANTS: Participants were 72 patients with CKP at the 2 hospitals. INTERVENTION: Participants were randomly and equally divided into the intervention group, the ESWT group, and a control group. The intervention group received ESWT, whereas those in the control group received a placebo treatment. Participants in both groups were treated 3 times weekly for a total of 10 wk. OUTCOME MEASURES: The primary outcome was pain intensity measured using an 11-point numeric rating scale (NRS). The secondary outcomes were measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and by tracking adverse events. All outcomes were evaluated at baseline and at the end of 5 wk and 10 wk of treatment (ie, postintervention). RESULTS: At both measured points, the ESWT exhibited greater benefits for patients with CKP, as measured by the scores for pain intensity on the NRS (P < .01) and the WOMAC subscale for pain (P < .01), compared with the placebo treatment. In addition, the ESWT group showed significantly less stiffness and greater improvements in function compared with the control group at the end of week 5 (P < .01) and of week 10 (P < .01). Furthermore, the study found no adverse events for either group. CONCLUSION: ESWT demonstrated an effective and safe profile for patients with CKP. Further studies with larger sample sizes are needed.

[Effect of Qufu Shengji ointment(QFSJO) on promoting the healing of infectious wounds].

OBJECTIVE: To explore the clinical effect of Qufu Shengji ointment(QFSJO) in promoting the wound healing after trauma. METHODS: From January 2014 to June 2018, 60 patients with soft tissue injury, skin defect and wound infection caused by violent trauma were admitted, including 32 males and 28 females, aged from 18 to 65 years, with an average age of 41.3 years. Among them, 30 patients were treated with QFSJO (QFSJO group) and 30 patients were treated with normal saline iodophor (control group). The reduction rate of wound area, the days of decayed flesh, the time of new epithelium and the recovery rate of 28 days after dressing change were compared between the two groups. RESULTS: In the QFSJO group, after using large dose of QFSJO, the pus of the wound increased, the granulation grew, and the new epithelium appeared on the edge of the wound, showing a rapid healing phenomenon. The wound healing rate of QFSJO group was higher than that of the control group at all time points, and the time of decaying flesh and new epithelium appeared in QFSJO group was earlier than that of the control group. The recovery rate of QFSJO group was significantly higher than that of the control group(P<0.05). All the patients were followed up, and the duration ranged form 6 to 12 months, with an average of 9.4 months. The exposed areas of bone and teadon were covered well. The vital signs of the two groups were stable and no adverse reactions occurred. CONCLUSIONS: QFSJO can promote the growth of granulation tissue, promote the production of new skin, and accelerate the healing of infectious wound after trauma.

[Effect of grain-moxibustion on neutrophil to lymphocyte ratio and quality of life in patients with advanced gastric cancer].

OBJECTIVE: To observe the effect of grain-moxibustion at Zusanli (ST 36) and Weishu (BL 21) on neutrophil to lymphocyte ratio (NLR) and quality of life (QOL) in patients with advanced gastric cancer. METHODS: Sixty patients with advanced gastric cancer were randomly divided into an observation group and a control group, 30 cases in each one. In the control group, conventional chemotherapy regimen combined with symptomatic treatment，such as antiemetic, acid-suppressive, liver-protecting drugs. On the basis of the treatment in the control group, grain-moxibustion was applied at Zusanli (ST 36) and Weishu (BL 21) in the observation group, 9 cones for each acupoint, once a day for a total of 90 days. The levels of NLR were observed before and after treatment, and the clinical efficacy and quality of life were evaluated in the two groups. RESULTS: After treatment, the value of NLR in the observation group was significantly lower than before treatment (P<0.05), there was no significant difference before and after treatment in the control group (P>0.05), and the descend range of observation group was larger than the control group (P<0.05). The effective rates (RR) were 33.3% (10/30) in the observation group and 36.7% (11/30) in the control group, there was no significant difference between the two groups (P>0.05). After treatment, the QOL in the observation group was improved in diarrhea, loss of appetite, fatigue, nausea and vomiting, general health states (P<0.05), there was no significant difference in the control group before and after treatment in varions scores (P>0.05), and the observation group was superior to the control group in fatigue, sleep disorder, loss of appetite, diarrhea and general health states after treatment (P<0.05). CONCLUSION: Grain-moxibustion at Zusanli (ST 36) and Weishu (BL 21) can decrease NLR and improve QOL of patients with advanced gastric cancer.

Fast-track multidisciplinary treatment versus conventional treatment for colorectal cancer: a multicenter, open-label randomized controlled study.

BACKGROUND: Laparoscopic surgery, fast-track perioperative treatment and XELOX chemotherapy are effective strategies for shortening the duration of hospital stay for cancer patients. This trial aimed to clarify the safety and efficacy of the fast-track multidisciplinary treatment (FTMDT) model compared to conventional surgery combined with chemotherapy in Chinese colorectal cancer patients. METHODS: This trial was a prospective randomized controlled study with a 2 × 2 balanced factorial design and was conducted at six hospitals. Patients in group 1 (FTMDT) received fast-track perioperative treatment and XELOX adjuvant chemotherapy. Patients in group 2 (conventional treatment) received conventional perioperative treatment and mFOLFOX6 adjuvant chemotherapy. Subgroups 1a and 2a had laparoscopic surgery and subgroups 1b and 2b had open surgery. The primary endpoint was total length of hospital stay during treatment. RESULTS: A total of 374 patients were randomly assigned to the four subgroups, and 342 patients were finally analyzed, including 87 patients in subgroup 1a, 85 in subgroup 1b, 86 in subgroup 2a, and 84 in subgroup 2b. The total hospital stay of group 1 was shorter than that of group 2 [13 days, (IQR, 11-17 days) vs. 23.5 days (IQR, 15-42 days), P = 0.0001]. Compared to group 2, group 1 had lower surgical costs, fewer in-hospital complications and faster recovery (all P < 0.05). Subgroup 1a showed faster surgical recovery than that of subgroup 1b (all P < 0.05). There was no difference in 5-year overall survival between groups 1 and 2 [87.1% (95% CI, 80.7-91.5%) vs. 87.1% (95% CI, 80.8-91.4%), P = 0.7420]. CONCLUSIONS: The FTMDT model, which integrates laparoscopic surgery, fast-track treatment, and XELOX chemotherapy, was the superior model for enhancing the recovery of Chinese patients with colorectal cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01080547 , registered on March 4, 2010.

Effect of Tong Xie Yao Fang on endogenous metabolites in urine of irritable bowel syndrome model rats.

BACKGROUND: Tong Xie Yao Fang is a representative traditional Chinese prescription for the treatment of liver and spleen deficiency, abdominal pain and diarrhea. It has a unique function in the treatment of gastrointestinal dysfunction including irritable bowel syndrome (IBS), is a common functional bowel disease. Its main symptoms are recurrent abdominal pain, diarrhea, constipation or alternations between diarrhea and constipation. There are obvious differences in metabolites between TCM syndromes. By comparing the body fluid metabolism maps of model animals, metabolomics can discover disease biomarkers, analyze the differences in metabolic pathways and understand the pathological process and the metabolic pathways of substances in the body. Thus, the evaluation of animal models tends to be comprehensive and objective. This may provide further understanding between the interaction between Tong Xie Yao Fang and the IBS model. AIM: To evaluate the effect of Tong Xie Yao Fang on IBS rats by using metabolomics method. METHODS: Wistar rats were used to establish IBS models, and then randomly divided into four groups: A model control group and three Tong Xie Yao Fang treatment groups (high, medium and low doses). A normal, non-IBS group was established. The rats were treated for 2 wk. On days 0 and 14 of the experimental model, urine was collected for 12 h and was analyzed by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry. Nine potential biomarkers were identified, and six major metabolic pathways were found to be related to IBS. RESULTS: In the study of metabonomics, nine potential biomarkers including L-serine, 4-methylgallic acid, L-threonine, succinylacetone, prolyl-hydroxyproline, valyl-serine, acetyl citrate, marmesin rutinoside and 5-hydroxy-L-tryptophan were identified in urine, which were assigned to amino acids, organic acids, succinyl and glycosides. Furthermore, the metabolic pathway of L-serine, L-threonine and 5-hydroxy-L-tryptophan was found in the Kyoto Encyclopedia of Genes and Genomes, which mainly involved the metabolism of cysteine and methionine, vitamin B6 metabolism, serotonin synapse, tryptophan metabolism, sphingolipid metabolism, digestion, absorption of protein and amino acid metabolism. These pathways are related to intestinal dysfunction, inflammatory syndrome, nervous system dysfunction and other diseases. CONCLUSION: Tong Xie Yao Fang has pharmacological effects on IBS, and its mechanism may be related to the metabolism of the nine potential biomarkers identified above in urine.

Therapeutic effectiveness of neuromuscular electrical stimulation for treating patients with chronic low back pain.

This retrospective study investigated the effectiveness and safety of neuromuscular electrical stimulation (NMES) for patients with chronic low back pain (CLBP).A total of 72 patients with CLBP were included in this retrospective study. All patients received usual care, and were assigned to a NMES group (n = 36) and a control group (n = 36). In addition, patients in the NMES group also received NMES for a total of 4 weeks. The primary outcome was pain intensity, measured by numerical rating scale (NRS). The secondary outcome was disability, assessed by the Roland-Morris Disability Questionnaire (RMDQ), and the Quebec Back Pain Disability Scale (QBPDS). The outcomes were evaluated before and after 4-week treatment.After 4-week treatment, the patients in the NMES group did not show better effectiveness in pain intensity relief, as measured by NRS (P = .11); and disability improvement, as evaluated by the RMDQ (P = .14), and QBPDS (P = .33), when compared with the patients in the control group. Additionally, no adverse events related to the NNES were recorded.The results of this study did not show promising effectiveness of NMES for patients with CLBP after 4-week treatment.

Disrupted amplitude of low-frequency fluctuations and causal connectivity in Parkinson's disease with apathy.

Apathy is a common non-motor symptom in Parkinson's disease (PD). We aimed to explore its associated neural substrates changes via amplitude of low-frequency fluctuations (ALFF) and granger causality analysis (GCA). Resting-state functional magnetic resonance imaging (rs-fMRI) scans were performed in 20 PD patients with apathy (PD-A), 22 PD patients without apathy (PD-NA) and 19 healthy volunteers. GCA, a new method exploring direction from one brain region to another, was based on brain regions showing alterations of neural activity as seeds, which were examined utilizing ALFF approach. The relationships between ALFF or GCA and apathetic symptoms were also assessed. Relative to PD-NA group, PD-A group indicated decreased ALFF in left orbital middle frontal gyrus and bilateral superior frontal gyrus (SFG). Only ALFF values in right SFG were negatively correlated with Apathy Scale (AS) scores. Then GCA with the seed of right SFG showed a positive feedback from right thalamus to ipsilateral SFG, which was positively correlated with AS scores. In conclusion, dysfunction in SFG and a positive feedback from thalamus to ipsilateral SFG contributed to presence of PD-related apathy, providing a new perspective for future studies on apathy in PD.

Jisuikang, a Chinese herbal formula, increases neurotrophic factor expression and promotes the recovery of neurological function after spinal cord injury.

The Chinese medicine compound, Jisuikang, can promote recovery of neurological function by inhibiting lipid peroxidation, scavenging oxygen free radicals, and effectively improving the local microenvironment after spinal cord injury. However, the mechanism remains unclear. Thus, we established a rat model of acute spinal cord injury using a modified version of Allen's method. Jisuikang (50, 25, and 12.5 g/kg/d) and prednisolone were administered 30 minutes after anesthesia. Basso, Beattie, and Bresnahan locomotor scale scores and the oblique board test showed improved motor function recovery in the prednisone group and moderate-dose Jisuikang group compared with the other groups at 3-7 days post-injury. The rats in the moderate-dose Jisuikang group recovered best at 14 days post-injury. Hematoxylin-eosin staining and transmission electron microscopy showed that the survival rate of neurons in treatment groups increased after 3-7 days of administration. Further, the structure of neurons and glial cells was more distinct, especially in prednisolone and moderate-dose Jisuikang groups. Western blot assay and immunohistochemistry showed that expression of brain-derived neurotrophic factor (BDNF) in injured segments was maintained at a high level after 7-14 days of treatment. In contrast, expression of nerve growth factor (NGF) was down-regulated at 7 days after spinal cord injury. Real-time fluorescence quantitative polymerase chain reaction showed that expression of BDNF and NGF mRNA was induced in injured segments by prednisolone and Jisuikang. At 3-7 days after injury, the effect of prednisolone was greater, while 14 days after injury, the effect of moderate-dose Jisuikang was greater. These results confirm that Jisuikang can upregulate BDNF and NGF expression for a prolonged period after spinal cord injury and promote repair of acute spinal cord injury, with its effect being similar to prednisolone.

[Effect of Tongxie Yaofang on endogenous metabolites in serum of IBS model rats].

To evaluate the effect of Tongxie Yaofang on cardiac endogenous metabolism in irritable bowel syndrome(IBS) rats by using metabolomics method, find its potential biomarkers, analyze the metabolic pathways, and explore the pharmacological effects, mechanisms of action and syndrome essence of syndrome model. Forty Wistar rats were used to establish IBS models, and then randomly divided into four groups： model control group and Tongxie Yaofang treatment groups (high, medium, low dose). Another 10 rats were used as normal group. The rats in Tongxie Yaofang-treated(low, medium and high dose) groups were orally administrated with Tongxie Yaofang extracts once a day for 2 weeks, respondingly with the doses of 0.203,0.406,0.812 g•mL⁻¹. The rats in normal group and model control group were given with equal volume of saline once a day for 2 weeks. On the 0 and 15th days, serum was collected and each sample extract was analyzed by UPLC-Q-TOF-MS. Eight potential biomarkers were identified and 8 major metabolic pathways were found to be related with IBS diseases neurotransmitter metabolism, inflammatory immunity, brain function and energy metabolism, etc. Tongxie Yaofang had certain pharmacological effects on IBS, and its mechanism may be related to serotonergic synapse, tryptophan metabolism, cysteine and methionine metabolism, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism and so on, which might be the biological basis of IBS liver-spleen deficiency syndrome.

Chemical Components, Biological Activities, and Toxicological Evaluation of the Fruit (Aril) of Two Precious Plant Species from Genus Taxus.

The fruit (aril) of the endangered genus Taxus plants is an abandoned herbal resource. Traditionally, people enthusiastically focus on its bark, its renewable, tremendous arils fall into the soil with seeds after they are mature. The present research investigated the fruit of two species from the genus Taxus, Taxus chinensis var. mairei, and Taxus media, with regards to their antioxidant and antihyperglycaemic activities, safety, and bioactive constituents. Results showed that T. chinensis var. mairei and T. media both had certain biological activities with T. chinensis var. mairei better in antioxidant activity and T. media better in antihyperglycaemic activity. Correlation analysis revealed that the differences in bioactivities depended on content of their mainly chemical components. The mice acute oral toxicity test indicated that the methanol extracts of the two biotypes of Taxus were safe. And nineteen compounds were tentatively assigned from the two varieties, via tandem mass spectrometry using a LC-ESI-Q-TOF-MS instrument, which included phenols, flavonoids, and terpenes. These results indicate a possible application of Taxus fruit extracts in various fields like in food industry, however, this still needs further investigations.

Comparative Evaluation of the Chemical Composition, Antioxidant and Antimicrobial Activities of the Volatile Oils of Hawk Tea from Six Botanical Origins.

In this study, volatile oils of six Hawk tea varieties were studied for their chemical composition, antioxidant and antimicrobial activities to screen the most suitable botanical origins of Hawk tea. A total of 72 components were separated and identified from the six oils. The major constituents of the volatile oils were: α-pinene, camphene, limonene, 1,8-cineole, linalool, cis-nerolidol, and germacrene B. Moreover, the volatile oils were evaluated for antioxidant potential and antimicrobial activities. The results showed that all volatile oils exhibited acceptable antioxidant and antimicrobial activities, which suggested that these volatile oils may serve as natural alternatives to synthetic antioxidants and preservatives to be applied in food and pharmaceutical industries. Principal component analysis results denoted that some major compounds may be closely related to the antioxidant and antimicrobial activities. It also showed that the volatile oils from Litsea coreana var. lanuginosa and Litsea pungens Hemsl. were characterized by positive values of first two principal components, indicating higher active chemical compounds and antioxidant and antimicrobial activities compared with other species. Thus, they were temporarily considered as good sources of Hawk tea.

Comparative efficacy of tamsulosin versus nifedipine for distal ureteral calculi: a meta-analysis.

OBJECTIVE: The aim of this study was to systematically compare the therapeutic effect and safety of tamsulosin with nifedipine in medical expulsive therapy for distal ureteral calculi. METHODS: Databases, including PubMed, EMBASE, the Cochrane Library, and Clinical Trial Register Centers, were comprehensively searched. Relevant randomized controlled trials (RCTs) were selected, and quality assessment was performed according to the Cochrane Handbook. RevMan software was used to analyze the outcome measures, which consisted of expulsion rate, expulsion time, and complications. RESULTS: Twelve RCTs consisting of 4,961 patients were included (tamsulosin group, 2,489 cases; nifedipine group, 2,472 cases). Compared with nifedipine, tamsulosin significantly increased the expulsion rate (risk ratio =1.29, 95% CI [1.25, 1.33], P<0.0001) and reduced the expulsion time (standard mean difference =-0.39, 95% CI [-0.72, -0.05], P=0.02). Regarding safety, tamsulosin was associated with fewer complications than nifedipine (risk ratio =0.45, 95% CI [0.28, 0.72], P=0.0008), and further subgroup analysis showed that tamsulosin was associated with a lower risk of both mild and moderate-to-severe complications. CONCLUSION: On the bias of current evidence, tamsulosin showed an overall superiority to nifedipine for distal ureteral calculi <10 mm in aspects of expulsion rate, expulsion time, and safety. Tamsulosin was supposed to be the first drug to be recommended to patients willing to receive medical expulsive therapy.

Venenum Bufonis induces rat neuroinflammation by activiating NF-κB pathway and attenuation of BDNF.

ETHNOPHARMACOLOGICAL RELEVANCE: Venenum Bufonis (VB), also called toad venom, has been widely used in clinic as a cardiotonic, anohyne and antineoplastic agents both in China and other Asian countries. However, its neurotoxicity and cardiotoxicity limit its wide clinical application. Compared with extensive attention attracted with cardiotoxicity, the toxic effect of VB on Central Nervous System (CNS) is much less studied. AIM OF THE RESEARCH: This study was performed to examine the neurotoxicity caused by VB on Sprague Dawley (SD) rats, then to clarify the mechanism in vivo by investigating its action on the neuroinflammation which possibly attributed to the activation of nuclear factor κB (NF-κB) pathway and the attenuation of brain-derived neurotrophic factor (BDNF). MATERIALS AND METHODS: Rats administrated with 0.5% carboxymethyl cellulose sodium salt (CMC-Na) aqueous solution and VB (100mg/kg, 200mg/kg and 400mg/kg) were sacrificed at 2h, 4h, 6h, 8h, 24h and 48h. The brain level of neurotransmitters and their corresponding receptors, pro-inflammatory cytokines, BDNF/TrkB and NF-κB pathway-related proteins were examined, respectively. RESULTS: VB administration induced severe neurologic damage and neuroinflammation, as indicated by the disordered 5-hydroxytryptamine (5-HT), dopamine (DA) and their corresponding receptors, together with the over production of inflammatory cytokines including interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α). VB also notably promoted the expression of p-NF-κBp65, p-IκBα, p-IKKα and p-IKKß and down-regulated the expression of BDNF and TrkB. CONCLUSION: This study demonstrates that VB triggers neurotoxicity which probably is induced by neuroinflammation via activating of NF-κB pathway and attenuating the expression of BDNF.