The potent analgesia of intrathecal 2R, 6R-HNK via TRPA1 inhibition in LF-PENS-induced chronic primary pain model.

BACKGROUND: Chronic primary pain (CPP) is an intractable pain of unknown cause with significant emotional distress and/or dysfunction that is a leading factor of disability globally. The lack of a suitable animal model that mimic CPP in humans has frustrated efforts to curb disease progression. 2R, 6R-hydroxynorketamine (2R, 6R-HNK) is the major antidepressant metabolite of ketamine and also exerts antinociceptive action. However, the analgesic mechanism and whether it is effective for CPP are still unknown. METHODS: Based on nociplastic pain is evoked by long-term potentiation (LTP)-inducible high- or low-frequency electrical stimulation (HFS/LFS), we wanted to develop a novel CPP mouse model with mood and cognitive comorbidities by noninvasive low-frequency percutaneous electrical nerve stimulation (LF-PENS). Single/repeated 2R, 6R-HNK or other drug was intraperitoneally (i.p.) or intrathecally (i.t.) injected into naïve or CPP mice to investigate their analgesic effect in CPP model. A variety of behavioral tests were used to detect the changes in pain, mood and memory. Immunofluorescent staining, western blot, reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and calcium imaging of in cultured dorsal root ganglia (DRG) neurons by Fluo-8-AM were used to elucidate the role and mechanisms of 2R, 6R-HNK in vivo or in vitro. RESULTS: Intrathecal 2R, 6R-HNK, rather than intraperitoneal 2R, 6R-HNK or intrathecal S-Ketamine, successfully mitigated HFS-induced pain. Importantly, intrathecal 2R, 6R-HNK displayed effective relief of bilateral pain hypersensitivity and depressive and cognitive comorbidities in a dose-dependent manner in LF-PENS-induced CPP model. Mechanically, 2R, 6R-HNK markedly attenuated neuronal hyperexcitability and the upregulation of calcitonin gene-related peptide (CGRP), transient receptor potential ankyrin 1 (TRPA1) or vanilloid-1 (TRPV1), and vesicular glutamate transporter-2 (VGLUT2) in peripheral nociceptive pathway. In addition, 2R, 6R-HNK suppressed calcium responses and CGRP overexpression in cultured DRG neurons elicited by the agonists of TRPA1 or/and TRPV1. Strikingly, the inhibitory effects of 2R, 6R-HNK on these pain-related molecules and mechanical allodynia were substantially occluded by TRPA1 antagonist menthol. CONCLUSIONS: In the newly designed CPP model, our findings highlighted the potential utility of intrathecal 2R, 6R-HNK for preventing and therapeutic modality of CPP. TRPA1-mediated uprgulation of CGRP and neuronal hyperexcitability in nociceptive pathways may undertake both unique characteristics and solving process of CPP.

[Multi-component content determination of Dracocephalum tanguticum by quantitative analysis of multi-components by single-marker].

This study aims to establish a method for the simultaneous determination of 7 active components in Dracocephalum tanguticum and to evaluate the quality of medicinal materials from different habitats. The method was established with high performance liquid chromatography(HPLC) and the gradient elution was performed with the mobile phase of acetonitrile-methanol-0.2% phosphoric acid solution at a column temperature of 35 ℃, an injection volume of 15 µL, and a flow rate of 0.6 mL·min~(-1). The detection wavelength was set as 215 nm. With rosmarinic acid as the internal reference, the relative correction factors and the content of other 6 components were calculated. The results were compared with those obtained with the external standard method. The results showed that the samples from Huangzhong county, Qinghai province had the best quality, with the highest content of p-hydroxybenzoic acid, cosmosiin, rosmarinic acid, oleanolic acid, and ursolic acid(9.29, 12.14, 6.02, 3.11, 17.67 mg·g~(-1) respectively). The samples from Chaya county, Tibet autonomous region ranked the second, with the highest content of betulin and betulinic acid(15.53, 7.17 mg·g~(-1), respectively). The method is accurate, reliable, and repeatable and suitable for the simultaneous determination of multiple components in D. tanguticum. The content of functional components varied in the samples from different producing areas and can be used as the indicator for the quality evaluation of medicinal materials.

NGS-based IgH gene rearrangement monitoring predicts relapse and guides maintenance therapy in DLBCL: A case report from indolent lymphoma to aggressive lymphoma.

This report describes a case of extranodal marginal zone B-cell lymphoma (ENMZL) of the mucosa-associated lymphoid tissue (MALT) lymphoma that transformed to diffuse large B cell lymphoma (DLBCL) in a 39-year-old female patient with Hashimoto's thyroiditis (HT). The patient presented with MALT lymphoma in the thyroid tissue and DLBCL in the multiple site invasions, including the ovary, breast, and lymph nodes. We assessed the Ig gene rearrangement and mutation profile in lymphoma involved tissues and the collected stem cells. V(D)J sequence of the tumor clonotype detected in thyroid, ovary, and breast was identical, revealing a shared origin of the malignant lymphoma. Noticeably, a small percentage of tumor clonotype (the highest-ranking clonotype in tumor tissues) was detected in the stem cell sample, suggesting the malignant cells was residual in the stem cells, likely conferred disease relapse following ASCT. This patient recieved BTK inhibitor combined with radiotherapy to eradicate the residual tumor cells based on the V(D)J sequence monitoring after ASCT. Now the patient remains in complete remission following 12 months of ASCT.

Neoadjuvant chemotherapy with modified FOLFOXIRI for locally advanced rectal cancer to transform effectively EMVI and MRF from positive to negative: results of a long-term single center phase 2 clinical trial.

PURPOSE: Chemoradiotherapy (CRT) remains the standard treatment for locally advanced rectal cancer (LARC). This phase 2 clinical trial was designed to evaluate the efficacy and safety of neoadjuvant triplet chemotherapy with mFOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, and irinotecan) in LARC. PATIENTS AND METHODS: The patients with LARC (the lower edge more than 5 cm from the anal verge) received up to 5 cycles of mFOLFOXIRI. MRI was performed to assess the baseline and postchemotherapy TN stage. Radical resection was performed within 4-6 weeks from the last dose of chemotherapy if the tumor shrank or remained stable. Adjuvant chemotherapy with mFOLFOX6 or XELOX was recommended. Postoperative radiation was planned for R1 resection, ypT4b, ypN2 and a positive CRM. The primary endpoint was the pathological complete response (pCR) rate. RESULTS: From February 2016 to March 2019, 50 patients were enrolled. Forty-eight (96%) were clinically node-positive, 28 (56.5%) with MRF invasion and 39 (78.4%) were EMVI positive. The median cycle of neoadjuvant mFOLFOXIRI chemotherapy was 5 (range,1-5). A total of 46/50 (92%) patients underwent total mesorectal excision (TME) surgery, all with R0 resection. The pCR rate was 4.3% (2/46). Twenty-three of 46 (50%) patients with cN + achieved a pathological node-negative status. The proportions of pathologically positive CRM and EMVI were 2.2% and 34.7%, respectively. Adjuvant radiotherapy was given to 14/46 (30.4%) patients. The most common Grade 3 or > toxicities included neutrocytopenia (50%), leukopenia (14%) and diarrhea (12%) during the neoadjuvant chemotherapy period. Clinically meaningful postoperative complications included pneumonia (n = 1), pelvic infection (n = 1) and anastomotic fistula (n = 1). With a median follow-up time of 51.2 months, local recurrences and distant metastases were confirmed in 3 (6.5%) and 9 (19.6%) of cases, respectively. The 3-year disease free survival (DFS) and overall survival (OS)rates were 75.8% and 86.8%. CONCLUSION: Neoadjuvant chemotherapy with mFOLFOXIRI yielded a significant down-staging effect and seemed to be effective in eliminating EMVI and transforming the positive MRF to negative in LARC. The survival results are promising. The long-term follow-up showed promising DFS and OS rates accompanied by a favorable safety profile. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03443661, 23/02/2018.

[Lutein inhibits the adhesion, invasiveness and metastasis of human prostate cancer PC-3M cells].

OBJECTIVE: To explore the effects of lutein on the adhesion, invasiveness and metastasis of human prostate cancer PC-3M cells and its action mechanism. METHODS: We divided human prostate cancer PC-3M cells into a control, a low-dose lutein, a medium-dose lutein and a high-dose lutein group, and treated them with 0, 10, 20 and 40 µmol/L lutein, respectively. Then we examined the adhesion of the cells to matrix by cell adhesion assay and the changes in cell pseudopodia by Phalloidin staining, detected the expressions of paxillin, matrix metalloproteinase 2 (MMP-2), MMP-9, recombinant tissue inhibitors of metalloproteinase 1 (TIMP-1), E-cadherin, N-cadherin and vimentin by Western blot, determined the invasiveness and migration of the cells by scratch and Transwell assays, and observed their dynamic movement by high-intension imaging. RESULTS: Compared with the control, the lutein intervention groups showed significant reduction in the number of the cells adhered to matrix, the number of cell pseudopodia, the expressions of paxillin, MMP-2, MMP-9, N-cadherin and vimentin, the rates of migration, invasion and metastasis, and the distances of displacement and movement of the cells. However, the expressions of TIMP-1 and epithelial-mesenchymal transition-related E-cadherin were upregulated significantly. CONCLUSION: Lutein can inhibit cell adhesion, reduce the expressions of MMPs, and suppress cell invasion and migration by inhibiting the process of epithelial-mesenchymal transition.

Perioperative management and operative treatment of malignant tumor of anal canal merging severe abdominal protuberance / 中华胃肠外科杂志

Objective: To report the perioperative management and robot-assisted minimally invasive surgery results of one case with malignant tumor of anal canal combined with severe abdominal distention. Methods: A 66-year-old male suffer from adenocarcinoma of anal canal (T3N0M0) with megacolon, megabladder and scoliosis. The extreme distention of the colon and bladder result in severe abdominal distention. The left diaphragm moved up markedly and the heart was moved to the right side of the thoracic cavity. Moreover, there was also anal stenosis with incomplete intestinal obstruction. Preoperative preparation: fluid diet, intravenous nutrition and repeated enema to void feces and gas in the large intestine 1 week before operation. Foley catheter was placed three days before surgery and irrigated with saline. After relief of abdominal distention, robotic-assisted abdominoperineal resection+ subtotal colectomy+colostomy was performed. Results: Water intake within 6 hours post-operatively; ambulance on Day 1; anal passage of gas on Day 2; semi-fluid diet on Day 3; safely discharged on Day 6. Conclusion: Robotic-assisted minimally invasive surgery is safe and feasible for patients with malignant tumor of anal canal combined with severe abdominal distention after appropriate and effective preoperative preparation to relieve abdominal distention.

Therapeutic effect of proprioception training combined with pelvic floor electrical stimulation biofeedback on postpartum pelvic floor dysfunction. / æœ¬ä½“æ„Ÿè§‰è®­ç»ƒè”åˆç›†åº•ç”µåˆºæ¿€ç”Ÿç‰©åé¦ˆå¯¹äº§åŽç›†åº•åŠŸèƒ½éšœç¢æ€§ç–¾ç— çš„æ²»ç–—æ•ˆæžœ.

OBJECTIVES: Pelvic floor tendons, fascia, and ligaments are rich in proprioceptors. Proprioceptive training can stimulate local proprioceptors to increase neuromuscular responses and promote the recovery of muscle and fascial ligament functions. This study aims to observe the therapeutic effect of proprioception training combined with pelvic floor electrical stimulation biofeedback on postpartum pelvic floor dysfunction (PFD), and to provide evidence for the treatment of postpartum PFD. METHODS: A total of 108 puerpera with postpartum PFD were selected and divided into a control group ( n =50) and an experimental group ( n =58). Puerpera in the control group received pelvic floor electrical stimulation biofeedback treatment. Puerpera in the experimental group received proprioception training combined with pelvic floor electrical stimulation biofeedback treatment. After one course of treatment, the pelvic floor muscle strength, muscle endurance, repetitive contraction ability, rapid contraction ability, percentage of normal vaginal posterior wall elevation, percentage of normal lower abdominal muscle synergistic contraction, percentage of normal reflex contraction during coughing, incidence of stress urinary incontinence (SUI), and staging of pelvic organ prolapse (POP) were compared before and after treatment between the 2 groups. RESULTS: After treatment, all indexes of the 2 groups were better than those before treatment; the pelvic floor muscle strength, muscular endurance, repetitive contraction ability, and rapid contraction ability of the experimental group were better than those of the control group (all P <0.05); the percentage of normal lower abdominal muscle synergistic contraction and percentage of normal reflex contraction during coughing of the experimental group were higher than those of the control group (both P <0.05); the incidence of SUI in the experimental group was lower than that in the control group ( P <0.05); the percentage of POP staging II in the experimental group was significantly lower than that in the control group ( P <0.05). There was no significant difference in the percentage of normal posterior vaginal wall elevation after treatment between the 2 groups ( P >0.05). CONCLUSIONS: Proprioception training combined with pelvic floor electrical stimulation biofeedback could improve the rehabilitation effect of postpartum pelvic floor dysfunction and promote the recovery of pelvic floor function, which possesses important clinical application value.

The efficacy and safety of the Xuesaitong soft capsule in the treatment of patients with ischemic stroke: systematic review and meta-analysis.

BACKGROUND: Ischaemic stroke is a common neurological disease and a leading cause of severe disability and death in developed countries. In most cases, stroke is thought to be a multifactorial disorder or complex trait for which classic patterns of inheritance cannot be shown. Xuesaitong is one of the most commonly used medicines for treating ischemic stroke in China. However, compared to the conventional therapy, the effectiveness and safety of Xuesaitong for ischemic stroke needs to be further systematically reviewed and determined. METHODS: Relevant randomized controlled trials (RCTs) examining the use of the Xuesaitong soft capsule in the treatment of patients with ischemic stroke were identified from databases, including the China National Knowledge Infrastructure, Wanfang, PubMed, Embase, and Web of Science databases. Next, 2 researchers independently extracted information from the included studies, analyzed the data using STATA 15.0 software, and evaluated the quality of the included studies using RevMan 5.3. RESULTS: A total of 17 RCTs (comprising 1,942 patients with ischemic stroke) were included in the meta-analysis. The meta-analysis results showed that the Xuesaitong soft capsule treatment increased patients' total effective rate compared to conventional or other drug treatments, and improved patients' Clinical Severity Score (CSS scores) or Barthel index (BI) score. A further subgroup analysis stratified by different treatment times showed that Xuesaitong soft capsule treatment at 4 and 8 weeks improved CSS scores more than treatment at 2 weeks in patients with ischemic stroke. Additionally, the Xuesaitong soft capsule also significantly improved plasma viscosity, whole-blood viscosity at high and low shear rates, fibrinogen, hematocrit, and the effect on traditional Chinese medicine (TCM) single symptoms or signs in patients with ischemic stroke. DISCUSSION: In summary, compared to conventional or other drug treatments, the Xuesaitong soft capsule treatment was beneficial in improving patients' TCM symptoms (e.g., crooked mouth and tongue, and dizziness) and various indicators. Further, Xuesaitong soft capsule may be a safe and effective drug for the treatment of ischemic stroke. And large-scale randomized clinical trials are needed to further confirm our findings.

Moderate sedation with single-dose remimazolam tosilate in elderly male patients undergoing transurethral resection of the prostate with spinal anesthesia: a prospective, single-arm, single-centre clinical trial.

BACKGROUND: Remimazolam tosilate (RT) is a newly listed benzodiazepine for sedation and anesthesia featuring quick onset of effects, short maintenance and recovery times, which is currently under research. This trial was conducted to determine the median effective dose (ED50) and the 95% effective dose (ED95) of single-dose remimazolam for moderate sedation in elderly patients undergoing transurethral resection of the prostate (TURP) under spinal anesthesia, and to evaluate its efficacy and safety. METHODS: Thirty male patients aged 65-80 years old were recruited for selective TURP. Remimazolam was administered intravenously to pain-free patients (VAS score < 1) within 1 min of successful spinal anesthesia by the same anesthesiologist. We used modified Dixon's up-and-down sequential allocation method to determine the ED50 and ED95 of the agent with an initial dosage of 0.1 mg/kg. Successful sedation was defined as an MOAA/S score ≤ 3 and above 1. A score of > 3 was deemed as failed sedation. Recruitment continued until ten independent pairs (from successful sedation to failed sedation) would give a reliable estimation of the ED50 and ED95 of RT and their 95% confidence intervals. RESULTS: The ED50 of remimazolam was 0.063 (95% C.I. 0.045-0.073) mg/kg. Its ED95 was 0.079 (95% C.I. 0.07-0.137) mg/kg. Remimazolam was safe in its application. CONCLUSIONS: A single-dose of RT proves to be safe for assisted sedation during TURP in elderly male patients under spinal anesthesia with a lower incidence of adverse events. Its ED50 and ED95 were 0.063 mg/kg and 0.079 mg/kg, respectively. TRIAL REGISTRATION: http://www.chictr.org.cn (ChiCTR2100051912).

Using a consensus acupoints regimen to explore the relationship between acupuncture sensation and lumbar spinal postoperative analgesia: A retrospective analysis of prospective clinical cooperation.

OBJECTIVE: This study evaluated the effectiveness of acupuncture treatment on postoperative pain in patients with degenerative lumbar spine disease, and explored the relationship between the postoperative analgesic effect of acupuncture and the sensation of acupuncture experienced by the patients. METHODS: This retrospective study analyzed the medical records of 97 patients who had undergone an operation by the same surgeon due to degenerative lumbar disease. These patients were divided into acupuncture group (n = 32), patient-controlled analgesia (PCA) group (n = 27), and oral analgesia group (n = 38) according to the different postoperative analgesic methods. During their hospitalization, patients completed daily evaluations of their pain using a visual analogue scale (VAS), and injection times of supplemental meperidine were recorded. Also, the Chinese version of the Massachusetts General Hospital Acupuncture Sensation Scale (C-MASS) was used in the acupuncture group. RESULTS: Each of the three treatment groups showed significant reductions in postoperative pain, as shown by reduced VAS scores. The acupuncture group, however, had less rebound pain (P < 0.05) than the other two groups. Both the acupuncture and PCA groups experienced acute analgesic effects that were superior to those in the oral analgesia group. In addition, the higher the C-MASS index on the second day after surgery, the lower the VAS score on the fourth day after surgery. There was also a significant difference in the "dull pain" in the acupuncture sensation. CONCLUSION: The results demonstrated that acupuncture was beneficial for postoperative pain and discomfort after simple surgery for degenerative spinal disease. It is worth noting that there was a disproportionate relevance between the patient's acupuncture sensation and the improvement of pain VAS score.

Postoperative Chemoradiotherapy With Capecitabine and Oxaliplatin vs Capecitabine for Stage II to III Rectal Cancer: A Randomized Clinical Trial.

Importance: Several studies have explored the efficacy and toxic effects of concurrent 5-fluorouracil (5-FU)- or capecitabine-based chemoradiotherapy (CRT) with or without oxaliplatin in the neoadjuvant setting. Addition of oxaliplatin to 5-FU or capecitabine elicited similar outcomes but with significantly increased toxic effects; however, there is a need for randomized clinical trials comparing 2 CRT regimens for patients receiving CRT in the adjuvant setting. Objective: To explore the efficacy and toxic effects of oxaliplatin combined with postoperative concurrent capecitabine and radiotherapy (RT) for pathological stage II and III rectal cancer. Design, Setting, and Participants: This multicenter randomized clinical trial enrolled patients from 7 centers in China between April 1, 2008, and December 30, 2015. Patients with pathologically confirmed stage II and III rectal cancer were randomized (1:1) to receive concurrent CRT with capecitabine or capecitabine plus oxaliplatin. Analysis was conducted from December 31, 2019, to March 15, 2020. Interventions: RT comprised 45 to 50 Gy in 25 fractions of 1.8 to 2.0 Gy over 5 weeks. In the capecitabine with RT group, concurrent chemotherapy included 2 cycles of capecitabine (1600 mg/m2) on days 1 to 14 and 22 to 35. The capecitabine and oxaliplatin with RT group received identical postoperative RT to that in the capecitabine with RT group combined with capecitabine (1300 mg/m2) on days 1 to 14 and 22 to 35 and a 2-hour infusion of oxaliplatin (60 mg/m2) on weeks 1, 2, 4, and 5. Patients in both groups received adjuvant chemotherapy (capecitabine or fluorouracil and oxaliplatin) after CRT. Main Outcomes and Measures: The primary end point was 3-year disease-free survival (DFS). Results: A total of 589 patients (median [IQR] age, 55 [47-52] years; 375 [63.7%] men and 214 [36.3%] women) were enrolled, including 294 patients randomized to the capecitabine with RT group and 295 patients randomized to the capecitabine and oxaliplatin with RT group. Median (IQR) follow-up was 68 (45-96) months. Most patients had stage III disease (574 patients [75.9%]). Three-year DFS was 76.3% for the capecitabine with RT group and 74.1% for the capecitabine and oxaliplatin with RT group, and 5-year DFS was 72.0% for the capecitabine with RT group and 71.1% for the capecitabine and oxaliplatin with RT group (hazard ratio [HR], 1.07; 95% CI, 0.79-1.44; P = .68). There was no significant difference between groups in overall survival (HR, 0.93; 95% CI, 0.64-1.34; P = .70) or local recurrence (HR, 0.61; 95% CI, 0.31-1.22; P = .16). More grade 3 and 4 acute toxic effects were observed in the capecitabine and oxaliplatin with RT group than in the capecitabine with RT group (114 patients [38.6%] vs 84 patients [28.6%]; P = .01). Conclusions and Relevance: This randomized clinical trial found that addition of oxaliplatin to capecitabine-based postoperative CRT did not improve the efficacy of treatment but increased the risk of severe acute toxic effects. This finding highlights the basic role of postoperative capecitabine with RT for patients with locally advanced rectal cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT00714077.

[Acupoint sensitization enhances inhibitory effect of electroacupuncture on jejunum mobility in rats].

OBJECTIVE: To observe the effect difference of electroacupuncture (EA) at the sensitized and non-sensitized acupoint "Tianshu" (ST25) on the motility of jejunum in rats. METHODS: Male SD rats were randomly divided into blank control, sensitized ST25 (sensitization), and non-sensitized ST25 (non-sensitization) groups (n=16 in each group). The sensitization and non-sensitization were induced by injection of 15% mustard oil (20 µL) and Paraffin oil (20 µL) into the left ST25 area respectively. The rats' behavior reactions were assessed by recording the numbers and duration of licking the local sensitized skin region. At the end of experiments and after regular trans-cardiac perfusion and fixing with 10% neutral formaldehyde, the skin and muscular tissues of the ST25 region (1 cm×1 cm) were taken for H.E. staining to observe the local histopathologic changes. The intestinal motility was detected by recording the contraction pressure waves of jejunum through a small balloon-connected pressure transducer and an amplifier, followed by calculating the ratios of amplitude and frequency of contraction waves between pre- and post-EA stimulation. EA (2 Hz, 0.2-6.0 mA) was applied to the sensitized and non-sensitized ST25 regions for 20 s for comparing their effects on jejunum motility. RESULTS: Compared with the blank control group, mustard oil injection but not Paraffin oil injection resulted in histological edema and neutrophils infiltration in tissues of ST25 region, and also striking increase of the number and duration of licking (P<0.01), suggesting a sensitization of ST25 area after mustard oil injection. The ratios of spontaneous contraction amplitude and frequency of jejunum were remarkably decreased in mustard oil-treated rats compared to baseline and Paraffin oil group (P<0.001，P<0.01). The maximum inhibitory effect of EA on the intestinal movement amplitude was significantly higher in the sensitization group than in the blank control and non-sensitization groups (P<0.05，P<0.01), and there was a dose-effect relationship between the current intensity of EA (0.5-3.0 mA) and the inhibitory rate 50% of the contraction amplitude (not the frequency) in the sensitization group (P<0.001), but not in the blank control and non-sensitization groups (P>0.05). Additionally, 1.5 mA EA stimulation at the sensitized ST25 (not at the non-sensitized ST25) had an inhibitory effect on the contraction amplitude (P<0.05) rather than on the contraction frequency (P>0.05) in comparison with the blank control group. CONCLUSION: Sensitization of acupoint ST25 can modulate the motility of jejunum and enhances the inhibitory effect of EA on the contraction amplitude of jejunum in rats. The inhibitory effect of sensitized ST25 EA is evidently stronger than that of the non-sensitized ST25 EA.

[Manual acupuncture stimulation of acupoints at the same and adjacent spinal segments promotes uterine contractility].

OBJECTIVE: To investigate the effect of manual acupuncture stimulation of acupoints at different spinal nerve segments on uterine motility and the complicated adrenergic and cholinergic receptors. METHODS: Eighteen adult non-pregnant SD rats were used in the present study. The contractive activities of the uterus were measured by using a pressure transducer which was connected to an inserted water-filled balloon in the uterus via a PE tube at one end and an amplifier at the other end. Manual acupuncture needle was applied to "Zigong"(EX-CA1),"Huiyin" (CV1), "Xuehai "(SP10) and "Taichong "(LR3) acupoints located at the same or adjacent spinal nerve segments of the uterus, and to "Neiguan" (PC6) situated at the distant spinal nerve segment at about 2 Hz for 1 min, followed by observing changes of the uterine contractility. After acupuncture, α-adrenoceptor antagonist phentolamine (0.5 mg/kg, n=9) or cholinergic muscarinic (M) receptor antagonist atropine (0.5 mg/kg，n=9) was given to the rats of different acupoints respectively through tail vein, followed by observing changes of the uterine automatic systolic pressure difference (value of systolic pressure peak minuses the trough value) and frequency after manual acupuncture stimulation as well as after blocking the activities of α-adrenoceptors and M receptors, separately. RESULTS: After acupuncture stimulation of EX-CA1, CV1, SP10 and LR3, but not PC6, the systolic pressure difference and frequency of the uterus were signi-ficantly increased (P<0.05,P<0.001, P<0.01). Following intravenous injection of phentolamine, both the systolic pressure difference and frequency had no marked changes after acupuncture at the 5 acupoints (P>0.05). After intravenous injection of atropine, the uterine systolic pressure difference and frequency were markedly decreased compared with the basic values before acupuncture stimulation (P<0.001), but had no obvious changes after acupuncture at the 5 acupoints at both the same and distant spinal segments to the uterus (P>0.05). CONCLUSION: Manual acupuncture stimulation of acupoints at the same and adjacent spinal segments can promote the contractility of uterus in normal rats, which is realized by activating both α-adrenoceptor and cholinergic M receptors.

Therapeutic effect of myofascial trigger point electroacupuncture technology on the treatment of overactive bladder syndrome in female. / 电针刺激肌筋膜触发点治疗女性膀胱过度活动症的临床疗效.

OBJECTIVES: To explore the therapeutic effect of myofascial trigger point electroacupuncture technology on treating female overactive bladder syndrome. METHODS: Forty female patients with overactive bladder were randomly divided into 2 groups: an experimental group and a control group. The experimental group was treated with myofascial trigger point electroacupuncture therapy combined with solifenacin succinate while the control group was only treated with solifenacin succinate. Patients in both groups were treated for 12 weeks. The overactive bladder symptom score (OABSS), urinary urgency score and urination frequency of 24 h in the 2 groups were compared to analyze the therapeutic effect. RESULTS: Before the comprehensive treatment, there was no significant difference between the experimental group and the control group (P>0.05). After 2 and 12 weeks of continuous treatment, the OABSS, urinary urgency symptoms score and 24 h urination frequency in the experimental group and the control group were lower than those before the treatment, and the degree of decline in the experimental group was more obvious, with significant difference (P<0.05). CONCLUSIONS: Treating overactive bladder syndrome in women with myofascial trigger point electroacupuncture combined with solifenacin succinate can significantly improve the OABSS and improve the life quality of the patients.

The atherosclerosis-ameliorating effects and molecular mechanisms of BuYangHuanWu decoction.

Atherosclerosis (AS) is one of the leading causes of cardiovascular disease and has a high rate of morbidity and mortality. Traditional Chinese Medicine (TCM) supplied many therapies for AS treatment for centuries. Among these treatments, BuYangHuanWu decoction (BYHWD) is a classic prescription. In this study, we analyzed the mechanisms of BYHWD in the treatment of AS by using a network pharmacology method. Our results revealed the mechanisms of BYHWD in treating AS, which is highly related to inflammation and apoptosis pathways, moreover, the genes including IL1ß, TGFB1, TNF, IL6, NFκB1 are proved to be the key pharmacological targets for the treatment of AS. Furthermore, an AS rat model was established and the rats in the treatment group received different amounts of BYHWD. Serum lipid levels (TC/TG/HDL-C/LDL-C) and tissue oxidative stress levels (SOD, GSH-Px, CAT and MDA) were ameliorated in a dose-dependent manner. The morphology of the aortic intima in the BYHWD-treated groups was improved. Real-time PCR and Western blot analysis results indicated that inflammatory cytokines were suppressed and that the NF-κB signaling pathway was blocked by BYHWD. All of this evidence suggested that BYHWD is an ideal prescription for treating AS.

Paris saponin VII extracted from trillium tschonoskii suppresses proliferation and induces apoptosis of human colorectal cancer cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Saponins of many herbs could inhibit the growth of colorectal cancer cells. In the study, we investigated the effects of Paris saponin Ⅶ (PSⅦ), and elucidated its mechanism in colorectal carcinoma cells and a xenograft mouse model. MATERIALS AND METHODS: HT-29 and HCT-116 cells were treated with different concentrations of PSⅦ (0-100 µM). The effects of PSⅦ on HCT-116 cells were assessed using a microarray. Then, apoptotic cells were detected by flow cytometric analysis and apoptosis related protein expression was evaluated by Western blot. A xenograft model of nude mice was used to assess the effect of PSⅦ in vivo. RESULTS: MTT assay showed the IC50 values of PSⅦ for growth inhibition of HT-29 and HCT-116 cells were 1.02 ±â€¯0.05 µM and 3.50 ±â€¯0.79 µM respectively. Edu assay demonstrated that PSⅦ effectively suppressed the growth of HT-29 and HCT-116 cells. Treatment with 0-3 µM PSⅦ not only triggered apoptosis, but also activated caspase-3 and caspase-9 of HT-29 and HCT-116 cells in a concentration dependent manner. In parallel to the alterations, Bax and Cyto-c expression increased while Bcl-2 decreased. In nude mice, PSⅦ reduced the tumor size and induced the apoptosis of tumor cells. PSVII could suppress IL-6-induced phosphorylation of STAT3 in vitro and blocked STAT3 phosphorylation in vivo. CONCLUSION: Our results suggest that PSVII suppressed the activation of IL-6/STAT3 pathway, consequently suppressed the growth and proliferation and triggered the apoptosis of CRC cells. These findings indicate that PSⅦ might be an effective tumouristatic agent for the treatment of colorectal cancer.

Enhancement of Detoxification of Petroleum Hydrocarbons and Heavy Metals in Oil-Contaminated Soil by Using Glycine-ß-Cyclodextrin.

Soil contamination with petroleum hydrocarbons and heavy metals is a widespread environmental problem. In recent years, cyclodextrin has attracted research interest because of its special hole structure that can form inclusion complexes with certain small molecules. However, the solubility of ß-cyclodextrin (ß-CD) in water is low and it crystallizes easily, leading to its low utilization in practice. In this experiment, we connected ß-CD with glycine under alkaline conditions to prepare glycine-ß-cyclodextrin (G-ß-CD), which is water soluble, has stronger coordinating ability with heavy metals, and is more suitable for treating oil-contaminated soil. The results show that G-ß-CD provides better desorption of petroleum hydrocarbons and heavy metals in soils with low organic matter content (1%) and NaNO3 of 0.25 mol/L at 70 g/L G-ß-CD under mildly acidic (pH 5⁻6) conditions. The results indicate that petroleum hydrocarbons and heavy metals were removed simultaneously by means of pretreatment with G-ß-CD, and the results can provide a theoretical basis for remediation of petroleum-contaminated soil.

Effective Heart Disease Detection Based on Quantitative Computerized Traditional Chinese Medicine Using Representation Based Classifiers.

At present, heart disease is the number one cause of death worldwide. Traditionally, heart disease is commonly detected using blood tests, electrocardiogram, cardiac computerized tomography scan, cardiac magnetic resonance imaging, and so on. However, these traditional diagnostic methods are time consuming and/or invasive. In this paper, we propose an effective noninvasive computerized method based on facial images to quantitatively detect heart disease. Specifically, facial key block color features are extracted from facial images and analyzed using the Probabilistic Collaborative Representation Based Classifier. The idea of facial key block color analysis is founded in Traditional Chinese Medicine. A new dataset consisting of 581 heart disease and 581 healthy samples was experimented by the proposed method. In order to optimize the Probabilistic Collaborative Representation Based Classifier, an analysis of its parameters was performed. According to the experimental results, the proposed method obtains the highest accuracy compared with other classifiers and is proven to be effective at heart disease detection.

Patients with pathological stage N2 rectal cancer treated with early adjuvant chemotherapy have a lower treatment failure rate.

BACKGROUND: In this era of oxaliplatin-based adjuvant therapy, the optimal sequence in which chemoradiotherapy should be administered for pathological stage N2 rectal cancer is unknown. The aim of this study was to investigate this sequence. METHODS: In the primary adjuvant concurrent chemoradiotherapy (A-CRT) group (n = 71), postoperative concurrent chemoradiotherapy was administered before adjuvant chemotherapy. In the primary adjuvant chemotherapy (A-CT) group (n = 43), postoperative concurrent chemoradiotherapy was administered during or after adjuvant chemotherapy. Postoperative radiotherapy comprised 45-50.4 Gy in 25-28 fractions. Concurrent chemotherapy comprised two cycles of oral capecitabine (1,600 mg/m2) on days 1-14 and 22-35. Patients receiving adjuvant chemotherapy with four or more cycles of XELOX (oxaliplatin plus capecitabine) or eight or more cycles of FOLFOX (fluorouracil, leucovorin, and oxaliplatin) were included. RESULTS: Between June 2005 and December 2013, data for 114 qualified rectal cancer patients were analyzed. The percentages of patients in whom treatment failed in the A-CRT and A-CT groups were 33.8% and 16.3%, respectively (p = 0.042). More patients had distant metastases in the A-CRT group than in the A-CT group (32.4% vs. 14.3%, p = 0.028). Multivariate analysis indicated that the sequence in which chemoradiotherapy was administered (A-CT vs. A-CRT) was an independent prognostic factor for both estimated disease-free survival [hazard ratio (HR) 0.345, 95% confidence interval (CI) 0.137-0.868, p = 0.024] and estimated distant metastasis-free survival (HR 0.366, 95% CI 0.143-0.938, p = 0.036). CONCLUSIONS: In pathological stage N2 rectal cancer patients, administering adjuvant chemotherapy before chemoradiotherapy led to a lower rate of treatment failure, especially with respect to distant metastasis. Adjuvant chemotherapy prescribed as early as possible might benefit this cohort of patients in this era of oxaliplatin-based adjuvant therapy.

Mechanism-based inhibition of Alantolactone on human cytochrome P450 3A4 in vitro and activity of hepatic cytochrome P450 in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Alantolactone (AL), one of the main active ingredients in Inula helenium L., has been included in various prescriptions of traditional Chinese medicine. The effects of AL on cytochrome P450 (CYP450) were still unclear. This study evaluated the inhibitory effect of AL on cytochrome P450s in vitro and in vivo. MATERIALS AND METHODS: The inhibitory effects of AL on the CYPs activity were evaluated in human liver microsomes (HLMs) and recombinant cDNA-expressed enzymes incubation system, and then determined by LC-MS/MS based CYPs probe substrate assay. C57BL/6 mice were treated AL orally (0, 25, 50, 100 mg/kg) for 15 days. The inhibitory effects of AL on major Cyps in mice were examined at both the mRNA and enzyme activity levels. RESULTS: AL showed a potent inhibitory effect on CYP3A4 activity with IC50 values of 3.599 (HLMs) and 3.90 (recombinant CYP3A4) µM, respectively. AL strongly decreased CYP3A4 activity in a dose-dependent but not time-dependent way in HLMs. Results from typical Lineweaver-Burk plots showed that AL could inhibit CYP3A4 activity noncompetitively, with a Ki value of 1.09 µM in HLMs. Moreover, activity of CYP2C19 could also be inhibited by AL with IC50 of 36.82 µM. Other CYP450 isoforms were not markedly affected by AL. The inhibition was also validated by in vivo study of mice. AL significantly decreased mRNA expression of Cyp2c and 3a family. CONCLUSION: The study indicates that herb-drug interaction should be paid more attention between AL and drugs metabolized by CYP3A4.