Free total rhubarb anthraquinones protect intestinal mucosal barrier of SAP rats via inhibiting the NLRP3/caspase-1/GSDMD pyroptotic pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhubarb is the peeled and dried roots of Rheum palmatum L. and Rheum tanguticum Maxim. ex Balf. or Rheum officinale Baill. Free total rhubarb anthraquinones (FTRAs) were isolated and extracted from rhubarb. Previous studies have revealed that the early administration of FTRAs protects the intestinal mucosal barrier in rats with severe acute pancreatitis (SAP), the mechanism of which is not yet clear. However, we observed an enhanced expression of intestinal pyroptotic factors in rats treated with SAP, which may be related to the mechanism of intestinal barrier protection by FTRAs. AIM OF THE STUDY: The main objective of this study was to investigate the mechanism by which FTRAs protect the intestinal mucosal barrier in SAP rats, focusing on the classical pyroptosis pathway. MATERIALS AND METHODS: SAP was induced in rats through retrograde injection of sodium taurocholate via the pancreaticobiliary duct. Subsequently, FTRAs (22.5, 45, and 90 mg/kg), rhubarb (900 mg/kg, positive control), and saline (control) were administered at 0 h (immediately), 12 h, and 24 h post-surgery. Pancreatic and intestinal tissue injury, positive PI staining rate, and expression levels of various factors in intestinal tissues were compared across different groups. These factors include diamine oxidase (DAO), lactate dehydrogenase (LDH), high mobility group box chromosomal protein 1(HMGB1) and pro-inflammatory factors in intestinal and serum, pyroptosis-associated factors, toll-like receptor 4 (TLR-4), nuclear factor kappa-B (NF-kB), apoptosis-associated speck-like protein (ASC), NOD-like receptor protein 3 (NLRP3), cysteine protease-1 (caspase-1) and Gasdermin (GSDMD). RESULTS: The findings indicated that FTRAs protected the damaged intestine and pancreas and restored the expression of intestinal epithelial junction proteins in SAP rats. Additionally, it reduced intestinal and serum levels of DAO, interleukin 1, interleukin 18, HMGB1, and LDH, attenuated intestinal Positive PI staining rate, and significantly decreased the expressions of TLR-4, NF-kB, ASC, NLRP3, caspase-1 and GSDMD in SAP rats. CONCLUSIONS: The results suggest that FTRAs inhibited pyroptosis through down-regulation of the NLRP3-Caspase-1-GSDMD and TLR-4- NF-kB signaling pathways of intestinal tissues., thereby protecting the intestinal barrier of SAP rats.

Ameliorating parkinsonian motor dysfunction by targeting histamine receptors in entopeduncular nucleus-thalamus circuitry.

In Parkinson's disease (PD), reduced dopamine levels in the basal ganglia have been associated with altered neuronal firing and motor dysfunction. It remains unclear whether the altered firing rate or pattern of basal ganglia neurons leads to parkinsonism-associated motor dysfunction. In the present study, we show that increased histaminergic innervation of the entopeduncular nucleus (EPN) in the mouse model of PD leads to activation of EPN parvalbumin (PV) neurons projecting to the thalamic motor nucleus via hyperpolarization-activated cyclic nucleotide-gated (HCN) channels coupled to postsynaptic H2R. Simultaneously, this effect is negatively regulated by presynaptic H3R activation in subthalamic nucleus (STN) glutamatergic neurons projecting to the EPN. Notably, the activation of both types of receptors ameliorates parkinsonism-associated motor dysfunction. Pharmacological activation of H2R or genetic upregulation of HCN2 in EPNPV neurons, which reduce neuronal burst firing, ameliorates parkinsonism-associated motor dysfunction independent of changes in the neuronal firing rate. In addition, optogenetic inhibition of EPNPV neurons and pharmacological activation or genetic upregulation of H3R in EPN-projecting STNGlu neurons ameliorate parkinsonism-associated motor dysfunction by reducing the firing rate rather than altering the firing pattern of EPNPV neurons. Thus, although a reduced firing rate and more regular firing pattern of EPNPV neurons correlate with amelioration in parkinsonism-associated motor dysfunction, the firing pattern appears to be more critical in this context. These results also confirm that targeting H2R and its downstream HCN2 channel in EPNPV neurons and H3R in EPN-projecting STNGlu neurons may represent potential therapeutic strategies for the clinical treatment of parkinsonism-associated motor dysfunction.

Optimal timing of free total rhubarb anthraquinones on immune regulation in rats with severe acute pancreatitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhubarb is the peeled and dried root of Rheum palmatum L., Rheum tanguticum Maxim. ex Balf. or Rheum officinale Baill. Free total rhubarb anthraquinones (FTRAs) isolated and extracted from rhubarb display the beneficial effects of anti-inflammation and immunological modulation. The timing of immune regulation is a major problem in the immunotherapy for severe acute pancreatitis (SAP). several studies reported that FTRAs could reduce systemic inflammatory responses by inhibiting early immune overactivity in the gut in rats with SAP. But, the optimal timing of rhubarb and FTRAs administration is not clear in clinical practice. Therefore, the time window for the best efficacy of rhubarb and FTRAs in the treatment of SAP patients should be further elucidated. AIM OF THE STUDY: The main purpose of the present study was to evaluate the efficacy and optimal timing of immune modulation with FTRAs in the treatment of SAP in rats. MATERIALS AND METHODS: FTRAs (22.5, 45 and 90 mg/kg), Rhubarb (RHU) (900 mg/kg, positive control) or normal saline (vehicle control) were initiated at 0 (immediately), 48 and 72 h every 12 h for three times in total. The therapeutic effects of FTRAs and RHU on pancreas and intestinal tissues injury, secondary infection with pseudomonas aeruginosa (PA), amylase, lipase, D-lactic acid (DLA), endotoxin (ET), proinflammatory and anti-inflammatory cytokines, macrophages, dendritic cells and regulatory T cells (Tregs) in the blood, small intestine and/or mesenteric lymph node (MLN) were determined in rats with SAP after treatment. RESULTS: The results showed that administration of FTRAs at 0 h was superior to 48 h and 72 h, which significantly protected the injury of pancreas and intestinal tissues, reduced the mortality induced by secondary infection with PA, decreased the levels of amylase, lipase, DLA, ET, tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), IL-6, IL-8, IL-18 and Tregs, and increased the levels of IL-4, sTNF-αR, macrophages and dendritic cells, secretary immunoglobulin A (SIgA) in the blood and/or small intestinal tissues in rats with SAP. CONCLUSIONS: In conclusion, our studies indicate that the treatment window of FTRAs for SAP is within 48 h of development, administration of FTRAs at the early stage (0 h, immune overreaction period) was the optimal time and superior to that of 48 h and 72 h for its therapeutic efficacy. The earlier the administration of FTRAs, the better the therapeutic efficacy. Therefore, our data may provide a scientific rationale for the clinical application and optimal timing of FTRAs in the treatment of SAP.

Clinical practice guideline for transurethral plasmakinetic resection of prostate for benign prostatic hyperplasia (2021 Edition).

Benign prostatic hyperplasia (BPH) is highly prevalent among older men, impacting on their quality of life, sexual function, and genitourinary health, and has become an important global burden of disease. Transurethral plasmakinetic resection of prostate (TUPKP) is one of the foremost surgical procedures for the treatment of BPH. It has become well established in clinical practice with good efficacy and safety. In 2018, we issued the guideline "2018 Standard Edition". However much new direct evidence has now emerged and this may change some of previous recommendations. The time is ripe to develop new evidence-based guidelines, so we formed a working group of clinical experts and methodologists. The steering group members posed 31 questions relevant to the management of TUPKP for BPH covering the following areas: questions relevant to the perioperative period (preoperative, intraoperative, and postoperative) of TUPKP in the treatment of BPH, postoperative complications and the level of surgeons' surgical skill. We searched the literature for direct evidence on the management of TUPKP for BPH, and assessed its certainty generated recommendations using the grade criteria by the European Association of Urology. Recommendations were either strong or weak, or in the form of an ungraded consensus-based statement. Finally, we issued 36 statements. Among them, 23 carried strong recommendations, and 13 carried weak recommendations for the stated procedure. They covered questions relevant to the aforementioned three areas. The preoperative period for TUPKP in the treatment of BPH included indications and contraindications for TUPKP, precautions for preoperative preparation in patients with renal impairment and urinary tract infection due to urinary retention, and preoperative prophylactic use of antibiotics. Questions relevant to the intraoperative period incorporated surgical operation techniques and prevention and management of bladder explosion. The application to different populations incorporating the efficacy and safety of TUPKP in the treatment of normal volume (< 80 ml) and large-volume (≥ 80 ml) BPH compared with transurethral urethral resection prostate, transurethral plasmakinetic enucleation of prostate and open prostatectomy; the efficacy and safety of TUPKP in high-risk populations and among people taking anticoagulant (antithrombotic) drugs. Questions relevant to the postoperative period incorporated the time and speed of flushing, the time indwelling catheters are needed, principles of postoperative therapeutic use of antibiotics, follow-up time and follow-up content. Questions related to complications incorporated types of complications and their incidence, postoperative leukocyturia, the treatment measures for the perforation and extravasation of the capsule, transurethral resection syndrome, postoperative bleeding, urinary catheter blockage, bladder spasm, overactive bladder, urinary incontinence, urethral stricture, rectal injury during surgery, postoperative erectile dysfunction and retrograde ejaculation. Final questions were related to surgeons' skills when performing TUPKP for the treatment of BPH. We hope these recommendations can help support healthcare workers caring for patients having TUPKP for the treatment of BPH.

[Analysis of curative effect of ultrasonic hyperthermia combined with TPF chemotherapy on 19 elderly with advanced oral squamous cell carcinoma].

PURPOSE: To evaluate the efficacy and safety of ultrasound hyperthermia combined with TPF chemotherapy for advanced oral squamous cell carcinoma in the elderly. METHODS: Nineteen elderly patients who had definite pathological diagnosis were enrolled in this clinical trail from June 2017 to January 2020. Docetaxel (75 mg/m2) + cisplatin (75 mg/m2) were given on the 1st day , and 5,Fu (750 mg/m2) on the 1st to 5th day of the cycle. Five times of hyperthermia were performed in the course of chemotherapy, respectively on the l, 3, 5, 7 and 9 days after the beginning of chemotherapy. All patients received 2 cycles of thermo -chemotherapy. Statistical analysis was performed using SPSS 20.0 software package. Kaplan-Meire method was used to calculate survival rate. RESULTS: According to the efficacy evaluation standard for solid tumor (version 1.0), complete response (CR) was seen in 3 cases, partial response (PR) was seen in 10 cases, stable disease(SD) was seen in 5 cases，progressive disease(PD) was seen in 1 case. The overall responding rate was 68.4%. The median follow-up time was 36 months(8-48 months), and the 2-year overall survival rates were 63.2%. No serious adverse reactions were observed. CONCLUSIONS: Ultrasound hyperthermic therapy combined with chemotherapy has a synergistic anti-tumor effect on patients with advanced oral squamous cell carcinoma, which is safe and effective, and is worthy of becoming another choice of tumor treatment.

A systematic review of Tuina for women with primary dysmenorrhea: A protocol for systematic review and meta-analysis.

BACKGROUND: Primary dysmenorrhea (PD) occurs most often in adolescent girls. Tuina, a kind of Chinese massage, can effectively relieve women's pain and is widely used in clinical practice. However, there is no relevant systematic review show its effectiveness and safety. The study aims to assess the effectiveness and safety of Tuina for PD. METHODS: The following electronic databases will be searched from the respective dates of database inception to September 1st, 2021: The Cochrane Library, Web of Science, EMBASE, Springer, MEDLINE, China National Knowledge Infrastructure, the Chinese Biomedical Literature Database, the World Health Organization International Clinical Trials Registry Platform, the Chinese Scientific Journal Database, Wanfang database, and other sources. RESULTS: This study will provide a high quality comprehensive and/or descriptive analysis of existing evidence on Tuina therapy for PD. CONCLUSION: This study will provide the evidence of whether Tuina is an effective and safe intervention for women with PD. PROSPERO REGISTRATION NUMBER: CRD42021257392.

Characteristics of prescriptions and costs for acute upper respiratory tract infections in Chinese outpatient pediatric patients: a nationwide cross-sectional study.

BACKGROUND: To understand the characteristics of prescriptions and costs in pediatric patients with acute upper respiratory infections (AURI) is important for the regulation of outpatient care and reimbursement policy. This study aims to provide evidence on these issues that was in short supply. METHODS: We conducted a retrospective cross-sectional study based on data from National Engineering Laboratory of Application Technology in Medical Big Data. All outpatient pediatric patients aged 0-14 years with an uncomplicated AURI from 1 January 2015 to 31 December 2017 in 138 hospitals across the country were included. We reported characteristics of patients, the average number of medications prescribed per encounter, the categories of medication used and their percentages, the cost per visit and prescription costs of drugs. For these measurements, discrepancies among diverse groups of age, regions, insurance types, and AURI categories were compared. Kruskal-Wallis nonparametric test and Student-Newman-Keuls test were performed to identify differences among subgroups. A multinomial logistic regression was conducted to examine the independent effects of those factors on the prescribing behavior. RESULTS: A total of 1,002,687 clinical records with 2,682,118 prescriptions were collected and analyzed. The average number of drugs prescribed per encounter was 2.8. The most frequently prescribed medication was Chinese traditional patent medicines (CTPM) (36.5% of overall prescriptions) followed by antibiotics (18.1%). It showed a preference of CPTM over conventional medicines. The median cost per visit was 17.91 USD. The median drug cost per visit was 13.84 USD. The expenditures of antibiotics and CTPM per visit (6.05 USD and 5.87 USD) were among the three highest categories of drugs. The percentage of out-of-pocket patients reached 65.9%. Disparities were showed among subgroups of different ages, regions, and insurance types. CONCLUSIONS: The high volume of CPTM usage is the typical feature in outpatient care of AURI pediatric patients in China. The rational and cost-effective use of CPTM and antibiotics still faces challenges. The reimbursement for child AURI cases needs to be enhanced.

Effect of Yijinjing exercise on cervical spondylosis: A protocol for systematic review.

BACKGROUND: Cervical spondylosis (CS) is a common disease due to the modern lifestyle. Yijinjin, a kind of traditional Chinese exercise, is frequently used for the prevention of CS by Traditional Chinese Medicine doctors. However, there is no relevant systematic review show its effectiveness and safety. The study aims to evaluate the effectiveness and safety of Yijinjing for patients with CS. METHODS: The following electronic databases will be searched from the respective dates of database inception to June 1st, 2020: The Cochrane Library, Web of Science, Springer, EMBASE, MEDLINE, the World Health Organization International Clinical Trials Registry Platform, the Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang database, the Chinese Scientific Journal Database, and other sources. All published randomized controlled trials (RCTs) and blinded researches that are relevant to the subject of interest only will be contained. Two independent researchers will operate article retrieval, duplication removing, screening, quality evaluation, and data analyses by Review Manager (V.5.3.5). Meta-analyses, subgroup analysis and/or descriptive analysis will be performed based on the included data conditions. RESULTS: High-quality synthesis and/or descriptive analysis of current evidence will be provided from the neck disability index, neck pain questionnaire questionnaires, patient satisfaction scale and adverse reactions. CONCLUSION: This study will provide the evidence of whether Yijinjing is an effective and safe intervention for people with CS. PROSPERO REGISTRATION NUMBER: CRD42020164706.

A systematic review protocol of Tuina for children with acute bronchitis: A protocol for systematic review.

BACKGROUND: Acute bronchitis (AB) is a common cause of childhood morbidity. Tuina, a kind of Chinese massage, is frequently used for the treatment of AB in children by traditional Chinese medicine doctors. However, there is no relevant systematic review show its effectiveness and safety. The study aims to evaluate the effectiveness and safety of Tuina for children with AB. METHODS: The following electronic databases will be searched from the respective dates of database inception to January 1st, 2020: The Cochrane Library, Web of Science, the World Health Organization International Clinical Trials Registry Platform, Springer, EMBASE, MEDLINE, China National Knowledge Infrastructure, the Chinese Biomedical Literature Database, Wanfang database, the Chinese Scientific Journal Database, and other sources. All published randomized controlled trials and blinded researches that are relevant to the subject of interest only will be contained. Two independent researchers will operate article retrieval, duplication removing, screening, quality evaluation, and data analyses by Review Manager (V.5.3.5). Meta-analyses, subgroup analysis and/or descriptive analysis will be performed based on the included data conditions. RESULTS: High-quality synthesis and/or descriptive analysis of current evidence will be provided from the bronchitis severity score, symptom, and quality-of-life questionnaires, the questionnaire of clinical symptoms of cough and sputum, Patient Satisfaction Scale and adverse reactions. CONCLUSION: This study will provide the evidence of whether Tuina is an effective and safe intervention for children with AB. PROSPERO REGISTRATION NUMBER: CRD42019140667.

Tuina for children with myopia: A protocol for a systematic review.

BACKGROUND: The study aims to evaluate the effectiveness and safety of Tuina for children with myopia. METHODS: The following electronic databases will be searched from establishment to July 2019: Cochrane Library, MEDLINE, EMBASE, Web of Science, Springer, World Health Organization International Clinical Trials Registry Platform (ICTRP), China National Knowledge Infrastructure (CNKI), Wan-fang database, Chinese Scientific Journal Database (VIP), Chinese Biomedical Literature Databases (CBM), and other databases. All published randomized controlled trials (RCTs) about this topic will be included. Two independent researchers will operate article retrieval, duplication removing, screening, quality evaluation, and data analyses by Review Manager (V.5.3.5). Meta-analyses, subgroup analysis, and/or descriptive analysis will be performed based on the included data conditions. RESULTS: High-quality synthesis and/or descriptive analysis of current evidence will be provided from improvement of distant vision, improvement of myopic diopter, and side effects. CONCLUSION: This study will provide the evidence of whether Tuina is an effective and safe intervention for children with myopia. PROSPERO REGISTRATION NUMBER: CRD42019142283.

[Safety and efficacy of ultrasound hyperthermia combined with chemotherapy and radical operation for advanced oral squamous cell carcinoma].

PURPOSE: To explore the safety and efficacy of ultrasound hyperthermia combined with chemotherapy and radical operation for advanced oral squamous cell carcinoma (OSCC). METHODS: Nine patients who had definite pathological diagnosis were enrolled in this clinical trail from 2015 to 2016. All patients underwent ultrasound hyperthermia combined with chemotherapy before radical operation. The treatment regime was as follows: Docetaxel and cisplatin (75mg/m2) used on the first day, fluorouracil (750 mg/m2) infused from 1st to 5th day. All patients received 2 cycles of thermo-chemotherapy, the therapeutic temperature was set to be 40-42 degrees centigrade, ultrasound hyperthermia was performed for 40 minutes every other day for 5 times. The therapeutic outcomes were evaluated by observation of clinical tumor regression. RESULTS: Of the 9 patients, complete response（CR）was seen in 1 case, partial response (PR) was seen in 3 cases, stable disease（SD）was seen in 5 cases. Complications were not severe and tolerable. CONCLUSIONS: Ultrasound hyperthermia combined with chemotherapy (TPF) may improve the therapeutic effect in advanced OSCC without obvious adverse reactions, and the toxicity and side effects are well tolerated.

[Thulium laser vaporization versus transurethral resection of the prostate and risk factors for postoperative urethral stricture].

OBJECTIVE: To compare thulium laser vaporization of the prostate (TLVP) and transurethral resection of the prostate (TURP) in the treatment of benign prostate hyperplasia (BPH) analyze the risk factors for postoperative urethral stricture. METHODS: From June 2015 to June 2016, 210 BPH patients in our hospital underwent TURP (n = 126) or TLVP (n = 84). We followed up the patients for 6 months, compared the effects of the two surgical strategies and analyzed the risk factors for postoperative urethral stricture by multivariate logistic regression analysis. RESULTS: Compared with TURP, TLVP achieved significantly shorter time of operation (ï¼»78.6 ± 27.5ï¼½ vs ï¼»53.2 ± 21.6ï¼½ min, P <0.01), postoperative bladder irrigation (ï¼»31.5 ± 2.9ï¼½ vs ï¼»26.1 ± 3.7ï¼½ h, P <0.01), urethral catheterization (ï¼»5.3 ± 1.7ï¼½ vs ï¼»3.7 ± 1.5ï¼½ d, P <0.01) and postoperative hospitalization (ï¼»7.9 ± 2.1ï¼½ vs ï¼»5.5 ± 1.4ï¼½ d, P <0.01) as well as lower urinary leukocyte count at 6 months after surgery (ï¼»32.1 ± 12.6ï¼½ vs ï¼»24.9 ± 11.7ï¼½ /µl, P <0.01) and incidence rate of postoperative complications (11.9% ï¼»15/126ï¼½ vs 3.6% ï¼»3/84ï¼½, P <0.05), particularly that of urethral stricture (7.9% ï¼»10/126ï¼½ vs 1.2% ï¼»1/84ï¼½, P <0.05). Logistic regression analysis showed that the preoperative urinary leukocyte count, postoperative urethral catheterization time, and surgical method were independent risk factors for postoperative urethral stricture. CONCLUSIONS: TLVP, in comparison with TURP, has the advantages of definite effect, fast recovery, high safety and low incidence of postoperative urethral stricture. The main risk factors for postoperative urethral stricture include preoperative urinary tract infection, postoperative urethral catheterization time and surgical method.

Hypothalamic histaminergic and orexinergic modulation on cerebellar and vestibular motor control.

Somatic-nonsomatic integration is critical for generation and execution of an appropriate and coordinated behavioral response to changes in internal and external environments. However, the underlying neural substrates and mechanisms are still enigmatic. Intriguingly, the central histaminergic and orexinergic systems originating from the hypothalamus, a high autonomic regulatory center, innervate almost the whole brain including various subcortical motor structures, particularly the cerebellum and vestibular nuclei. Here, we suggest that the hypothalamic histaminergic and orexinergic system bridging the nonsomatic center to somatic motor structures may actively modulate the cerebellar and vestibular nuclear neurons and subsequently participate in motor control and somatic-nonsomatic integration.