Identification of Flavonoids from Scutellaria barbata D. Don as Inhibitors of HIV-1 and Cathepsin L Proteases and Their Structure-Activity Relationships.

Scutellaria barbata D. Don (SB, Chinese: Ban Zhi Lian), a well-known medicinal plant used in traditional Chinese medicine, is rich in flavonoids. It possesses antitumor, anti-inflammatory, and antiviral activities. In this study, we evaluated the inhibitory activities of SB extracts and its active components against HIV-1 protease (HIV-1 PR) and SARS-CoV2 viral cathepsin L protease (Cat L PR). UPLC/HRMS was used to identify and quantify the major active flavonoids in different SB extracts, and fluorescence resonance energy transfer (FRET) assays were used to determine HIV-1 PR and Cat L PR inhibitions and identify structure-activity relationships. Molecular docking was also performed, to explore the diversification in bonding patterns of the active flavonoids upon binding to the two PRs. Three SB extracts (SBW, SB30, and SB60) and nine flavonoids inhibited HIV-1 PR with an IC50 range from 0.006 to 0.83 mg/mL. Six of the flavonoids showed 10~37.6% inhibition of Cat L PR at a concentration of 0.1 mg/mL. The results showed that the introduction of the 4'-hydroxyl and 6-hydroxyl/methoxy groups was essential in the 5,6,7-trihydroxyl and 5,7,4'-trihydroxyl flavones, respectively, to enhance their dual anti-PR activities. Hence, the 5,6,7,4'-tetrahydroxyl flavone scutellarein (HIV-1 PR, IC50 = 0.068 mg/mL; Cat L PR, IC50 = 0.43 mg/mL) may serve as a lead compound to develop more effective dual protease inhibitors. The 5,7,3',4'-tetrahydroxyl flavone luteolin also showed a potent and selective inhibition of HIV-1 PR (IC50 = 0.039 mg/mL).

Identification and quantitative analysis of bioactive components from Potentilla kleiniana Wight et Arn with anti HIV-1 proteases activity.

Potentilla kleiniana Wight et Arn（PK, 'Wu Pi Feng' in Chinese） was recorded as Miao ethnic medicine for treatment of fever, cough, ulcer, and erysipelas for thousands years. This study aimed to evaluate the antiviral activity of four PK extracts and seven compounds by using HIV-1 protease (HIV-1 PR). In addition, Ultra-High Performance Liquid Chromatography and High Resolution Mass Spectrometry (UPLC-HRMS) was employed to identify the bioactive components. The toxicity assessment of the extracts was done before antiviral screening using a highly specific human aspartyl protease, renin protease by fluorimetric method. As a result, seven compounds and four extracts of PK inhibited HIV-1 PR with IC50 range from 0.009 to 0.36 mg/mL, and did not appreciably inhibit the general human protease renin. This study first demonstrated that four PK extracts, ellagic acid and ursolic acid potent inhibit HIV-1 protease, could be used as an efficacious drug candidate to treat SARS-CoV-2 infection.

Inhibitors of HIV-1 and Cathepsin L Proteases Identified from the Insect Gall of Hypericum kouytchense.

Hypericum kouytchense Lévl is a semi-evergreen plant of the Hypericaceae family. Its roots and seeds have been used in a number of traditional remedies for antipyretic, detoxification, anti-inflammatory, antimicrobial and antiviral functions. However, to date, no bioactivity compounds have been characterized from the insect gall of H. kouytchens. In this study, we evaluated the antiviral activities of different extracts from the insect gall of H. kouytchen against cathepsin L, HIV-1 and renin proteases and identified the active ingredients using UPLC-HRMS. Four different polar extracts (HW, H30, H60 and H85) of the H. kouytchense insect gall exhibited antiviral activities with IC50 values of 10.0, 4.0, 3.2 and 17.0 µg/mL against HIV-1 protease; 210.0, 34.0, 24.0 and 30.0 µg/mL against cathepsin L protease; and 180.0, 65.0, 44.0 and 39.0 µg/mL against human renin, respectively. Ten compounds were identified and quantified in the H. kouytchense insect gall extracts. Epicatechin, eriodictyol and naringenin chalcone were major ingredients in the extracts with contents ranging from 3.9 to 479.2 µg/mg. For HIV-1 protease, seven compounds showed more than 65% inhibition at a concentration of 1000.0 µg/mL, especially for hypericin and naringenin chalcone with IC50 values of 1.8 and 33.0 µg/mL, respectively. However, only hypericin was active against cathepsin L protease with an IC50 value of 17100.0 µg/mL, and its contents were from 0.99 to 11.65 µg/mg. Furthermore, we attempted to pinpoint the interactions between the active compounds and the proteases using molecular docking analysis. Our current results imply that the extracts and active ingredients could be further formulated and/or developed for potential prevention and treatment of HIV or SARS-CoV-2 infections.

Comparison of invasive dynamic blood pressure between superior mesenteric artery and common carotid artery in rats / 世界急诊医学杂志（英文）

@#BACKGROUND: The purpose of this study was to identify the consistency of invasive dynamic blood pressure (BP) monitoring between the superior mesenteric artery (SMA) and the common carotid artery (CCA). METHODS: Eight male Sprague-Dawley rats were cannulated in SMA and CCA simultaneously for BP monitoring, respectively. The abdominal aorta was prepared for the induction of BP change through clamping/de-clamping by a microvascular clip. The dynamic BP monitoring was performed by a polygraph system. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) values would be recorded during different time periods: the baseline (T1), the increasing period after clamping (T2), the platform period during clamping (T3), the decreasing period after de-clamping (T4), and the final platform period (T5). Three trials were performed on each rat with 15-minute intervals between consecutive monitoring. RESULTS: Systolic BP showed no significant differences between SMA and CCA. However, significant difference was found in diastolic blood pressure except at T5 (P=0.534). Mean arterial pressure of two arteries were signifi cantly different only at T1 (P=0.015). The strength of association was significantly high between BP measurements through SMA and CCA (P<0.001). The Bland- Altman analyses showed that mean bias of MAP changed no more than 5 mmHg and standard deviation less than 8 mmHg during T2 and T4, respectively. CONCLUSION: The study indicates SMA might be an alternative site for invasive BP monitoring during abdominal aorta occlusion and release, especially in cerebrovascular-related research.

Annoyance-rate-and-casualty-reality-based method of comfort evaluation of military ambulance / 医疗卫生装备

Objective To explore an method for comfort evaluation of the military ambulance to enhance ride comfort during casualty transport. Methods The method executed quantitative evaluation of vibrational comfort by the existing vibration comfortableness evaluation ways for non-ambulatory casualty, different reactions of casualty to vibrational excitement and annoyance rate analysis based on psychophysics, which took considerations on the ratio of injured sites at war or natural disaster conditions as well as susceptibility analysis. Trials of the the method were carried out on the vibrational comfort analysis of some military ambulance during the road test.Results The method had feasibility for vibration comfortableness evaluation of non-ambulatory casualty,and improved the traditional ways in quantitative analysis.Conclusion The method gains advantages over the international ways, and contributes to the related researches on vibration reduction.

Clinical study of laparoscopic sphincter-preserving proctectomy for low rectal cancer using transanal telescopic anastomosis / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the safety, feasibility and clinical outcomes of laparoscopic sphincter-preserving proctectomy for low rectal cancer using transanal telescopic anastomosis.</p><p><b>METHODS</b>Five patients underwent laparoscopic sphincter-preserving proctectomy for low rectal cancer using transanal telescopic anastomosis between March 2011 and April 2011 at the General Hospital of Beijing Military Command. After lymph node dissection around the mesentery using harmonic scalpel, the root of the inferior mesenteric vessel was ligated and transected. Rectal dissection was further carried out until 5 cm distal to the lower margin of the tumor. A circumferential incision was made 1.0 cm above the dentate line using 5 support stitches for exposure. The submucous layer was striped upward to the level of the levator ani, and rectum was transected. Rectum and sigmoid colon were extracted transanally and removed. Finally, colonanal anastomosis was made using telescopic technique.</p><p><b>RESULTS</b>Five patients underwent the procedure successfully. The mean operative time was 178 minutes. The mean intraoperative blood loss was 76 ml. The mean lymph nodes retrieval was 14. Bowel function recovered after a mean of 3 days. There were no postoperative complications. No obvious scars were seen in the abdomen or the anus. The mean hospital stay was 12 days. After one year of follow-up, all the patients survived cancer-free.</p><p><b>CONCLUSIONS</b>Laparoscopic anterior resection with sphincter preservation by transanal telescopic anastomosis for low rectal cancer is feasible and safe. Abdominal incision is minimal. However, the long-term outcomes require further investigation.</p>

Analysis of 61 cases undergoing sphincter-preserving procedure with intersphincteric resection by telescopic anastomosis for ultra-low rectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and safety of sphincter-preserving procedure with transabdominal intersphincteric resection for ultra-low rectal cancer.</p><p><b>METHODS</b>Clinical data of 61 cases with ultra-low rectal cancer (distance from anal verge ranged from 4-5 cm) were analyzed retrospectively. The patients underwent sphincter-preserving procedure with intersphincteric resection and telescopic anastomosis.</p><p><b>RESULTS</b>There were 34 males and 27 females. The mean age was 56.7 years. The inferior border of the tumor was 4 cm above the anal verge in 21 cases, and 5 cm in 40 cases. There 55 patients with rectal adenocarcinoma in this cohort. The tumor was well-differentiated in 24 cases, moderately-differentiated in 29 cases, and poorly-differentiated in 2 cases. There were 6 cases with malignant adenoma. The TNM staging was T1N0M0 in 36 cases, T2N0M0 in 23, and T3N1M0 in 2. The ability to control defecation significantly improved in 1-3 months postoperatively, and returned to normal in 6-12 months. Two patients developed anastomotic leak (3.3%), and 3 anastomotic stenosis (4.9%) postoperatively. Fifty-four patients(88.5%) had follow-up. The median follow-up time was 6.2 years. The local recurrence rate was 5.6%, and the 5-year-survival rate was 73.5%.</p><p><b>CONCLUSION</b>Sphincter-preserving procedure with intersphincteric resection and telescopic anastomosis is a safe and effective procedure for ultra-low rectal cancer.</p>

Clinical experience of 371 cases of sphincter-preservation with telescopic anastomosis after radical excision for low-middle rectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the clinical efficacy, feasibility and safety of sphincter-preservation with telescopic anastomosis of colon and rectal mucosa in low-middle rectal cancer.</p><p><b>METHODS</b>A retrospective analysis was carried out in 371 patients with low-middle rectal cancer in whom telescopic anastomosis was used. There were 224 males and 147 females, with a mean age of 57.9 (21-99) years. The lower margins of the tumors located between 5-8 cm from the anal verge. On histopathology, there were 361 adenocarcinomas, including 138 well-differentiated, 201 moderately differentiated, 11 poorly differentiated, 11 mucinous adenocarcinoma, and 10 adenomas with neoplastic changes. According to the Duke's stage classification, 120 were TNM stage I, 222 stage II, 26 stage III, and 3 stage IV.</p><p><b>RESULTS</b>Three hundred and eighteen (318/371, 85.7%) cases were followed up, and the median follow up time was 5.8 years. Postoperative complications were observed, including 16(4.3%) cases with anastomotic leak, and 8 (2.1%) with anastomotic stenosis. All the patients resumed normal bowel function during 12-24 weeks after operation, with 1-3 times per day. The local recurrence rate was 6.3% (20/318). Hepatic and lung metastasis was 14.5% (46/318) and 2.5% (8/318), respectively. The 5-year survival rate was 69.7%.</p><p><b>CONCLUSION</b>The sphincter-preservation with telescopic anastomosis procedure is safe and effective for low-middle rectal cancer, and the sphincter function can be well-preserved.</p>

Clinical study of 231 cases of radical excision with sphincter preservation by casing anastomosis in low rectal cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the clinical efficacy, feasibility and safety of sphincter-preserving procedure by casing anastomosis of colon and rectal mucosa in low rectal cancer.</p><p><b>METHODS</b>A retrospective analysis was carried out in 231 cases of low rectal cancer performed casing anastomosis.</p><p><b>RESULTS</b>One hundred and ninety-seven (197/231, 85.3%) cases were followed up, the median time of the follow up was 5.9 years (range, 2 months-14 years). Eight (3.4%) cases of stoma leak and 3 (1.2%) cases of stoma stenosis were found post operation. Defecating function recovered normally (1 - 3 times per day) in 12 - 24 weeks after operation in all patients. Local recurrence was found in 5.1% (10/197) of the cases. Hepatic and lung metastasis was found in 15.2% (30/197) and 2.5% (5/197) of the patients, respectively. The five-year survival rate was 71.6% totally.</p><p><b>CONCLUSIONS</b>The casing anastomosis procedure with sphincter preservation is safe and efficacy for low rectal cancer. With the procedure, the anal function can be preserved well, stoma leak is decreased, and the five-year survival rate is the same as Miles operation.</p>

Clinical analysis of therapeutic effects of sphincter-preserving operation and Miles operation for rectal cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate and compare therapeutic effects of sphincter-preserving operation and Miles operation for rectal cancer.</p><p><b>METHODS</b>A retrospective analysis was carried out in 572 cases of rectal cancer operations performed from January 1980 to December 2006.</p><p><b>RESULTS</b>Sphincter-preserving operation was carried out in 403 cases and Miles procedure in 169 cases. The follow-up rate was 76.2% (436/572) with a period of 0.5 - 25.0 years (median, 9.5 years). Local recurrence occurred in 6.3% (20/317) of sphincter-preserving operation and 7.6% (9/119) of Miles operation, the differences was not significant (chi2 = 1.3942, P > 0.05). Distal metastasis was found in 50 cases (15.7%) of sphincter-preserving operation and 19 cases (16.2%) of the Miles operation with no significant difference (chi2 = 0.6672, P > 0.05). There was no significant difference in five-year survival rate between the two groups, with 67.8% in sphincter-preserving operation and 67.2% in Miles operation.</p><p><b>CONCLUSIONS</b>Sphincter-preserving operations can improve the quality of life in rectal cancer although with the same five-year survival rate and recurrence rate as Miles operation. The operation for rectal cancer should be performed individually according to the location, the bionomics and the clinical stage.</p>

[Clinical observation of hand-assisted laparoscopic live donor nephrectomy].

OBJECTIVE: To investigate the feasibility and advantage of hand-assisted laparoscopic live donor nephrectomy in renal transplantation. METHODS: Six living relative donors received retroperitoneal left-side laparoscopic nephrectomy. The operating time of nephrectomy, the warm ischemic time, the recovery time of allograft and donors were recorded and analyzed. RESULTS: The mean operating time of nephrectomy was 150 minutes, the mean warm ischemic time was 3.5 minutes, and the mean time of micturition after graft reperfusion was 82 seconds. The donors recovered rapidly and returned to normal within 30 days . The urine volume and renal function of the 6 recipients were normal without complications in the following 3 months. CONCLUSION: Hand-assisted laparoscopic live donor nephrectomy is feasible with short operating time and warm ischemic time; the donors experience less pain, and recover rapidly. This technique may be widely used in living donor nephrectomy.