[Characteristics of PD-L1 expression in tumor cells and tumor microenvironment of DLBCL with MYD88 L265P mutation].

Objective: To study the effect of MYD88 L265P mutation on the expression of PD-L1 in tumor cells and tumor microenvironment in diffuse large B-cell lymphoma (DLBCL), and to provide theoretical basis for immunotherapy for patients. Methods: Multiplex ligation-dependent probe amplification (MLPA) was used to detect the frequency of MYD88 L265P mutation in 72 cases of DLBCL diagnosed by pathologists in Cancer Hospital of Chinese Academy of Medical Sciences from August 2008 to May 2010. Expression of PD-L1 in tumor cells and tumor microenvironment in all samples was evaluated using PD-L1 (22C3) and PD-L1 (SP142) with Ventana automatic immunohistochemical (IHC) platform. The relationship between MYD88 L265P mutation and the expression of PD-L1 in DLBCL tumor cells and tumor microenvironment was assessed. Results: Of the 72 cases of DLBCL, MYD88 L265P mutation was detected in 15 (20.8%) cases. Nine cases with JAK2 amplification were excluded, and the remaining 63 cases of DLBCL were divided into MYD88 L265P mutant group (n=14) and MYD88 L265P wild-type group (n=49). IHC results showed that among the 14 cases of MYD88 L265P mutant groups, PD-L1 (22C3) was positive in 7 cases (7/14) of tumor cells and PD-L1 (SP142) was positive in 4 cases (4/14) of tumor microenvironment. Among the 49 cases of MYD88 L265P wild-type group, 9 cases (18.4%) were positive for PD-L1 (22C3) in tumor cells, and 38 cases (77.6%) were positive for PD-L1(SP142) in tumor microenvironment. In addition, among the 16 cases with PD-L1(22C3) expression in tumor cells, only 2 of the 7 cases with MYD88 L265P mutation were positive for PD-L1 (SP142) in tumor microenvironment. All 9 cases with wild-type MYD88 L265P were positive for PD-L1 (SP142) in tumor microenvironment. Statistical analysis showed that the expression level of PD-L1 (22C3) in tumor cells in the MYD88 L265P mutant group was significantly higher than that in the MYD88 L265P wild-type group (P=0.017). The expression level of PD-L1 (SP142) in tumor microenvironment in the MYD88 L265P mutant group was significantly lower than that in the MYD88 L265P wild-type group (P=0.001). Conclusions: MYD88 L265P mutation may play an important role in the regulation of PD-L1 expression in DLBCL tumor cells and tumor microenvironment. Further studies will provide a theoretical basis for immunotherapy of DLBCL patients with MYD88 L265P mutation.

[Endoscopic lateral neck dissection via the breast and transoral approaches for papillary thyroid carcinoma: a report of 10 cases].

Objective: To investigate the feasibility of endoscopic lateral neck dissection via the breast and transoral approaches (ELNDBTOA) for papillary thyroid carcinoma (PTC). Methods: From February 2015 to April 2019, 10 patients with PTC (cN1b) including 1 male and 9 females aged from 22 to 53 years old received ELNDBTOA in the General Surgery Department of Zhongshan Hospital, Xiamen University. Total thyroidectomy, the central lymph node dissection and the selective neck dissection (levels Ⅱ, Ⅲ and Ⅳ) were performed endoscopically via the breast approach, and then the residual lymph nodes were dissected via transoral approach. The medical records, operation time, blood loss, complications and postoperative follow-up outcomes were analyzed retrospectively. SPSS 22.0 software package was used for statistical processing of clinical data of patients. Results: All cases were successfully treated with ELNDBTOA without transfer to open surgery. The average operative time was (362.5±79.7) min, the blood loss was (23.0±14.9) ml, and the postoperative hospital stay was (5.1±1.3) days. The mean number of harvested cervical lymph nodes were (34.2±25.8), and the mean number of positive lymph nodes were (6.5±4.9). Lymph nodes were dissected by the further dissection via oral approach in 6 patients and a total of 9 lateral lymph nodes were havested from 2 of the 6 patients, with 3 positive lymph nodes. Two patients had transient skin numbness in the mandibular area and recovered within two weeks. One patient developed transient hypoparathyroidism and recovered within two months. No secondary bleeding, recurrent laryngeal nerve paralysis, chylous leakage, neck infection, permanent hypoparathyroidism or other complications were observed. The follow-up time was from 16 to 66 months with a median of 42.5 months, no tumor recurrence or metastasis occurred, and also no obvious deformity, abnormal sensation or movement in the chest, neck and mouth was observed. Conclusions: ELNBTOA is safe and feasible, with good cosmetic outcome.

[Clinical experience in transoral endoscopic thyroidectomy via sublingual and vestibular approach: a report of 98 cases].

Objective: To summarize the clinical experience in transoral endoscopic thyroidectomy via sublingual and vestibular approach (TOETSLVA). Methods: We retrospectively reviewed the medical record of patients who underwent TOETSLVA in our department from November 2011 to May 2020, including 3 males and 95 females, aged from 18 to 57 years old. Initial 81 cases were categorized in "Period A (November 2011-November 2015)" and subsequent 17 cases in "Period B (August 2019-May 2020)" . Data about demographics, operation time and complications were collected. SPSS 22.0 software was used for statistical analysis. Results: In Period A, the average age of patients was (34.2±9.4) years old; the mean tumor diameter was (2.33±0.80) cm; postoperative pathology showed benign nodules in 76 cases and malignant carcinoma in 5 cases; there were 65 cases of unilateral subtotal thyroid lobectomy, 6 cases of isthmus lobectomy, and 5 cases of bilateral subtotal thyroid lobectomy, with the mean operation time of (132.70±47.22) min; in 5 cases of unilateral thyroid lobectomy with central lymph node dissection, the mean operation time was (185.4±31.40) min; postoperative neck infections occurred in 6 cases; temporary vocal cord paralysis occurred in 1 case, which it recovered within two months; and CO(2) gas embolism occurred in 2 cases. In Period B, the average age of patients was (35.1±8.5) years old; mean tumor diameter was (1.32±0.67) cm; postoperative pathology indicated malignant nodules in 15 cases and benign nodules in 2 cases; in 2 cases of unilateral thyroid lobectomy, the mean operation time was (153.5±34.64) min; in 15 cases of unilateral thyroid lobectomy with central lymph node dissection, the mean operation time was (123.73±14.26) min; and none of patients developed postoperative neck infections or CO(2) gas embolism. All patients had different degree of cutaneous numbness in the submandibular region after surgery, which recovered within 1-2 weeks. There were no complications such as postoperative secondary hemorrhage, permanent vocal cord paralysis, hypoparathyroidism in both the periods. The median follow-up time was 86 months (57-105 months) in Peroid A and 5 months (3-12 months) in Peroid B. During the follow-up periods, there were no obvious abnormalities in swallowing, chewing, oral sensory function and neck activity, and also no tumor recurrence or metastasis. Conclusions: TOETSLVA is a safe and feasible surgery method, with a good cosmetic result. This approach will not lead to a postoperative cutaneous numbness of the submandibular region for a long time.

A standard technique with potential diagnostic value for estimating the quadriceps muscle strength of critically ill patients.

OBJECTIVE: Intensive care unit-acquired weakness (ICUAW) is common, and so far, there is no digital technology with a standard procedure to estimate the muscle strength of these patients. Quadriceps maximal isometric voluntary contraction (QMVC) is a precise and reliable procedure to detect quadriceps muscle strength. Therefore, this research aimed to explore whether QMVC measurements can be used in critically ill patients at the bedside as a potential diagnostic method. PATIENTS AND METHODS: Tailor-made computerized equipment was designed to measure the QMVC of critically ill patients at the bedside, following a standard procedure. A total of 22 critically ill patients and 22 age- and sex-matched healthy subjects were divided into group 1 and group 2, respectively. SPASS 21.0 (IBM, Armonk, NY, USA) software was used to analyze the data. RESULTS: All subjects showed good endurance with the QMVC measurements and there were no side effects among these subjects. There was a significant decline in QMVC between group 1 and group 2 (p=0.000). QMVC was correlated closely with the APACHE II Score in group 1 (Pearson correlation, r=-0.427, p=0.047). Among the 10 patients with a Medical Research Council sum score (MRC SS) less than 60 in group 1, it was also correlated closely with the MRC SS (Pearson correlation, r=0.837, p=0.003). CONCLUSIONS: This study describes a standard technique for quantifying quadriceps muscle strength that is feasible for use with critical patients. QMVC can accurately detect the decline of quadriceps muscle strength of critical patients, and it may also decline with the severity of the disease. In the future, this technique might be a potential diagnostic tool for ICUAW.

[Incidence of postoperative venous thromboembolism after thoracic surgery and its characteristic: a single center, prospective cohort study].

Objective: To evaluate the incidence of postoperative venous thromboembolism (VTE) after thoracic surgery and its characteristic. Methods: This was a single-center, prospective cohort study. Patients undergoing major thoracic surgeries between July 2016 and March 2017 at Department of Thoracic Surgery, Beijing Chaoyang Hospital Affiliated to Capital Medical University were enrolled in this study. Besides the routine examination, all patients were screened for deep venous thrombosis (DVT) by using noninvasive duplex lower-extremity ultrasonography after surgery. CT pulmonary angiography (CTPA) was carried out if patients had one of the following conditions including typical symptoms of PE, high Caprini score (>9 points) or new diagnosed postoperative DVT. Caprini risk assessment model was used to detect high risk patients. No patients received any prophylaxis of VTE before surgery. Further data was analyzed for identifying the incidence of postoperative VTE. The t-test, χ2 test or Wilcoxon rank-sum test was used to analyze the quantitative data and classification data, respectively. Results: Totally 345 patients who undergoing major thoracic surgery were enrolled in this study including 145 benign diseases and 200 malignant diseases.There were 207 male and 138 female, aging from 15 to 85 years. Surgery procedures included 285 lung surgeries, 27 esophagectomies, 22 mediastinal surgeries and 11 other procedures. The overall incidence of VTE was 13.9% (48 of 345) after major thoracic surgery including 39 patients with newly diagnosed DVT (81.2%), 1 patient with PE (2.1%) and 8 patients with DVT+ PE (16.7%). The median time of VTE detected was 4.5 days postoperative. There were 89.6% (43/48) VTE cases diagnosed in 1 week. The incidence of VTE was 9.0% in patients with benign diseases, while 17.5% in malignant diseases (χ2=5.112, P<0.05). The incidence of VTE in patients with pulmonary diseases was 12.6%, among that, in patients with lung cancer and benign lung diseases was 16.4% and 7.5 % (χ2=4.946, P<0.05), respectively. Regarding to Caprini risk assessment model, the incidence of VTE in low risk patients, moderate risk patients (Caprini score 5 to 8 points)and high risk patients(≥9 points)were 0(0/77), 15.2%(33/217) and 29.4%(15/51), respectively(Z=-12.166, P<0.05). In patients with lung cancer, 98.2% of patients were moderate risk or high risk; only 3 cases scored low risk. The incidence of VTE in moderate risk and high risk patients was 13.4%(18/134) and 32.1%(9/28), respectively, while it was 0(0/3) in low risk patients. Conclusions: The overall incidence of VTE after major thoracic surgeries is 13.9%, and the incidence of VTE after lung cancer surgeries was 16.4%. Most of the VTE cases occurr within one week after the surgery. Caprini risk assessment model can identify high risk patients effectively.

Combined detection of uMCP-1 and uTWEAK for rapid discrimination of severe lupus nephritis.

Reliable markers for the rapid discrimination of severe renal damage remain a vital concern for lupus nephritis (LN). To determine a better tool for kidney damage detection, the present study compared the evaluation ability of novel urinary cytokines and chemokines (namely urinary monocyte chemoattractant protein 1 (uMCP-1), tumor necrosis factor-like weak inducer of apoptosis (uTWEAK)) with traditional serum or urinary markers (namely urinary alpha 1-microgrobulin (uα1-MG), beta 2-microglobulin (uß2-MG) and serum complement C3 (C3), complement C4 (C4), creatinine (Cr), blood urea nitrogen (BUN) and cystatin C (Cys C)) in discriminating LN renal damage. Correlations between markers with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) renal SLEDAI scores, biopsy activity index (BAI) and biopsy chronicity index (BCI) scores were evaluated. Receiver operating characteristic (ROC) curves were generated to evaluate a single or combined model in discriminating active renal involvement (rSLEDAI scores > 0) and patients with poor pathological outcome (BAI scores ≥ 7). uMCP-1 and uTWEAK possess higher correlation coefficients with renal damage and larger areas under ROC curves (AUCs) than other markers. A combined model of uMCP-1 and uTWEAK showed an AUC of 0.887, sensitivity of 86.67% and specificity of 80.00% to discriminate active LN, and an AUC of 0.778, sensitivity of 75.00% and specificity of 81.82% to discriminate LN with poor outcome, which are better than the utility of any markers individually.

[Survey of current status of prevention of venous thromboembolism after thoracic surgery in China].

Objective: To investigate the current status of prevention and treatment of venous thromboembolism (VTE) after thoracic surgery in China. Method: Chinese thoracic surgeons were investigated by the online questionnaire which was based on the Chinese version of International VTE questionnaire added with 6 extra questions with Chinese characteristics. Results: A total of 1 150 valid questionnaires were retrieved, accounting for about 20% of all the Chinese thoracic surgeons. The surgeons participating in this survey came from all over the country, most of whom were experienced professionals with high academic titles.For lung cancer patients, 66.96% (770/1 150) of the surgeons suggested that VTE prophylaxis should start 1 day after lung cancer resection, and 64.61% (743/1 150) of the surgeons suggested extending after discharge. For esophagestomy patients, and 48.35% (514/1 063) of the surgeons suggested that there was no need for patients to extend VTE prophylaxis after discharge. More than half of the surgeons participating in this survey made decision of the method and duration of VTE prophylaxis after lung cancer resection (53.91% (620/1 150)) or esophagectomy (52.49% (558/1 063)) depending on the clinical experience.Low molecular weight heparin was the common choice of most surgeons in VTE prophylaxis. More than half of the surgeons thought that previous history of VTE, advanced age, complicated with thrombophilia, obesity (body mass index>30 kg/m2), duration of surgery longer than 6 hours and family history of VTE were key risk factors of the occurrence of postoperative VTE. Conclusions: The results of this survey are highly credible and are a good reflection of the current status of VTE prevention and treatment after thoracic surgery in China. This survey will play an important role in promoting VTE prevention and treatment in Chinese thoracic surgery department, it will also provide data support for government setting new policies, hospital construction of VTE prevention and control as well as raising physicians' awareness.

Antidiabetic drug metformin mitigates ovarian cancer SKOV3 cell growth by triggering G2/M cell cycle arrest and inhibition of m-TOR/PI3K/Akt signaling pathway.

OBJECTIVE: Metformin is one of most extensively prescribed oral hypoglycemic drug and has received increased attention in recent times for its antitumorigenic potential. Many possible mechanisms have been proposed for the ability of metformin to overturn cancer growth in vitro and in vivo. The objective of the present study was to evaluate the anticancer activity of metformin against ovarian SKOV3 cancer cells. MATERIALS AND METHODS: Anticancer activity and IC50 value of metformin were determined by MTT assay. Reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and effect on cycle were determined by flow cytometry. Protein expression was estimated by Western blotting. RESULTS: Results indicated that metformin exhibited an IC50 of 20 mM against ovarian SKOV3 cancer cell line. Metformin also caused DNA damage in SKOV3 cells and also prompted ROS-mediated alterations in mitochondrial membrane potential. Nonetheless, it triggered cell cycle arrest of SKOV3 at G2/M checkpoint. The activation of the PI3K/AKT/mTOR pathway plays a vital role in ovarian cancer tumorigenesis, progression and chemotherapy resistance. The results showed that metformin significantly inhibited the expression levels of key proteins of PI3K/Akt/mTOR signaling pathway. CONCLUSIONS: We propose that metformin exhibits anticancer activity in SKOV3 cells and may prove beneficial in the management of ovarian cancers.

HPV genotype analysis for women in Shaanxi Province of China.

The aim of this study was to examine the subtype distribution of human papilloma virus (HPV) in women in the Shaanxi Province of China. A DNA chip, along with polymerase chain reaction amplification and reverse dot blot technology, was adopted to analyze the HPV genotypes of 22,937 cases of cervical cell specimens. The HPV infection rate was 18.70%, wherein high-risk, low-risk, and high- and low-risk multiple infection rates were 15.75, 2.96 and 1.91%, respectively. High-risk infections accounted for 84.20% of total infections. The rate of HPV infection in women with rural residence, high school education or less, a low income, or age over 40 years was significantly higher than that in the control group (negative HPV infection women). Of the 18 detected high-risk HPV subtypes, the most common in single infections were, in the order of prevalence, HPV16, 58, 18, 52, 33, and 56. For multiple high-risk infections, the most common subtypes in the order of prevalence were HPV16, 52, 58, 18, 56, and 33. Age was a factor in the rate of infection, as the 41-50-year age group had a significantly higher risk of infection than the other groups (P < 0.05). In multiple infections, double infections were common, accounting for 77.10% of multiple infections, and triple or more infections were more common in women aged 51-60 years. In Shaanxi Province, high-risk HPV infection in women was mainly attributed to rural residence, age over 40 years, low income, and low education level.

Prevalence of human papillomavirus genotypes among women with cervical lesions in the Shaanxi Province of China.

This study aimed to investigate human papilloma virus (HPV) genotypes among women with cervical lesions in Shaanxi Province, China, to obtain information regarding cervical lesion prevention and treatment. The study included 4508 HPV-positive subjects; cervical swab specimens were collected and tested for HPV infection status and HPV genotypes using polymerase chain reaction and reverse dot-blot hybridization. Women positive for HPV with cervical lesions, including chronic cervicitis, cervical intraepithelial neoplasia, and cervical squamous cell carcinoma (SCC), were examined; HPV-positive women with no cervical lesions were controls. Data were pooled and weighted estimates have been presented. For women with no cervical lesions and positive for one HPV genotype, HPV 52, 16, 58, 81, 33, and 56 were the most common; for multiple-HPV genotype infection, HPV 16, 52, 6, 18, 58, and 66 were the most common. Collectively, HPV 16, 58, 52, 18, 33, and 81 were the most common in women with cervical lesions. HPV 16 comprised 26.71% of single-genotype and 15.64% of multiple-genotype infections. The proportion of HPV-16-positive cases was 29.15%, which was the highest among all HPV genotypes (P < 0.01). Single-HPV genotype infection was the most common in cervical HPV infection (77.48%); infection with two HPV genotypes comprised 72.22% of multiple-genotype infections. The proportion of single-low-risk HPV genotype infections decreased with increase in cervical lesion severity; there were no single- or multiple-low-risk genotype HPV infections in cervical SCC patients. The proportion of multiple-genotype HPV infections with at least one high-risk genotype increased with cervical lesion severity.

Prevalence and patterns of multimorbidity in northeastern China: a cross-sectional study.

OBJECTIVES: Information on multimorbidity in the general populations of developing countries is lacking. We examine the prevalence and patterns of multimorbidity in northeastern China. STUDY DESIGN: A cross-sectional study was conducted on adult residents in Jilin Province, northeastern China from June 2012 to August 2012. METHODS: Data were collected from a large cross-sectional study (n = 21,435) of adult community residents in Jilin Province in northeastern China. Multimorbidity, or co-morbidity, was defined as having two or more of 18 specified prevalent chronic diseases. A range of demographics, socio-economic factors, other risk factors and general mental health were used in describing the distribution of multimorbidity and in exploring the associations between them. RESULTS: Almost a quarter (24.7%) of the adults were found to be multimorbid for chronic diseases. Multimorbidity was more common among older adults, women, rural residents and those with low income. Smoking, increasing BMI and psychological distress were independently associated with multimorbidity. Multimorbid patients were frequent users of primary care. Most dyads of chronic diseases co-occurred more frequently than would be expected on the basis of chance. CONCLUSIONS: Researchers, clinicians and policy makers need to pay special attention to the health care challenges of multimorbidity and develop effective intervention strategies and programs to reduce the burden of multimorbidity.

Metabolic and muscular responses during and after a 100 km hill walk.

AIM: Aim of the study was to assess different metabolic and muscular responses of recreational hikers during and after a hill walk of 100 km duration. METHODS: Nine subjects (6 males and 3 females) completed the 100 km hill walk within 40 hrs. Physiological and muscular responses, and biomarkers were measured during- and 18 hrs after the exercise. RESULTS: On average, exercise intensity was moderate with reference to %HRmax (64±7.1), with a declining trend. Energy expenditure ranged from 102.5 kcal/km to 186.2 kcal/km in different sections. Using a visual analog scale, left and right quadriceps, and left and right calf muscles had elevated values of perceived muscular soreness (5±2.4, 5±2.4, 4.6±2.7 and 4.6±2.7, respectively). Ranges of motion at hip and knee joints decreased at 47.4 km (P<0.05). Creatine kinase for male subjects increased 16-fold (from 106.8±95 U/L to 1747.6±1834.2 U/L) at 79.6 km. Creatine kinase-MB and lactate dehydrogenase for males were also elevated at 79.6 km and peaked at 100 km. Following recovery, creatine kinase for male subjects was still slightly higher than resting level (321.1±283.6 U/L vs. 106.8±95 U/L). Ranges of motion at hip and knee joints were higher than pre-walk level (P<0.05). CONCLUSION: The data suggest that healthy recreational hikers with average physical fitness can complete a 100 km hill walk within 40 hours without showing excessively stressful physiological responses. However, complete recovery would probably require more than 18 hours.

An in vitro investigation of image-guided steerable catheter navigation.

The objective of this study is to provide catheterization with a three-dimensional (3D) guiding image and reduce the collision probability between the catheter tip and vascular wall. A bidirectional steerable catheter was integrated with two magnetic position-tracking sensors on both sides of its bending segment. The tracking information was displayed on the guiding image, which helped the surgeons to determine the relative position between the catheter tip and surrounding vessels. The navigation path was generated on the basis of the vascular skeleton. Moreover, along the path, a series of guiding circular planes were set as the guidance for the catheter. Three operations (bending, advancing, and twisting) were jointly conducted to get the catheter through these guiding planes in turn and eventually into the target vessel. The effectiveness of the proposed navigation method was verified by experiments implemented in an aorta vascular phantom. The navigation system has a mean error of 0.19 mm, a root mean square of 0.49 mm, and a standard deviation of 0.46 mm.

Mesenchymal stem cells treated with rat pancreatic extract secrete cytokines that improve the glycometabolism of diabetic rats.

BACKGROUND: Mesenchymal stem cells (MSCs) under favorable conditions secrete a spectrum of cytokines that promote the survival of surrounding cells via paracrine mechanisms. We explored the impact of rat pancreatic extract (RPE) on cytokine secretion by MSCs and examined the influence of administration of conditioned media of MSCs treated with RPE on blood glucose levels in diabetic rats. METHODS: Cytokine levels (IGF-1, VEGF, bFGF) in conditioned media of MSCs treated with RPE were measured using enzyme-linked immunosorbent assays. We estimated blood glucose levels of STZ-induced diabetic rats following intraperitoneal injection of conditioned media from RPE-treated MSCs. We analyzed histopathology of pancreatic islets by insulin immunostaining and apoptosis through a TUNEL assay. RESULTS: Levels of IGF-1, VEGF, and bFGF were significantly increased in RPE-CM compared with control media. Administration of conditioned media of RPE-treated MSCs significantly lowered the blood glucose levels of diabetic rats. After RPE treatment the insulin-positive area was increased and apoptosis of pancreatic beta cells decreased. CONCLUSION: RPE enhanced the secretion of cytokines by MSCs. MSCs in the pancreatic microenvironment may exert indirect salutary effects via paracrine mediators on injured pancreatic cells in an STZ-induced diabetic animal model. The secreted factors may exert their therapeutic benefits by preventing apoptosis of pancreatic beta cells.

Pennogenin glycosides with a spirostanol structure are strong platelet agonists: structural requirement for activity and mode of platelet agonist synergism.

BACKGROUND: Steroidal saponins have long attracted scientific attention, due to their structural diversity and significant biological activities. For example, total steroidal saponins extracted from the rhizome of Paris polyphylla Sm. var. yunnanensis (TSSPs) constitute an effective treatment for abnormal uterine bleeding. OBJECTIVE: To determine the active constituents in TSSPs and elucidate the mechanisms that underlie their in vivo pharmacologic actions on hemostasis. METHODS: Steroidal saponins were purified by chromatography, and their effects upon hemostasis and platelet function were evaluated by tail bleeding time in mice and rats, aggregometry, flow cytometry and Western blotting. RESULTS: TSSPs promoted hemostasis in vivo and dose-dependently induced rat or human platelet aggregation in vitro. Using bioassay-guided separation, four known pennogenin glycosides with a spirostanol structure were identified as the active ingredients of TSSPs. A structure-activity assay showed that the aglycone and sugar moieties of pennogenin glycosides are both essential for their aggregatory activity. Their synergistic actions on platelet aggregation were observed with pennogenin glycosides and with other known platelet agonists, suggesting that these glycosides are platelet agonists. Aggregation in response to the pennogenin glycosides involved alpha(IIb)beta(3) activation, was inhibited by cAMP, was dependent upon extracellular calcium, secreted ADP and thromboxane synthesis, and was mediated by phosphatidylinositol-3-kinase. CONCLUSION: We identified pennogenin glycosides with a spirostanol structure as the active ingredients of Paris polyphylla Sm. var. yunnanensis in promoting hemostasis in vivo. Their mode of their action on platelets suggests that they represent a new type of platelet agonist.

[Inhibition of platelet function by L-arginine.L-aspartate salt].

The effects of L-arginine.L-aspartate salt (DR) on platelet aggregation, adhesion and release were investigated. Platelet aggregation induced by adenosine 5 -diphosphate (ADP) was significantly inhibited (P<0.01) by intravenous injection of DR (15 mg/kg) in rats or oral administration (15 mg/kg) in rabbits, the inhibitory effect on rabbit platelet aggregation lasting for more than 8 h (P<0.01). Platelet aggregation induced by ADP, collagen or thrombin in rats was all markedly inhibited by 7.5, 15 or 30 mg/kg of DR (bid for 3.5 d, ig, P<0.01). Platelet adhesion to foreign objects was inhibited by 30 mg/kg of DR (ig). Bleeding time in rat tails was prolonged by 30 mg/kg of DR (P<0.05). Furthermore, PGI(2) released from the vascular wall was increased in DR-treated rats (P<0.05), however, TXA(2) released from platelets was not affected. These data demonstrate the inhibitory effect of DR on platelet function, suggesting that its action target may be different from that of acetylsalicylic acid, and that the increase of PGI(2) release may be responsible partly for this effect. It is suggested that DR may probably be used as a new agent for regulating platelet function.

Management of descending necrotizing mediastinitis.

BACKGROUND: Descending necrotizing mediastinitis (DNM) is uncommon, and may be lethal if not treated adequately and promptly. Delayed diagnosis of the disease is sometimes encountered in clinical practice. METHODS: Eight consecutive patients with acute DNM were identified between 1991 and 1995, including five men and three women. The mean age was 45.8 years (range, 22-71 years). The infectious sources consisted of six esophageal perforations, one cervical cutting injury and one tonsillitis. The clinical presentations were evaluated. Diagnostic procedures including chest radiograph, sonogram and computerized tomography scans of the chest and neck were examined. Diagnosis and treatment, including culture results from drained fluids and debrided tissues, and antibiotic and supportive therapies were reviewed. RESULTS: Six patients who underwent aggressive surgical treatment recovered well. Two patients who received supportive treatment died of sepsis alone. The cultured bacteria included: Klebsiella oxytoca, Staphylococcus aureus, Trichosporum and other mixed oral cavity flora. CONCLUSIONS: Early diagnosis and adequate antibiotic and support therapies are essential to achieve good patient outcomes in acute descending mediastinitis. Adequate drainage and debridement, appropriate antibiotic therapy, and sufficient nutritional and respiratory support are the main treatment elements.

Absence of relationship between Schistosoma japonicum and hepatitis B virus infection in the Dongting lake region, China.

In order to determine whether infection with Schistosoma japonicum is related to a higher rate of infection with hepatitis B virus and/or to a higher probability of HBsAg chronic carriage, a population based survey was carried out in China in which HBV markers were studied in 112 subjects with long-lasting S. japonicum infection, and 93 subjects with no S. japonicum infection 37.5% of the cases and 40.9% of controls showed no markers of HBV infection. The prevalence rate of HBsAg was 12.5% in the cases and 12.9% in the controls. For anti-HBc and anti-HBs the figures were 59.8% and 59.8%, and 27.9% and 35.0%, respectively. These data do not support the hypothesis of an interaction between infection with hepatitis B virus and S. japonicum.

The distribution of Schistosoma japonicum eggs in faeces and the effect of stirring faecal specimens.

Experiments were performed to determine whether Schistosoma japonicum eggs are randomly dispersed in faeces and the effect of stirring faecal specimens prior to sampling. For each of 13 patients infected with S. japonicum, eggs were counted in 150 subsamples from a single stool specimen, using the Kato-Katz smear technique. Eggs were non-randomly distributed in all 13 stools, and showed an aggregated distribution. In most patients there were significant differences in the distribution of eggs between the centre and the surface of the stool. Stirring of the stool prior to sampling decreased the variability of counts.