[Quality Control Indexes for Oncology (2023 edition) and hot topics in breast surgery].

The National Health Commission of the People's Republic of China has formulated the Quality Control Indexes for Oncology (2023 edition), with the objective of improving medical quality scientifically, refined and standardized. Among these indexes, the rate of pretreatment clinical TNM staging and the coincidence rate of evaluation of pretreatment TNM staging lay national standards for patients to formulate rational and targeted treatment strategies. This article reviewed the literature and referred to Chinese Medical Association Clinical Practice Guide for Breast Surgery, and presented recommendations for the hot topics of breast surgery, such as pathological sampling of the breast specimen, sentinel lymph node biopsy for early-stage breast cancer, breast conserving surgery, axillary lymph node dissection, breast reconstruction surgery, endoscopic-assisted breast surgery, the principles of surgical treatment for metastatic breast cancer, neoadjuvant treatment for advanced disease, and surgical grade of breast surgery, which have been widely concerned in recent years, to help improve homogenization of breast cancer treatment in China.

[Association of greenness, nitrogen dioxide with the prevalence of hypertension among the elderly over 65 years old in China].

Objective: To investigate the association of mixed exposure to greenness and nitrogen dioxide(NO2) and hypertension among the older adults aged 65 years and over in China. Methods: The study subjects were from the Chinese Longitudinal Healthy Longevity Survey from 2017 to 2018. A total of 15 423 older adults aged 65 years and over meeting the criteria were finally included in the study. A questionnaire survey was used to collect information on demographic characteristics, lifestyle habits and self-reported prevalence of hypertension. Blood pressure values were obtained through physical examination. The level of normalized difference vegetation index(NDVI) was measured by the Medium-resolution Imaging Spectral Radiator(MODIS) of the National Aeronautics and Space Administration(NASA). The concentration of NO2 was from China's surface air pollutant data set. Meteorological data was from NASA MERRA-2. The exposure to NDVI and NO2 for each study subject was calculated based on the area within a 1 km radius around their residence. The association between mixed exposure of NDVI and NO2 as well as their interaction and hypertension in older adults was analyzed by using the multivariate logistic regression model. The restrictive cubic spline(RCS) function was used to explore the exposure-response relationship between greenness and NO2 and the risk of hypertension in study subjects. Results: The mean age of 15 423 older adults were (85.6±11.6). Women accounted for 56.3%(8 685/15 423) and 55.6%(8 578/15 423) lived in urban areas. The mean time of residence was (60.9±28.5) years. 59.8% of participants were with hypertension. The mean NDVI level was 0.41±0.13, and the mean NO2 concentration was (32.18±10.36) µg/cm3. The results of multivariate logistic regression analysis showed that NDVI was inversely and linearly associated with the hypertension in older adults, with the OR(95%CI) value of 0.959(0.928-0.992). Compared with the T1 group of NDVI, the risk of hypertension was lower in the T3 group, with the OR(95%CI) value of 0.852(0.769-0.944), and the trend test was statistically significant(P<0.05). Compared with the T1 group of NO2, the risk of hypertension was higher in the T2 and T3 groups, with OR(95%CI) values of 1.160(1.055-1.275) and 1.244(1.111-1.393), and the trend test was statistically significant (P<0.05). The result of the RCS showed that NDVI was inversely and linearly associated with hypertension in older adults. NO2 was nonlinearly associated with hypertension in older adults. The interaction analysis showed that NDVI and NO2 had a negative multiplicative interaction on the risk of hypertension, with OR(95%CI) value of 0.995(0.992-0.997). Conclusion: Exposure to greenness and NO2 are associated with hypertension in older adults.

[Association of greenness exposure with waist circumference and central obesity in Chinese adults aged 65 years and over].

Objective: To examine the association of greenness exposure with waist circumference (WC) and central obesity in older adults in China. Methods: Based on the cross-sectional data from the Chinese Longitudinal Healthy Longevity Survey in 2017-2018, 14 056 participants aged 65 years and over were included. Demographic characteristics, lifestyle, WC, and other information were collected through a questionnaire and physical examination. Based on the satellite monitoring data of moderate-resolution imaging spectroradiometer (MODIS) provided by NASA, the annual mean of normalized difference vegetation index (NDVI) within a radius of 1 000 meters was obtained as the measurement value of greenness exposure. Multivariate linear regression model, multivariate logistic regression model, and restricted cubic splines (RCS) model were used to analyze the association and dose-response relationship between greenness exposure and WC and central obesity in older adults in China. Results: A total of 14 056 participants were enrolled with a median age of 84.0 years [IQR: 75.0-94.0 years]. About 45.0% (6 330) of them were male and 48.6% (5 853) were illiterate. There were 10 964 (78.0%) participants from rural. The mean of WC was (84.4±10.8) cm. Central obesity accounted for 60.2% (8 465), and the NDVI range was (-0.06, 0.78). After adjusting for confounding factors, the multivariate linear regression model showed that the change value of WC in the urban group [ß (95%CI):-0.49 (-0.93, -0.06)] was smaller than that in the rural [-0.78 (-0.98, -0.58)] for every 0.1 unit increase in NDVI (Pinteraction=0.022). Compared with the Q1 group in NDVI, WC of Q2 and Q3 groups in rural decreased, and the ß (95%CI) values were-1.74 (-2.5, -0.98) and-2.78 (-3.55, -2.00), respectively. The multivariate logistic regression model showed that after adjusting for confounding factors, the risk of central obesity decreased for urban and rural older adults with an increase of 0.1 unit in NDVI, and the OR (95%CI) values were 0.87 (0.80, 0.95) and 0.86 (0.82, 0.89), respectively (Pinteraction=0.284). Compared with the Q1 group in NDVI, the risk of central obesity in the Q2 and Q3 groups in rural was lower, and the OR (95%CI) values were 0.68 (0.58, 0.80) and 0.57 (0.49, 0.68), respectively. The results of the multivariate regression model with RCS showed that there was a non-linear association of NDVI with WC (Pnonlinear=0.006) and central obesity (Pnonlinear=0.025). Conclusion: Greenness exposure is negatively associated with WC and central obesity in older adults in China.

[Docetaxel, carboplatin plus trastuzumab as neoadjuvant setting in patients with early-stage human epidermal growth factor receptor 2 positive breast cancer: a retrospective analysis].

Objective: To examine the efficacy of docetaxel, carboplatin plus trastuzumab regimen (TCH) as neoadjuvant setting in early-stage human epidermal growth factor receptor 2 (HER2) positive breast cancer. Methods: Totally 522 patients diagnosed with early-stage HER2 positive breast cancer at Breast Disease Center, Peking University First Hospital between January 2013 to December 2018 were enrolled, which constituted 21.8% (522/2 394) of early-stage invasive breast cancer. Clinical pathological factors were retrospectively analyzed. There were 113 female patients underwent TCH neoadjuvant chemotherapy, aging 52(13) years (range: 23 to 69 years). Pathologic complete pathological response(pCR) was defined as ypT0N0M0, and the rate of pCR was calculated. Kaplan-Meier method and Log-rank test were used for survival comparison. Results: Patients who received trastuzumab-based therapy(n=294) had higher disease-free survival (DFS) compared with those who omitted trastuzumab(n=177) (84.4% vs. 72.4%, χ²=4.095, P=0.046). Eighteen of 113 patients (15.9%) experienced grade 3 to 4 chemotherapy-realted toxicity. Grade 3 to 4 neutropenia occurred in 12 patients, while grade 3 to 4 diarrhea occurred in 6 patients. Thirty-one of 113 (27.4%) patients achieved pCR. DFS and overall survival (OS) were similar between patients who achieved pCR and non-pCR (DFS: 91.8% vs. 85.0%, OS: 92.5% vs. 90.5%, all P>0.05). According to Miller-Payne system, patients who achieved G4 to G5 had improved DFS compared with G1 to G3 (89.6% vs. 81.5%, χ²=5.340, P=0.021), but they had similar OS (91.4% vs. 89.1%, χ²=1.008, P=0.315). Conclusions: TCH is an effective regimen in neoadjuvant setting for patients with HER2 positive breast cancer. Patients who achieved G4 to G5 had improved DFS.

[The Breast Cancer Cohort Study in Chinese Women: research design and preliminary results of clinical multi-center cohort].

Objective: The incidence of breast cancer in Chinese women continues to rise. The large breast cancer cohort studies in China are relatively scarce. There are many bottlenecks in the construction of large clinical cohort for breast cancer diagnosis, treatment, and prognoses, such as inconsistent standards, high rates of lost follow-up, repeated construction, and inability to share. To better solving the difficulties and problems faced by large-scale clinical cohort research in China, this project will cooperate with several tertiary A hospitals to establish a breast cancer cohort in Chinese women. It also provides a data platform and technical support for breast cancer multi-center clinical cohort research. Methods: Based on the evidence-based medicine and expert opinion and consensus, we established a breast cancer cohort standardized indicator set-recording baseline information, diagnosis and treatment-related information of the enrolled patients, and collecting biological specimens. According to the technical specification of long-term follow-up for the endpoint, data management, and data security and in the large population-based cohort study, a standardized follow-up system for the diagnosis, treatment, and prognosis of breast cancer prospective cohorts is formed. Results: Based on standardized data sets and the computer discipline's advantage from the University of Science and Technology Beijing, we integrate the new information technology methods, including dynamic information collection terminals and social networks. Thus, the quality of control programs on compliance and intelligence data was improved, and a Chinese women breast cancer cohort database was developed. By February 2020, 12 147 patients were included in the clinical cohort database. Biological specimens'resources in cohort construction were collected and cooperated with Shandong University to research the multi-center quality control system and shared evaluation system of biobanks. Building an open and shared biobank network and forming a full chain of breast cancer research platform. Conclusion: With the implementation of the "13(th) Five-Year Plan" precision medicine research, this study provides a research foundation for precision diagnosis and treatment of breast cancer and provides data support for the country to formulate relevant medical policies.

[Characteristics of peripheral blood leukocyte differential counts in patients with COVID-19].

To investigate the early changes of peripheral blood leukocyte differential counts in patients with COVID-19. Ten patients with COVID-19 and 30 patients with other viral pneumonia (non-COVID-19) admitted to The Sixth People's Hospital of Shanghai and Jinshan Branch Hospital from January 22 to February 17, 2020 were enrolled in this study. The differential counts of white blood cells (WBC) were analyzed. Patients in COVID-19 group showed relatively lower absolute WBC count 4.95(3.90,6.03)×10(9)/L, lymphocyte absolute count 1.20(0.98,1.50)×10(9)/L and eosinophil absolute count 0.01(0.01,0.01)×10(9)/L. Leukopenia developed in two patients(2/10), lymphocytopenia also in two patients(2/10). Seven over ten patients presented with eosinophil cytopenia. In non-COVID-19 group, absolute WBC count was 8.20(6.78,9.03)×10(9)/L (P<0.001), lymphocyte absolute count 1.75(1.20,2.53)×10(9)/L(P=0.036), eosinophil absolute count 0.02(0.01,0.03)×10(9)/L(P=0.005). Lymphocytopenia occurred in 16.7% patients, eosinophil cytopenia in 16.7% patients too. In conclusion, leukopenia, lymphocytopenia and eosinophil cytopenia are more common in COVID-19 patients than those in non-COVID-19 patients.

[Characteristics of peripheral blood leukocyte differential counts in patients with COVID-19].

To investigate the early changes of peripheral blood leukocyte differential counts in patients with COVID-19. Ten patients with COVID-19 and 30 patients with other viral pneumonia (non-COVID-19) admitted to Shanghai Jiao Tong University Affiliated Sixth People's Hospital and Jinshan Branch Hospital from January 22 to February 17, 2020 were enrolled in this study. The differential counts of white blood cells were analyzed. Patients in COVID-19 group showed relatively lower absolute white blood cell (WBC) count 4.95(3.90,6.03)×10(9)/L, lymphocyte absolute count 1.20(0.98,1.50)×10(9)/L and eosinophil absolute count 0.01(0.01,0.01)×10(9)/L. Leukopenia developed in two patients(2/10), lymphocytopenia also in two patients(2/10). Seven over ten patients presented with eosinophil cytopenia. In non-COVID-19 group, absolute WBC count was 8.20 (6.78,9.03) ×10(9)/L (P<0.001), lymphocyte absolute count 1.75(1.20,2.53)×10(9)/L(P=0.036), eosinophil absolute count 0.02(0.01,0.03)×10(9)/L(P=0.05). Lymphocytopenia occurred in (16.7%) patients, eosinophil cytopenia in 16.7% patients too. In conclusion, leukopenia, lymphocytopenia and eosinophil cytopenia are more common in COVID-19 patients than those in non- COVID-19 patients.

[A retrospective analysis on the prognostic evaluation of triple-negative breast cancer with prognostic staging according to the AJCC Breast Cancer Staging System, Eighth Edition].

Objective: To investigate the clinical relevance of prognostic staging according to the AJCC Breast Cancer Staging System, Eighth Edition for evaluation of the prognosis of triple-negative breast cancer. Methods: The clinical data of 293 patients with triple-negative breast cancer who were treated at the Breast Disease Center, Peking University First Hospital, between January 2008 and December 2014, were retrospectively analyzed. All patients were female, with age of 53(16) years (M(Q(R))). The patients were staged according to the AJCC Breast Cancer Staging System, Eighth Edition. Survival analysis was performed by Kaplan-Meier method and Log-rank test. The role of clinical staging and prognostic staging in prognostic evaluation was investigated. Results: In all, 293 patients with triple-negative invasive breast cancer with complete clinical data and follow-up data were treated over a 7-year period. The follow-up time was 64.5(32.8) months, the 5-year overall survival (OS) rate was 83.9%, and the 5-year disease-free survival (DFS) rate was 84.1%. The results showed that clinical staging and prognostic staging were correlated with the DFS rate and OS rate of patients with triple-negative breast cancer (χ(2) were 15.395 to 50.084,P=0.00). However, these two staging systems yielded different results. The prognostic stage of 91.8%(269/293) patients was higher than that of the original anatomical stage. There were significant differences in disease-free survival rate (χ(2)=22.357,P=0.00) and overall survival rate (χ(2)=50.084, P=0.00) among patients with different clinical stages. There were significant differences in disease-free survival rate (χ(2)=15.395,P=0.00) and overall survival rate (χ(2)=29.187,P=0.00)among patients with different prognostic stages. Conclusions: The prognostic stage according to the AJCC Breast Cancer Staging System, Eighth Edition complements the clinical stage. It has a good predictive value for the prognosis of triple-negative breast cancer.

[Breast reconstruction after mastectomy in breast cancer patients: specialization and standardization].

In recent years, with the improvement of screening and early diagnosis, the overall prognosis of breast cancer patients has been greatly improved in China. Breast reconstruction is an option to improve cosmetic outcomes and quality of life for the patients received mastectomy, this procedure has attracted a lot of attention. The breast reconstruction surgery is recommended by the 2018 NCCN Clinical Practice Guidelines in Oncology for Breast Cancer in patients with appropriate indications. Despite the high proportion of breast reconstruction after mastectomy in western countries, Chinese breast surgeon should objectively understand the differences in breast structure and cultural backgrounds between Chinese and foreign women, and conduct rigorous clinical practice on the basis of calm thinking. In particular, it should be clearly recognized that we have more local advanced and high-risk cases in newly diagnosed breast cancer patients. Making efforts to improve the overall survival for patients with breast cancer must be the top priority for our surgeon. Breast reconstruction for all patients without identifying the distinction of personal characters and indications should be avoided, and the pursuing of high proportion of clinical data with no consideration of the realities of clinical practice in China should also be avoided. The indication of breast reconstruction for breast cancer patients received mastectomy must be strictly determined by the surgeon.

[Analysis of neoadjuvant docetaxel, carboplatin and trastuzumab (TCH) in HER-2-positive breast cancer].

Objective: To analyze docetaxel (T) and carboplatin (C) combined with trastuzumab (H) -TCH regimen as neoadjuvant systemic therapy in early breast cancer patients with human epidermal growth factor receptor 2 (HER-2) positive. Methods: From January 2008 to December 2014, the data of patients diagnosed as early breast cancer in Breast Disease Center of Peking University First Hospital were retrospective reviewed. The data of patients with HER-2 positive conducted TCH neoadjuvant therapy and surgery, and with the complete clinicopathological information were analyzed. Results: A total of 77 cases were enrolled in this study. We defined G2+ G3+ G4+ G5 as responsive group according to Miller-Payne grading system, the responsive rate was 84.4% (65/77). The rate of complete pathological remission (pCR) was 39.0% (30/77). The 5-year disease free survival (DFS) was 87.3%, and 5-year overall survival (OS) was 93.6%. There was a significant difference between DFS and OS in the responsive group and non-responsive group (DFS: χ2=6.762, P=0.009; OS: χ2=5.062, P=0.024). Conclusion: TCH is an effective neoadjuvant therapy for patients with HER-2 positive breast cancer, and the toxic and side effects were under control.

[Current situation and prospect of breast cancer liquid biopsy].

Liquid biopsy is a diagnostic approach by analyzing body fluid samples. Peripheral blood is the most common sample. Urine, saliva, pleural effusion and ascites are also used. Now liquid biopsy is mainly used in the area of neoplasm diagnosis and treatment. Compared with traditional tissue biopsy, liquid biopsy is minimally invasive, convenient to sample and easy to repeat. Liquid biopsy mainly includes circulating tumor cells and circulating tumor DNA (ctDNA) detection. Detection of ctDNA requires sensitive and accurate methods. The progression of next-generation sequencing (NGS) and digital PCR promote the process of studies in ctDNA. In 2016, Nature published the result of whole-genome sequencing study of breast cancer. The study found 1 628 mutations of 93 protein-coding genes which may be driver mutations of breast cancer. The result of this study provided a new platform for breast cancer ctDNA studies. In recent years, there were many studies using ctDNA detection to monitor therapeutic effect and guide treatment. NGS is a promising technique in accessing genetic information and guiding targeted therapy. It must be emphasized that ctDNA detection using NGS is still at research stage. It is important to standardize ctDNA detection technique and perform prospective clinical researches. The time is not ripe for using ctDNA detection to guide large-scale breast cancer clinical practice at present.

[An analysis of 68 invasive lobular breast cancer cases in clinicopathological characteristics and the prognostic determinants].

Objective: To study the clinicopathological characteristics and the prognostic determinants of the invasive lobular carcinoma breast cancer. Methods: This was a retrospective single-center study of invasive lobular breast cancer cases diagnosed from January 2008 to December 2014 at Peking University First Hospital Breast Disease Center. The study enrolled 68 invasive lobular breast cancer patients, which represented 3.64% (68/1 870) of total invasive breast cancer. The median age of all selected patients was 46 years ranging from 36 to 83 years. All patients were restaged based on the 8(th) edition of AJCC cancer staging system and follow-up data including disease-free survival (DFS) and overall survival (OS) were analyzed to explore the prognostic determinants. The 5-year OS and DFS were calculated using Kaplan-Meier method; the significance of correlations between clinicopathological features and prognostic factors was estimated using log-rank test. Results: There were significant differences in OS between patients with different anatomic stage, prognostic stage, lymph node metastasis, progesterone receptor (PR) expression, lymphvascular invasion and perineural invasion (χ(2:) 4.318 to 32.394, all P<0.05); significant differences in DFS were also observed between patients with different anatomic stage, prognostic stage, lymph node metastasis, PR expression, human epidermal growth factor receptor-2 expression, Ki-67 level, histological grade and lymphvascular invasion (χ(2:) 4.347 to 27.369, all P<0.05). Prognostic stages of 52.9% patients changed compared with anatomic stage, among which Luminal subtype mainly downstaged (22/30), however, triple negative subtype mainly upstaged (6/6). Conclusions: Anatomic stage, prognostic stage, lymph node metastasis, PR expression, lymphvascular invasion are the prognostic factors of invasive lobular breast cancer. Regard to invasive lobular breast cancer patients, clinicians should pay close attention to the differences between prognostic stage and anatomic stage.

[Impact of carbon dioxide pneumoperitoneum in operating rooms on the health of medical staffs].

Objective: To evaluate the impact of CO(2) pneumoperitoneum in operating rooms on the health of medical staffs. Methods: In June 2016, the thirty-three medical staffs in operating rooms were chosen as the object of the research.Seventeen people who took part in the pneumoperitoneum operation were selected as a exposure group and sixteen people who took part in the laparotomy operation were selected as a control group.Vital signs and arterial blood gases of medical staffs in the two groups were both measured in pre-operation and post-operation. Occupational Health Questionnaires were conducted to collect information on age, weight and postoperative symptoms. The level of CO(2) in operating room was determined by a portable infrared CO(2) analyzer. Results: Compared with the control group, the concentration of CO(2) in the exposed group was higherat T(1), T(2) and T(3) (t=22.227, 13.583, 17.408, P<0.05) . Heart rates and PaCO(2) in the exposure group raised greatly (t=2.132, 2.129, P<0.05) , while pH decreased (t=-3.015, P<0.05) . The differences between the two groups were statistically significant. Conclusion: The increase of mild acidosis and thesense of job burnout in medical staffs could be caused by CO(2) pollution in the operating rooms.

Apocynin and ebselen reduce influenza A virus-induced lung inflammation in cigarette smoke-exposed mice.

Influenza A virus (IAV) infections are a common cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Oxidative stress is increased in COPD, IAV-induced lung inflammation and AECOPD. Therefore, we investigated whether targeting oxidative stress with the Nox2 oxidase inhibitors and ROS scavengers, apocynin and ebselen could ameliorate lung inflammation in a mouse model of AECOPD. Male BALB/c mice were exposed to cigarette smoke (CS) generated from 9 cigarettes per day for 4 days. On day 5, mice were infected with 1 × 10(4.5) PFUs of the IAV Mem71 (H3N1). BALF inflammation, viral titers, superoxide production and whole lung cytokine, chemokine and protease mRNA expression were assessed 3 and 7 days post infection. IAV infection resulted in a greater increase in BALF inflammation in mice that had been exposed to CS compared to non-smoking mice. This increase in BALF inflammation in CS-exposed mice caused by IAV infection was associated with elevated gene expression of pro-inflammatory cytokines, chemokines and proteases, compared to CS alone mice. Apocynin and ebselen significantly reduced the exacerbated BALF inflammation and pro-inflammatory cytokine, chemokine and protease expression caused by IAV infection in CS mice. Targeting oxidative stress using apocynin and ebselen reduces IAV-induced lung inflammation in CS-exposed mice and may be therapeutically exploited to alleviate AECOPD.

Expression level and distribution of HMGB1 in Sombati's cell model and kainic acid-induced epilepsy model.

OBJECTIVE: Observe the expression and distribution of HMGB1 in Sombati's cell model and kainic acid-induced epileptic rats' model. MATERIALS AND METHODS: Dissociated hippocampal neurons from neonatal SD rats and cultured those for 9 days, then changed medium to Mg2+-free medium for 3 hours to induce Sombati's cell model. The expression level of HMGB1 in the neurons was detected at 24h and 72h by Western Blotting. Appropriate kainic acid was injected into the lateral ventricles to induced epileptic rats' model in vivo trial, the expression level and distribution of HMGB1 at 24h and 72h were established by immunohistochemistry. RESULTS: The expression level of HMGB1 showed significantly different between model group and control group both in vitro and in vivo trials. At 24h, the expression level of HMGB1 in the model group was lower than the control group (p < 0.05), and became higher than the control group at 72h (p < 0.05). From the in vivotrial, a nucleus-to-cytoplasm translocation was also discovered. CONCLUSIONS: This investigation indicates that HMGB1 plays a crucial role in the pathophysiology of epilepsy, by altering its quantity and distribution.

Selected ginsenosides of the protopanaxdiol series are novel positive allosteric modulators of P2X7 receptors.

BACKGROUND AND PURPOSE: The P2X7 receptor is an ATP-gated ion channel predominantly expressed in immune cells and plays a key role in inflammatory processes. Ginseng is a well-known Chinese herb with both pro- and anti-inflammatory properties and many of its actions have been ascribed to constituent ginsenosides. We screened a number of ginsenoside compounds for pharmacological activity at P2X7 receptors, that might contribute to the reported immunomodulatory actions of ginseng. EXPERIMENTAL APPROACH: We used several assays to measure responses of P2X7 receptors, ATP-mediated dye uptake, intracellular calcium measurement and whole-cell patch-clamp recordings. HEK-293 cells stably expressing human P2X7 receptors were used in addition to mouse macrophages endogenously expressing P2X7 receptors. KEY RESULTS: Four ginsenosides of the protopanaxdiol series, Rb1, Rh2, Rd and the metabolite compound K (CK) potentiated the dye uptake responses of P2X7 receptors, whereas other ginsenosides tested were ineffective (1-10 µM). The potentiation was rapid in onset, required a threshold concentration of ATP (>50 µM) and had an EC50 of 1.08 µM. CK markedly enhanced ATP-activated P2X7 currents, probably via an extracellular site of action. One of the consequences of this potentiation effect is a sustained rise in intracellular Ca(2+) that could account for the decrease in cell viability in mouse macrophages after a combination of 500 µM ATP and 10 µM CK that are non-toxic when applied alone. CONCLUSIONS AND IMPLICATIONS: This study identifies selected ginsenosides as novel potent allosteric modulators of P2X7 channels that may account for some of the reported immune modulatory actions of protopanaxdiol ginsenosides in vivo.

Ginsenoside Rg1 protects chronic cyclosporin a nephropathy from tubular cell apoptosis by inhibiting endoplasmic reticulum stress in rats.

INTRODUCTION: This study tested the effect of ginsenoside Rg1 (G-Rg1) in cyclosporin A (CsA)-induced endoplasmic reticulum (ER) stress on renal tubular cell apoptosis in a rat model of chronic CsA nephropathy. MATERIALS AND METHODS: Twenty-two Sprague-Dawley rats were randomized into 3 groups: a control group, a model group (CsA 25 mg/kg per day), and a G-Rg1 treatment group (CsA 25 mg/kg per day and G-Rg1 20 mg/kg per day). We examined the effects of G-Rg1 on histopathology, terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, and expression of glucose-regulated protein 78, CCAAT/enhancer-binding protein homologous protein, and caspase-3 by using Western blot analysis. RESULTS: G-Rg1 attenuated CsA-induced tubulointerstitial fibrosis and reduced tubular epithelial cell apoptosis as assessed by terminal deoxynucleotidyl transferase dUTP nick-end labeling staining and caspase-3 expression. Compared with the model group, it reduced the expression of glucose-regulated protein 78 and CCAAT/enhancer-binding protein homologous protein (0.12 ± 0.03 vs 0.48 ± 0.05 [P < .01]; 0.55 ± 0.11 vs 1.08 ± 0.07 [P < .05]), respectively. CONCLUSIONS: G-Rg1 mitigates the progression of chronic CsA nephropathy, at least in part, through inhibition of ER stress-triggered tubular cell apoptosis.

Therapeutic potential of Panax ginseng and ginsenosides in the treatment of chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major global health burden and will become the third largest cause of death in the world by 2030. It is currently believed that an exaggerated inflammatory response to inhaled irritants, in particular cigarette smoke, cause progressive airflow limitation. This inflammation, where macrophages, neutrophils and lymphocytes are prominent, leads to oxidative stress, emphysema, airways fibrosis and mucus hypersecretion. COPD responds poorly to current anti-inflammatory treatments including corticosteroids, which produce little or no benefit. Panax ginseng has a long history of use in Chinese medicine for respiratory conditions, including asthma and COPD. OBJECTIVES: In this perspective we consider the therapeutic potential of Panax ginseng for the treatment of COPD. RESULTS: Panax ginseng and its compounds, ginsenosides, have reported effects through multiple mechanisms but primarily have anti-inflammatory and anti-oxidative effects. Ginsenosides are functional ligands of glucocorticoid receptors and appear to inhibit kinase phosphorylation including MAPK and ERK1/2, NF-κB transcription factor induction/translocation, and DNA binding. They also inhibit pro-inflammatory mediators, TNF-α, IL-6, IL-8, ROS, and proteases such as MMP-9. Panax ginseng protects against oxidative stress by increasing anti-oxidative enzymes and reducing the production of oxidants. CONCLUSION: Given that Panax ginseng and ginsenosides appear to inhibit processes related to COPD pathogenesis, they represent an attractive therapeutic target for the treatment of COPD.

Inhibition of glycogen synthesis by increased lipid availability is associated with subcellular redistribution of glycogen synthase.

Increased lipid availability is associated with diminished insulin-stimulated glucose uptake and glycogen synthesis in muscle, but it is not clear whether alterations in glycogen synthase activity itself play a direct role. Because intracellular localization of this enzyme is involved in its regulation, we investigated whether fat oversupply causes an inhibitory redistribution. We examined the recovery of glycogen synthase in subcellular fractions from muscle of insulin-resistant, fat-fed rats and chow-fed controls, either maintained in the basal state or after a euglycaemic-hyperinsulinaemic clamp. Although glycogen synthase protein and activity were mostly recovered in an insoluble fraction, insulin caused translocation of activity from the smaller soluble pool to the insoluble fraction. Fat-feeding, which led to a reduction in glycogen synthesis during the clamp, was associated with a depletion in the soluble pool, consistent with an important role for this component. A similar depletion was also observed in cytosolic fractions of muscles from obese db/db mice, another model of lipid-induced insulin resistance. To investigate this in more detail, we employed lipid-pretreated L6 myotubes, which exhibited a reduction in insulin-stimulated glycogen synthesis independently of alterations in glucose flux or insulin signalling through protein kinase B. In control cells, insulin caused redistribution of a minor cytosolic pool of glycogen synthase to an insoluble fraction, which was again forestalled by lipid pretreatment. Glycogen synthase recovered in the insoluble fraction from pre-treated cells exhibited a low fractional velocity that was not increased in response to insulin. Our results suggest that the initial localization of glycogen synthase in a soluble pool plays an important role in glycogen synthesis, and that its sequestration in an insulin-resistant insoluble pool may explain in part the reduced glycogen synthesis caused by lipid oversupply.