Research progress of TCM treatment of atopic dermatitis based on gut-brain-skin axis / 国际中医中药杂志

Based on the introduction of gut-brain-skin axis, this article discussed the relationship between psychological behavior, intestinal flora, and atopic dermatitis. By combing the literature on the treatment of atopic dermatitis with TCM, it is found that TCM therapy can regulate the relative abundance of intestinal flora, participate in immune metabolism and restore skin barrier function by intervening in the gut-brain-skin axis, so as to achieve the purpose of treating atopic dermatitis.

Dementia Risk and Disadvantaged Neighborhoods.

Importance: Residence in a disadvantaged neighborhood may be associated with an increased risk for cognitive impairment and dementia but is understudied in nationally representative populations. Objective: To investigate the association between the Area Deprivation Index (ADI) and dementia. Design, Setting, and Participants: Retrospective cohort study within the US Veterans Health Administration from October 1, 1999, to September 30, 2021, with a national cohort of older veterans receiving care in the largest integrated health care system in the United States. For each fiscal year, a 5% random sample was selected from all patients (n = 2 398 659). Patients with missing ADI information (n = 492 721) or missing sex information (n = 6) and prevalent dementia cases (n = 25 379) were excluded. Participants had to have at least 1 follow-up visit (n = 1 662 863). The final analytic sample was 1 637 484. Exposure: Neighborhoods were characterized with the ADI, which combines several sociodemographic indicators (eg, income, education, employment, and housing) into a census block group-level index of disadvantage. Participants were categorized into ADI rank quintiles by their census block group of residence (higher ADI rank quintile corresponds with more deprivation). Main Outcome and Measures: Time to dementia diagnosis (using International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes) was estimated with Cox proportional hazards models with age as the time scale, and the sensitivity of the findings was evaluated with Fine-Gray proportional hazards models, accounting for competing risk of death. Results: Among the 1 637 484 Veterans Health Administration patients, the mean (SD) age was 68.6 (7.7) years, and 1 604 677 (98.0%) were men. A total of 7318 patients were Asian (0.4%), 151 818 (9.3%) were Black, 10 591 were Hispanic (0.6%), 1 422 713 (86.9%) were White, and 45 044 (2.8%) were of other or unknown race and ethnicity. During a mean (SD) follow-up of 11.0 (4.8) years, 12.8% of veterans developed dementia. Compared with veterans in the least disadvantaged neighborhood quintile, those in greater disadvantage groups had an increased risk of dementia in models adjusted for sex, race and ethnicity, and psychiatric and medical comorbid conditions (first quintile = reference; second quintile adjusted hazard ratio [HR], 1.09 [95% CI, 1.07-1.10]; third quintile adjusted HR, 1.14 [95% CI, 1.12-1.15]; fourth quintile adjusted HR, 1.16 [95% CI, 1.14-1.18]; and fifth quintile adjusted HR, 1.22 [95% CI, 1.21-1.24]). Repeating the main analysis using competing risk for mortality led to similar results. Conclusions and Relevance: Results of this study suggest that residence within more disadvantaged neighborhoods was associated with higher risk of dementia among older veterans integrated in a national health care system.

Quantitative comparison and rapid discrimination of Panax notoginseng powder and Caulis clematidis armandii using NMR combined with pattern recognition.

BACKGROUND: The market demand for Panax notoginseng (P. notoginseng) is growing rapidly because of its useful properties in food and medicine. However, the frequent adulteration of P. notoginseng seriously affects the health of consumers and is a great challenge to food safety. In this study, low- and high-field nuclear magnetic resonance (LF/HF-NMR) were applied to detect the transverse relaxation distribution of P. notoginseng contaminated with different ratios of Caulis clematidis armandii (CCA) and the components in P. notoginseng and CCA, respectively. RESULTS: Fifty-seven kinds of major and minor components in P. notoginseng and CCA were identified and quantified from their high-resolution NMR spectra, and there were significant differences in ginsenosides, sucrose, and glucose between P. notoginseng and CCA. Furthermore, the partial least squares regression analysis results indicated that LF-NMR parameters (T21 and S21 ) changed linearly as the ratio of CCA increased, and these changes were attributed to the variations in polysaccharide and sucrose in adulterated P. notoginseng. CONCLUSION: In the relaxation time-based pattern recognition models, the authentic P. notoginseng powder could be classified with 100% accuracy from adulterated P. notoginseng when the adulteration ratio was greater than 30%, demonstrating the possibility of LF-NMR, in combination with pattern recognition, for rapid discrimination of food authenticity. © 2022 Society of Chemical Industry.

Systemic Therapy for Hepatocellular Carcinoma: Chinese Consensus-Based Interdisciplinary Expert Statements.

Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer and causes many cancer-related deaths worldwide; in China, it is the second most prevalent cause of cancer deaths. Most patients are diagnosed clinically with advanced stage disease. Summary: For more than a decade, sorafenib, a small-molecular-weight tyrosine kinase inhibitor (SMW-TKI) was the only molecular targeted drug available with a survival benefit for the treatment of advanced HCC. With the development of novel TKIs and immune checkpoint inhibitors for advanced HCC, the management of patients has been greatly improved. However, though angiogenic-based targeted therapy remains the backbone for the systemic treatment of HCC, to date, no Chinese guidelines for novel molecular targeted therapies to treat advanced HCC have been established. Our interdisciplinary panel on the treatment of advanced HCC comprising hepatologists, hepatobiliary surgeons, oncologists, radiologists, pathologists, orthopedic surgeons, traditional Chinese medicine physicians, and interventional radiologists has reviewed the literature in order to develop updated treatment regimens. Key Messages: Panel consensus statements for the appropriate use of new molecular -targeted drugs including doses, combination therapies, adverse reaction management as well as efficacy evaluation, and predictions for treatment of advanced HCC with evidence levels based on published data are presented, thereby providing an overview of molecular targeted therapies for healthcare professionals.

Association of Race and Ethnicity With Incidence of Dementia Among Older Adults.

Importance: The racial and ethnic diversity of the US, including among patients receiving their care at the Veterans Health Administration (VHA), is increasing. Dementia is a significant public health challenge and may have greater incidence among older adults from underrepresented racial and ethnic minority groups. Objective: To determine dementia incidence across 5 racial and ethnic groups and by US geographical region within a large, diverse, national cohort of older veterans who received care in the largest integrated health care system in the US. Design, Setting, and Participants: Retrospective cohort study within the VHA of a random sample (5% sample selected for each fiscal year) of 1 869 090 participants aged 55 years or older evaluated from October 1, 1999, to September 30, 2019 (the date of final follow-up). Exposures: Self-reported racial and ethnic data were obtained from the National Patient Care Database. US region was determined using Centers for Disease Control and Prevention (CDC) regions from residential zip codes. Main Outcomes and Measures: Incident diagnosis of dementia (9th and 10th editions of the International Classification of Diseases). Fine-Gray proportional hazards models were used to examine time to diagnosis, with age as the time scale and accounting for competing risk of death. Results: Among the 1 869 090 study participants (mean age, 69.4 [SD, 7.9] years; 42 870 women [2%]; 6865 American Indian or Alaska Native [0.4%], 9391 Asian [0.5%], 176 795 Black [9.5%], 20 663 Hispanic [1.0%], and 1 655 376 White [88.6%]), 13% received a diagnosis of dementia over a mean follow-up of 10.1 years. Age-adjusted incidence of dementia per 1000 person-years was 14.2 (95% CI, 13.3-15.1) for American Indian or Alaska Native participants, 12.4 (95% CI, 11.7-13.1) for Asian participants, 19.4 (95% CI, 19.2-19.6) for Black participants, 20.7 (95% CI, 20.1-21.3) for Hispanic participants, and 11.5 (95% CI, 11.4-11.6) for White participants. Compared with White participants, the fully adjusted hazard ratios were 1.05 (95% CI, 0.98-1.13) for American Indian or Alaska Native participants, 1.20 (95% CI, 1.13-1.28) for Asian participants, 1.54 (95% CI, 1.51-1.57) for Black participants, and 1.92 (95% CI, 1.82-2.02) for Hispanic participants. Across most US regions, age-adjusted dementia incidence rates were highest for Black and Hispanic participants, with rates similar among American Indian or Alaska Native, Asian, and White participants. Conclusions and Relevance: Among older adults who received care at VHA medical centers, there were significant differences in dementia incidence based on race and ethnicity. Further research is needed to understand the mechanisms responsible for these differences.

Sex Differences in the Risk of Dementia in Older Veterans.

BACKGROUND: Studies have demonstrated women to have a higher prevalence of dementia compared to men. However, sex differences in dementia incidence are controversial with conflicting reports showing women with higher, lower, or similar incidence. Source of difference may be due to clinical setting and lack of consideration of competing risk of death. We examined dementia incidence in a sample of the national Veteran population to determine differences by sex. METHODS: We examined data from the Veterans Health Administration (VHA), the largest integrated health care system in the United States. We studied 947 797 Veterans aged ≥55 years (mean age: 69.9 ± 8.4, 3% female) evaluated in the VHA from October 1, 1999 to September 30, 2019. We estimated age-adjusted incidence rates of dementia (International Classification of Diseases, 9th and 10th Edition codes) by sex, and used Fine-Gray proportional hazards models with age as time scale to examine time to diagnosis, accounting for competing risk of death. RESULTS: During the follow-up (mean 8.4 years), 11.3% (n = 106 977, 11.4% men and 8.0% women) of Veterans developed dementia. Age-adjusted incidence was 12.6/1 000 person-years for men and 12.7/1 000 person-years for women. Compared to male Veterans, risk dementia was slightly higher among females (hazard ratio = 1.15; 95% confidence interval: 1.10-1.20), and on average, female Veterans developed dementia 0.2 years earlier than male Veterans. After additional adjustment for race, education, medical, and psychiatric conditions, results were similar. CONCLUSIONS: Among older Veterans in a national cohort, women had a slightly increased risk for developing dementia compared to men after accounting for competing risk of death.

Guidelines on the treatment with integrated traditional Chinese medicine and western medicine for severe coronavirus disease 2019.

Severe Coronavirus Disease 2019 (COVID-19) is characterized by numerous complications, complex disease, and high mortality, making its treatment a top priority in the treatment of COVID-19. Integrated traditional Chinese medicine (TCM) and western medicine played an important role in the prevention, treatment, and rehabilitation of COVID-19 during the epidemic. However, currently there are no evidence-based guidelines for the integrated treatment of severe COVID-19 with TCM and western medicine. Therefore, it is important to develop an evidence-based guideline on the treatment of severe COVID-19 with integrated TCM and western medicine, in order to provide clinical guidance and decision basis for healthcare professionals, public health personnel, and scientific researchers involved in the diagnosis, treatment, and care of COVID-19 patients. We developed and completed the guideline by referring to the standardization process of the "WHO handbook for guideline development", the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, and the Reporting Items for Practice Guidelines in Healthcare (RIGHT).

Composition Profiling and Authenticity Assessment of Camellia Oil Using High Field and Low Field 1H NMR.

Camellia oil (CA), mainly produced in southern China, has always been called Oriental olive oil (OL) due to its similar physicochemical properties to OL. The high nutritional value and high selling price of CA make mixing it with other low-quality oils prevalent, in order to make huge profits. In this paper, the transverse relaxation time (T2) distribution of different brands of CA and OL, and the variation in transverse relaxation parameters when adulterated with corn oil (CO), were assessed via low field nuclear magnetic resonance (LF-NMR) imagery. The nutritional compositions of CA and OL and their quality indices were obtained via high field NMR (HF-NMR) spectroscopy. The results show that the fatty acid evaluation indices values, including for squalene, oleic acid, linolenic acid and iodine, were higher in CA than in OL, indicating the nutritional value of CA. The adulterated CA with a content of CO more than 20% can be correctly identified by principal component analysis or partial least squares discriminant analysis, and the blended oils could be successfully classified by orthogonal partial least squares discriminant analysis, with an accuracy of 100% when the adulteration ratio was above 30%. These results indicate the practicability of LF-NMR in the rapid screening of food authenticity.

Performance Comparison of Public Hospitals Between 2014 and 2018 in Different Regions of Guangdong Province, China, Following 2017 Medical Service Price Reforms.

This study analyzed performance of public hospitals and regional differences in performance following reform of medical service prices in Guangdong province, China. From three cities in four regions, we randomly selected a total of 12 traditional Chinese medicine hospitals and 12 general tertiary hospitals. Six questionnaires were completed by the hospitals, using 2014-2018 internal data. Principal components analysis was used to compare performances of the hospitals and regions following price reform. The extent to which medical service prices were adjusted varied considerable for different procedures in the same region and for the same category of procedures among regions. After reform, compensation for medical services in public hospitals reached the target of 80%, except in the Western region. However, annual growth of costs to patients was generally above 4%; the burden on patients was not alleviated by fee control. Reforms were more effective for comprehensive than Chinese traditional medicine hospitals. Performance scores of general hospitals in the Pearl River Delta, Eastern, Western, and Northern regions were 1.24, 1.16, -0.22, and -1.01, respectively. This is consistent with ranking by level of economic development of each region. The government should implement a regional medical service pricing mechanism. Additionally, comprehensive and traditional Chinese medicine hospitals should each have appropriate pricing policies. Future policies should focus on controlling costs incurred by patients.

Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): a randomised, open-label, phase 2-3 study.

BACKGROUND: China has a high burden of hepatocellular carcinoma, and hepatitis B virus (HBV) infection is the main causative factor. Patients with hepatocellular carcinoma have a poor prognosis and a substantial unmet clinical need. The phase 2-3 ORIENT-32 study aimed to assess sintilimab (a PD-1 inhibitor) plus IBI305, a bevacizumab biosimilar, versus sorafenib as a first-line treatment for unresectable HBV-associated hepatocellular carcinoma. METHODS: This randomised, open-label, phase 2-3 study was done at 50 clinical sites in China. Patients aged 18 years or older with histologically or cytologically diagnosed or clinically confirmed unresectable or metastatic hepatocellular carcinoma, no previous systemic treatment, and a baseline Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 were eligible for inclusion. In the phase 2 part of the study, patients received intravenous sintilimab (200 mg every 3 weeks) plus intravenous IBI305 (15 mg/kg every 3 weeks). In the phase 3 part, patients were randomly assigned (2:1) to receive either sintilimab plus IBI305 (sintilimab-bevacizumab biosimilar group) or sorafenib (400 mg orally twice daily; sorafenib group), until disease progression or unacceptable toxicity. Randomisation was done using permuted block randomisation, with a block size of six, via an interactive web response system, and stratified by macrovascular invasion or extrahepatic metastasis, baseline α-fetoprotein, and ECOG performance status. The primary endpoint of the phase 2 part of the study was safety, assessed in all patients who received at least one dose of study drug. The co-primary endpoints of the phase 3 part of the study were overall survival and independent radiological review committee (IRRC)-assessed progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT03794440. The study is closed to new participants and follow-up is ongoing for long-term outcomes. FINDINGS: Between Feb 11, 2019 and Jan 15, 2020, we enrolled 595 patients: 24 were enrolled directly into the phase 2 safety run-in and 571 were randomly assigned to sintilimab-bevacizumab biosimilar (n=380) or sorafenib (n=191). In the phase 2 part of the trial, 24 patients received at least one dose of the study drug, with an objective response rate of 25·0% (95% CI 9·8-46·7). Based on the preliminary safety and activity data of the phase 2 part, in which grade 3 or worse treatment-related adverse events occurred in seven (29%) of 24 patients, the randomised phase 3 part was started. At data cutoff (Aug 15, 2020), the median follow-up was 10·0 months (IQR 8·5-11·7) in the sintilimab-bevacizumab biosimilar group and 10·0 months (8·4-11·7) in the sorafenib group. Patients in the sintilimab-bevacizumab biosimilar group had a significantly longer IRRC-assessed median progression-free survival (4·6 months [95% CI 4·1-5·7]) than did patients in the sorafenib group (2·8 months [2·7-3·2]; stratified hazard ratio [HR] 0·56, 95% CI 0·46-0·70; p<0·0001). In the first interim analysis of overall survival, sintilimab-bevacizumab biosimilar showed a significantly longer overall survival than did sorafenib (median not reached [95% CI not reached-not reached] vs 10·4 months [8·5-not reached]; HR 0·57, 95% CI 0·43-0·75; p<0·0001). The most common grade 3-4 treatment-emergent adverse events were hypertension (55 [14%] of 380 patients in the sintilimab-bevacizumab biosimilar group vs 11 [6%] of 185 patients in the sorafenib group) and palmar-plantar erythrodysaesthesia syndrome (none vs 22 [12%]). 123 (32%) patients in the sintilimab-bevacizumab biosimilar group and 36 (19%) patients in the sorafenib group had serious adverse events. Treatment-related adverse events that led to death occurred in six (2%) patients in the sintilimab-bevacizumab biosimilar group (one patient with abnormal liver function, one patient with both hepatic failure and gastrointestinal haemorrhage, one patient with interstitial lung disease, one patient with both hepatic faliure and hyperkalemia, one patient with upper gastrointestinal haemorrhage, and one patient with intestinal volvulus) and two (1%) patients in the sorafenib group (one patient with gastrointestinal haemorrhage and one patient with death of unknown cause). INTERPRETATION: Sintilimab plus IBI305 showed a significant overall survival and progression-free survival benefit versus sorafenib in the first-line setting for Chinese patients with unresectable, HBV-associated hepatocellular carcinoma, with an acceptable safety profile. This combination regimen could provide a novel treatment option for such patients. FUNDING: Innovent Biologics. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

The effectiveness and safety of ultrasound-guided hydrostatic reduction for pediatric acute intussusception / 中华超声影像学杂志

Objective:To evaluate the effectiveness and safety of ultrasound-guided hydrostatic reduction for pediatric acute intussusception.Methods:One thousand eight hundred and thirty patients with acute intussusception diagnosed by ultrasound in Shenzhen Children′s Hospital from September 2017 to July 2020 were treated with ultrasound-guided hydrostatic reduction method. The therapeutic effects, complications and ultrasonic features were observed.Results:Among 1 830 cases, 1 791 cases were diagnosed as primary intussusception, and 39 cases were secondary intussusception. The overall rate of successful ultrasound enema reduction were 1 780/1 830(93.7%) patients. All 50/1 830(2.7%) patients underwent surgery after unsuccessful enema reduction, including 42 cases of primary intussusception, and 8 cases of secondary intussusception. The complication of intestinal perforation occurred in 3 cases (0.16%), and there were no deaths.Conclusions:Ultrasound-guided enema reduction for pediatric acute intussusception is an effective and safe method without radiation exposure, and can be used as the preferred method for non-operative treatment of intussusception.

Metabolic Effect of Dietary Taurine Supplementation on Grouper (Epinephelus coioides): A 1H-NMR-Based Metabolomics Study.

Taurine is an indispensable amino acid for many fish species and taurine supplementation is needed when plant-based diets are used as the primary protein source for these species. However, there is limited information available to understand the physiological or metabolic effects of taurine on fish. In this study, 1H nuclear magnetic resonance (NMR)-based metabolomic analysis was conducted to identify the metabolic profile change in the fish intestine with the aim to assess the effect of dietary taurine supplementation on the physiological and metabolomic variation of fish, and reveal the possible mechanism of taurine's metabolic effect. Grouper (Epinephelus coioides) were divided into four groups and fed diets containing 0.0%, 0.5%, 1.0%, and 1.5% taurine supplementation for 84 days. After extraction using aqueous and organic solvents, 25 significant taurine-induced metabolic changes were identified. These metabolic changes in grouper intestine were characterized by differences in carbohydrate, amino acid, lipid and nucleotide. The results reflected both the physiological state and growth of the fish, and indicated that taurine supplementation significantly affects the metabolome of fish, improves energy utilization and amino acid uptake, promotes protein, lipid and purine synthesis, and accelerates fish growth.

Ginsenoside Reduces Cognitive Impairment During Chronic Cerebral Hypoperfusion Through Brain-Derived Neurotrophic Factor Regulated by Epigenetic Modulation.

Increased expression of brain-derived neurotrophic factor (BDNF) has been associated with memory-enhancing and neuroprotective properties of some drugs under chronic cerebral hypoperfusion (CCH) condition. Ginsenoside Rd (GSRd), one of the main active ingredients in Panax ginseng, is widely used for brain protection. However, it is poorly understood whether epigenetic mechanisms implied in the BDNF modulation after GSRd treatment for CCH remain elusive. Here, we investigated the neuroprotective effects of GSRd and the involved mechanisms. We demonstrated that GSRd administration ameliorated CCH-induced impairment of learning and memory behaviors, evidenced by decreased escape latency and increased number of crossing the platform in Morris water maze test. This improvement was associated with promoted neuron survival and increased BDNF expression in the hippocampus and prefrontal cortex of CCH mice. GSRd improved neuron survival and decreased neuron apoptosis and the level of caspase-3 under oxygen-glucose deprivation/reoxygenation (OGD/R) by upregulation of BDNF as well as in vitro. The levels of acetylated histone H3 (Ac-H3) and histone deacetylase (histone deacetylase 2 (HDAC2)) were altered under OGD/R in a time-dependent manner, and GSRd reestablished the balance between Ac-H3 and HDAC2 which resulted in upregulation of BDNF and increased neuron survival. MS-275, an inhibitor of class I HDACs, abolished the levels of Ac-H3 at the bdnf promoters and enhanced upregulation of BDNF after GSRd administration, suggesting a synergistic effect between GSRd and MS-275. All the data suggested that GSRd provided neuroprotection by epigenetic modulation which accounted for the regulation of BDNF in CCH mice.

Adjuvant sorafenib after heptectomy for Barcelona Clinic Liver Cancer-stage C hepatocellular carcinoma patients.

AIM: To investigate the efficacy and safety of adjuvant sorafenib after curative resection for patients with Barcelona Clinic Liver Cancer (BCLC)-stage C hepatocellular carcinoma (HCC). METHODS: Thirty-four HCC patients, classified as BCLC-stage C, received adjuvant sorafenib for high-risk of tumor recurrence after curative hepatectomy at a tertiary care university hospital. The study group was compared with a case-matched control group of 68 patients who received curative hepatectomy for HCC during the study period in a 1:2 ratio. RESULTS: The tumor recurrence rate was markedly lower in the sorafenib group (15/34, 44.1%) than in the control group (51/68, 75%, P = 0.002). The median disease-free survival was 12 mo in the study group and 10 mo in the control group. Tumor number more than 3, macrovascular invasion, hilar lymph nodes metastasis, and treatment with sorafenib were significant factors of disease-free survival by univariate analysis. Tumor number more than 3 and treatment with sorafenib were significant risk factors of disease-free survival by multivariate analysis in the Cox proportional hazards model. The disease-free survival and cumulative overall survival in the study group were significantly better than in the control group (P = 0.034 and 0.016, respectively). CONCLUSION: Our study verifies the potential benefit and safety of adjuvant sorafenib for both decreasing HCC recurrence and extending disease-free and overall survival rates for patients with BCLC-stage C HCC after curative resection.

Ginsenoside-Rd Promotes Neurite Outgrowth of PC12 Cells through MAPK/ERK- and PI3K/AKT-Dependent Pathways.

Panax ginseng is a famous herbal medicine widely used in Asia. Ginsenosides have been identified as the principle active ingredients for Panax ginseng's biological activity, among which ginsenoside Rd (Rd) attracts extensive attention for its obvious neuroprotective activities. Here we investigated the effect of Rd on neurite outgrowth, a crucial process associated with neuronal repair. PC12 cells, which respond to nerve growth factor (NGF) and serve as a model for neuronal cells, were treated with different concentrations of Rd, and then their neurite outgrowth was evaluated. Our results showed that 10 µM Rd significantly increased the percentages of long neurite- and branching neurite-bearing cells, compared with respective controls. The length of the longest neurites and the total length of neurites in Rd-treated PC12 cells were much longer than that of respective controls. We also showed that Rd activated ERK1/2 and AKT but not PKC signalings, and inhibition of ERK1/2 by PD98059 or/and AKT by LY294002 effectively attenuated Rd-induced neurite outgrowth. Moreover, Rd upregulated the expression of GAP-43, a neuron-specific protein involved in neurite outgrowth, while PD98059 or/and LY294002 decreased Rd-induced increased GAP-43 expression. Taken together, our results provided the first evidence that Rd may promote the neurite outgrowth of PC12 cells by upregulating GAP-43 expression via ERK- and ARK-dependent signaling pathways.

Ginsenoside Rd Is Efficacious Against Acute Ischemic Stroke by Suppressing Microglial Proteasome-Mediated Inflammation.

A great deal of attention has been paid to neuroprotective therapies for cerebral ischemic stroke. Our two recent clinical trials showed that ginsenoside Rd (Rd), a kind of monomeric compound extracted from Chinese herbs, Panax ginseng and Panax notoginseng, was safe and efficacious for the treatment of ischemic stroke. In this study, we conducted a pooled analysis of the data from 199 patients with acute ischemic stroke in the first trial and 390 in the second to reanalyze the efficacy and safety of Rd. Moreover, animal stroke models were carried out to explore the possible molecular mechanisms underlying Rd neuroprotection. The pooled analysis showed that compared with placebo group, Rd could improve patients' disability as assessed by modified Rankin Scale (mRS) score on day 90 post-stroke and reduce neurologic deficits on day 15 or day 90 post-stroke as assessed by NIH Stroke Scale (NIHSS) and Barthel Index (BI) scores. For neuroprotective mechanisms, administration of Rd 4 h after stroke could inhibit ischemia-induced microglial activation, decrease the expression levels of various proinflammatory cytokines, and suppress nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha (IκBα) phosphorylation and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) nuclear translocation. An in vitro proteasome activity assay revealed a significant inhibitory effect of Rd on proteasome activity in microglia. Interestingly, Rd was showed to have less side effects than glucocorticoid. Therefore, our study demonstrated that Rd could safely improve the outcome of patients with ischemic stroke, and this therapeutic effect may result from its capability of suppressing microglial proteasome activity and sequential inflammation.

A high baseline HBV load and antiviral therapy affect the survival of patients with advanced HBV-related HCC treated with sorafenib.

BACKGROUND AND AIMS: Although a high viral load is an independent risk factor for recurrence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after surgery, the prognostic impact of viral load on advanced HCC is unclear. This study investigated the impact of baseline HBV load and antiviral therapy on survival of patients with advanced HCC treated with sorafenib. METHODS: Of 130 patients with advanced HBV-related HCC received first-line sorafenib therapy were evaluated in a multicenter, retrospective study. RESULTS: No patients experienced severe hepatic impairment because of HBV reactivation during sorafenib therapy. The median progression-free survival (PFS) and overall survival (OS) of all patients were 5.7 and 9.6 months respectively. Patients with a baseline HBV DNA ≤10(4) copies/ml had significantly better OS than those with >10(4) copies/ml (10.4 vs 6.6 months; P = 0.002), but PFS showed an increasing trend (5.8 vs 4.8 months; P = 0.068). Patients who received antiviral therapy had a better trend in OS than those who did not (12.0 vs 8.3 months; P = 0.058), but there was no difference in PFS (6.4 vs 4.1 months; P = 0.280). In a multivariate analysis, the baseline HBV DNA level >10(4) copies/ml (P = 0.001; hazard ration [HR] = 2.294; 95% CI 1.429-3.676) and antiviral therapy (P = 0.038; HR 0.617; 95% CI 0.390-0.975) were independent predictors of OS. CONCLUSION: In patients with advanced HBV-related HCC treated with sorafenib, a high baseline HBV load was an adverse prognostic factor for survival. However, survival was significantly improved with the use of antiviral therapy.

Effect of triptolide on expressions of Notch receptors and ligands in rats with adjuvant- induced arthritis and reduced pulmonary function / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of triptolide on Notch receptor and ligand expressions in rats with adjuvant-induced arthritis (AA).</p><p><b>METHODS</b>Forty rats were randomly divided into normal control (NC) group, model (MC) group, methotrexate group and triptolide groups. Rat models of AA were established by an intradermal injection of 0.1 mL Freund's complete adjuvant into the right paw. Twelve days after the injection, the rats were treated with corresponding drugs for 30 days; the rats in NC group and MC group were given saline only. Paw edema volume (E), arthritis index (AI), pulmonary function, histomorphologies, and Notch receptor/ ligand expression in the lung tissue were analyzed after the treatments.</p><p><b>RESULTS</b>Compared with the NC group, E, AI, Notch3, Notch4, and Delta1 expressions in the lung tissues significantly increased while pulmonary function and pulmonary expressions of Notch1, Jagged1, and Jagged2 significantly decreased the model rats (P<0.01). Compared with the MC group, triptolide-treated rats showed significantly improved pulmonary functions, increased expressions of Notch1, Jagged1, and Jagged2 and decreased expressions of Notch3, Notch4, and Delta1 in the lungs (P<0.05, P<0.01); the therapeutic effect of triptolide was better than that of methotrexate.</p><p><b>CONCLUSION</b>Triptolide can reduce inflammatory reaction and immune complex deposition to improve joint and pulmonary symptoms in rats with AA possibly by up-regulating the expressions of Notch3, Notch4, and Delta1 and down-regulating the expressions of Jagged1, Jagged2, and Notch1.</p>

[Bacterial culture and drug sensitivity analysis of upper urinary tract calculi complicating with infection].

OBJECTIVE: To investigate the bacteriology and drug sensitivity of upper urinary tract calculi patients, and to provide information for choosing suitable antibiotics. METHODS: In the study, 21 patients who suffered from lithiasis in upper urinary tract and required an emergency drainage for acute obstruction and infection were the "acute group"; 64 patients with calculi in upper urinary tract and accompanied with no infectious symptoms were the "common group". The bacteriology and drug sensitivity of the two groups were investigated. RESULTS: Gram-negative bacteria infected the most common of upper urinary tract calculi patients with infection, accounting for 71.4% in the acute group and 65.7% in the common group, among which Escherichia coli were the predominant ones (35.7% in the acute group and 32.9% in the common group). No difference was found between these two groups in bacterial distribution (P>0.05). Although the average drug resistance rate of Gram-negative bacteria in the acute group was higher than that in the common group, it revealed no significant difference (P>0.05). The drug resistance rate to semisynthetic penicillin, cefuroxime and ceftriaxone were more than 50%, 60%, and 50%, respectively. Quinolones, such as ciprofloxacin and levofloxacin, got a 45% drug resistance. Aminoglycoside, carbapenema were sensitive to Gram-negative bacteria. Cefoperazone/sulbactam and piperacillin/tazobactam were more effective than ceftriaxone and piperacillin, respectively. CONCLUSION: There was no significant difference between upper urinary tract calculi patients with acute infection and common infection in bacteriology and drug sensitivity. Semisynthetic penicillin, the second generation of cephalosporin and quinolone were no longer the good choices of empirical use. Antibiotics combined with ß-lactamase inhibitors would be an ideal empirical therapeutic choice.

Complete response to sorafenib in a patient with recurrent hepatocellular carcinoma.

Partial hepatectomy is still the treatment of choice aiming at a cure for patients with hepatocellular carcinoma (HCC), provided that the patient can tolerate the treatment. For patients with multiple recurrent HCC after partial hepatectomy which cannot be treated by re-hepatectomy or local ablative therapy, the prognosis is extremely poor. Sorafenib is a molecular-targeted agent which has been demonstrated in two global phase III randomized controlled trials to show survival benefit for advanced HCC. Here, we present a 56-year-old patient with HCC who showed complete clinical response after sorafenib was used for tumor recurrence which developed 3 mo after partial hepatectomy. There was no evidence of progression of disease for 60 mo till now after continuous treatment with sorafenib.