[Progress in treatment for malignant pleural mesothelioma].

Malignant pleural mesothelioma (MPM) is a kind of invasive malignant tumor originated from pleural tissue. The incidence of MPM is not high in the population, but the prognosis is very poor. The median survival time is only about 12 months. Pemetrexed combined with platinum is the first-line chemotherapy regimen recommended by the current guidelines. The use of bevacizumab will further prolong the survival of chemotherapy. Once resistance happened, no anti-tumor treatment has been confirmed to achieve survival benefits. Therefore, there is no recommended standard second-line MPM regimen in international and domestic guidelines, including National Comprehensive Cancer Network (NCCN) guidelines. Vinorelbine, gemcitabine and other monotherapy regimens are commonly used in clinical practice, but the median progression free survival (PFS) is only about 3 months. Immune checkpoint inhibitors (ICIS) have been proved to have a significant inhibitory effect on tumor growth in a variety of malignant tumors, and their efficacy is related to the expression of programmed death-ligand 1(PD-L1). In unresectable MPM, programmed death 1 (PD-1)/PD-L1 inhibitors have been used in a series of clinical studies in the first-line, second-line and above treatment. Some of the results have been cited and recommended by international guidelines, but the overall efficacy improvement is still limited. This review summarizes the latest clinical studies and researches in the field of MPM treatment and predicts the directions and prospect of improving the therapeutic effect in the future.

Short communication: A decrease in diameter of milk fat globules accompanies milk fat depression induced by conjugated linoleic acid supplementation in lactating dairy cows.

Milk fat is secreted from the mammary gland in the form of milk fat globules (MFG). Although milk fat depression has been studied since the beginning of the last century, the extent to which this phenomenon alters MFG synthesis is not fully understood. The aim of this study was to evaluate the effect of conjugated linoleic acid (CLA) on the size and distribution of MFG during milk fat depression in dairy cows. Twelve Holstein cows in mid lactation (145 ± 31 d in milk, 583 ± 34.6 kg of body weight, and 27.2 ± 2.4 kg of milk/d) were randomly assigned to a control diet or control plus Ca-protected CLA at 15 g/kg of dry matter for a 6-d period. The average diameter and particle size distribution of MFG were measured using a Mastersizer 3000 laser particle size analyzer (Malvern Instruments Ltd., Malvern, UK). Feeding CLA did not affect dry matter intake (16.2 ± 0.4 kg/d), milk production (28.4 ± 0.4 kg/d), milk protein, or lactose, but it decreased milk fat content (3.46 vs. 2.52%). In addition, surface area-related mean diameter of fat globules in cows fed CLA was lower compared with controls (3.02 vs. 3.45 µm). The percentage of large fat globules decreased and that of small fat globules increased in response to CLA. Overall, the data suggest that the milk fat depression induced by CLA is accompanied by a decrease in average diameter of MFG.

[Insights into Hangzhou patent medicine industry business characteristics in Qing dynasty from drug indexes of three large pharmacies].

Drug Indexes are of significance for investigation on ancient patent medicine industry. Herein, we compared Zhang Tongtai Wan San Gao Dan Quanlu (10th year of Jiaqing Reign, 1805), Ye Zhongde Tang Dan Wan Quanlu (4th year of Xianfeng Reign, 1854 and 5th year of Tongzhi Reign, 1866) and Hu Qingyu Tang Wan San Gao Dan Quanji(3th year of Guangxu Reign, 1877) to illustrate the business features of Hangzhou patent medicine industry in Qing Dynasty.The three pharmacies, Zhang Tongtai Tang, Ye Zhongde Tang and Hu Qingyu Tang, were all adept in utilizing ancient prescriptions that contained various preparations, emphasized commercial ethics and product qualities, distributed their products in flexible pattern and focused on distillation formula. Moreover, each of the three pharmacies exhibited their own characteristics in product types and commercialization.

[Clinical features of long segmental myelopathy caused by nitrous oxide].

OBJECTIVE: To analyze the clinical and imaging characteristics of the neurological damage caused by nitrous oxide (N2O). METHODS: In the study, 10 patients in the Department of Neurology of China-Japan Friendship Hospital from October 2015 to February 2018 were retrospectively analyzed for the demographic data, the history of inhaled N2O, clinical features, blood examination, electrophysiological examination, spinal magnetic resonance imaging and therapeutic efficacy profiles. RESULTS: The male-to-female ratio was 4:6 and it presented with an age-of-onset 17-26 years [the average age: (20.80±3.12) years]. The time from inhaled N2O to onset was 1 month to 1 year [the average time: (6.95±4.19) months]. Paralysis in all the patients and numbness in 9 patients were the main clinical features, while positive Lhermitte's sign in 3 patients, urinary and defecation disturbance in 4 patients were also found. Blood examination indicated anemia in 2 patients, giant cell anemia in 1 case and small cell hypochromic anemia in 1 case. 3 cases had been treated with vitamin B12 in an external hospital, and the other 7 cases had abnormal increase in homocysteine levels. Electrophysiological examinations showed sensory and motor nerve involvement in 9 patients, and motor nerve involvement in 1 patient. The severity of lower extremity lesion was significantly heavier than that of upper extremity. Spinal magnetic resonance imagings showed that long segmental lesions were present in the cervical spinal cord of all the patients, 3 cases with long segmental lesions of the thoracic cord and 2 cases with spinal cord swelling. In 6 cases, the horizontal axis had an "inverted V-type" T2 high signal, 1 case was classified as "crescent", and 3 cases were "eight-shaped". The symptoms in these 10 cases were alleviated in varying degrees after stopping the inhalation of nitrous oxide, actively supplementing high doses of vitamin B12 and doing early rehabilitation exercises. CONCLUSION: Myelopathy with nitrous oxide presents as paralysis and numbness in limb extremities. In imaging, cervical spinal cord damage is common, accompanied by thoracic spinal cord damage. The horizontal axis is more common in the "inverted V-type". Treatment with high doses of vitamin B12 is effective.

[Effects of calcium supplementation during the pregnancy and early infancy stage on the body mass index and gut microbiota in the infants].

Objective: To investigate the effects of calcium supplementation during the pregnancy and early infancy stage on body mass index (BMI) and gut microbiota in the infants. Methods: A total of 1 752 healthy pregnant women and their infants (breast feeding) in two maternal and child health care hospitals of Beijing were chosen as the subjects in this study from May to October 2016. Questionnaires were used to obtain the general information and supplementation of calcium and vitamin D in mothers and their infants. The body length and weight of infants at birth and 6 months were recorded to calculate the BMI. The random number table method was used to randomly select 40 infants from each group for gut microbiota analysis (If less than 40 infants were all included in this study, 23 infants in the pregnancy and early infancy would be all treated with calcium supplements. There were 6 infants who was not added calcium during the pregnancy but added in the early infancy). Then it was compared that the effects of calcium supplementation during the pregnancy and early infancy on the BMI and gut microbiota composition of infants were determined at birth and 6 months. Results: Compared to the group with no calcium supplementation during the pregnancy ((12.76±1.23), (17.68±0.76)kg/m(2)), the BMI of infants at birth and 6 months in the group with calcium supplementation during the pregnancy ((13.51±0.47), (17.91±0.23)kg/m(2)) were significantly higher(P<0.05). In the group with maternal calcium supplementation, the BMI at 6 months ((18.63±0.52)kg/m(2)), BMI increment ((5.71±0.54)kg/m(2)) and the content of lactobacillus (21.04%±3.68%) in the only calcium supplementation subgroup in the early infancy were higher than those in only vitamin D supplementation subgroup ((17.69±0.89) kg/m(2), (4.17±1.01) kg/m(2) and 12.28%±3.86%) (P<0.05). In the group without maternal calcium supplementation, the content of lactobacillus (20.15%±4.87%) in the only calcium supplementation subgroup were also higher than those in only vitamin D supplementation subgroup (14.64%±3.71%) (P<0.05). Conclusion: Appropriate calcium supplementation during the pregnancy is good for the growth and development of the fetus. Calcium supplementation in the early infancy could increase the BMI of infants, and promote the growth of intestinal lactobacillus.

Distribution of tumor stage and initial treatment modality in patients with primary hepatocellular carcinoma.

OBJECTIVE: This study reviewed the distribution of each tumor stage and each type of initial treatment modality among patients with primary hepatocellular carcinoma (HCC) treated at a tertiary tumor hospital between January 2003 and October 2013. METHODS: Baseline data of patients with primary hepatocellular carcinoma treated between January 2003 and October 2013 were retrospectively collected. Tumor stage was determined according to the Barcelona Clinic Liver Cancer (BCLC) staging system and Hong Kong Clinic Liver Cancer (HKLC) staging system. RESULTS: A total of 6241 patients with primary hepatocellular carcinoma were included in the analysis. In accordance with the BCLC, 28.9% of patients were in stage 0/A, 16.2% in stage B, 53.6% in stage C, and 1.3% in stage D. According to the HKLC stage system, 8.4% patients were in stage I, 1.5% in stage IIa, 29.0% in stage IIb, 10.0% in stage IIIa, 33.6% in stage IIIb, 3.4% in stage IVa, 2.5% in stage IVb, 0.2% in stage Va, and 11.4% in stage Vb. Treatment modalities applied to this patient group were as follows: 33.3% of patients underwent hepatic resection, 36.7% underwent transarterial chemoembolization (TACE), 2.2% underwent radiotherapy, 0.9% underwent local ablated therapy, 8.8% underwent systemic chemotherapy, 4.2% underwent traditional herbal medicine therapy, 0.1% underwent targeted drug therapy, and 13.8% received no treatment. Hepatic resection was the most frequent therapy for patients with BCLC 0/A/B disease, and TACE was the initial therapy for patients with BCLC C disease. In the Hong Kong Clinic Liver Cancer staging system, the main treatments for HKLC I to IIIb disease is hepatic resection and TACE. Systemic chemotherapy was the initial therapy for patients with HKLC IVa/IVb disease. Most HKLC Va/Vb patients received traditional Chinese medicine treatment. CONCLUSION: Prevalence of stage BCLC B and C disease was high among our hepatocellular carcinoma patients. In Hong Kong Clinic Liver Cancer staging system, HKLC I to IIIb disease was high among our HCC patients. Hepatic resection and TACE are initial therapies.

[Philosophical basis of original thinking in Chinese medicine].

Chinese Medicine, being one of the most creative disciplines, with the superiority of its disciplinary theory and thinking pattern closely related to the studies of Sinology.Chinese Medicine has taken on its great aspect with good favorable prospects of timing, geographical and unity and coordination of human relationship, hence, the development of CM needs the recognition of its original advantage, making clear of its sources of original thought.The XIANG thought (iconic thinking) is the basic connotation and basic features of traditional Chinese thinking. The imported western culture depresses the XIANG (iconic) thinking of original thought, and, as a result, conceptual thinking of scientism and western medicine became the mainstream. Actually, conceptual thinking shouldn't be rejected, whereas the original thinking and original superiority characterized by our own nation should also be manifested. The knowledge, both oriental and occidental, are to be accepted simultaneously, while Chinese medicine and western medicine should be all mastered thoroughly and integrated as a whole so as to further proceed together.

A double-blind comparative study of Chinese herbal medicine Jinlianqingre Effervescent Tablets in combination with conventional therapy for the treatment of uncomplicated hand, foot, and mouth disease.

Chinese herbal medicine Jinlianqingre Effervescent Tablets (JET) are the recommended control measure for uncomplicated hand, foot, and mouth disease (HFMD) by the Ministry of Health of China. However, high-quality evidence to support this recommendation is limited. A total of 288 patients ranging in age from 1 to 13 years were randomly assigned to JET in combination with conventional therapy (mainly including the reduction of temperature by applying physical cooling paste or warm bathing), or conventional therapy with placebo group for 7 days. The objective was to test the hypothesis that JET combination therapy is more effective than conventional therapy for uncomplicated HFMD. A randomized, double-blind, placebo-controlled trial was designed. Our study showed that, compared with conventional therapy, the median time to fever resolution was significantly shorter in the JET combination therapy (8 vs. 80 h; p < 0.0001); the risk of fever resolution increased in the JET combination therapy [hazard ratio, 19.8; 95% confidence interval (CI), 12.8 to 30.7]; the median healing time of rash or oral ulcer was significantly shorter in the JET combination therapy (14 vs. 74 h; p < 0.0001); and the median symptom score for skin or oral mucosa lesions improved more rapidly in the JET combination therapy during the follow-up period. The median duration of hospital stay was 6 days in the JET combination therapy and 7 days in the conventional therapy (p < 0.0001). No significant adverse events and complications were found in both groups. The addition of JET to conventional therapy reduced fever clearance time, healing time of skin or oral mucosa lesions, and duration of hospital stay in children with uncomplicated HFMD.

Comparative antioxidant activity of cultivated and wild Vaccinium species investigated by EPR, human neutrophil burst and COMET assay.

OBJECTIVES: The Vaccinium (V.) spp. berries are considered a source of antioxidants, mainly belonging to polyphenols, specifically flavonoids and anthocyanins. Wild genotypes generally contain more antioxidants than cultivated counterparts. So, seven different antioxidants assays on extracts from cultivated and wild Vaccinium berries were performed, to evaluate their difference in terms of bioactivity on oxidative protection and minimum dosage to have a significant action. MATERIALS AND METHODS: Four cell-free antioxidant assays (ABTS radical scavenging and electronic paramagnetic resonance using Fremy's salt, superoxide anion and hydroxyl radical), and three assays on human cells (two luminol amplified chemiluminescence, LACL, one on DNA damage, COMET) were used to measure the effects of cultivated blueberry (V. corymbosum) and wild bilberry (V. myrtillus) on the differently induced oxidative stress. Concentrations vs activity patterns were obtained by successive dilutions of extracts in order to identify both EC50 and minimum significant activity (MSA). RESULTS: All the assays (except for the hydroxyl radical scavenging) showed a good relationship mainly with anthocyanin and polyphenol content and the significant greater activity of wild Vaccinium extracts. In fact, LACL data gave an EC50 of 11.8 and an MSA of 5.2 g were calculated as fresh weight dosage in cultivated berries, compared with lower doses in wild berries, EC50 of 5.7 g and MSA of 3.4 g. CONCLUSIONS: Wild Vaccinium extracts averaged 3.04 and 2.40 fold more activity than cultivated extracts by EC50 and MSA, respectively. COMET assay confirmed the stronger action on DNA protection in wild samples.

Characterisation of the antioxidant effects of Aesculus hippocastanum L. bark extract on the basis of radical scavenging activity, the chemiluminescence of human neutrophil bursts and lipoperoxidation assay.

OBJECTIVES: Oxidative stress is increasingly recognised as a pivotal factor that plays a number of roles in the inflammatory response to environmental signals. It has been claimed that Aesculus hippocastanum extracts have antioxidant and anti-inflammatory activity, but these claims are mainly based on the results of chemical reactions and folk-medicine. MATERIALS AND METHODS: The aim of this study was to examine whether a bark extract of Aesculus hippocastanum interferes with reactive oxygen/nitrogen species (ROS/RNS) during the course of human neutrophil respiratory bursts, and to establish the lowest concentration at which it still has antioxidant activity by means of luminol amplified chemiluminescence (LACL). We also studied its ability to counteract lipid peroxidation (LPO) in human cells. Before investigating its antioxidant effects on human cells, we analysed its scavenging activity against ABTS*+, hydroxyl radical, superoxide anion, and Fremy's salt (those last three by means of electron paramagnetic resonance (EPR) spectrometry). RESULTS: The extract of Aesculus hippocastanum exerted its anti-ROS/RNS activity in a concentration-dependent manner with significant effects being observed for even very low concentrations: 10 microg/ml without L-Arg, and 5 microg/ml when L-Arg was added to the fMLP test. The LPO assay confirmed these results, which were paralleled by the EPR study. CONCLUSIONS: These findings are interesting for improving the antioxidant network and restoring redox balance in human cells, and extend the possibility of using plant-derived molecules to antagonise the oxidative stress generated in living organisms when the balance is in favour of free radicals as a result of the depletion of cell antioxidants.

Carnitine and carnitine orotate affect the expression of the prolactin-releasing peptide gene.

Carnitine is involved in fatty acid metabolism in mammals and is widely used as a nutritional supplement; carnitine orotate is a more absorbable form of carnitine. We investigated the effects of carnitine and carnitine orotate on mouse prolactin-releasing peptide (PrRP) mRNA expression. Twenty-four female mice were randomly divided into four groups of six; control mice were orally drenched with physiological saline solution (250 mg/kg body weight) and treatment mice were orally drenched with carnitine (250 mg/kg) or carnitine orotate (250 or 750 mg/kg), once a day, for 20 days from parturition. The carnitine or carnitine orotate was dissolved in saline solution before administration. The hypothalamus, pituitary and ovary were sampled on day 21 after parturition, and PrRP mRNA levels in these tissues were measured by semi-quantitative PCR, with glyceraldehyde 3-phosphate dehydrogenase as a control. Expression of PrRP in mice treated with carnitine and carnitine orotate was significantly increased in the ovary and significantly reduced in the pituitary gland. Compared with the control, hypothalamus PrRP mRNA increased significantly in the carnitine and low-dose carnitine orotate groups and decreased significantly in the high-dose carnitine orotate group. We conclude that carnitine and carnitine orotate regulate expression of PrRP in the pituitary gland and ovaries.

Effect of narrow-band UVB phototherapy on soluble cell adhesion molecules in patients with psoriasis vulgaris.

This study investigated the effect of narrow-band ultraviolet B (NB-UVB) phototherapy on serum levels of the soluble cell adhesion molecules sE-selectin, sP-selectin, sL-selectin and soluble intercellular adhesion molecule-1 (sICAM-1) in 58 patients with psoriasis vulgaris. Psoriasis Area and Severity Index (PASI) scores significantly decreased after treatment, confirming the efficacy of NB-UVB phototherapy. Serum levels of sE-selectin also decreased significantly after treatment, and levels of sICAM-1 showed a significant correlation with PASI score and with levels of sE-selectin. The efficacy of NB-UVB phototherapy in improving psoriatic lesions may be a function of decreased serum levels of E-selectin. These findings emphasize the complex roles of soluble cell adhesion molecules in the immunopathogenesis of psoriasis.

Effect of triterpene acids of Eriobotrya japonica (Thunb.) Lindl. leaf on inflammatory cytokine and mediator induction from alveolar macrophages of chronic bronchitic rats.

OBJECTIVE: The study was to evaluate the effect of triterpene acids of Eriobotrya japonica (thunb.) lindl. leaf (TAL) on inflammatory cytokine and mediator expression in alveolar macrophages (AM) of chronic bronchitic (CB) rats. METHODS: CB was induced by endotracheal instillation of lipopolysaccharide (LPS) followed by Bacillus Calmette Guerin (BCG) injection via the caudal vein one week later. Treatment groups received TAL at there different doses (50, 150, or 450 mg/kg daily i. g.), Ketotifen fumarate (5 mg/kg daily i. g.) or dexamethasone (1.2 mg/kg daily i. g.) for two weeks, 7 days after LPS injection. AM were then isolated and incubated for 24 h. IL-1, TNF-alpha and PGE2 levels in cultured supernatants were measured by thymocyte co-stimulating assay and radioimmunoassay. Immunocytochemistry staining and western-blot were used for intracellular location and activation of p65 subunit of NF-kB. LTB(4) level was analyzed by reverse-phase high performance liquid chromatography (RP-HPLC). RESULTS: The levels of TNF-alpha, IL-1, NF-kB, PGE2 and LTB(4) expression in AM of TAL groups were significantly decreased compared to the CB group (P < 0.05 or P < 0.01), in a dose dependent manner. CONCLUSION: TAL inhibited NF-kB activation in AM from CB rats and led to down regulation of TNF-alpha, IL-1, PGE(2) and LTB(4) expression, which might be a mechanism for its anti-inflammatory effects in CB rats.

Understanding ZHENG in traditional Chinese medicine in the context of neuro-endocrine-immune network.

Traditional Chinese medicine uses ZHENG as the key pathological principle to understand the human homeostasis and guide the applications of Chinese herbs. Here, a systems biology approach with the combination of computational analysis and animal experiment is used to investigate this complex issue, ZHENG, in the context of the neuro-endocrine-immune (NEI) system. By using the methods of literature mining, network analysis and topological comparison, it is found that hormones are predominant in the Cold ZHENG network, immune factors are predominant in the Hot ZHENG network, and these two networks are connected by neuro-transmitters. In addition, genes related to Hot ZHENG-related diseases are mainly present in the cytokine-cytokine receptor interaction pathway, whereas genes related to both the Cold-related and Hot-related diseases are linked to the neuroactive ligand-receptor interaction pathway. These computational findings were subsequently verified by experiments on a rat model of collagen-induced arthritis, which indicate that the Cold ZHENG-oriented herbs tend to affect the hub nodes in the Cold ZHENG network, and the Hot ZHENG-oriented herbs tend to affect the hub nodes in the Hot ZHENG network. These investigations demonstrate that the thousand-year-old concept of ZHENG may have a molecular basis with NEI as background.

Raising harmonic variation of arterial pulse in dying rats.

Our previous study revealed that the coefficient of variation of harmonic magnitude (HCV) of radial arterial pulse was significantly raised before the death of cancer patients. In this study, we recorded the caudate arterial pulse of 24 Sprague-Dawley rats that had a fatal dose of urethane injected into their abdomens. Twenty rats were dead within 3 hours after the injection and four survived. We defined the last 100 minutes of each rat's life as the dying process. During the dying process, we found that both the systolic blood pressure and diastolic blood pressure dropped steeply during the last 5 minutes. However, all HCVs, except HCV1, climbed steeply before the last 5 minutes. The HCV1 of the dying rats was significantly higher than that of rats that survived, starting from the first minute (P < 0.01). The HCV2 of the dying rats was significantly higher than that of the survived rats starting from the 52nd minute (P < 0.05). The HCV3 and HCV4 of the dying rats were significantly higher than those of the survived rats until the 70th minute and the 80th minute, respectively (P < 0.05). Furthermore, HCV2-HCV4 proceeded with the dying process and increased gradually. We concluded that HCVs, which failed first in the high-frequency components and then in the low-frequency components, could provide physicians with earlier information to prevent the coming failure of circulatory system, and could reflect quantitatively pathological severity and predict patient outcome. The specific Fourier components in the pulse provide more physiological information than systolic and diastolic blood pressures.

Phosphorus removal under anoxic conditions in a continuous-flow A2N two-sludge process.

The Anaerobic-Anoxic/Nitrification (A2N) system is a continuous-flow, two-sludge process in which Poly-P bacteria are capable of taking up phosphate under anoxic conditions using nitrate as an electron acceptor. The process is very efficient because it maximizes the utilization of organic substrate for phosphorus and nitrogen removal. An experimental lab-scale A2N system fed with domestic sewage was tested over a period of 260 days. The purpose of the experiment was to examine phosphorus removal capacity of a modified A2N two-sludge system. Factors affecting phosphorus and nitrogen removal by the A2N system were investigated. These factors were the influent COD/TN ratio, Sludge Retention Time (SRT), Bypass Sludge Flow rate (BSF) and Return Sludge Flow rate (RSF). Results indicated that optimum conditions for phosphorus and nitrogen removal were the influent COD/TN ratio around 6.49, the SRT of 14 days, and the BSF and RSF were fixed at about 26-33% of influent flow rate.

Influence of ORP variation, carbon source and nitrate concentration on denitrifying phosphorus removal by DPB sludge from dephanox process.

The effect of added carbon source and nitrate concentration on the denitrifying phosphorus removal by denitrifying phosphorus removal bacteria sludge was systematically studied using batch experiments, at the same time the variation of ORP was investigated. Results showed that the denitrifying and phosphorus uptake rate in the anoxic phase increased with the high initial anaerobic carbon source addition. However, once the initial COD concentration reached a certain level, which was in excess of the PHB saturation of Poly-p bacteria, residual COD carried over to the anoxic phase inhibited the subsequent denitrifying phosphorus uptake. This was equal to supplementing the external carbon source to the anoxic phase, furthermore the higher the external carbon source concentration the more powerful the inhibition caused. High nitrate concentration in the anoxic phase increased the initial denitrifying phosphorus rate. Oncethe nitrate was exhausted, phosphate uptake changed to phosphate release. Moreover, the time of this turning point occurred later with the higher nitrate addition. On the other hand, through on-line monitoring the variation of the ORP with different initial COD concentration, it was found that ORP could be used as a control parameter for phosphorus release, but it is impossible to utilize ORP for controlling the dinitrification and anoxic phosphorus uptake operations.