COVID-19-induced acute loss of consciousness in Marchiafava-Bignami disease: a case report.

Among the various manifestations of COVID-19, the neurological implications of SARS-CoV-2 infection are of significant concern. Marchiafava-Bignami disease (MBD), a neurodegenerative disorder, exhibits a clinical spectrum ranging from mild progressive dementia in its chronic form to states of acute coma and varied mortality rates. Acute MBD primarily occurs in chronic alcoholics and malnourished individuals and is characterized by sudden loss of consciousness, seizures, confusion, and psychosis. We herein report a case of MBD presenting as acute loss of consciousness after the development of COVID-19. The patient presented with a history of fever and upper respiratory infection and was diagnosed with SARS-CoV-2 infection. He developed a neurological syndrome characterized by altered consciousness and convulsions, and brain magnetic resonance imaging revealed abnormal signals in the corpus callosum and frontoparietal lobes. Considering his alcohol intake history and the absence of other differential diagnoses, we diagnosed him with acute MBD triggered by COVID-19. After high-dose vitamin B1 and corticosteroid therapy, his clinical symptoms improved. In this case, we observed a temporal sequence between the development of COVID-19 and acute exacerbation of MBD. This case adds to the mounting evidence suggesting the potential effect of SARS-CoV-2 on the neurological system.

Effect of Traditional Chinese Non-Pharmacological Therapies on Knee Osteoarthritis: A Narrative Review of Clinical Application and Mechanism.

Knee osteoarthritis (KOA) stands as a degenerative ailment with a substantial and escalating prevalence. The practice of traditional Chinese non-pharmacological therapy has become a prevalent complementary and adjunctive approach. A mounting body of evidence suggests its efficacy in addressing KOA. Recent investigations have delved into its underlying mechanism, yielding some headway. Consequently, this comprehensive analysis seeks to encapsulate the clinical application and molecular mechanism of traditional Chinese non-pharmacological therapy in KOA treatment. The review reveals that various therapies, such as acupuncture, electroacupuncture, warm needle acupuncture, tuina, and acupotomy, primarily target localized knee components like cartilage, subchondral bone, and synovium. Moreover, their impact extends to the central nervous system and intestinal flora. More perfect experimental design and more comprehensive research remain a promising avenue in the future.

Short-term and long-term effectiveness of acupuncture and Tuina on knee osteoarthritis: study protocol for a randomized controlled trial.

Background: The effectiveness of acupuncture and tuina in treating knee osteoarthritis (KOA) is still controversial, which limits their clinical application in practice. This study aims to evaluate the short-term and long-term effectiveness of acupuncture and tuina on KOA. Methods/design: This parallel-group, multicenter randomized clinical trial (RCT) will be conducted at the outpatient clinic of five traditional Chinese medicine hospitals in China. Three hundred and thirty participants with KOA will be randomly assigned to acupuncture, tuina, or home-based exercise group with a ratio of 1:1:1. The primary outcome is the proportion of participants achieving a minimal clinically important improvement defined as a ≥ 12% reduction on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain dimension on short term (week 8) and long term (week 26) compared with baseline. Secondary outcomes are knee joint conditions (pain, function, and stiffness), self-efficacy of arthritis, quality of life, and psychological conditions, which will be evaluated by the WOMAC score and the Patient Global Assessment (PGA), and in addition, the respondents index of OMERACT-OARSI, Short Form 12 Health Survey (SF-12), arthritis self-efficacy scale, and European five-dimensional health scale (EQ-5D). Adverse events will be collected by self-reported questionnaires predefined. Clinical trial registration: https://www.chictr.org.cn.

Development of CORE-CM core outcome domain sets for trials of Chinese medicine for lumbar spinal stenosis.

OBJECTIVES: Most Asian countries have employed Chinese medicine (CM) and Western medicine to treat lumbar spinal stenosis (LSS). Evidence synthesis and comparison of effectiveness are difficult since outcomes examined and presented through trials possess heterogeneity. This study aimed to solve the outcome problems for CM clinical trials in LSS by building a core outcome set (COS). METHODS: To achieve an agreement on a set of core outcome domains, a four-phase study was carried out. First, we identified candidate outcome domains by systematically reviewing trials. In addition, we identified outcome domains associated with patients by conducting semistructured interviews with patients. Next, outcome domains were processed through a national two-round Delphi survey, in which 18 patients and 21 experts were recruited. Finally, the above domains were converted as a core outcome domain set based on a consensus meeting, in which 24 stakeholders were recruited. RESULTS: Seventeen outcome subdomains were identified by the systematic review and interviews. The Delphi survey assigned a priority to four outcome domains in the first round and four outcomes additionally in the second round. The core outcome domains were determined through discussion and redefinition of outcomes in the consensus meeting: pain and discomfort, health-related quality of life, lumbar function, activities of daily living, measures of walking, patient global assessment, adverse events and CM-specific outcomes. CONCLUSION: COS-CM-LSS is likely to enhance the consistency of outcomes reported in clinical trials. In-depth research should be conducted for the exploration of the best methods to examine the above outcomes.

Antibacterial activity of a polysaccharide isolated from Artemisia argyi leaf against Staphylococcus aureus and mechanism investigation.

Abuse of antibiotics has led to excessive amounts of antibiotic residues in food and environment, thus enhancing pathogenic bacterium resistance and threatening human health. Therefore, searching and developing safe and green antibiotic alternatives are necessary. In this study, an Artemisia argyi leaf polysaccharide (AALP) fraction was extracted and analyzed. Chemical composition analysis showed that the carbohydrate, uronic acid, protein, and polyphenol content in AALP were 68.3 % ± 4.13 %, 9.4 % ± 0.86 %, 1.79 % ± 0.27 %, and 0.16 % ± 0.035 %, respectively. Chromatographic results suggested that AALP contained rhamnose, arabinose, glucosamine, galactose, glucose, xylose, mannose, galacturonic acid, and glucuronic acid in a molar ratio of 9.26, 1.35, 1.18, 3.04, 48.51, 2.33, 31.26, 3.93, and 9.08; the weight average molecular weight, number average molecular weight, and polydispersity of AALP were 5.41 kDa, 4.63 kDa, and 1.168, respectively. Fourier transform infrared spectroscopy indicated that AALP constituted the polysaccharide-specific groups of CH, CO, and OH. Meanwhile, AALP showed a dose-dependent inhibitory effect on Staphylococcus aureus in the inhibition zone assay, and the minimal inhibitory concentration was 1.25 mg/mL. Furthermore, AALP disrupted the cell wall, depolarized the inner membrane potential, and inhibited the activities of succinate dehydrogenase and malate dehydrogenase in S. aureus.

Non-pharmaceutical Chinese medical therapies for degenerative lumbar spinal stenosis: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: The objective of the study was to assess the effectiveness of utilizing Non-Pharmaceutical Chinese Medical (NPCM) therapy singularly or in combination for the treatment of Degenerative Lumbar Spinal Stenosis (DLSS). METHODS: The comprehensive search for all randomized controlled trials regarding NPCM therapies for the treatment of DLSS was performed through online databases searches, commencing from their inception to January 1st, 2023. The relevant literature underwent a thorough screening process, and the data was meticulously extracted and subjected to analysis through the implementation of RevMan 5.3 software. The Cochrane Risk of Bias tool was employed to assess the potential risk of bias. The synthesis of evidence was performed Grading of Recommendations Assessment, Development, and Evaluation. RESULTS: The extensive search procedure produced 5674 records, including data from 37 studies of 38 comparisons (2965 participants). Moderate evidence was obtained demonstrating that the application of acupuncture for a duration of 6-8 weeks was significantly superior to sham acupuncture in terms of intermediate-term (6 months) alleviation of back pain (2 trials, n = 128; MD, -1.08; 95% CI, -1.81∼-0.34) and improvement in lumbar function (2 trials, n = 128; MD, -1.40; 95% CI, -2.93∼-0.13). The available low evidence suggested that, as compared to sham acupuncture, acupuncture was effective in reducing short-term (3 months) back pain and enhancing lumbar function but had no impact on leg pain. A trial with low risk of bias found that acupuncture was more effective than sham acupuncture in enhancing disability and walking capabilities. The other studies presented inconsistent evidence with regards to the efficacy of the various interventions employed. CONCLUSIONS: Evidence of low-to-moderate quality suggests that for DLSS patients, the implementation of acupuncture in comparison to sham acupuncture presents favorable outcomes in terms of short- and intermediate-term alleviation of back pain, improvement in lumbar function, enhancement of disability and walking capacity. The conclusion regarding the efficacy of other NPCM therapies was not obtained due to the insufficient quality of the available evidence. REGISTRATION: PROSPERO CRD42022307631.

Bushen Jianpi Formula Combined with Entecavir for the Treatment of HBeAg-Negative Chronic Hepatitis B: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Bushen Jianpi formula (BSJPF, also known as Lingmao formula) is a traditional Chinese medicine for chronic hepatitis B (CHB). The previous study has suggested that the treatment combination of BSJPF and entecavir (ETV) can achieve a significant loss of hepatitis B e antigen (HBeAg) and a significant decrease in serum level of hepatitis B virus (HBV) DNA in HBeAg-positive CHB patients with mildly elevated alanine aminotransferase. Objective: This study aimed to evaluate the efficacy and safety of BSJPF combined with ETV for treating HBeAg-negative CHB patients. Methods: A total of 640 patients were assigned randomly to the treatment group (receiving BSJPF combined with ETV for 96 weeks) or the control group (receiving a placebo combined with ETV for 96 weeks) in a 1 : 1 ratio. The primary endpoints are the rate of loss of hepatitis B surface antigen (HBsAg). The secondary outcomes included the rate of decrease in the HBsAg concentration to ≥1 lg·IU/mL, the HBV DNA suppression, the decline of the level of covalently closed circular DNA (cccDNA) in the liver, histological improvements, and the rate of ALT normalization. Results: The rate of HBsAg loss in the treatment group was significantly higher than that of the control group (5.5% versus 1.8%, P=0.031). There were 11.1% of patients in the treatment group who recorded a reduction in HBsAg ≥1 lg·IU/mL, which is better than 5.9% of patients in the control group (P=0.043). There was no significant difference between the two groups with regard to the rate of HBV DNA clearance, the reduction in intrahepatic cccDNA, and the rate of ALT normalization (P > 0.05). The rate of liver fibrosis improvement in the treatment group was better than that of the control group (35.5% versus 11.8%, P=0.031), but there was no difference in necroinflammatory improvement (P > 0.05). The adverse events (AEs) were similar between the two groups, except for the abnormal kidney function, with 2.2% in the control group and 0.0% in the treatment group (P=0.028). Conclusion: The combination of BSJPF and ETV can increase the rate of HBsAg loss and the rate of histological fibrosis improvement without serious adverse events in CHB patients. Trial Registration. This trial is registered with ChiCTR-IOR-16009880 on November 16, 2016-retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=16836.

[Effect of Nrf2/HO-1 signaling pathway in intestinal protection by Sishen Pills against ulcerative colitis in mice].

The present study aimed to explore the effect of nuclear factor erythroid 2 related factor 2(Nrf2)/heme oxygenase-1(HO-1) signaling pathway in intestinal protection by Sishen Pills against ulcerative colitis(UC). After the UC model was induced by 3% dextran sodium sulfate(DSS), experimental animals were randomly divided into control group, model group, salazosulfapyridine(SASP) group, and low-and high-dose Sishen Pills groups. Drug intervention(ig) was performed for seven consecutive days during modeling. On the 7 th day, the mice were euthanized. The body weight and colon length were recorded, and the histopathological changes of the colon were observed by HE staining. Serum interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), total antioxidant capacity(T-AOC), malondialdehyde(MDA), and reactive oxygen species(ROS) were detected by ELISA. The protein and mRNA expression of Nrf2, HO-1, and NADPH quinine oxidoreductase-1(NQO-1) was determined by Western blot and reverse transcription-polymerase chain reaction(RT-PCR). Compared with the normal group, the model group exhibited reduced body weight, colon length, and T-AOC, increased IL-6, TNF-α, MDA, and ROS, and diminished protein and mRNA expression of Nrf2, HO-1, and NQO-1 in the colon tissues. Compared with the model group, the SASP group and high-dose Sishen Pills group showed elevated body weight, colon length, and T-AOC, lowered IL-6, TNF-α, MDA, and ROS levels, and increased protein and mRNA expression of Nrf2, HO-1, and NQO-1 in the colon tissues. As assessed by HE staining, Sishen Pills could improve the pathological changes of the colon. The findings suggested that Sishen Pills could protect the colon against UC induced by 3% DSS. The specific mechanism of action may be related to the anti-inflammatory and anti-oxidative stress effects by the activation of the Nrf2/HO-1 signaling pathway.

A network-based predictive gene expression signature for recurrence risks in stage II colorectal cancer.

The current criteria for defining the recurrence risks of stage II colorectal cancer (CRC) are not robust; therefore, we aimed to explore novel gene signatures to predict recurrence risks and to reveal the underlying mechanisms of stage II CRC. First, the gene expression profiles of 124 patients with stage II CRC from The Cancer Genome Atlas (TCGA) database were obtained to screen differentially expressed genes (DEGs). A total of 202 DEGs, including 128 upregulated and 74 downregulated, were identified in the recurrence group (n = 24) compared to the nonrecurrence group (n = 100). Furthermore, the top 5 DEGs (ZNF561, WFS1, SLC2A1, MFI2, and PTGR1) were identified by random forest variable hunting, and four (ZNF561, WFS1, SLC2A1, and PTGR1) were selected to create a four-gene recurrent model (GRM), with an area under the curve (AUC) of 0.882 according to the receiver operating characteristic curve, and the robust diagnostic effectiveness of the GRM was further validated with another gene expression profiling dataset (GSE12032), with an AUC of 0.943. The diagnostic effectiveness of the GRM regarding recurrence was associated with poor disease-free survival in all stages of CRC. In addition, gene ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed 18 enriched functions and 6 enriched pathways. Four genes, ABCG2, CACNA1F, CYP19A1, and TF, were identified as hub genes by the protein-protein interaction network, which further validated that these genes were correlated with a poor pathologic stage and overall survival in all stages of CRC. In conclusion, the GRM can effectively classify stage II CRC into groups of high and low risks of recurrence, thereby making up for the prognostic value of the traditional clinicopathological risk factors defined by the National Comprehensive Cancer Network guidelines. The hub genes may be useful therapeutic targets for recurrence. Thus, the GRM and hub genes could offer clinical value in directing individualized and precision therapeutic regimens for stage II CRC patients.

Bioassay-guided isolation of a Mycobacterium tuberculosis bioflim inhibitor from Arisaema sinii Krause.

Mycobacterium tuberculosis biofilms harbour drug-tolerant bacteria. Identification of drugs that inhibit biofilm formation could enable the dramatic shortening of tuberculosis treatments using standard antibiotics. Arisaema sinii Krause is used to treat pulmonary and lymphatic tuberculosis by Dong People of China. Current study was aimed to purify the active components against M. tuberculosis biofilms from Arisaema sinii extract by using bioassay-guided isolation. (E)-2-(methyl (phenyl) amino) ethyl 2-(2-hydroxyundecanamido)-7, 11-dimethyl-3-oxotetradec-4-enoate, compound 1, was identified as the active component. It could inhibit mycobacterial biofilm formation, disperse the preformed biofilms, and disrupt the mature biofilms at concentration of 4, 8, and 32 µg/ml, respectively. At the dose of 32 µg/ml, it could potentiate the bactericidal activity of isoniazid against M. tuberculosis in mature biofilms. The results of this study indicate that compound 1 might be a novel lead compound against mycobacterial biofilm formation.

GRGM-13 comprising 13 plant and animal products, inhibited oxidative stress induced apoptosis in retinal ganglion cells by inhibiting P2RX7/p38 MAPK signaling pathway.

OBJECTIVE: To determine the effectiveness of GRGM-13 on oxidative stress induced apoptosis of retinal ganglion cells (RGCs) and revealed its possible mechanism. MATERIALS AND METHODS: Caspase-3 activity, MDA level, and glutathione peroxidase level were detected by Caspase-3 assay kit, Lipid Peroxidation MDA Assay Kit, and Total Glutathione Peroxidase Assay Kit, respectively. Protein levels of Bax, Bcl-2, p-p38 and p38 were observed by Western Blot. Reactive oxygen species assay kit was used to determine intracellular ROS level. Apoptotic cells were measured by flow cytometry. RESULTS: GRGM-13 inhibited apoptosis of RGCs and ROS level in rat retinal tissue and RGC-5 cells, and the decrease degree strengthened with the increase of GRGM-13 concentration. In addition, ROS upregulated p-p38 expression, while GRGM-13 reversed this effect. We also found that p38 inhibitor SB202190 did not change L-glutamate (Glu) or H2O2-induced ROS level, while SB202190 inhibited apoptosis of RGC-5 cells. Finally, we observed that P2 × 7R agonist BzATP reversed the inhibition effect of GRGM-13 on RGC-5 cell apoptosis, ROS level and p-p38 expression, while si-P2 × 7R inhibited oxidative stress-induced phosphorylation of p38. CONCLUSION: GRGM-13 could inhibit oxidative stress-induced RGCs apoptosis via inhibiting P2RX7/p38 MAPK pathway, which revealed the possible mechanism of GRGM-13 on stress-induced RGCs apoptosis and provided new Chinese medicine for the treatment of glaucoma.

Construction of innovation ability training system for postgraduates of health service management in higher medical colleges and universities / 中华医学教育探索杂志

Targeting the common fact that colleges and universities of traditional Chinese medicine neglect management post practice,are lack of cutting-edge,cross-disciplinary and methodological courses,fail to reflect the traditional Chinese medicine's singularity and update courses slowly during the process of cultivating their graduate students,Heilongjiang University of Chinese Medicine innovates its culture system of graduate student in related major.It is also devoted to developing problem-based learning,introducing bitutor system,reforming course system,which may hopefully improve their graduate students' innovative thoughts and abilities,strengthen their innovative knowledge theory system to finally discover an appropriate reform model for the culture system which can be perfectly replicable.

Clinical features and imaging diagnosis of colonic stenosis in infants / 天津医药

Objective To explore clinical features and imaging diagnosis of colonic stenosis in infants. Methods Seven patients with congenital and acquired colonic stenosis proved by surgery were included in this study. The clinical features, erect abdominal plain radiograph and barium enema were analyzed. Results Of the 7 patients, 4 were congenital colonic stenosis with progressive abdominal distention and vomiting. The erect abdominal plain radiograph showed that intestinal inflation in 3 patients, low-set mechanical intestinal obstruction in 1 patient. In the remaining 3 patients who underwent ileostomy after neonatal necrotizing enterocolitis (NEC). Barium enema showed colonic stenosis in 5 patients and 2 were missed diagnosed who underwent contrast examination in the small intestine, and which showed stenosis in ascending colon near the ileocecus. Seven patients were all proved by surgery. The stenosis sites were located in sigmoid colon in 2 cases, in descending colon in 2 cases, in ascending colon in 2 cases and in transverse colon in 1 case. In 4 cases of congenital colonic stenosis, 2 cases underwent surgical staging, 1 case was followed up for half a year, showing normal defecation and well development, the other 1 case was lost visit after hospital discharge. The other 2 cases received end-to-end ileum and colon anastomosis, the abdominal distension was relieved in outpatient review, showing well-developed. Three cases with NEC and secondary colonic stenosis underwent staged surgery. Two patients were followed up in outpatient 2 weeks after operation. They were followed up for half a year, showing normal defecation and well-developed. The other 1 case was lost visit after hospital discharge. Conclusion Clinical features of colonic stenosis are very different and depend on the stenosis degree. NEC is the main cause of acquired colonic stenosis and it can be diagnosed by barium enema.

Analysis on excessive heavy metal problem of Chinese materia medica exports to EU from perspective of UK ban / 中草药

The EU is a key export market of Chinese materia medica (CMM). Following "The Traditional Herbal Medicinal Products Directive" (2004/24/EC) of EU, the UK enacted the restriction law on the sales of traditional herbs, which made the sales of CMM more difficult in the EU market. The prime reason is that the production or registration of CMM is difficult to meet the standards of the EU relevant technical regulations. In particular, the excess of heavy metals in CMM becomes a very serious problem which has not only influenced its quality and reputation but also has hindered the CMM to the world. By means of analyzing the relevant directives and standards of heavy metals in herbal management of EU, we analyze the impact of the UK ban on CMM exports in depth, and propose the countermeasures of CMM companies, so we can accelerate the internationalization of CMM.

Calcium intake and the risk of stroke: an up-dated meta-analysis of prospective studies.

BACKGROUND AND PURPOSE: Calcium intake has been associated with stroke risk in a prior meta-analysis, however, newly published results are inconsistent. Dairy food benefits on stroke incidence may involve a calcium-related mechanism. We have therefore updated this meta-analysis with particular references to any possibility of a calcium-mediated dairy food risk reduction of stroke risk. METHODS: We searched multiple databases and bibliographies for prospective cohort studies. Reports with multivariate-adjusted relative risk (RR) and corresponding 95% confidence intervals (CI) for the association of calcium intake with stroke incidence were considered. RESULTS: Ten studies with 371,495 participants and 10,408 stroke events were analyzed. The pooled analysis showed no statistically significant association of the risk of total stroke (RR=0.96; 95% CI: 0.89-1.04) and stroke subtypes with the highest and lowest calcium intake quantiles. Nevertheless, high dairy calcium intake was significantly associated with an approximately 24% reduction of stroke risk. (RR=0.76; 95% CI: 0.66-0.86). Furthermore, a long-term follow-up (>=14 years) was helpful to reduce the risk of stroke (RR=0.67; 95% CI: 0.51-0.88). Additionally, a non-linear dose-response relationship was predicted between calcium intake and stroke risk. CONCLUSIONS: Dairy calcium intake is inversely associated with stroke incidence. There is a non-linear dose-response relationship between calcium intake and stroke risk. However, when the follow-up time is long enough, the inverse relationship is independent of dose. Additional large cohort studies are required to illustrate this relationship in detail.

Penehyclidine hydrochloride postconditioning on lipopolysaccharide-induced acute lung injury by inhibition of inflammatory factors in a rodent model.

BACKGROUND: Sepsis is associated with acute lung injury (ALI) and high mortality. The aim of this study was to investigate the effects of different doses of penehyclidine hydrochloride (PHC) postconditioning on ALI induced by sepsis in a rat model. METHODS: A rat model of ALI was induced by intravenous injection of lipopolysaccharide (LPS). The different doses of PHC were administrated intravenously at 30 min after LPS administration (low dose, 0.3 mg/kg; medium dose, 1.0 mg/kg, and high dose, 3.0 mg/kg). After 6 h, arterial blood samples were obtained for blood gas analyses. Meanwhile, lung tissue was harvested and lung injury was assessed by the histopathologic changes (hematoxylin and eosin staining) and wet-to-dry lung weight ratio. The tumor necrosis factor-α and interleukin-6 levels in bronchoalveolar lavage fluid, as well as the nuclear factor-kappa B protein expressions, and the myeloperoxidase activities in lung tissues were measured by immunohistochemistry or enzyme-linked immunosorbent assay, respectively. RESULTS: LPS-induced severe lung injury evidenced by increased pathologic scores and lung wet-to-dry weight ratio, which was accompanied by increases in the expression of pulmonary nuclear factor-kappa B protein and the activity of pulmonary myeloperoxidase and the levels of interleukin-6 and tumor necrosis factor-α in bronchoalveolar lavage fluid. The arterial oxygen tension (PaO2), pH, and the PaO2/fraction of inspired oxygen ratio (PaO2/FiO2) decreased significantly and the carbon dioxide tension (PaCO2) increased notedly after an LPS injection. All doses of PHC could significantly ameliorate lung injury and improve the previously mentioned variables (P < 0.05 or 0.01). Furthermore, the protection of medium dose (1.0 mg/kg) could be better than that of low or high dose. CONCLUSIONS: These findings indicated that different doses of PHC, especially to medium dose, could prevent LPS-induced ALI in rats, at least in part, by inhibiting inflammatory response. Moreover, the protection of pharmacologic postconditioning with PHC is limited by a "ceiling effect."

Impact of SLCO1B1 521T > C variant on leucovorin rescue and risk of relapse in childhood acute lymphoblastic leukemia treated with high-dose methotrexate.

BACKGROUND: Recent studies suggest that SLCO1B1 c.521T > C variant decreases the clearance of methotrexate (MTX) and elevates its plasma concentration, hence leucovorin doses may need to be adjusted. However, high leucovorin doses may affect the cure rate in childhood acute lymphoblastic leukemia (ALL). Hitherto neither the appropriate dose of leucovorin in carriers of SLCO1B1 c.521T > C variant nor the impact of SLCO1B1 polymorphism on the risk of ALL relapse has been clarified. PROCEDURE: A double-blind and controlled study was conducted in 136 children with ALL. They were genotyped for rs4149056 single nucleotide polymorphism into wild-type group and variant group, and received MTX at 3-5 g/m(2) . Plasma concentration MTX and its metabolite were determined by HPLC. The toxicity of MTX, dose of leucovorin and 5-year relapse rate of ALL were recorded. RESULTS: Compared with wild-type group, area under the concentration time curve of MTX increased by 4.2-fold and peripheral clearance rate decreased significantly in variant group. Patients carrying rs4149056 C allele endured a remarkable longer time above the MTX safety threshold and suffered from a higher frequency of toxicity, so 2.2-fold leucovorin was given. However, no association was found between SLCO1B1 c.521T > C variant and the relapse risk in five years. CONCLUSIONS: The SLCO1B1 c.521T > C variant was an important determinant of MTX disposition and their carriers were exposed to increased intensity and time of MTX. An appropriate leucovorin dose raise in variant group was beneficial to reducing the serious toxicity. The c.521T > C variant wasn't associated with the risk of ALL relapse.

Protective effects of neferine on amiodarone-induced pulmonary fibrosis in mice.

The effects of neferine, a bisbenzylisoquinline alkaloid extracted from the Chinese traditional medicine seed embryo of Nelumbo nucifera Gaertn, on amiodarone-induced pulmonary fibrosis in mice were evaluated. Adult Kunming mice were induced to develop pulmonary fibrosis through intratracheal instillation of amiodarone (6.25 mg/kg) on the 1st, 3rd and 5th day. Mice were treated orally with saline, neferine (20 mg/kg), prednisolone (15 mg/kg), pirfenidone (100 mg/kg) twice a day after the third amiodarone instillation. On Day 21, all the lung tissues were collected for hydroxyproline measurement and the histological examination by hematoxylin-eosin and Masson staining. All the blood sample were collected for surfactant protein-D (SP-D) levels assay, Th1/Th2 balance valuation, CD4+CD25+ regulatory T cells (Tregs) analysis by Enzyme-linked immunosorbent assay and flow cytometry. Our data showed that neferine significantly restored the significant reductions in body weights, the increased levels of lung index and hydroxyproline, the abnormal histological findings, the serum SP-D increase, the Th1/Th2 imbalance by decreasing IL-4 and increasing IFN-γ levels and the increases in the population of CD4+CD25+ Tregs associated with amiodarone instillation in mice. Similar changes were also observed in the prednisolone or pirfenidone treated mice. In conclusion, these results indicated that neferine possessed a significant inhibitory effect on amiodarone-induced pulmonary fibrosis, probably due to its properties of anti-inflammation, SP-D inhibition and restoring increased CD4+CD25+ Tregs which may modulate Th1/Th2 imbalance by suppressing Th2 response (from Th2 polarity toward a Th1 dominant response).

Professor He Pu-ren: the founder of Santong method of acupuncture and moxibustion / 中国针灸

Professor He Pu-ren, the founder of Santong method of acupuncture and moxibustion, is a well known acupuncturist at home and abroad. His main contributions include combined martial arts and Chinese medicine, showing obvious therapeutic effect; taking part in establishment of The Department of Acupuncture, Beijing Chinese Medicine Hospital; creating Santong method of acupuncture and moxibustion; advocating fire needle therapy; writing medical books and teaching students; advocating the culture of acupuncture; making the metal model of acupuncture and moxibustion, and others. His achievements have become an important part of acupuncture and moxibustion science.

Protective effect of (+/-) isoborneol against 6-OHDA-induced apoptosis in SH-SY5Y cells.

Oxidative stress caused by dopamine (DA) may play an important role in the pathogenesis of Parkinson's disease (PD). (+/-) Isoborneol is a monoterpenoid alcohol present in the essential oils of numerous medicinal plants and is a known antioxidant. In this study, we investigated the neuroprotective effect of isoborneol against 6-hydroxydopamine (6-OHDA)-induced cell death in human neuroblastoma SH-SY5Y cells. Pretreatment of SH-SY5Y cells with isoborneol significantly reduced 6-OHDA-induced generation of reactive oxygen species (ROS) and 6-OHDA-induced increases in intracellular calcium. Furthermore, apoptosis induced by 6-OHDA was reversed by isoborneol treatment. Isoborneol protected against 6-OHDA-induced increases in caspase-3 activity and cytochrome C translocation into the cytosol from mitochondria. Isoborneol prevented 6-OHDA from decreasing the Bax/Bcl-2 ratio. We also observed that isoborneol decreased the activation of c-Jun N-terminal kinase and induced activation of protein kinase C (PKC) which had been suppressed by 6-OHDA. Our results indicate that the protective function of isoborneol is dependent upon its antioxidant potential and strongly suggest that isoborneol may be an effective treatment for neurodegenerative diseases associated with oxidative stress.