Predictive role of impulsivity, anxiety, and depression in the efficacy of intermittent theta burst transcranial magnetic stimulation modalities for treating methamphetamine use disorder: A randomized clinical trial.

INTRODUCTION: Methamphetamine use disorder (MUD) can cause impulsive behavior, anxiety, and depression. Stimulation of the left dorsolateral prefrontal cortex in MUD patients by intermittent theta burst repetitive transcranial magnetic stimulation (iTBS-rTMS) is effective in reducing cravings, impulsive behavior, anxiety, and depression. The purpose of this study was to explore whether these psychological factors helped to predict MUD patients' responses to iTBS-rTMS treatment. METHODS: Fifty MUD patients and sixty healthy subjects matched for general conditions were used as study subjects. The study randomly divided MUD patients into iTBS-rTMS and sham stimulation groups and received 20 sessions of real or sham iTBS-rTMS treatment, and the study collected cue-related evoked craving data before and after treatment. All subjects completed the Barratt Impulsiveness Scale (BIS-11), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS). RESULTS: The MUD patients showed significantly higher levels of impulsivity, anxiety, and depression than the healthy subjects. The MUD patients who received the real treatment had significantly lower impulsivity, anxiety, and depression scores, and better treatment effects on cravings than the sham stimulation group. The Spearman rank correlation and stepwise multiple regression analyses showed that the baseline BIS-11 and the reduction rate (RR) of BIS-11 and RR of SDS were positively correlated with the decrease in cravings in the iTBS-rTMS group. ROC curve analysis showed that RR of SDS (AUC = 91.6 %; 95 % CI = 0.804-1.000) had predictive power to iTBS- rTMS therapeutic efficacy, the cutoff value is 15.102 %. CONCLUSIONS: iTBS-rTMS had a good therapeutic effect in MUD patients and the baseline impulsivity, the improved depression and impulsivity were associated with therapeutic effect of iTBS-rTMS. The improved depression had the potential to predict the efficacy of the iTBS-rTMS modality for MUD treatment.

Increasing demand for point-of-care testing and the potential to incorporate the Internet of medical things in an integrated health management system.

As the number of people with COVID-19 increases daily around the world, point-of-care testing (POCT) is gaining attention as a tool that can provide immediate test results and greatly help to deter infection and determine what to do next. POCT has several drawbacks such as a low sensitivity and specificity, but according to studies POCT has increased sensitivity on par with that of polymerase chain reaction testing. The advantage of POCT is that the results can be obtained quickly, regardless of the location. To further enhance its benefits, POCT is being developed and researched in conjunction with the Internet of medical things (IoMT), which allows POCT results to be collected, recorded, and managed over a network. IoMT will be beneficial not only for the use of POCT simply as a testing tool but also for its integration into diagnostic and health management systems. IoMT will enable people to regularly receive their test results in their daily lives and to provide personalized diagnosis and treatment of individual conditions, which will be beneficial in terms of disease prevention and maintenance of health.

Predictive Role of Executive Function in the Efficacy of Intermittent Theta Burst Transcranial Magnetic Stimulation Modalities for Treating Methamphetamine Use Disorder-A Randomized Clinical Trial.

Background: Repetitive transcranial magnetic stimulation (rTMS) has therapeutic effects on craving in methamphetamine (METH) use disorder (MUD). The chronic abuse of METH causes impairments in executive function, and improving executive function reduces relapse and improves treatment outcomes for drug use disorder. The purpose of this study was to determine whether executive function helped predict patients' responses to rTMS treatment. Methods: This study employed intermittent theta burst stimulation (iTBS) rTMS modalities and observed their therapeutic effects on executive function and craving in MUD patients. MUD patients from an isolated Drug Rehabilitation Institute in China were chosen and randomly allocated to the iTBS group and sham-stimulation group. All participants underwent the Behavior Rating Inventory of Executive Function - Adult Version Scale (BRIEF-A) and Visual Analog Scales (VAS) measurements. Sixty-five healthy adults matched to the general condition of MUD patients were also recruited as healthy controls. Findings: Patients with MUD had significantly worse executive function. iTBS groups had better treatment effects on the MUD group than the sham-stimulation group. Further Spearman rank correlation and stepwise multivariate regression analysis revealed that reduction rates of the total score of the BRIEF-A and subscale scores of the inhibition factor and working memory factor in the iTBS group positively correlated with improvements in craving. ROC curve analysis showed that working memory (AUC = 87.4%; 95% CI = 0.220, 0.631) and GEC (AUC = 0.761%; 95% CI = 0.209, 0.659) had predictive power to iTBS therapeutic efficacy. The cutoff values are 13.393 and 59.804, respectively. Conclusions: The iTBS rTMS had a better therapeutic effect on the executive function of patients with MUD, and the improved executive function had the potential to become a predictor for the efficacy of iTBS modality for MUD treatment. Clinical Trial Registration: ClinicalTrials.gov, identifier: ChiCTR2100046954.

Saccharogenic refining of Ginkgo biloba leaf residues using a cost-effective enzyme cocktail prepared by the fungal strain A32 isolated from ancient ginkgo biloba tree.

To reduce environmental pollution and waste of biomass from Ginkgo biloba leaf residues (GBLRs), we developed a cost-effective enzyme system to hydrolyze GBLRs into available reducing sugars (RS). Biomass characteristics of GBLRs were investigated, which indicated that the acid hydrolyzed fraction was 49.43% of the dry weight of GBLRs. The fraction could be effectively converted into RS by an enzyme cocktail with high polygalacturonase activity without traditionally intricate pretreatment. The strain A32 isolated from the ancient ginkgo soil was used for the production of the enzyme cocktail, and a response surface methodology was used to optimize the enzymatic production. The enzyme cocktail released 87.2% of RS from GBLRs at 35 â„ƒ for 72 h with 1% (m/v) of loading, and the RS concentration arrived 8.95 ± 0.39 mg/ml with 9% of GBLRs loading. The cost-effective system of self-prepared enzyme cocktail is promising for facilitating GBLRs' bio-based industry.

Progress on drug pricing negotiations in China.

On November 28th, 2019, the National Healthcare Security Administration (NHSA) and the Ministry of Human Resources and Social Security (MOHRSS) of China announced the results of drug pricing negotiations. Seventy first-negotiated drugs with 60.7% average price decrease and twenty-seven re-negotiated medicines with 26.4% average price fall, involving 11 disease categories, were successfully incorporated into National Reimbursement Drug List (NRDL). Medicines that successfully get accessed to NRDL are mostly new listings with high clinical value, and more than half of them are manufactured by Chinese enterprises. Compared to the negotiated drug list of 2017, the biggest increase in western medicines is the digestive system medications (10 drugs added), and the traditional Chinese medicine is internal medicine (17 drugs added). The negotiation follows the process including preparation, examination, negotiation, and announcement. There are several innovations in the procedure, such as the parallel calculation of the floor price, the introduction to competitive negotiations, allowing companies to apply for price confidentiality, and increasing government-enterprise communication before negotiations. Incorporating patent drugs into NRDL by negotiation not only helps patients reduce the economic burden, but also encourages pharmaceutical companies to innovate.

The community-based integrated care system in Japan: Health care and nursing care challenges posed by super-aged society.

Japan is experiencing unprecedented aging of its population. People age 65 years or older accounted for 28.1% of the total population in 2018, and that proportion is expected to reach 33.3% in 2036 and 38.4% in 2065. In 2017, the average life expectancy in Japan was 81.09 years for men and 87.26 years for women. By 2065, it is expected to reach 84.95 years for men and 91.35 years for women. Population aging affects health and long-term care systems. The government proposed the establishment of "a community-based integrated care system" by 2025 with the purpose of comprehensively ensuring the provision of health care, nursing care, preventive care, housing, and livelihood support. This will require health care and nursing care professionals who are capable of fully understanding the physical and mental characteristics of elderly people and the fostering of organic collaboration with others professionals in the community-based integrated care system. A department of gerontology or geriatric medicine is desired to be established in each medical school to teach students medicine and efficient medical care, to conduct research, and to develop personnel to facilitate this paradigm shift. In 2018, there were 263 colleges of nursing with an admissions capacity of 23,667. In Japan, Certified Nurse Specialists can specialize in 13 areas as of December 2016. The number of Certified Nurse Specialists increased to 2,279 as of December 2018. One hundred and forty-four of those specialists specialized in Gerontological Nursing while 53 specialized in Home Care Nursing. The number of nurses specializing in Gerontological Nursing and Home Care Nursing is desired to be increased in order to implement and improve community-based comprehensive care.

Shufeng Jiedu Capsule and its active ingredients induce apoptosis, inhibit migration and invasion, and enhances doxorubicin therapeutic efficacy in hepatocellular carcinoma.

BACKGROUND: Shufeng Jiedu Capsule (SFJDC), a traditional Chinese medicine, has been used widely as antiviral, antibacterial, antitumor, and anti-inflammatory drugs. Previous studies indicated that some active ingredients of Shufeng Jiedu Capsule, such as resveratrol and quercetin, could suppress hepatocellular carcinoma (HCC) cells through various signaling pathways. However, anti-HCC activity of SFJDC as a complementary medicine remains unexplored. Here, we use a combination of Shufeng Jiedu Capsule and doxorubicin to treat HCC cells and investigated the effects and mechanisms of SFJDC and its ingredientsin vitro. METHODS: In this study, two HCC cell lines, HepG2 and HepG2.2.15, were employed and all cells were separated into seven groups: doxorubicin group, SFJDC group, combination of doxorubicin and SFJDC group, resveratrol group, quercetin group, resveratrol and quercetin group, and control group. Through this research, the cellular functional experiments, such as MTT assay, Hoechst 33,258 staining, would healing assay, and transwell assay, were took to observe the effects of those agents on proliferation, apoptosis, migration and invasion of cells. Then, apoptosis and invasion related genes and proteins were detected by real-time PCR and western blot to illuminate the signaling pathways. RESULTS: The combination group induced more significant apoptosis and inhibition of migration and invasion by affecting proteins and mRNA of apoptosis, migration, and invasion related elements, such as Bcl-2, Bax, mTOR, and NF-?B. Furthermore, the research suggested SFJDC, as a mixture of a number of ingredients, had stronger activities than particular component or simple mixture of a few components. CONCLUSIONS: SFJDC and its active ingredients could play a role as complementary medicine to increase antitumor effect of doxorubicin by targeting mitochondrial, Akt/mTOR, and NF-?B signaling pathways.

Combination of Cinobufacini and Doxorubicin Increases Apoptosis of Hepatocellular Carcinoma Cells through the Fas- and Mitochondria-Mediated Pathways.

Cinobufacini, a traditional Chinese medicine, has been used widely for cancer treatment, such as hepatocellular carcinoma (HCC), sarcoma, and leukemia. Previous studies done by our lab indicated that cinobufacini could suppress HCC cells through mitochondria-mediated and Fas-mediated apoptotic pathways. Here, we use a combination of cinobufacini and doxorubicin to inhibit the growth of HCC cells. The combination group induced more significant apoptosis by affecting proteins and RNA of apoptosis-related elements, such as Bcl-2, Bax, Bid, and cytochrome c. Furthermore, cinobufacini, as a mixture of a number of components, had stronger apoptosis-inducing activity than particular individual components or a simple mixture of a few components. Overall, these results suggested that the combination of cinobufacini and doxorubicin may provide a new strategy for inhibiting the proliferation of HCC cells.

Researchers of chronic obstructive pulmonary disease gathered at the 2017 Japan-China Joint Medical Workshop on Aging and Health.

As the number of elderly and the size of the total population increase, population aging will become a major problem because of an increase in diseases associated with aging, such as chronic obstructive pulmonary disease (COPD). The 2017 Japan-China Joint Medical Workshop on Aging and Health was held at The University of Tokyo on December 2, 2017 with a focus on management of COPD. More than 50 experts in the fields of respiratory medicine, emergency medicine, traditional Chinese medicine, and Kampo (traditional Japanese medicine) from Japan and China presented the results of their research and shared their experiences treating COPD from different perspectives. Guidelines for diagnosis and management of COPD in different countries were described at the workshop, and advances in recent research into the treatment of COPD with Kampo and traditional Chinese medicine were fully discussed. The results of the workshop should help to improve GOLD guidelines and they should greatly help to optimize COPD treatment.

Chinese medicine as complementary therapy for female infertility.

Chinese medicine (CM) has been used in clinical treatment for thousands of years in China, Japan, Korea, and other countries. CM is at present attracting many attentions around the world for reproductive health care and disease prevention, including treatment of female infertility. This review focuses on the CM treatment for female infertility patients, and supplies a summary on the efficacy, safety, and mechanism of some Chinese herbal medicines, herbal medicine-derived active compounds, and acupuncture. A large number of researches have reported that CM could alleviate or even cure female infertility by regulating hormone, improving reproductive outcome of in vivo fertilization, affecting embryonic implantation, curing polycystic ovarian syndrome, endometriosis, pelvic inflammatory disease, relieving mental stress, and regulating immune system. Meanwhile, a few studies claimed that there was little adverse reaction of CM in randomized controlled trials. However, up to present there is a lack of adequate evidences with molecular mechanistic researches and randomized controlled trials to prove the CM as an effective and safe treatment for infertility. Thus, utility of CM as a complementary medicine will be a feasible method to improve the outcome of female infertility treatment.

Advance in studies on traditional Chinese medicines to treat infection with the hepatitis B virus and hepatitis C virus.

Traditional Chinese medicine (TCM), as a type of complementary and alternative medicine (CAM), is a sophisticated and time-honored form of healthcare in China. Many TCMs are widely used to treat hepatitis B and hepatitis C in countries like China, Japan, and South Korea. Since conventional clinical preparations like interferon-α cause obvious dose-dependent adverse reactions and drug resistance, TCMs and related bioactive compounds have garnered increasing attention from physicians and medical researchers. Thus far, a number of TCMs and compounds have been used to inhibit the hepatitis B virus (HBV) or hepatitis C virus (HCV) in vitro, in vivo, and even in clinical trials. The current review summarizes TCMs and related compounds that have been used to inhibit HBV or HCV. Most of these medicines are derived from herbs. HepG2.2.15 cells have been used to study HBV in vitro and Huh7.5 cells have been similarly used to study HCV. Ducks have been used to study the anti-HBV effect of new medication in vivo, but there are few animal models for anti-HCV research at the present time. Thus far, a number of preclinical studies have been conducted but few clinical trials have been conducted. In addition, a few chemically modified compounds have displayed greater efficacy than natural products. However, advances in TCM research are hampered by mechanisms of action of many bioactive compounds that have yet to be identified. In short, TCMs and related active compounds are a CAM that could be used to treat HBV and HCV infections.

Traditional, complementary, and alternative medicine: Focusing on research into traditional Tibetan medicine in China.

As a form of traditional, complementary, and alternative medicine (TCAM), traditional Tibetan medicine has developed into a mainstay of medical care in Tibet and has spread from there to China and then to the rest of the world. Thus far, research on traditional Tibetan medicine has focused on the study of the plant and animal sources of traditional medicines, study of the histology of those plants and animals, chemical analysis of traditional medicines, pharmacological study of those medicines, and evaluation of the clinical efficacy of those medicines. A number of papers on traditional Tibetan medicines have been published, providing some evidence of the efficacy of traditional Tibetan medicine. However, many traditional Tibetan medicines have unknown active ingredients, hampering the establishment of drug quality standards, the development of new medicines, commercial production of medicines, and market availability of those medicines. Traditional Tibetan medicine must take several steps to modernize and spread to the rest of the world: the pharmacodynamics of traditional Tibetan medicines need to be determined, the clinical efficacy of those medicines needs to be verified, criteria to evaluate the efficacy of those medicines need to be established in order to guide their clinical use, and efficacious medicines need to be acknowledged by the pharmaceutical market. The components of traditional Tibetan medicine should be studied, traditional Tibetan medicines should be screened for their active ingredients, and techniques should be devised to prepare and manufacture those medicines.

Controversies regarding and perspectives on clinical utility of biomarkers in hepatocellular carcinoma.

The prevalence of hepatocellular carcinoma (HCC) worldwide parallels that of persistent infection with the hepatitis B virus (HBV) and/or hepatitis C virus (HCV). According to recommendations by the World Health Organization guidelines for HBV/HCV, alpha-fetoprotein (AFP) testing and abdominal ultrasound should be performed in routine surveillance of HCC every 6 mo for high-risk patients. These examinations have also been recommended worldwide by many other HCC guidelines over the past few decades. In recent years, however, the role of AFP in HCC surveillance and diagnosis has diminished due to advances in imaging modalities. AFP was excluded from the surveillance and/or diagnostic criteria in the HCC guidelines published by the American Association for the Study of Liver Diseases in 2010, the European Association for the Study of the Liver in 2012, and the National Comprehensive Cancer Network in 2014. Other biomarkers, including the Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), des-γ-carboxyprothrombin, Dickkopf-1, midkine, and microRNA, are being studied in this regard. Furthermore, increasing attention has focused on the clinical utility of biomarkers as pre-treatment predictors for tumor recurrence and as post-treatment monitors. Serum and tissue-based biomarkers and genomics may aid in the diagnosis of HCC, determination of patient prognosis, and selection of appropriate treatment. However, further studies are needed to better characterize the accuracy and potential role of these approaches in clinical practice.

A map describing the association between effective components of traditional Chinese medicine and signaling pathways in cancer cells in vitro and in vivo.

Cancer is the second leading cause of death by disease in the world. Chemotherapy is one of three major therapeutic methods for cancer treatment, but cancer cells gradually evolve resistance to chemotherapeutic reagents. For centuries, traditional Chinese medicine (TCM) was used to fight against cancer. In recent years, a number of effective component mechanisms of TCM have been increasingly illuminated. As we know, chemical structures of reagents decide or affect their activities on target pathways. Thus, we classified some antitumor-related TCM components reported in the last five years into thirteen groups by their chemical structures, such as, alkaloids, diterpenoids, triterpenes, sesquiterpenes, anthraquinones, benzoquinones, flavonoids, berbamines, xanthones, saponins, steroids, polysaccharides, and glycosides. In various cancer cell lines, these constituents target dozens of signaling pathways in vitro and in vivo. Among these components, there are three sets: i) mainly apoptosis-related groups, such as, alkaloids, diterpenoids, anthraquinones, berbamines, and xanthones, target pathways like the mitochondrial pathway, NF-κB pathway, p53 pathway and so on; ii) mainly proliferation, invasion and metastasis-related groups, such as, triterpenes, sesquiterpenes, polysaccharides, and glycosides, target pathways like the mTOR pathway, ß-catenin pathway, ERK pathway and so on; iii) both apoptosis and proliferation, invasion and metastasis-related groups, such as benzoquinones, flavonoids, saponins, and steroids, target the pathways in i) and ii) synchronously. These will provide association information between TCM components and signaling pathways to promote studies on mechanisms of effective constituents, target drug development, and combinational chemotherapy. TCM could be alternative medicine for cancer treatment in the future.