Heat and Acupuncture to Manage Osteoarthritis of the Knee (HARMOKnee): Protocol for an Effectiveness-Implementation Hybrid Randomized Controlled Trial.

BACKGROUND: Knee osteoarthritis (KOA) is one of most prevalent and fastest-growing causes of pain, impaired mobility, and poor quality of life in the rapidly aging population worldwide. There is a lack of high-quality evidence on the efficacy of traditional Chinese medicine (TCM), particularly acupuncture, and a lack of KOA practice guidelines that are tailored to unique population demographics and tropical climates. OBJECTIVE: Our HARMOKnee (Heat and Acupuncture to Manage Osteoarthritis of the Knee) trial aims to address these gaps by evaluating the short- and medium-term clinical and cost-effectiveness of acupuncture with heat therapy in addition to standard care, compared to standard care alone. Through a robust process and economic evaluation, we aim to inform evidence-based practice for patients with KOA to facilitate the large-scale implementation of a comprehensive and holistic model of care that harmonizes elements of Western medicine and TCM. We hypothesize that acupuncture with heat therapy as an adjunct to standard care is clinically more effective than standard care alone. METHODS: A multicenter, pragmatic, parallel-arm, single-blinded, effectiveness-implementation hybrid randomized controlled trial will be conducted. We intend to recruit 100 patients with KOA randomized to either the control arm (standard care only) or intervention arm (acupuncture with heat therapy, in addition to standard care). The inclusion criteria are being a community ambulator and having primary KOA, excluding patients with secondary arthritis or previous knee replacements. The primary outcome measure is the Knee Osteoarthritis Outcome Score at 6 weeks. Secondary outcome measures include psychological, physical, quality of life, satisfaction, and global outcome measures at 6, 12, and 26 weeks. A mixed method approach through an embedded process evaluation will facilitate large-scale implementation. An economic evaluation will be performed to assess financial sustainability. RESULTS: Patient enrollment has been ongoing since August 2022. The recruitment process is anticipated to conclude by July 2024, and the findings will be analyzed and publicized as they are obtained. As of November 6, 2023, our patient enrollment stands at 65 individuals. CONCLUSIONS: The findings of our HARMOKnee study will contribute substantial evidence to the current body of literature regarding the effectiveness of acupuncture treatment for KOA. Additionally, we aim to facilitate the creation of standardized national guidelines for evidence-based practice that are specifically tailored to our unique population demographics. Furthermore, we seek to promote the adoption and integration of acupuncture and heat therapy into existing treatment models. TRIAL REGISTRATION: ClinicalTrials.gov NCT05507619; https://clinicaltrials.gov/study/NCT05507619. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54352.

The chemometrics analysis and integrated pharmacology approach to decipher the effect and mechanism between raw and processed cistanche tubulosa.

ETHNOPHARMACOLOGICAL RELEVANCE: Cistanche tubulosa (CT) is the dried fleshy stem with scaly leaves of Cistanche tubiflora (Schenk) Wight, which has the effects of tonifying the kidney-yang, benefiting the vital essence and blood, and moisturizing the intestines and laxatives. There are differences in the activity of CT before and after processing, but the mechanism of processing is not clear. AIM OF THE STUDY: The study aimed to compare the strength of action of CT before and after yellow-wine processing in the treatment of constipation and kidney yang deficiency and to identify the active ingredients responsible for the differences in activity before and after yellow-wine processing. MATERIALS AND METHODS: This study established the fingerprints of CT and PCT using HPLC to identify their shared components. Then efficacy of KYDS and FC were carried out to compare the differences between CT and PCT in terms of efficacy. Next, this study established the spectrum-effect relationship between the shared chemical components and the medical effects of CT and PCT using the gray correlation analysis and entropy methods. Ultimately, the activity of the analyzed chemical components was verified using the zebrafish model. RESULTS: CT was more effective than PCT in promoting intestinal peristalsis, regulating gastrointestinal hormone levels, and thus treating FC. PCT was more effective than CT in improving the level of hormone indexes of the hypothalamus-pituitary-target gland axis, replenishing blood, and enhancing immunity. Through the analysis of the spectrum-effect relationship, it was finally found that 5, 6, 12 (tubuloside A), and 13 (isoacteoside) might be more closely related to the activity of tonifying kidney yang, and peaks 9, 10, and 11 (acteoside) are more closely associated with the treatment of constipation, and peaks 3 (salidroside), 4, 1, 2 (geniposidic acid), and 8 (echinacoside) were associated with both kidney yang tonic and treatment of constipation. At the same time, an activity verification experiment showed that echinacoside, geniposidic acid, and salidroside were effective in the treatment of FC and KYDS, while acteoside was very effective in the treatment of FC, and tubuloside A was significant in supplementing the blood, which validated the spectrum-effect relationship analysis. CONCLUSION: This study proved that the raw CT had a better laxative effect, while the yellow-wine processed CT had a better kidney-yang tonic effect; moreover, spectrum-effect relationships were established to analyze the chemical components leading to changes in the activity of CT before and after yellow-wine processing.

Glycyrrhizae radix et rhizoma processing ameliorates adverse reactions of polygalae radix in zebra fish and rabbit models.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygala tenuifilia Willd (Polygalaceae), a traditional Chinese medicine, has been used for a long time to treat various illnesses with serious adverse reactions. Glycyrrhizae radix et rhizoma processing is generally used to reduce the adverse reactions. AIM OF THE STUDY: The aim of this study was to validate the irritation caused by raw Polygalaceae (RPA), to investigate whether processed Polygalaceae (PGA) was less irritating, and to screen and validate irritant properties of virgaureagenin G (polygala acid, PA), 3,6'-disinapoylsucrose (DSS), Tenuifolia (TEN) and polygalaxanthone III (POL), which had pharmacologically active in Polygalaceae. Zebrafish model, Draize test and High-Performance Liquid Chromatography (HPLC) were utilized to achieve the aim. MATERIALS AND METHODS: Scanning Electron Microscopy (SEM) and optical microscope were used to determine the presence of calcium oxalate needle crystal in RPA and PGA. Zebrafish egg spinning changes and zebrafish embryo behavior were used for irritation validation, irritation comparison and irritant screening. For additional evidence, the Draize test, HE staining of rabbit eyes and ELISA kit were used. Finally, changes in the composition of RPA and PGA were investigated using HPLC. RESULTS: SEM and optical microscopy revealed no calcium oxalate needle crystals in Polygalaceae. RPA, PGA, PA and DSS were able to accelerate the spinning of zebrafish eggs and the movement of embryos, while TEN and POL were not. RPA, PGA, DSS and PA may cause rabbit eyes to become hyperemic and swollen, resulting in damage to the iris, cornea and conjunctiva and increased levels of interleukin-6 (IL-6) and interleukin-10 (IL-10). Comparatively, the effects caused by PGA were less severe than those caused by RPA. In addition, compared to RPA, PGA had lower levels of DSS and PA. CONCLUSIONS: RPA, PGA, DSS, and PA were irritating. However, processing and curing could reduce the irritation by reducing the levels of DSS and PA. DSS and PA could be two potential irritants of Polygalaceae.

Usage Patterns of Traditional Chinese Medicine for Patients with Bipolar Disorder: A Population-Based Study in Taiwan.

BACKGROUND: Patients with bipolar disorder (BD) receive traditional Chinese medicine (TCM) for clinical needs unmet with psychotropic medications. However, the clinical characteristics of practices and outcomes of TCM in BD are not fully understood. This cohort study investigated the clinical characteristics, principal diagnoses, TCM interventions, and TCM prescriptions in patients with BD. METHODS: Data for a total of 12,113 patients with BD between 1996 and 2013 were withdrawn from Taiwan's longitudinal health insurance database 2000 (LHID 2000). The chi-square test was used for categorical variables, and the independent t-test was used for continuous variables. A p-value less than 0.05 indicated significance. RESULTS: One thousand three hundred nineteen patients who visited TCM clinics after the diagnosis of BD were in the TCM group, while those who never visited TCM were in the non-TCM group (n = 1053). Compared to the non-TCM group, patients in the TCM group had younger average age, a higher percentage of female individuals, more comorbidities of anxiety and alcohol use disorders, and higher mood stabilizer usage rates. The TCM group exhibited pain-related indications, including joint pain, myalgia, myositis, headache, and sleep disturbances. Corydalis yanhusuo and Shu-Jing-Huo-Xue-Tang were the most useful single herbs and herbal formulae. CONCLUSIONS: Physicians need to be aware of the use of TCM in patients with BD.

Technology enabled home-based cardiac rehabilitation among women with cardiovascular disease: A longitudinal cohort study.

Technology-enabled home-based cardiac rehabilitation (HBCR) is an emerging alternative to traditional center-based cardiac rehabilitation (CBCR), but little is known about outcomes in women. We analyzed 753 diverse and medically complex women who participated in HBCR and CBCR within an integrated health system and found both groups had similar clinical outcomes. Results suggest HBCR is a viable alternative to CBCR among women, including women with multiple comorbidities.

TFIIB-Related Protein BRP5/PTF2 Is Required for Both Male and Female Gametogenesis and for Grain Formation in Rice.

Transcription factor IIB (TFIIB) is a general transcription factor for RNA polymerase II, exerting its influence across various biological contexts. In the majority of eukaryotes, TFIIB typically has two homologs, serving as general transcription factors for RNA polymerase I and III. In plants, however, the TFIIB-related protein family has expanded greatly, with 14 and 9 members in Arabidopsis and rice, respectively. BRP5/pollen-expressed transcription factor 2 (PTF2) proteins belong to a subfamily of TFIIB-related proteins found only in plants and algae. The prior analysis of an Arabidopsis atbrp5 mutant, characterized by a T-DNA insertion at the 5' untranslated region, demonstrated the essential role of BRP5/PTF2 during the process of pollen germination and embryogenesis in Arabidopsis. Using a rice transformation system based on CRISPR/Cas9 technology, we have generated transgenic rice plants containing loss-of-function frameshift mutations in the BRP5/PTF2 gene. Unlike in the Arabidopsis atbrp5 mutant, the brp5/ptf2 frameshift mutations were not transmitted to progeny in rice, indicating an essential role of BRP5/PTF2 in both male and female gamete development or viability. The silencing of rice BRP5/PTF2 expression through RNA interference (RNAi) had little effect on vegetative growth and panicle formation but strongly affected pollen development and grain formation. Genetic analysis revealed that strong RNAi silencing of rice BRP5/PTF2 was still transmissible to progeny almost exclusively through female gametes, as found in the Arabidopsis atbrp5 knockdown mutant. Thus, reduced rice BRP5/PTF2 expression impacted pollen preferentially by interfering with male gamete development or viability. Drawing upon these findings, we posit that BRP5/PTF2 assumes a distinct and imperative function in the realm of plant sexual reproduction.

Metabolomics Analysis of Electroacupuncture Pretreatment Induced Neuroprotection on Mice with Ischemic Stroke.

The brain metabolic changes caused by the interruption of blood supply are the initial factors of brain injury in ischemic stroke. Electroacupuncture (EA) pretreatment has been shown to protect against ischemic stroke, but whether its neuroprotective mechanism involves metabolic regulation remains unclear. Based on our finding that EA pretreatment significantly alleviated ischemic brain injury in mice by reducing neuronal injury and death, we performed a gas chromatography-time of flight mass spectrometry (GC-TOF/MS) to investigate the metabolic changes in the ischemic brain and whether EA pretreatment influenced these changes. First, we found that some glycolytic metabolites in the normal brain tissues were reduced by EA pretreatment, which may lay the foundation of neuroprotection for EA pretreatment against ischemic stroke. Then, 6[Formula: see text]h of cerebral ischemia-induced brain metabolic changes, especially the enhanced glycolysis, were partially reversed by EA pretreatment, which was manifested by the brain levels of 11 of 35 up-regulated metabolites and 18 of 27 down-regulated metabolites caused by cerebral ischemia significantly decreasing and increasing, respectively, due to EA pretreatment. A further pathway analysis showed that these 11 and 18 markedly changed metabolites were mainly involved in starch and sucrose metabolism, purine metabolism, aspartate metabolism, and the citric acid cycle. Additionally, we found that EA pretreatment raised the levels of neuroprotective metabolites in both normal and ischemic brain tissues. In conclusion, our study revealed that EA pretreatment may attenuate the ischemic brain injury by inhibiting glycolysis and increasing the levels of some neuroprotective metabolites.

Comparison of Home-Based vs Center-Based Cardiac Rehabilitation in Hospitalization, Medication Adherence, and Risk Factor Control Among Patients With Cardiovascular Disease.

Importance: Prior studies have suggested that participation in home-based cardiac rehabilitation (HBCR) vs center-based cardiac rehabilitation (CBCR) results in similar clinical outcomes in patients with low to moderate risk; however, outcome data from demographically diverse populations and patients who are medically complex are lacking. Objective: To compare hospitalizations, medication adherence, and cardiovascular risk factor control between participants in HBCR vs CBCR. Design, Setting, and Participants: This retrospective cohort study was conducted among patients in Kaiser Permanente Southern California (KPSC), an integrated health care system serving approximately 4.7 million patients, who participated in CR between April 1, 2018, and April 30, 2019, and with follow-up through April 30, 2020. Data were analyzed from January 2021 to January 2022. Exposures: Participation in 1 or more HBCR or CBCR sessions. Main Outcomes and Measures: The primary outcome was 12-month all-cause hospitalization. Secondary outcomes included all-cause hospitalizations at 30 and 90 days; 30-day, 90-day, and 12-month cardiovascular hospitalizations; and medication adherence and cardiovascular risk factor control at 12 months. Logistic regression was used to compare hospitalization, medication adherence, and cardiovascular risk factor control, with inverse probability treatment weighting (IPTW) to adjust for demographic and clinical characteristics. Results: Of 2556 patients who participated in CR (mean [SD] age, 66.7 [11.2] years; 754 [29.5%] women; 1196 participants [46.8%] with Charlson Comorbidity Index ≥4), there were 289 Asian or Pacific Islander patients (11.3%), 193 Black patients (7.6%), 611 Hispanic patients (23.9%), and 1419 White patients (55.5%). A total of 1241 participants (48.5%) received HBCR and 1315 participants (51.5%) received CBCR. After IPTW, patients who received HBCR had lower odds of hospitalization at 12 months (odds ratio [OR], 0.79; 95% CI, 0.64-0.97) but similar odds of adherence to ß-blockers (OR, 1.18; 95% CI, 0.98-1.42) and statins (OR, 1.02; 95% CI, 0.84-1.25) and of control of blood pressure (OR, 0.98; 95% CI, 0.81-1.17), low-density lipoprotein cholesterol (OR, 0.98; 95% CI, 0.81-1.20), and hemoglobin A1c (OR, 0.98; 95% CI, 0.82-1.18) at 12 months compared with patients who received CBCR. Conclusions and Relevance: These findings suggest that HBCR in a demographically diverse population, including patients with high risk who are medically complex, was associated with fewer hospitalizations at 12 months compared with patients who participated in CBCR. This study strengthens the evidence supporting HBCR in previously understudied patient populations.

Efficacy of Prophylactic Traditional Chinese Medicine on Skin Toxicity of Afatinib in EGFR Mutation-Positive Advanced Lung Adenocarcinoma: A Single-Center, Prospective, Double-Blinded, Randomized-Controlled Pilot Trial.

OBJECTIVES: To evaluate the efficacy of prophylactic traditional Chinese medicine (TCM) on skin toxicities in patients with advanced lung adenocarcinoma treated with first-line epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in a randomized-controlled trial (RCT). MATERIALS AND METHODS: This pilot study was a prospective, single-center, double-blinded RCT. The study enrolled patients with a new diagnosis of locally advanced and metastatic lung adenocarcinoma harboring EGFR mutations who were treated with first-line afatinib from July 1, 2016 to December 31, 2017. Thirty patients who met the inclusion and exclusion criteria were assigned to the TCM and placebo groups with simple randomization. TCM and placebo were initiated at the same time as afatinib and were administered for 3 months. The survival of each subject was followed until 3 years. RESULTS: There were 36 patients with newly diagnosed lung adenocarcinoma during the study period. After the exclusion of 6 patients, the remaining 30 patients were assigned to the TCM (n = 14) and placebo (n = 16) groups comprising the intention-to-treat population. The time to first skin toxicity was 22.3 days in the TCM group and 17.6 days in the placebo group (P = .510) in the per-protocol population. The analysis of the present pilot study results determined that the difference in time to first skin toxicity between the 2 groups would reach statistical significance with a sample size of 237 based on a power of 0.8. There were significant differences in certain subscales of quality of life between the TCM and placebo groups; however, there was no significant difference in progression-free survival or overall survival between the 2 groups. CONCLUSIONS: Integrative TCM may prolong the time to first skin toxicity in patients with advanced lung adenocarcinoma treated with first-line afatinib. Prophylactic TCM could delay skin toxicity of any grade and reduce the incidence of grade 3 skin toxicity. Future large-scale RCTs are warranted to validate these findings. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05204758. Registered on 24 Jan 2022.

Urgent PC Versus a Generic Posterior Tibial Neurostimulator for Overactive Bladder: A Retrospective Noninferiority Study.

OBJECTIVE: The aim of the study was to determine whether a generic posterior tibial neurostimulator was noninferior to Urgent PC in the treatment of nonneurogenic OAB, urgency urinary incontinence, and mixed urinary incontinence. Secondary outcomes include rates of starting and completing 3 months of maintenance therapy, treatment success after 3 months, and adverse events. METHODS: We performed a retrospective cohort analysis of women whose nonneurogenic OAB, urgency urinary incontinence, or mixed urinary incontinence was treated with either Urgent PC or a generic posterior tibial neurostimulator. Previous research shows a 55% treatment success rate for posterior tibial nerve stimulation (PTNS). To demonstrate noninferiority with a limit of 14% and 80% power, our analysis required 157 patients per group. RESULTS: We included 267 Urgent PC and 234 generic patients and excluded 51 patients from analysis. A per-protocol analysis demonstrated treatment success in 55.3% (121 of 219) of the Urgent PC and 48.6% (85 of 175) of the generic cohort (P = 0.187). An intention-to-treat analysis showed treatment success in 45.3% (121 of 267) of the Urgent PC and 36.3% (85 of 234) of the generic cohort (P = 0.690). There were no significant differences in rates of starting (82.2% vs 78.2%, P = 0.409) or completing (79.9% vs 70.9%, P = 0.129) 3 months of maintenance therapy, treatment success after 3 months (78.5% vs 73.8%, P = 0.485), and adverse events (0.37% vs 0.85%, P = 1.000) in the Urgent PC versus generic group, respectively. CONCLUSIONS: In this cohort of women undergoing PTNS for nonneurogenic OAB, urgency urinary incontinence, or mixed urinary incontinence, the generic neurostimulator demonstrated noninferior rates of treatment success compared with Urgent PC.

Parkinson's Disease in Traditional Chinese and Western Medicine： A Review / 中国实验方剂学杂志

Parkinson's disease （PD） is a neurodegenerative disease that seriously endangers the health of the middle-aged and elderly people. The main clinical manifestations include motor symptoms such as bradykinesia， static tremor， and myotonia and non-motor symptoms like constipation， mental disorders， sleep disorders， and autonomic nervous dysfunction. Its etiology and pathogenesis have not been fully understood， and the clinical efficacy is not satisfactory. By searching the relevant literature in China and abroad in recent years， this paper summarized the etiology， pathogenesis， and treatment of PD in both traditional Chinese medicine （TCM） and western medicine as well as the integrated TCM and Western medicine treatment. In general， liver and kidney deficiency is recognized by domestic experts in related fields as the main pathogenesis of PD. The abnormal aggregation of α-synuclein， oxidative stress， mitochondrial dysfunction， ubiquitin-proteasome system dysfunction， neuroinflammation， autophagy， microbiota-gut-brain axis regulation， and excitatory neurotoxicity are closely related to the pathogenesis of this disease. At present， treatment based on syndrome differentiation， empirical formulae from famous doctors， single Chinese herbs， and acupuncture and moxibustion are mainly adopted for the tackling of PD in TCM. Western medicine is still dominated by drug replacement therapy， supplemented by such surgical treatments as traditional immunotherapy， neurotrophic factors， and deep brain stimulation （DBS）， rehabilitation and exercise therapy， and scientific nursing. Gene therapy has become a new technical means for the treatment of this disease in recent years. In addition， the combined therapy of TCM and Western medicine has received increasing importance. This paper reviewed the pathogenesis and treatment of PD in TCM and Western medicine， so as to provide reference for its clinical diagnosis and treatment.

Design and clinical developments of aptamer-drug conjugates for targeted cancer therapy.

BACKGROUND: Aptamer has been called "chemical antibody" which displays the specific affinity to target molecules compared to that of antibodies and possesses several therapeutic advantages over antibodies in terms of size, accessibility to synthesis, and modification. Based on the attractive properties, aptamers have been interested in many directions and now are emerged as new target-designed cancer drug. MAIN BODY: Currently, new types of aptamers have been reported and attracted many scientists' interesting. Due to simplicity of chemical modification and ready-made molecular engineering, scientists have developed newly designed aptamers conjugated with a wide range of therapeutics, aptamer-drug conjugates; ApDCs, from chemotherapy to phototherapy, gene therapy, and vaccines. ApDCs display synergistic therapeutic effects in cancer treatment. CONCLUSION: In this paper, we reviewed various kinds of ApDCs, i.e., ApDC nucleotide analogs, ApDC by drug intercalation, and ApDC by using chemical linker. Current data prove these ApDCs have sufficient potential to complete clinical development soon. Advanced technology of cancer drug delivery and combination treatment of cancers enables aptamer and conjugated drug (ApDCs) efficient means for targeted cancer treatment that reduces potential toxicity and increases therapeutic efficacy.

Acupuncture Treatment Associated with Functional Connectivity Changes in Primary Dysmenorrhea: A Resting State fMRI Study.

Primary dysmenorrhea (PDM) is the most commonly encountered gynecological problem in reproductive-age women. Acupuncture has been suggested as an effective treatment of PDM that may modulate descending pain modulation systems. In the present study, we used resting-state functional magnetic resonance imaging to investigate possible changes in descending pain modulation systems after acupuncture treatment in women with PDM. Thirty-four right-handed adult women with PDM participated in this randomized, single-blinded, sham-controlled study. Each patient was randomly allocated to an 8-week verum or sham acupuncture intervention on the bilateral Sanyinjiao (SP6). Resting-state functional magnetic resonance imaging was conducted before, during, and after the intervention to measure the spontaneous activity in brain. After the 8-week intervention, both verum and sham groups reported decreased menstrual pain. However, the cessation of decreased functional connectivity (FC) between periaqueductal gray matter and the regions associated with affective pain modulation and attention-related pain modulation were found in the verum but not in the sham group after the 8-week intervention. More decreased FC has been found in the region associated with non-specific effects of acupuncture intervention after the early stage of acupuncture intervention. These results indicated that verum acupuncture may intercept the altered FC in descending pain modulation systems in PDM.

Predictors of hepatitis A immunity in adults in California in order to better utilize hepatitis A vaccine.

BACKGROUND: Hepatitis A vaccine recommendations now include homelessness, illegal drug use, and HIV, as well as traditional risk factors and travel to areas endemic for hepatitis A. We examined a large diverse population for predictors of Hepatitis A immunity in order to better utilize Hepatitis A vaccine. METHODS: We performed a cross-sectional descriptive study of members of a large integrated health plan with a test for Hepatitis A Immunoglobulin G (IgG) between January 1st, 2007, and December 31st, 2017. Exclusion criteria included age <18 years, <6 months of continuous enrollment, and Hepatitis A vaccine prior to Hepatitis A test. Variables of interest were age, gender, primary language spoken, ethnicity/race, neighborhood household income, and history of travel or history of jaundice. Multivariable logistic regression was performed to evaluate the association of risk factors on Hepatitis A immunity. RESULTS: Of the 318,170 persons ≥ 18 years tested for Hepatitis A immunity, 155, 842 persons had a reactive Hepatitis A IgG test (49%). The lowest prevalence was for Whites at 28.1% followed by Blacks at 35.8%. Hispanics and Asian/Pacific Islanders had prevalence rates of 63% and 68.2% respectively. In adjusted analyses, Asian/Pacific Islanders, Hispanics and Blacks were 5.17, 3.44 and 1.42 times more likely to have Hepatitis A immunity than Whites. Those that spoke Spanish or language other than English or Spanish as their primary preferred language were 6.11 and 3.27 time more likely to have immunity than English speakers. Known travel history conferred a 2.16 likelihood of Hepatitis A immunity. CONCLUSIONS: Persons of Hispanic and Asian/Pacific Islander background as well as persons with a preferred spoken language other than English have a high prevalence of Hepatitis A immunity. Testing for Hepatitis A immunity prior to vaccination should be considered for these groups.

Retrospective assessment of antimicrobial stewardship initiative in outpatient use of ertapenem for uncomplicated extended spectrum beta lactamase Enterobacteriaceae urinary tract infections.

BACKGROUND: Urinary tract infections (UTI) are often over-diagnosed and over-treated, which can induce and select for resistant pathogens. After observing wide-spread outpatient use of ertapenem, a broad-spectrum antibiotic, a structured antimicrobial stewardship initiative (ASI) to improve appropriate antimicrobial prescribing was undertaken. ASI objectives were to achieve a goal of reducing ertapenem utilization for extended spectrum beta lactamase Enterobacteriaceae (ESBL-EB) UTI by 10% and evaluate the clinical outcomes associated with the ASI. METHODS: A pre-to-post cohort study was conducted at a single-center integrated healthcare system between November 1, 2014 and February 26, 2017. An intensive, 90-day, pharmacist-driven, structured ASI was implemented between November 1, 2015 and January 29, 2016. Female patients aged ≥18 years who were treated for an uncomplicated, ESBL-EB urinary tract infection (UTI) were included. Primary outcome was clinical resolution defined as cure, persistence, relapse and recurrence. Secondary outcome measured was monthly ertapenem use expressed as number of days of therapy (DOT)/1000 adjusted patient days (APD). Segmented regression analysis for interrupted time series was performed to estimate ASI intervention effect. RESULTS: A total of 184 patients were included in the study. Ertapenem utilization decreased from 0.0145 DOT/1000 APD in Nov. 2014 to 0.0078 DOT/1000 APD Feb. 2017(p < 0.01). The mean ertapenem DOT declined 19% overall from the pre vs. post intervention periods (32 vs 26, p < 0.01). Frequency of recurrent UTIs between treatments did not significantly differ and no adverse effects were reported in patients treated with aminoglycosides. CONCLUSIONS: A structured ASI for uncomplicated ESBL-EB UTI was associated with a clinically meaningful decrease in ertapenem utilization and once-daily, 5-day aminoglycoside treatment was well-tolerated.

Full-length transcriptome analysis reveals the mechanism of acupuncture at PC6 improves cardiac function in myocardial ischemia model.

BACKGROUND: The pathological process of myocardial ischemia (MI) is very complicated. Acupuncture at PC6 has been proved to be effective against MI injury, but the mechanism remains unclear. This study investigated the mechanism that underlies the effect of acupuncture on MI through full-length transcriptome. METHODS: Adult male C57/BL6 mice were randomly divided into control, MI, and PC6 groups. Mice in MI and PC6 group generated MI model by ligating the left anterior descending (LAD) coronary artery. The samples were collected 5 days after acupuncture treatment. RESULTS: The results showed that treatment by acupuncture improved cardiac function, decreased myocardial infraction area, and reduced the levels of cTnT and cTnI. Based on full-length transcriptome sequencing, 5083 differential expression genes (DEGs) and 324 DEGs were identified in the MI group and PC6 group, respectively. These genes regulated by acupuncture were mainly enriched in the inflammatory response pathway. Alternative splicing (AS) is a post-transcriptional action that contributes to the diversity of protein. In all samples, 8237 AS events associated with 1994 genes were found. Some differential AS-involved genes were enriched in the pathway related to heart disease. We also identified 602 new genes, 4 of which may the novel targets of acupuncture in MI. CONCLUSIONS: Our findings suggest that the effect of acupuncture on MI may be based on the multi-level regulation of the transcriptome.

Camu-Camu Fruit Extract Inhibits Oxidative Stress and Inflammatory Responses by Regulating NFAT and Nrf2 Signaling Pathways in High Glucose-Induced Human Keratinocytes.

Myrciaria dubia (HBK) McVaugh (camu-camu) belongs to the family Myrtaceae. Although camu-camu has received a great deal of attention for its potential pharmacological activities, there is little information on the anti-oxidative stress and anti-inflammatory effects of camu-camu fruit in skin diseases. In the present study, we investigated the preventative effect of 70% ethanol camu-camu fruit extract against high glucose-induced human keratinocytes. High glucose-induced overproduction of reactive oxygen species (ROS) was inhibited by camu-camu fruit treatment. In response to ROS reduction, camu-camu fruit modulated the mitogen-activated protein kinases (MAPK)/activator protein-1 (AP-1), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and nuclear factor of activated T cells (NFAT) signaling pathways related to inflammation by downregulating the expression of proinflammatory cytokines and chemokines. Furthermore, camu-camu fruit treatment activated the expression of nuclear factor E2-related factor 2 (Nrf2) and subsequently increased the NAD(P)H:quinone oxidoreductase1 (NQO1) expression to protect keratinocytes against high-glucose-induced oxidative stress. These results indicate that camu-camu fruit is a promising material for preventing oxidative stress and skin inflammation induced by high glucose level.

Prevalence and Characteristics of Chronic Hepatitis C Among Asian Americans Are Distinct From Other Ethnic Groups.

GOAL: The goal of this study was to determine the prevalence and characteristics of chronic hepatitis C (CHC) among Asian Americans compared with other ethnicities. BACKGROUND: Chronic hepatitis C virus (HCV) affects an estimated 2.7 million in the United States, but there are limited data on HCV among Asian Americans. STUDY: A total of 3,369,881 adults over the age of 18 who were patients of the integrated health care system in Southern California and 4903 Asian participants at community hepatitis screenings were included in a cross-sectional study. Variables included HCV serology, HCV genotype, comorbidities, and coinfections. RESULTS: The prevalence of CHC was 1.3% in the general population (8271 adults) and 0.6% among Asians. The prevalence of CHC was significantly higher in the 1945-1965 birth cohort with 2.7% (5876) in the general population and 1.0% (313) among Asians (P<0.001). Asians had the highest rates of hepatitis B coinfection (2.9% vs. 0.2%, P<0.001). The distribution of genotypes among Asians differed from the general population with the most common genotype being 1b (27.5%) and a higher presence of genotype 6 (9.5%) (P<0.001). The presence of cirrhosis was 17.6% in Asians. Disaggregated Asian data showed that CHC was highest among Vietnamese and Cambodian and that genotype 6 was predominant among these 2 subgroups. CONCLUSIONS: The prevalence of chronic HCV was significantly lower in Asians compared with other ethnicities. However, disaggregated data among Asians showed the highest prevalence rates among adults from Vietnam and Cambodia.

Insights on SNP types, detection methods and their utilization in Brassica species: Recent progress and future perspectives.

The genus Brassica, family Brassicaceae (Cruciferae), comprises many important species of oil crops, vegetables and medicinal plants including B. rapa, B. oleracea, B. nigra, B. napus, B. juncea, B. carinata. Genomic researches in Brassica species is constrained by polyploidization, mainly due to its complicated genomic structure. However, rapid development of methods for detecting single nucleotide polymorphisms (SNP), such as next generation sequencing and SNP microarray, has accelerated release of reference Brassica species genomes as well as discovery of large numbers and genome-wide SNPs, thus intensifying forward genetics in this genus. In this review, we summarize biological characteristics, classification and various methods for detecting SNPs, focusing on high-throughput techniques. Moreover, we describe the pivotal roles of SNPs in genetic diversity, linkage map construction and QTL mapping, comparative genomics, linkage disequilibrium and genome-wide association studies. These insights are expected to deepen our understanding and guide further advancements in Brassica species research.

Efficacy and safety of fire needle therapy for blood stasis syndrome of plaque psoriasis: protocol for a randomized, single-blind, multicenter clinical trial.

BACKGROUND: Fire needle therapy is a characteristic treatment in traditional Chinese medicine (TCM). An increasing number of studies have indicated that fire needle treatment for psoriasis provides satisfactory results with few side effects and a low recurrence rate. We herein describe the protocol for a multicenter, randomized, single-blind, placebo-controlled trial that will provide high-quality evidence on the efficacy and safety of fire needle therapy for plaque psoriasis. METHODS: Ninety-two patients with blood stasis syndrome (BSS) of plaque psoriasis will be enrolled and randomly assigned to receive fire needle therapy (intervention group) or fire needle control therapy (control group) once a week for 4 weeks. The Psoriasis Area and Severity Index (PASI) score will serve as the major efficacy index, while the body surface area (BSA), Physician Global Assessment (PGA) score, Dermatology Life Quality Index (DLQI) score, patient-reported quality of life (PRQoL), visual analog scale (VAS) score for itching, TCM symptom score, and relapse rate will be assessed as secondary outcomes. The PASI score, BSA, PGA score, and VAS score for itching will be evaluated at baseline and during the 4-week treatment and follow-up periods. DLQI score, PRQoL, and TCM symptom score will be assessed at baseline and during the treatment period. Recurrence will be evaluated during the follow-up period. Safety assessments include vital sign monitoring, routine blood tests, blood biochemistry, routine urine tests, pregnancy tests, physical examinations, and adverse-event recording. SAS software will be used for data analysis. The data network platform will be designed by the data management center of Nanjing Ningqi Medical Technology Co., Ltd. DISCUSSION: It is believed that fire needle therapy can activate the meridians, promote blood circulation, and regulate skin immunity. BSS of plaque psoriasis is related to not only immune dysfunction but also poor or stagnant blood flow. We anticipate that the results of the trial described in this protocol will provide strong evidence for the safety and efficacy of fire needle therapy for BSS of plaque psoriasis. TRIAL REGISTRATION: Clinicaltrials.gov NCT03953885 . Registered on May 15, 2019. Name: Fire Needle Therapy on Plaque Psoriasis with Blood Stasis Syndrome.