Boosting the immunogenicity of the CoronaVac SARS-CoV-2 inactivated vaccine with Huoxiang Suling Shuanghua Decoction: a randomized, double-blind, placebo-controlled study.

Introduction: In light of the public health burden of the COVID-19 pandemic, boosting the safety and immunogenicity of COVID-19 vaccines is of great concern. Numerous Traditional Chinese medicine (TCM) preparations have shown to beneficially modulate immunity. Based on pilot experiments in mice that showed that supplementation with Huoxiang Suling Shuanghua Decoction (HSSD) significantly enhances serum anti-RBD IgG titers after inoculation with recombinant SARS-CoV-2 S-RBD protein, we conducted this randomized, double-blind, placebo-controlled clinical trial aimed to evaluate the potential immunogenicity boosting effect of oral HSSD after a third homologous immunization with Sinovac's CoronaVac SARS-CoV-2 (CVS) inactivated vaccine. Methods: A total of 70 participants were randomly assigned (1:1 ratio) to receive a third dose of CVS vaccination and either oral placebo or oral HSSD for 7 days. Safety aspects were assessed by recording local and systemic adverse events, and by blood and urine biochemistry and liver and kidney function tests. Main outcomes evaluated included serum anti-RBD IgG titer, T lymphocyte subsets, serum IgG and IgM levels, complement components (C3 and C4), and serum cytokines (IL-6 and IFN-γ). In addition, metabolomics technology was used to analyze differential metabolite expression after supplementation with HSSD. Results: Following a third CVS vaccination, significantly increased serum anti-RBD IgG titer, reduced serum IL-6 levels, increased serum IgG, IgM, and C3 and C4 levels, and improved cellular immunity, evidenced by reduce balance deviations in the distribution of lymphocyte subsets, was observed in the HSSD group compared with the placebo group. No serious adverse events were recorded in either group. Serum metabolomics results suggested that the mechanisms by which HSSD boosted the immunogenicity of the CVS vaccine are related to differential regulation of purine metabolism, vitamin B6 metabolism, folate biosynthesis, arginine and proline metabolism, and steroid hormone biosynthesis. Conclusion: Oral HSSD boosts the immunogenicity of the CVS vaccine in young and adult individuals. This trial provides clinical reference for evaluation of TCM immunomodulators to improve the immune response to COVID-19 vaccines.

Change in function and homeostasis of HPA axis: The role of vitamin family.

With the improvement of living quality, people pay more and more attention to vitamin supplements. The vitamins in the daily diet can meet the needs of the body. Whether additional vitamin supplementation is necessary still needs to be further explored. Many studies have reported that vitamin deficiency and excessive vitamin supplementation could lead to abnormal development in the body or increase the risk of diseases. Here, we summarize the abnormal levels of vitamins can cause the homeostasis imbalance of hypothalamus-pituitary-adrenal (HPA) axis by affecting its development and function. It can lead to abnormal synthesis and secretion of glucocorticoid in the body, which mediates the occurrence and development of metabolic diseases and psychoneurotic diseases. In addition, vitamin has a strong antioxidant effect, which can eliminate oxygen free radicals. Thereby, vitamins can alter HPA axis function and homeostasis maintenance by combating oxidative stress. This review provides a theoretical basis for clarifying the role of abnormal levels of vitamin in the occurrence and development of multiple diseases and its intervention strategy, and also provides reference value and guiding significance for rational use of vitamins.

Early vs Delayed Transurethral Surgery in Acute Urinary Retention: Does Timing Make a Difference?

PURPOSE: Our goal was to compare outcomes of early vs delayed transurethral surgery for benign prostatic hyperplasia after an episode of acute urinary retention compared to men without preoperative acute retention. MATERIALS AND METHODS: We conducted a retrospective cohort analysis using data from the New York Statewide Planning and Research Cooperative System from 2002-2016. We identified men ≥40 years old who underwent primary ambulatory transurethral resection or photoselective vaporization of the prostate, assessing surgical failure as time to reoperation or recatheterization. We categorized presurgical acute urinary retention by number of episodes: none (reference), 1, or ≥2 precatheterizations, and time from first retention episode to surgery: none (reference), 0-6 months, and >6 months. We used Fine-Gray competing-risk models to predict surgical failure at 10 years, with presurgical acute retention as the primary predictor, adjusted for age, race, insurance, Charlson Comorbidity Index score, preoperative urinary infection, and procedure type, with death as the competing risk. RESULTS: Among 17,474 patients undergoing transurethral surgery, 10% had preoperative acute retention with a median time to surgery of 2.4 months (IQR: 1-18). Among men with preoperative retention, 37% had ≥6 months of delay to surgery. The 10-year cumulative treatment failure rate was 17.2% among catheter naïve men vs 34.0% with ≥2 precatheterizations and 32.9% with ≥6 months delay to surgery. Delays from catheterization to surgery were associated with higher rates of treatment failure (<6 months SHR 1.49, P < .001; ≥6 months SHR 2.11, P < .001) vs catheter naïve men. CONCLUSIONS: Preoperative acute urinary retention and delay to surgery once catheterized are associated with poorer long-term postoperative outcomes after surgery for benign prostatic hyperplasia.

Improvement influenza vaccine immune responses with traditional Chinese medicine and its active ingredients.

The current influenza vaccines are unable to provide effective protection in many cases, like influenza viruses strain antigenic drift or shift, and the influenza continues to cause significant annual morbidity and mortality. Improving the immune response to influenza vaccination is an unmet need. Traditional Chinese medicine (TCM) and its active ingredients are commonly known to have immunomodulatory properties. We therefore compared influenza vaccination alone or formulated with Astragali Radix (Huangqi in Chinese), and several representative ingredients of TCM, including lentinan (polysaccharide), panax notoginseng saponins (saponin), breviscapine (flavone), andrographolide (terpenoid), and a Chinese herbal compound (kangai) for their potential to enhance immune responses to influenza vaccine in mice. We found that all these TCM-adjuvants were able to increase hemagglutination inhibition (HAI) antibody titers, splenocyte proliferation, splenic T cell differentiation, bone marrow dendritic cell maturity, and both Th1 and Th2 cytokine secretion of influenza vaccine to varying degrees, and that had the characteristics of no excessive inflammatory responses and bidirectional regulation simultaneously. Taken together, our findings show that Astragali Radix exerts a more comprehensive effect on vaccine immunity, on both innate and adaptive immunity. The effects of lentinan and andrographolide on adaptive immunity were more significant, while the effects of breviscapine on innate immunity were stronger, and the other two TCM adjuvants were weaker. As the first report of a comprehensive evaluation of TCM adjuvants in influenza vaccines, the results suggest that TCM and their active ingredients are good candidates for enhancing the immune response of influenza vaccines, and that suitable TCMs can be selected based on the adjuvant requirements of different vaccines.

A clinical study to observe the efficacy and safety of Besunyen Detox Tea for constipation.

INTRODUCTION: Functional constipation (FC) is a common functional gastrointestinal disease and is one of the most common outpatient diseases. The purpose of this study was to investigate the efficacy and safety of the traditional Chinese medicine Besunyen Detox Tea (BDT) for FC and to compare the effect of BDT between constipation patients with and non-dryness-heat syndrome. METHODS AND ANALYSIS: This multicenter, prospective, observational registry study included 1000 participants diagnosed with FC. This study will collaborate with 3 comprehensive hospitals and 15 community hospitals and recruit patients into the registry between July 2022 and July 2023. After enrollment, we will collect the individual characteristics of each patient, anthropometric data and general condition, bowel movement, patient assessment of constipation symptoms, patient assessment of constipation quality of life, TCM syndrome scale, and time to take the laxative product again after treatment. We will also record adverse events and economic indicators at each visit. DISCUSSION: This is the first registry-based study to collect real-world data of participants diagnosed with FC receiving BDT treatment. The results of this registry may also reflect these characteristics and provide direct clinical evidence to verify the importance of syndrome differentiation and treatment for the use of TCM health care products.

A Claims Based Assessment of Reoperation and Acute Urinary Retention after Ambulatory Transurethral Surgery for Benign Prostatic Hyperplasia.

PURPOSE: We evaluated real-world use of common transurethral prostate procedures in the ambulatory surgical setting and compare subsequent rates of tr!eatment failure. MATERIALS AND METHODS: Using the New York Statewide Planning and Research Cooperative System database we identified men 40 years old or older undergoing ambulatory surgeries categorized as transurethral resection of the prostate, photoselective vaporization of the prostate, endoscopic enucleation or other (transurethral incision, microwave/radiofrequency ablation) from 2010 to 2016. Multivariate Cox proportional hazards regression was used to predict treatment failure, defined as reoperation or postoperative acute urinary retention greater than 30 days after procedure. RESULTS: We identified 15,982 men, median age 69 years (IQR 63-76), 61% of whom underwent photoselective vaporization of the prostate, 36% transurethral resection of the prostate, 1.5% endoscopic enucleation and 1.5% other transurethral prostate procedures from 2010 to 2016. At 7 years cumulative failure rates were 15.3% (transurethral resection of the prostate), 13.9% (photoselective vaporization of the prostate), 6.7% (endoscopic enucleation) and 17.8% (other procedures). Compared to transurethral resection of the prostate, photoselective vaporization of the prostate was not associated with increased hazards of treatment failure HR 1.07 (95% CI 0.93-1.22). Compared to transurethral resection of the prostate, endoscopic enucleation was associated with a nonsignificant trend toward lower treatment failure (HR 0.67, 95% CI 0.36-1.22), while other surgical modalities were associated with significantly higher treatment failure (HR 1.68. 95% CI 1.12-2.52). Among men treated from 2011 to 2012, endoscopic enucleations were associated with significantly lower failure than transurethral resection of the prostate (HR: 0.24, 95% CI 0.06-0.97). CONCLUSIONS: Supporting the generalizability of previous randomized trial findings, in real-world practice we found no differences in treatment failure up to 7 years after photoselective vaporization of the prostate or transurethral resection of the prostate. By comparison, endoscopic enucleation, although underused, may be associated with lower rates of treatment failure than transurethral resection of the prostate.

Association of coffee consumption with risk of colorectal cancer: a meta-analysis of prospective cohort studies.

A meta-analysis was performed to assess the association of coffee consumption with colorectal cancer and to investigate the shape of the association. Relevant prospective cohort studies were identified by a comprehensive search of the PubMed, Embase and Web of Science databases from their inception through August 2015. Either a random-effects model or fixed-effects model was used to compute the pooled risk estimates when appropriate. Linear and nonlinear dose-response meta-analyses were also performed. Nineteen prospective cohort studies involving 2,046,575 participants and 22,629 patients with colorectal cancer were included. The risk of colon cancer was decreased by 7% for every 4 cups per day of coffee (RR=0.93, 95%CI, 0.88-0.99; P=0.199). There was a threshold approximately five cups of coffee per day, and the inverse association for colorectal cancer appeared to be stronger at a higher range of intake. However, a nonlinear association of rectal cancer with coffee consumption was not observed (P for nonlinearity = 0.214). In conclusion, coffee consumption is significantly associated with a decreased risk of colorectal cancer at ≥ 5 cups per day of coffee consumption. The findings support the recommendations of including coffee as a healthy beverage for the prevention of colorectal cancer.

Gadoxetic acid-enhanced MRI and sonoelastography: non-invasive assessments of chemoprevention of liver fibrosis in thioacetamide-induced rats with Sho-Saiko-To.

BACKGROUND: This study aimed to compare the performance of gadoxetic acid -enhanced magnetic resonance imaging (MRI) and sonoelastography in evaluating chemopreventive effects of Sho-Saiko-To (SST) in thioacetamide (TAA)-induced early liver fibrosis in rats. MATERIALS AND METHODS: Ten of Sprague-Dawley rats receiving TAA (200 mg/kg of body weight) intraperitoneal injection were divided into three groups: Group 1 (TAA only, n = 3), Group 2 (TAA +0.25 g/kg SST, n = 4) and Group 3 (TAA+1 g/kg SST, n = 3). Core needle liver biopsy at week 2 and liver specimens after sacrifice at week 6 confirmed liver fibrosis using histological examinations, including Sirius red staining, Ishak and Metavir scoring systems. Gadoxetic acid-enhanced MRI and shear-wave sonoelastography were employed to evaluate liver fibrosis. The expression of hepatic transporter organic anion transporter 1 (Oatp1), multidrug-resistant protein 2 (Mrp2) and alpha-smooth muscle actin (α-Sma) were also analyzed in each group by immunohistochemistry (IHC) and Western blot. RESULTS: According to histological grading by Sirius red staining, Ishak scores of liver fibrosis in Groups 1, 2 and 3 were 3, 2 and 1, respectively. As shown in gadoxetic acid-enhanced MRI, the ratio of relative enhancement was significantly lower in Group 1 (1.87 ± 0.21) than in Group 2 of low-dose (2.82 ± 0.25) and Group 3 of high-dose (2.72 ± 0.12) SST treatment at 10 minutes after gadoxetic acid intravenous injection (p < 0.05). Sonoelastography showed that the mean difference before and after experiments in Groups 1, 2 and 3 were 4.66 ± 0.1, 4.4 ± 0.57 and 3 ± 0.4 KPa (p < 0.1), respectively. Chemopreventive effects of SST reduced the Mrp2 protein level (p < 0.01) but not Oatp1 and α-Sma levels. CONCLUSION: Sonoelastography and gadoxetic acid-enhanced MRI could monitor the treatment effect of SST in an animal model of early hepatic fibrosis.

Lotus leaf (Nelumbo nucifera) and its active constituents prevent inflammatory responses in macrophages via JNK/NF-κB signaling pathway.

Inflammation is a serious health issue worldwide that induces many diseases, such as inflammatory bowel disease (IBD), sepsis, acute pancreatitis and lung injury. Thus, there is a great deal of interest in new methods of limiting inflammation. In this study, we investigated the leaves of Nelumbo nucifera Gaertn, an aquatic perennial plant cultivated in eastern Asia and India, in anti-inflammatory pharmacological effects in the murine macrophage cell line RAW264.7. Results showed that lipopolysaccharide (LPS) increased the protein expression of inducible nitric oxide synthase (iNOS) and COX-2, as well as the mRNA expression and level of IL-6 and TNF-α, while NNE significantly reduced these effects of LPS. LPS also induced phospho-JNK protein expression. The JNK-specific inhibitor SP600125 decreased the proteins expression of phospho-JNK, iNOS, COX-2, and the mRNAs expression and levels of IL-6 and TNF-α. Further, NNE reduced the protein expression of phospho-JNK. LPS was also found to promote the translocation of NF-κB from the cytosol to the nucleus and to decrease the expression of cytosolic IκB. NNE and SP600125 treatment recovered the LPS-induced expression of NF-κB and IκB. While phospho-ERK and phospho-p38 induced by LPS, could not be reversed by NNE. To further investigate the major components of NNE in anti-inflammatory effects, we determined the quercetin and catechin in inflammatory signals. Results showed that quercetin and catechin significantly decreased the proteins expression of iNOS, COX-2 and phospho-JNK. Besides, the mRNAs and levels of IL-6 and TNF-α also decreased by quercetin and catechin treatment in LPS-induced RAW264.7 cells. These results showed that NNE and its major components quercetin and catechin exhibit anti-inflammatory activities by inhibiting the JNK- and NF-κB-regulated pathways and could therefore be an useful anti-inflammatory agent.

The effectiveness of acupressure on relieving pain: a systematic review.

Acupressure is a complementary treatment that uses fingers and hands to stimulate acupoints and maintains the balance of energy. The objective of this study was to review the application of acupressure in managing different pains and the effectiveness of acupressure on relieving pain in various settings. A systematic review of English articles using the databases of MEDLINE, PubMed, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) was performed using the search terms of "acupressure" and "pain." Studies during which acupressure was applied as an intervention and assessed for its effectiveness on relieving pain were selected. The studies selected were those published from January 1, 1996 to December 31, 2011 that met the inclusion and exclusion criteria. The participants included patients with dysmenorrhea, labor pain, low back pain, chronic headache, and other traumatic pains. The Oxford 2011 Levels of Evidence was used to appraise the literature. Fifteen studies were extracted for reducing dysmenorrhea (menstrual distress), labor pain, low back pain, chronic headache, and other traumatic pain. These papers were further reviewed for their study design, adequacy of randomization and concealment of allocation, blinding of participants, interventions, and outcome measurements. Acupressure has been shown to be effective for relieving a variety of pains in different populations. The review begins to establish a credible evidence base for the use of acupressure in pain relief. The implication for health care providers would be incorporating acupressure into their practice as an alternative therapy to facilitate patients who suffer from pain.

Caffeic acid phenethyl ester suppresses proliferation and survival of TW2.6 human oral cancer cells via inhibition of Akt signaling.

Caffeic acid phenethyl ester (CAPE) is a bioactive component extracted from honeybee hive propolis. Our observations indicated that CAPE treatment suppressed cell proliferation and colony formation of TW2.6 human oral squamous cell carcinoma (OSCC) cells dose-dependently. CAPE treatment decreased G1 phase cell population, increased G2/M phase cell population, and induced apoptosis in TW2.6 cells. Treatment with CAPE decreased protein abundance of Akt, Akt1, Akt2, Akt3, phospho-Akt Ser473, phospho-Akt Thr 308, GSK3ß, FOXO1, FOXO3a, phospho-FOXO1 Thr24, phospho-FoxO3a Thr32, NF-κB, phospho-NF-κB Ser536, Rb, phospho-Rb Ser807/811, Skp2, and cyclin D1, but increased cell cycle inhibitor p27Kip. Overexpression of Akt1 or Akt2 in TW2.6 cells rescued growth inhibition caused by CAPE treatment. Co-treating TW2.6 cells with CAPE and 5-fluorouracil, a commonly used chemotherapeutic drug for oral cancers, exhibited additive cell proliferation inhibition. Our study suggested that administration of CAPE is a potential adjuvant therapy for patients with OSCC oral cancer.

Dioscorin pre-treatment protects A549 human airway epithelial cells from hydrogen peroxide-induced oxidative stress.

Hydrogen peroxide (H(2)O(2)) is a highly reactive oxygen species involved in lung and bronchial epithelium injury. Increased H(2)O(2) levels have been reported in expired breath condensates of patients with inflammatory airway diseases such as chronic obstructive pulmonary disease. Protecting airway epithelial cells from oxidative stress is an important task in the prevention and management of airway diseases. Previous studies demonstrate that yam (Dioscorea batatas Decne) has antioxidant and anti-trypsin activities. This study evaluated the validity of dioscorin in vitro. The results showed that dioscorin attenuated the alteration of H(2)O(2) on G2/M cell cycle arrest. This might be associated with the activation of IκB and subsequent inactivation of NF-κB. Furthermore, dioscorin suppressed IL-8 secretion and reduced changes of adhesion molecule expressions in H(2)O(2)-injured A549 cells. These results help in understanding the potential of traditional Chinese herbal medicine as treatment for airway inflammatory diseases.

Antidiabetic effects of pterosin A, a small-molecular-weight natural product, on diabetic mouse models.

The therapeutic effect of pterosin A, a small-molecular-weight natural product, on diabetes was investigated. Pterosin A, administered orally for 4 weeks, effectively improved hyperglycemia and glucose intolerance in streptozotocin, high-fat diet-fed, and db/db diabetic mice. There were no adverse effects in normal or diabetic mice treated with pterosin A for 4 weeks. Pterosin A significantly reversed the increased serum insulin and insulin resistance (IR) in dexamethasone-IR mice and in db/db mice. Pterosin A significantly reversed the reduced muscle GLUT-4 translocation and the increased liver phosphoenolpyruvate carboxyl kinase (PEPCK) expression in diabetic mice. Pterosin A also significantly reversed the decreased phosphorylations of AMP-activated protein kinase (AMPK) and Akt in muscles of diabetic mice. The decreased AMPK phosphorylation and increased p38 phosphorylation in livers of db/db mice were effectively reversed by pterosin A. Pterosin A enhanced glucose uptake and AMPK phosphorylation in cultured human muscle cells. In cultured liver cells, pterosin A inhibited inducer-enhanced PEPCK expression, triggered the phosphorylations of AMPK, acetyl CoA carboxylase, and glycogen synthase kinase-3, decreased glycogen synthase phosphorylation, and increased the intracellular glycogen level. These findings indicate that pterosin A may be a potential therapeutic option for diabetes.

Analgesic and Antiinflammatory Activities of the Aqueous Extract from Plectranthus amboinicus (Lour.) Spreng. Both In Vitro and In Vivo.

Plectranthus amboinicus (Lour.) Spreng. is a native Labiatae plant of Taiwan. The plants are commonly used in Chinese folk medicine for the treatment of cough, fever, sore throats, mumps, and mosquito bite. The aim of this study was to investigate the analgesic and antiinflammatory properties of the aqueous extract from Plectranthus amboinicus (PA) in vivo and in vitro. PA inhibited pain induced by acetic acid and formalin, and inflammation induced by carrageenan. The anti-inflammatory effect of PA was related to modulating antioxidant enzymes' activities in the liver and decreasing the Malondialdehyde (MDA) level and the production of tumor necrosis factor alpha (TNF-α), and cyclooxygenase2 (COX-2) in edema-paw tissue in mice. In vitro studies show that PA inhibited the proinflammatory mediators in RAW 264.7 cells stimulated with lipopolysaccharide (LPS). PA blocked the degradation of IκB-α and nuclear translocation of NF-κB p65 subunit. Finally, the amount of carvacrol in the aqueous extract of PA was 1.88 mg/g extract. Our findings suggest that PA has analgesic and anti-inflammatory activities. These effects were mediated by inhibiting the proinflammatory mediators through blocking NF-κB activation. Meanwhile, the effects observed in this study provide evidence for folkloric uses of Plectranthus amboinicus (Lour.) Spreng. in relieving pain and inflammation.