Waterlogging in soil restricts the growth of Gleditsia sinensis seedlings and inhibits the accumulation of lignans and phenolic acids in thorns.

Gleditsia sinensis, commonly known as Chinese Zaojiao, has important economic value and medicinal compounds in its fruits and thorns, making it widely cultivated artificially in China. However, the available literature on the impact of waterlogging on the growth of G. sinensis seedlings and the accumulation of metabolite compounds in its thorns is limited. To address this knowledge gap, G. sinensis seedlings were planted in soil supplemented with pindstrup substrate, which enhances the water-holding capacity of the soil. The analyses of morphological traits and nutrient elements in one-year-old G. sinensis seedlings grown naturally under ambient conditions and metabolite accumulation in its thorns were conducted. The results showed that the waterlogged soil significantly diminished the height, fresh weight, and dry weight of seedling roots and stems (P < 0.05). Furthermore, waterlogging hindered the uptake of iron (Fe) and manganese (Mn), as well as the transport of potassium (K). The identified metabolites within the thorns were categorized into 16 distinct groups. Relative to the control soil, fatty acids and derivatives were the most down-regulated metabolites in the waterlogged soil, accounting for 40.58% of the total metabolites, followed by lignans (38.71%), phenolic acids (34.48%), saccharides and alcohols (34.15%), steroids (16.67%), alkaloids (12.24%), flavonoids (9.28%), and glycerophospholipids (7.41%). Conversely, nucleotides and derivatives experienced the greatest up-regulation in the waterlogged soil, accounting for 50.00% of the total metabolites. In conclusion, waterlogging negatively impacted the growth of G. sinensis seedlings and inhibited the accumulation of metabolites. Hence, when considering the accumulation of secondary metabolites such as lignans and phenolic acids, appropriate management of soil moisture levels should be taken into account.

Influence of nutritional supplements on antibody levels in pregnant women vaccinated with inactivated SARS-CoV-2 vaccines.

BACKGROUND: Because of the significantly higher demand for nutrients during pregnancy, pregnant women are more likely to have nutrient deficiencies, which may adversely affect maternal and fetal health. The influence of nutritional supplements on the immune effects of inactivated SARS-CoV-2 vaccines during pregnancy is not clear. METHODS: In a multicenter cross-sectional study, we enrolled 873 pregnant women aged 18-45 y in Guangdong, China. The general demographic characteristics of pregnant women and their use of nutritional supplements were investigated, and the serum antibody levels induced by inactivated SARS-CoV-2 vaccines were measured. A logistic regression model was used to analyze the association between nutritional supplements and SARS-CoV-2 antibody levels. RESULTS: Of the 873 pregnant women enrolled, 825 (94.5%) took folic acid during pregnancy, 165 (18.9%) took iron supplements, and 197 (22.6%) took DHA. All pregnant women received at least one dose of inactivated SARS-CoV-2 vaccine, and the positive rates of serum SARS-CoV-2 neutralizing antibodies (NAbs) and immunoglobulin G (IgG) antibodies were 44.7% and 46.4%, respectively. After adjustment for confounding factors, whether pregnant women took folic acid, iron supplements, or DHA did not influence NAb positivity or IgG positivity (P > 0.05). Compared with pregnant women who did not take folic acid, the odds ratios (ORs) for the presence of SARS-CoV-2 NAb and IgG antibody in pregnant women who took folic acid were 0.67 (P = 0.255; 95% CI, 0.34-1.32) and 1.24 (P = 0.547; 95% CI, 0.60-2.55), respectively. Compared with pregnant women who did not take iron supplements, the ORs for the presence of NAb and IgG antibody in pregnant women who took iron supplements were 1.16(P = 0.465; 95% CI, 0.77-1.76) and 0.98 (P = 0.931; 95% CI, 0.64-1.49), respectively. Similarly, the ORs for NAb and IgG antibody were 0.71 (P = 0.085; 95% CI, 0.49-1.04) and 0.95 (P = 0.801; 95% CI, 0.65-1.38) in pregnant women who took DHA compared with those who did not. CONCLUSIONS: Nutritional supplementation with folic acid, iron, or DHA during pregnancy was not associated with antibody levels in pregnant women who received inactivated SARS-CoV-2 vaccines.

Natural compound Byakangelicin suppresses breast tumor growth and motility by regulating SHP-1/JAK2/STAT3 signal pathway.

Byakangelicin mostly obtained from the root of Angelica dahurica and has protective effect on liver injury and fibrosis. In addition, Byakangelicin, as a traditional medicine, is also used to treat colds, headache and toothache. Recent studies have shown that Byakangelicin exhibits anti-tumor function; however, the role of Byakangelicin in breast tumor progression and related mechanism has not yet been elucidated. Our study aims to investigate the role of Byakangelicin in breast tumor progression and the underlying mechanism. To measure the effect of Byakangelicin on JAK2/STAT3 signaling, a dual luciferase reporter assay and a Western blot assay were performed. CCK8, colony formation, apoptosis and cell invasion assays were used to examine the inhibitory potential of Byakangelicin on breast cancer cells. Additionally, SHP-1 was silenced by specific siRNA duplex and the function of SHP-1 on Byakangelicin-mediated inhibition of JAK2/STAT3 signaling was evaluated. Byakangelicin treatment significantly inhibited STAT3 transcriptional activity. In addition, Byakangelicin treatment blocked JAK2/STAT3 signaling in a dose-dependent manner. Byakangelicin-treated tumor cells showed a dramatically reduced proliferation, colony formation and invasion ability. Moreover, Byakangelicin remarkedly induced breast cancer cell apoptosis. Furthermore, Byakangelicin regulated the expression of SHP1.In conclusion, our current study indicated that Byakangelicin, a natural compound, inhibits SHP-1/JAK2/STAT3 signaling and thus blocks tumor growth and motility.

Hydroxysafflor Yellow A Exerts Neuroprotective Effects by Inhibiting Protein Carbonyl Formation in Cerebral Ischemia-Reperfusion Injury.

Protein carbonylation by reactive oxygen species (ROS) is an important factor in the pathogenesis of cerebral ischemia-reperfusion injury (CIRI). Carbonyls are mainly produced by peroxynitrite (ONOO-) and hemin/hydrogen peroxide (H2O2)/sodium nitrite (NaNO2)-mediated reactions. As the main active water-soluble chalcone chemical ingredient derived from Carthamus tinctorius L, hydroxysafflor yellow A (HSYA) has been increasingly applied in the treatment of cerebrovascular disease (CVD). In this study, rats were randomly divided into 3 groups: the sham-surgery group (sham), the CIRI group (CIRI) and the CIRI treated with HSYA group (HSYA). We evaluated the protective properties of HSYA in a CIRI model in vivo, assessed its efficacy against ONOO- and hemin/H2O2/NaNO2-induced oxidative damage to cerebral cortical tissues in vitro, and explored the probable molecular mechanisms underlying its neuroprotective effects. The results showed that HSYA protected rats against CIRI by improving their neurological function score (P < .05), reducing infarct volume (P < .01), decreasing the content of protein carbonyls (P < .01) and elevating the glutathione (GSH) levels (P < .01). Further in vitro investigations found that HSYA pretreatment could inhibit protein carbonylation induced by exogenous ONOO- application in cortical brain tissues in a dose-dependent manner (P < .01). In terms of hemin/H2O2/NaNO2-triggered oxidative damage, HSYA slightly promoted the formation of carbonyl groups (P < .05). In conclusion, this study demonstrates that the neuroprotective capabilities of HSYA in CIRI are attributable, at least in part, to the enhancement in antioxidant capacity and the attenuation of protein oxidation, probably via the combined processes of ONOO- scavenging and the suppression of protein carbonyl formation.

Concentrations, Sources and Health Risk Assessment of Polycyclic Aromatic Hydrocarbons in Chinese Herbal Medicines.

The determination and evaluation of 16 polycyclic aromatic hydrocarbons (PAHs) in seven Chinese herbal medicines (CHMs) were conducted through a rapid and straightforward extraction and purification method, coupled with GC-MS. A sample-based solid-phase extraction (SPE) pretreatment technique, incorporating isotopic internal standards, was employed for detecting various medicinal parts of CHMs. The assay exhibited linearity within the range of 5 to 500 ng/mL, with linear coefficients (R2) for PAHs exceeding 0.999. The recoveries of spiked standards ranged from 63.37% to 133.12%, with relative standard deviations (RSDs) ranging from 0.75% to 14.54%. The total PAH content varied from 176.906 to 1414.087 µg/kg. Among the 16 PAHs, phenanthrene (Phe) was consistently detected at the highest levels (47.045-168.640 µg/kg). Characteristic ratio analysis indicated that oil, coal, and biomass combustion were the primary sources of PAHs in CHMs. The health risk associated with CHMs was assessed using the lifetime carcinogenic risk approach, revealing potential health risks from the consumption of honeysuckle, while the health risks of consuming Lycium chinense berries were deemed negligible. For the other five CHMs (glycyrrhizae, Coix lacryma, ginseng, lotus seed, seed of Sterculia lychnophora), the health risk from consumption fell within acceptable ranges. Furthermore, sensitivity analyses utilizing Monte Carlo exposure assessment methods identified PAH levels in CHMs as health risk sensitizers. It is crucial to recognize that the consumption of herbal medicines is not a continuous process but entails potential health risks. Hence, the monitoring and risk assessment of PAH residues in CHMs demand careful attention.

Rutin ameliorated lipid metabolism dysfunction of diabetic NAFLD via AMPK/SREBP1 pathway.

BACKGROUND: In diabetic liver injury, nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease. Rutin is a bioflavonoid produced by the hydrolysis of glucosidases to quercetin. Its biological activities include lowering blood glucose, regulating insulin secretion, regulating dyslipidemia, and exerting anti-inflammatory effects have been demonstrated. However, its effect on diabetic NAFLD is rarely reported. PURPOSE: Our study aimed to investigate the protective effects of Rutin on diabetic NAFLD and potential pharmacological mechanism. METHODS: We used db/db mice as the animal model to investigate diabetic NAFLD. Oleic acid-treated (OA) HeLa cells were examined whether Rutin had the ability to ameliorate lipid accumulation. HepG2 cells treated with 30 mM/l d-glucose and palmitic acid (PA) were used as diabetic NAFLD in vitro models. Total cholesterol (TC) and Triglycerides (TG) levels were determined. Oil red O staining and BODIPY 493/503 were used to detect lipid deposition within cells. The indicators of inflammation and oxidative stress were detected. The mechanism of Rutin in diabetic liver injury with NAFLD was analyzed using RNA-sequence and 16S rRNA, and the expression of fat-synthesizing proteins in the 5' adenosine monophosphate-activated protein kinase (AMPK) pathway was investigated. Compound C inhibitors were used to further verify the relationship between AMPK and Rutin in diabetic NAFLD. RESULTS: Rutin ameliorated lipid accumulation in OA-treated HeLa. In in vitro and in vivo models of diabetic NAFLD, Rutin alleviated lipid accumulation, inflammation, and oxidative stress. 16S analysis showed that Rutin could reduce gut microbiota dysregulation, such as the ratio of Firmicutes to Bacteroidetes. RNA-seq showed that the significantly differentially genes were mainly related to liver lipid metabolism. And the ameliorating effect of Rutin on diabetic NAFLD was through AMPK/SREBP1 pathway and the related lipid synthesis proteins was involved in this process. CONCLUSION: Rutin ameliorated diabetic NAFLD by activating the AMPK pathway and Rutin might be a potential new drug ingredient for diabetic NAFLD.

Suggested Electroacupuncture for Postoperative Nausea and Vomiting: A Comprehensive Meta-Analysis and Systematic Review of Randomized Controlled Trials.

BACKGROUND The purpose of this meta-analysis was to evaluate the effectiveness of electroacupuncture in preventing and treating postoperative nausea and vomiting (PONV) after general anesthesia. MATERIAL AND METHODS We searched for papers on randomized controlled trials on electroacupuncture for PONV prevention after general anesthesia published in PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) since October 1, 2016. Primary outcome was incidence of PONV; secondary outcomes were incidence of postoperative nausea (PON) at 6 h, postoperative vomiting (POV) at 6 h, and postoperative antiemetic requirement. Data were combined and analyzed using RevMan 5.4.1 software. RESULTS Eight randomized controlled trials, with 899 total participants, were included. Findings showed (1) there was no significant difference in occurrence rate of PONV between electroacupuncture and control groups (OR=0.31, 95% CI [0.06, 1.49], P=0.14, I²=82%); (2) electroacupuncture reduced incidence of PON at 6 h postoperatively, compared with controls (OR=0.43, 95% CI [0.27, 0.67], P=0.0002, I²=0%); (3) compared with control group, electroacupuncture reduced POV incidence 0-6 h postoperatively (OR=0.38, 95% CI [0.23, 0.63], P=0.0001, I²=0%); (4) electroacupuncture group demonstrated a significant reduction in postoperative requirement for antiemetic medications (OR=0.44, 95% CI [0.25, 0.78], P=0.005, I²=61%); (5) one study reported adverse reactions during observation, with 3 patients experiencing pain and itching at acupuncture site and 2 patients refusing a second acupuncture treatment; all symptoms lasted less than 2 h. CONCLUSIONS Based on current evidence, electroacupuncture significantly reduces the occurrence rate of PON and POV at 6 h after surgery and the use of antiemetic medication postoperatively. However, more high-quality, large-sample randomized controlled trials are needed to further validate its efficacy.

[The skin surface microcirculation of conception vessel, governor vessel and thoroughfare vessel in patients with primary dysmenorrhea].

OBJECTIVE: To observe the skin surface microcirculation of acupoints of conception vessel, governor vessel and thoroughfare vessel in patients with primary dysmenorrhea using laser speckle contrast imaging (LSCI), and provide acupoint selection basis of acupuncture-moxibustion for primary dysmenorrhea. METHODS: Ninety-nine healthy female college students with regular menstrual cycles (normal group) and 94 female college students with primary dysmenorrhea (dysmenorrhea group) were recruited. Before menstrual period, on the first day of menstruation, and on the third day after menstruation, LSCI was used to observe the surface microcirculation at the abdominal acupoints of conception vessel, i. e. Yinjiao (CV 7), Qihai (CV 6), Shimen (CV 5), Guanyuan (CV 4), Zhongji (CV 3) and Qugou (CV 2), acupoints of thoroughfare vessel, i. e. Huangshu (KI 16), Zhongzhu (KI 15), Siman (KI 14), Qixue (KI 13), Dahe (KI 12), Henggu (KI 11) and acupoints of lumbosacral region of governor vessel, i. e. Xuanshu (GV 5), Mingmen (GV 4), Yaoyangguan (GV 3), Yaoshu (GV 2) as well as two non-acupoints. RESULTS: Before menstrual period, there was no significant difference in the surface blood perfusion of the acupoints between the dysmenorrhea group and the normal group (P>0.05). On the first day of menstruation, the surface blood perfusion of Xuanshu (GV 5), Mingmen (GV 4), Yaoyangguan (GV 3) and right Huangshu (KI 16) in the dysmenorrhea group was higher than that in the normal group (P<0.05, P<0.01). On the third day after menstruation, the surface blood perfusion of the right Henggu (KI 11) in the dysmenorrhea group was lower than that in the normal group (P<0.05). CONCLUSION: In patients with primary dysmenorrhea, on the first day of menstruation, the surface blood perfusion of Xuanshu (GV 5), Mingmen (GV 4), Yaoyangguan (GV 3) of governor vessel, and the right Huangshu (KI 16) of thoroughfare vessel is increased, while on the third day after menstruation, the surface blood perfusion of the right Henggu (KI 11) of thoroughfare vessel is decreased. These findings might provide a basis for acupoint selection in the acupuncture-moxibustion treatment of primary dysmenorrhea.

Effects of Compound Danshen Dripping Pills on Ventricular Remodeling and Cardiac Function after Acute Anterior Wall ST-Segment Elevation Myocardial Infarction (CODE-AAMI): Protocol for a Randomized Placebo-Controlled Trial.

BACKGROUND: Ventricular remodeling after acute anterior wall ST-segment elevation myocardial infarction (AAMI) is an important factor in occurrence of heart failure which additionally results in poor prognosis. Therefore, the treatment of ventricular remodeling needs to be further optimized. Compound Danshen Dripping Pills (CDDP), a traditional Chinese medicine, exerts a protective effect on microcirculatory disturbance caused by ischemia-reperfusion injury and attenuates ventricular remodeling after myocardial infarction. OBJECTIVE: This study is designed to evaluate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function after AAMI on a larger scale. METHODS: This study is a multi-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The total of 268 patients with AAMI after primary percutaneous coronary intervention (pPCI) will be randomly assigned 1:1 to the CDDP group (n=134) and control group (n=134) with a follow-up of 48 weeks. Both groups will be treated with standard therapy of ST-segment elevation myocardial infarction (STEMI), with the CDDP group administrating 20 tablets of CDDP before pPCI and 10 tablets 3 times daily after pPCI, and the control group treated with a placebo simultaneously. The primary endpoint is 48-week echocardiographic outcomes including left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVI), and left ventricular end-systolic volume index (LVESVI). The secondary endpoint includes the change in N terminal pro-B-type natriuretic peptide (NT-proBNP) level, arrhythmias, and cardiovascular events (death, cardiac arrest, or cardiopulmonary resuscitation, rehospitalization due to heart failure or angina pectoris, deterioration of cardiac function, and stroke). Investigators and patients are both blinded to the allocated treatment. DISCUSSION: This prospective study will investigate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function in patients undergoing pPCI for a first AAMI. Patients in the CDDP group will be compared with those in the control group. If certified to be effective, CDDP treatment in AAMI will probably be advised on a larger scale. (Trial registration No. NCT05000411).

Integrating serum metabolomics and network analysis to explore the antidepressant activity of crocin in rats with chronic unexpected mild stress-induced depression.

CONTEXT: Crocin exhibits anti-depressant properties. However, its underlying mechanisms and its relationship with metabolomics remain unclear. OBJECTIVE: This study elucidates the mechanism of action and potential targets of crocin in treating chronic unexpected mild stress (CUMS)-induced depression in rats. MATERIALS AND METHODS: Male Sprague-Dawley (SD) rats underwent 4 weeks of CUMS to establish the depression model. The normal control (distilled water), crocin (25 mg/kg), and fluoxetine (5.4 mg/kg) groups were orally administered for 4-weeks. Behavioural tests evaluated the effects of crocin, while liquid chromatography-mass spectrometry metabolomics identified differential metabolites and their associated metabolic pathways. Subsequently, network pharmacology was utilized to predict the targets of crocin. RESULTS: Crocin significantly increased body weight (from 319.16 ± 4.84 g to 325.67 ± 2.84 g), sucrose preference (from 0.46 ± 0.09 to 0.70 ± 0.09), vertical activity (from 2.83 ± 1.94 to 8 ± 2.36), horizontal activity (from 1 ± 0.63 to 4.5 ± 3.08) and decreased immobilization time (from 13.16 ± 2.69 to 3.97 ± 3.00). Metabolomics analysis identified 7 metabolites and 5 associated metabolic pathways. From the combined analysis of network pharmacology and metabolomics, three targets (PRMT1, CYP3A4, and GLB1) are the overlapping targets and the two most important metabolic pathways are tryptophan metabolism and glycerolipid metabolism. DISCUSSION AND CONCLUSIONS: This study provides insights into the antidepressant therapeutic effect of crocin and its underlying mechanisms. The findings contribute to a better understanding of the metabolic mechanism involved in the anti-depressant effect of crocin, establishing a strong foundation for future research in this area.

Study on the protective effect of chondroitin sulfate from sturgeons on rat chondrocytes and its potential mechanisms.

OBJECTIVE: To investigate the protective effect of Chondroitin Sulfate from Sturgeons on rat chondrocytes and its possible mechanism. METHODS: The model of chondrocyte injury induced by hydrogen peroxide was established and chondrocytes were cultured and divided into the following groups: control group, sham group, model group, Sofast group, Low dose of Chondroitin Sulfate from Sturgeon B (CSSB-L) group, Moderate dose of Chondroitin Sulfate from Sturgeon B (CSSB-M) group and High dose of Chondroitin Sulfate from Sturgeon B (CSSB-H) group. The cell proliferation was analyzed by Cell Counting Kit-8 (CCK-8) assay. The cell apoptosis was detected by flow cytometer. The expression levels of Interleukin-6 (IL-6), Interleukin-8 (IL-8) and Interferon gamma (IFN-γ) in cell supernatants were examined by Enzyme-linked immunosorbent assay (ELISA). Western blot analysis was used to detect the levels of proteins associated with Wnt signal pathway in chondrocytes. RESULTS: Compared with the control group and sham group, the cell proliferation was decreased significantly, cell apoptosis was increased obviously, and the levels of IL-6, IL-8 and IFN-γ were remarkably increased in the model group. For Wnt signal pathway related proteins, the levels of Wnt3a, Frizzled5, Dsh, ß-Catenin and C-myc proteins in the model group were significantly reduced, and p-GSK3ß expression level was obviously increased (all P<0.05). Compared with the model group, CSSB could promote cell viability, and inhibit cell apoptosis and the levels of IL-6, IL-8 and IFN-γ (all P<0.05). The levels of Wnt signaling pathways related proteins in the CSSB-M group and CSSB-H group were obviously expressed. CONCLUSIONS: Chondroitin sulfate from sturgeons protected rat chondrocytes from injuries induced by hydrogen peroxide, which may be associated with the Wnt signaling pathway.

Acupoint Thread Embedding Combined With Wenshen Bugu Decoction for the Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptom Among Postmenopausal Breast Cancer Patients: Study Protocol of a Randomized Controlled Trial.

BACKGROUND: Aromatase inhibitors (AIs) are recommended as the preferred therapy for postmenopausal women with hormone receptor-positive (HR+) breast cancer. As a result, aromatase inhibitor-associated musculoskeletal symptom (AIMSS) have become a major problem leading to therapy discontinuation and decreased quality of life in patients receiving adjuvant AIs treatment. Multiple therapies have been attempted, but have yielded limited clinical results. This study will be performed to determine whether acupoint thread embedding (ATE) combined with Wenshen Bugu Decoction can effectively treat AIMSS, so as to improve the AIs medication compliance of postmenopausal breast cancer patients. METHODS: This study will utilize a randomized, 2 parallel groups controlled trial design. A total of 128 eligible postmenopausal breast cancer women with AIMSS will be randomized to receive a 12-week treatment with Wenshen Bugu Decoction alone (control group) or in combination with ATE (treatment group) in a 1:1 ratio. The primary outcome will be the 12 week Brief Pain Inventory Worst Pain (BPI-WP) score. The secondary outcome measures will include response rate, Brief Pain Inventory-Short Form (BFI-SF), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Functional Assessment of Cancer Therapy-Endocrine Symptom (FACT-ES), Functional Assessment of Cancer Therapy-Breast (FACT-B), bone marrow density (BMD), blood markers of bone metabolite, Morisky medication adherence scale-8 (MMAS-8), credibility and expectancy, and survival outcomes. DISCUSSION: This trial may provide clinical evidence that ATE combined with Wenshen Bugu Decoction can be beneficial for treating AIMSS among postmenopausal breast cancer survivors. Our findings will be helpful to enhance the quality of life and reduce the occurrence of AIs withdrawal.

Ginsenoside Rg1 improves anti-tumor efficacy of adoptive cell therapy by enhancing T cell effector functions.

Adoptive cell therapy (ACT) has emerged with remarkable efficacies for tumor immunotherapy. Chimeric antigen receptor (CAR) T cell therapy, as one of most promising ACTs, has achieved prominent effects in treating malignant hematological tumors. However, the insufficient killing activity and limited persistence of T cells in the immunosuppressive tumor microenvironment limit the further application of ACTs for cancer patients. Many studies have focused on improving cytotoxicity and persistence of T cells to achieve improved therapeutic effects. In this study, we explored the potential function in ACT of ginsenoside Rg1, the main pharmacologically active component of ginseng. We introduced Rg1 during the in vitro activation and expansion phase of T cells, and found that Rg1 treatment upregulated two T cell activation markers, CD69 and CD25, while promoting T cell differentiation towards a mature state. Transcriptome sequencing revealed that Rg1 influenced T cell metabolic reprogramming by strengthening mitochondrial biosynthesis. When co-cultured with tumor cells, Rg1-treated T cells showed stronger cytotoxicity than untreated cells. Moreover, adding Rg1 to the culture endowed CAR-T cells with enhanced anti-tumor efficacy. This study suggests that ginsenoside Rg1 provides a potential approach for improving the anti-tumor efficacy of ACT by enhancing T cell effector functions.

Electroacupuncture ameliorates pain in cervical spondylotic radiculopathy rat by inhibiting the CaMKII/CREB/BDNF signaling pathway and regulating spinal synaptic plasticity.

BACKGROUND: Central sensitization is one of the important mechanisms underlying neuropathic and radicular pain due to cervical spondylotic radiculopathy (CSR). Recent studies have shown that the calmodulin-dependent protein kinase II (CaMKII)/cAMP-response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway mediates central sensitization through its involvement in spinal cord synaptic plasticity. Our group has previously found that electroacupuncture (EA) has a good analgesic effect on CSR. However, the central analgesic mechanism of EA for CSR is not yet clear. METHODS: The rats were randomly divided into Blank group, Sham-operated group, CSR group, and EA group. We prepared the CSR rat model using the fish wire extrusion method. The behavioral and mechanical pain thresholds of the rats in each group were measured 5 days after successful modeling and 7 days after the intervention. The first intervention was started 5 days after successful modeling, and the EA group was treated by acupuncture at the bilateral LI4 and LR3 points on the same side as one group, connected to a G6805-I electroacupuncture apparatus with continuous waves at 1.5 Hz. The remaining groups were not subjected to EA intervention. The treatment was administered once a day for 7 consecutive days and then executed. We used WB, immunofluorescence, and qRT-PCR to detect the expression of CaMKII/CREB/BDNF signaling pathway-related factors in the synaptic of rat spinal cord in each group. RESULTS: EA improved pain threshold and motor function in CSR rats, inhibited the expression of BDNF, P-TrkB, CAMKII, and P-CREB in spinal cord synapses, reduced the expression of pain factor c-fos and postsynaptic membrane protein molecule neuroligin2, exerted a modulating effect on spinal cord synaptic plasticity in CSR rats, and suppressed the overactive synaptic efficacy. CONCLUSION: EA mediates central sensitization and exerts analgesic effects on CSR by modulating spinal synaptic plasticity, which may be related to the inhibition of CaMKII/CREB/BDNF signaling pathway.

Chinese expert consensus on the construction of the fluoroless cardiac electrophysiology laboratory and related techniques.

Transcatheter radiofrequency ablation has been widely introduced for the treatment of tachyarrhythmias. The demand for catheter ablation continues to grow rapidly as the level of recommendation for catheter ablation. Traditional catheter ablation is performed under the guidance of X-rays. X-rays can help display the heart contour and catheter position, but the radiobiological effects caused by ionizing radiation and the occupational injuries worn caused by medical staff wearing heavy protective equipment cannot be ignored. Three-dimensional mapping system and intracardiac echocardiography can provide detailed anatomical and electrical information during cardiac electrophysiological study and ablation procedure, and can also greatly reduce or avoid the use of X-rays. In recent years, fluoroless catheter ablation technique has been well demonstrated for most arrhythmic diseases. Several centers have reported performing procedures in a purposefully designed fluoroless electrophysiology catheterization laboratory (EP Lab) without fixed digital subtraction angiography equipment. In view of the lack of relevant standardized configurations and operating procedures, this expert task force has written this consensus statement in combination with relevant research and experience from China and abroad, with the aim of providing guidance for hospitals (institutions) and physicians intending to build a fluoroless cardiac EP Lab, implement relevant technologies, promote the standardized construction of the fluoroless cardiac EP Lab.

Characteristics of PM2.5-bound metals in Japan over six years: Spatial distribution, health risk, and source analysis.

Air sampling campaigns were conducted at 100 survey sites across Japan from April 2014 to February 2020, and a comprehensive database of atmospheric particles was obtained. In this study, the characteristics of PM2.5 and 26 metals were investigated in depth. Spatially, the concentration of PM2.5 gradually increased from the northeast to the southwest of Japan. The pollution in Kitakyushu City was the most serious, reaching 19.8 µg m-3. As an important particle component, metals did not show obviously spatial variation in Japan, with a sum concentration of 0.4 µg m-3. Anthropogenic metals only accounted for about 8% of the total metals, but they could pose a serious threat to public health. For children, the non-carcinogenic risk and carcinogenic risk due to exposure to anthropogenic metals could not be neglected in Japan; the corresponding HI and CR values at 100 survey sites ranged from 2.7 to 15.0 and 4.1 × 10-5 to 3.4 × 10-4, respectively. Adults faced lower health risks than children, with HI values ranging from 0.2 to 2.0 and CR values ranging from 2.0 × 10-5 to 1.6 × 10-4. The integrated health risk assessment results showed that the coastal region of the Seto Inland Sea and the north Tohoku Region were the most heavily polluted areas of Japan; in this study, 20 survey sites were finally determined to be high-risk sites, among which pollution control for Niihama City, Kitakyushu City, Hachinohe City, and Shimonoseki City were of first priority. With further combination with a positive matrix factorization model, it can be known that these four cities mainly had five to seven metal sources, and their heavy pollution was mainly caused by ship emissions, industrial emissions, biomass burning, and coal combustion. Overall, our study comprehensively revealed the regional patterns of PM2.5-bound metal pollution across Japan, which can help in making cost-effective risk management policies with limited national/local budgets.

Electroacupuncture Attenuates Neuropathic Pain in a Rat Model of Cervical Spondylotic Radiculopathy: Involvement of Spinal Cord Synaptic Plasticity.

Purpose: Cervical spondylotic radiculopathy (CSR) is a common neurologic condition that causes chronic neck pain and motor functions, with neuropathic pain (NP) being the primary symptom. Although it has been established that electroacupuncture (EA) can yield an analgesic effect in clinics and synaptic plasticity plays a critical role in the development and maintenance of NP, the underlying mechanisms have not been fully elucidated. In this study, we explored the potential mechanisms underlying EA's effect on synaptic plasticity in CSR rat models. Materials and Methods: The CSR rat model was established by spinal cord compression (SCC). Electroacupuncture stimulation was applied to LI4 (Hegu) and LR3 (Taichong) acupoints for 20 min once a day for 7 days. Pressure pain threshold (PPT) and mechanical pain threshold (MPT) were utilized to detect the pain response of rats. A gait score was used to evaluate the motor function of rats. Enzyme-linked immunosorbent assay (ELISA), Western blot (WB), immunohistochemistry (IHC), immunofluorescence (IF), and transmission electron microscopy (TEM) were performed to investigate the effects of EA. Results: Our results showed that EA alleviated SCC-induced spontaneous pain and gait disturbance. ELISA showed that EA could decrease the concentration of pain mediators in the cervical nerve root. WB, IHC, and IF results showed that EA could downregulate the expression of synaptic proteins in spinal cord tissues and promote synaptic plasticity. TEM revealed that the EA could reverse the synaptic ultrastructural changes induced by CSR. Conclusion: Our findings reveal that EA can inhibit SCC-induced NP by modulating the synaptic plasticity in the spinal cord and provide the foothold for the clinical treatment of CSR with EA.

A new method to treat onychopapilloma with pulsed dye laser irradiation: a 13-case series report.

Purpose: Onychopapilloma is a rare benign nail tumor affecting the distal matrix and the nail bed. Currently, the only available treatment is surgical resection, which has a recurrence rate of 20% and may lead to various complications. Here we report a new method to treat onychopapilloma with pulsed dye laser (PDL).Materials and methods: We retrospectively analyzed 13 cases and evaluated disease classification, dermoscopic examination, laser treatment parameters, photographs before and after treatment, and treatment outcome.Results: The site distribution of onychopapilloma was consistent with previous reports. PDL treatment was performed with 595 nm laser, with 1.5 ms pulse duration, spot diameter 3-5 mm, and 11.5-13.5 J/cm2 fluence. Irradiation covered the telangiectatic area up to the edge of the nail folds, with the terminal response of purpura occurrence. The overall effective rate was 77%; the effective rates for erythronychia, leukonychia, and melanonychia were 88%, 67%, and 50%, respectively.Conclusions: PDL treatment for onychopapilloma provides an alternative to traditional surgery with comparable effectiveness but much less risk for complications.

Proteomics and transcriptomics explore the effect of mixture of herbal extract on diabetic wound healing process.

BACKGROUND: The annual incidence of diabetic foot ulcers (DFUs) has been reported to vary from 0.2% to 11% in diabetes-specific clinical settings and less than 0.1% to 8% in community- and population-based cohorts. According to the International Diabetes Foundation, approximately 40 million to 60 million people worldwide are affected by DFUs, and a recent meta-analysis indicates a global prevalence of 6.3% among adults with diabetes, or about 33 million individuals. The cost of diabetes care is significant, amounting to $273 billion in direct and $90 billion in indirect expenses annually, in America. Foot complications in diabetes care excess annual expenditures ranging from 50% to 200% above the baseline cost of diabetes-related care. The cost of advanced-stage ulcers can be more than $50,000 per wound episode, and the direct expenses of major amputation are even higher. DFUs can be treated using various methods, including wound dressings, antibiotics, pressure-off loading, skin substitutes, stem cells, debridement, topical oxygen therapy, gene therapy and growth factors. For severe DFUs patients are at risk of amputation if treatment is not timely or appropriate. Amputating limbs not only causes physical pain to patients, but also brings economic burden due to lost productivity, and decreased employment linked to DFUs. Currently, long-term use of local antibiotics in clinical practice is prone to induce drug resistance, while growth factors do not effectively inhibit bacterial growth and control inflammation in wounds. Stem cell and gene therapies are still in the experimental stage. The method of local debridement combined with negative pressure therapy is expensive. Therefore, we urgently need an affordable, non-surgical method to treat diabetic ulcers. Extracts of bark of Bauhinia purpurea, Paeoniae rubrae, Angelica dahurica (Hoffm.) Benth. & Hook.f. ex Franch. & Sav. (Hoffm.) Benth. & Hook.f. ex Franch. & Sav., Acorus calamus L, and Radix Angelicae biseratae have been used as traditional remedies to treat inflammation-related diseases and cutaneous wounds due to their anti-inflammatory properties and their ability to promote vascular renewal. However, there have been few studies on the mixture of these five herbal extracts on diabetic wound healing. PURPOSE: This study was designed to assess the healing effect of a mixture of five aforementioned herbal extracts on diabetic ulcer wounds in rats, and to reveal the potential mechanisms behind any potential wound healing using transcriptomics and proteomics. STUDY DESIGN: We designed the experiment to explore the effects of five herbal extracts on diabetic wound healing process through in vivo experiments and to investigate the underlying mechanisms through proteomics and transcriptomics. METHODS: We used a mixture of five aforementioned herbal extract to treat rat model of diabetic established by intraperitoneal injection of streptozotocin, and a 2 × 2 cm round full-thickness skin defect was created on the back of the rat. Staphylococcus aureus (1 ml of 1.5 × 109 cfu/ml) was evenly applied to the wound. The wound was then observed for 72 h. The infected ulcer model of diabetic rats was considered to be successfully established if the wound was found to be infected with S. aureus. According to different medications, the rats were divided into three groups, namely mixture of herbal extract (MHE), Kangfuxin solution (KFS) and control (Ctrl). The effects of the medicine on wound healing were observed. HE staining and Masson staining were performed to evaluate the histopathological changes and collagen synthesis. IHC staining was used to assess the neovascularization, and M2 macrophage proliferation was determined by immunofluorescence staining. Proteomic and transcriptomic studies were performed to explore potential mechanism of five herbal extracts to promote wound healing. UHPLC-QE-MS was performed to identify the chemical composition of mixture of herbal extract. RESULTS: The study show that the mixed herbal extract promotes angiogenesis, proliferation of M2 macrophages, and collagen synthesis. Transcriptomics showed that rno-miR-1298, rno-miR-144-5p, and rno-miR-92a-1-5p are vital miRNAs which also play a significant role in role in regulating wound healing. Proteomics results showed that the following proteins were important in wounds treated with MHE: Rack1, LOC100362366, Cops2, Cops6, Eif4e, Eif3c, Rpl12, Srp54, Rpl13 and Lsm7. Autophagy, PI3-Akt and mTOR signaling pathways were enriched after treatment with MHE compared to other groups. CONCLUSION: Herein, we have shown that MHE containing extracts of bark of Bauhinia purpurea, P. rubrae, A. dahurica (Hoffm.) Benth. & Hook.f. ex Franch. & Sav., A. calamus L, and R. A. biseratae has significant wound healing effects in the diabetic ulcer wound rat model. These results suggest that local application of MHE in diabetic wounds can accelerate the wound healing process. Moreover, in vivo experiments revealed that the diabetic wound healing process was primarily mediated by angiogenesis and M2 macrophage transition. Therefore, this study may provide a promising and non-surgical therapeutic strategy to accelerate diabetic wound healing, thereby decreasing the number of limb amputations in diabetic patients.

Progress in traditional Chinese medicine against chronic gastritis: From chronic non-atrophic gastritis to gastric precancerous lesions.

Chronic gastritis (CG) is a persistent inflammation of the gastric mucosa that can cause uncomfortable symptoms in patients. Traditional Chinese medicine (TCM) has been widely used to treat CG due to its precise efficacy, minimal side effects, and holistic approach. Clinical studies have confirmed the effectiveness of TCM in treating CG, although the mechanisms underlying this treatment have not yet been fully elucidated. In this review, we summarized the clinical research and mechanisms of TCM used to treat CG. Studies have shown that TCM mechanisms for CG treatment include H. pylori eradication, anti-inflammatory effects, immune modulation, regulation of gastric mucosal cell proliferation, apoptosis, and autophagy levels.