Study on the Effect of Laser Marker in the Treatment of Osteoarthritis of the Knee Joint and the Accuracy of Reconstruction of Lower Extremity Alignment.

Objective: Knee osteoarthritis (KOA) is a prevalent joint disease characterized by cartilage degradation and periarticular bone hyperplasia. Accurate assessment of knee alignment is fundamental for effective treatment, as it directly influences surgical planning and postoperative outcomes. This study assesses the effectiveness of laser marker technology in KOA treatment and its precision in reconstructing lower extremity alignment. Methods: Sixty KOA patients admitted to our orthopedics department from March 2020 to December 2021 were randomized into two groups via random number table method, with 30 patients in each. All patients underwent knee replacement surgery. The experiment group received laser marker assessments, while the control group had X-ray examinations. Postoperative Hospital for Special Surgery (HSS) scores and knee mobility of the patients were compared. Results: At 6 weeks, 3 months, and 6 months postoperatively, the experimental group exhibited significnatly higher HSS scores (89.75±3.81, 91.78±2.15, and 91.84±1.79) than the control group (84.28±2.56, 87.15±1.98, and 88.02±1.21) (P < .05). Better knee mobility (111.17±4.94) was observed in the experimental group versus the control group (108.07±3.08) at 6 months postoperatively (P < .05). Conclusion: Laser marker technology provides a clear visualization of lower extremity structures, offering a comprehensive assessment of KOA deformities. This could potentially lead to improved diagnostic precision and enhanced surgical outcomes. The study encourages further research into the broader application of laser marker technology in knee osteoarthritis treatment, such as the evaluation of its cost-effectiveness versus traditional methods.

Effective constituents and protective effect of Mudan granules against Schwann cell injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes. Mudan granules (MD) is a Chinese patent medicine for treating DPN, which is composed of nine Chinese medicinal herbs, including the radix of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao or Astragalus membranaceus (Fisch.) Bge. (Huangqi in Chinese), rhizome of Corydalis yanhusuo W.T. Wang (Yanhusuo), radix and rhizome of Panax notoginseng (Burk.) F. H. Chen (Sanqi), radix of Paeonia lactiflora Pall. or Paeonia veitchii Lynch (Chishao), radix and rhizome of Salvia miltiorrhiza Bge. (Danshen), rhizome of Ligusticum chuanxiong Hort. (Chuanxiong), flowers of Carthamus tinctorius L. (Honghua), lignum of Caesalpinia sappan L. (Sumu), and caulis of Spatholobus suberectus Dunn (Jixueteng). MD was reported to have a protective effect on Schwann cell (SC) that is considered as an important therapeutic target of DPN. However, the constituents of MD have not been reported, and the effective constituents and protective pathways for MD against SC injury remain unclear. AIM OF THE STUDY: This study aimed to identify the constituents in MD, and to investigate the effective constituents and protective pathways of MD against high-glucose/lipid injury in SC. MATERIALS AND METHODS: The chemical constituents of MD were identified using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Protective effect and effective constituents screening were performed in an in vitro SC injury model induced by high glucose and lipid levels. The protective pathways of MD and its effective constituents were investigated by western blotting assay of related proteins. RESULTS: A total of 136 constituents were identified in MD. MD downregulated the phosphorylation of extracellular-regulated protein kinases 1/2 (ERK1/2) and expression of cyclooxygenase-2 (COX-2) and upregulated the expression of sirtuin 2 (SIRT2). Seven effective constituents were screened out, including three from Sanqi [20(R)-ginsenoside Rh2, 20(S)-ginsenoside Rh2, and ginsenoside Rk3], one from Huangqi (astragaloside II), one from Danshen (danshensu), and two from Chuanxiong (chlorogenic and cryptochlorogenic acid). Six of the seven compounds, excluding danshensu, inhibited the phosphorylation of ERK1/2. Both astragaloside II and chlorogenic acid upregulated the expression of SIRT2, and cryptochlorogenic acid and danshensu downregulated the expression of COX-2. CONCLUSIONS: The constituents of MD were firstly identified, and seven effective constituents were found. MD can protect SC against high-glucose and -lipid injury by downregulating ERK1/2 phosphorylation and COX-2 expression and upregulating SIRT2 expression. Seven effective constituents regulated the expression of these proteins. This study presented an important advance toward elucidating the chemical constituents, and the effective constituents and protective pathways of MD against high-glucose/lipid injury in SC, which is very helpful for investigating the action mechanism of MD on treating DPN, and could ultimately inform the development of effective quality control procedures for MD production.

Light at night exposure and risk of breast cancer: a meta-analysis of observational studies.

Objective: The aim of this meta-analysis is to evaluate the impact of light at night (LAN) exposure on the risk of breast cancer across varying factors. Method: We conducted a systematic search of literature up to July 15, 2023, including PubMed, Cochrane Library, and Embase databases, using keywords related to breast cancer and LAN exposure. Cohort study and case-control study literature on night light exposure and breast cancer risk were included. Statistical analyses were performed using Stata software version 17.0. To address heterogeneity among different studies, we employed a random-effects model for analysis and assessed publication bias using funnel plots and Egger's test. Results: We included 13 case-control and 8 cohort studies with 734,372 participants worldwide. In the Newcastle-Ottawa Scale (NOS) assessments, the average score was 7.43 (ranging from 5 to 9). The overall meta-analysis demonstrated a significant association between exposure to LAN and risk of breast cancer (RR = 1.12; 95% CI: 1.06-1.17; I2 = 31.3%, p < 0.001). In the subgroup analysis, the results of the analysis for study types (case-control studies: RR = 1.16; 95% CI: 1.06-1.27; I2 = 40.4%, p = 0.001; cohort studies: RR = 1.08; 95% CI: 1.04-1.14; I2 = 0.0%, p < 0.001) and the results for light exposure types (outdoor LAN: RR = 1.07; 95% CI: 1.02-1.13; I2 = 30.9%, p = 0.004) are presented. In the analysis conducted for continents, the highest breast cancer risk was observed in the Asian population (Asian: RR = 1.24; 95% CI: 1.15-1.34; I2 = 0.0%, p < 0.001) and in the analysis of estrogen receptor status (ER+: RR = 1.10; 95% CI: 1.03-1.18; I2 = 17.0%, p = 0.005;). We also conducted an analysis on menopausal status and various lifestyles but did not find any statistically significant findings. Conclusion: Our study demonstrates that LAN exposure is associated with an increased risk of breast cancer, particularly in the Asian population. Among the existing hypotheses, the idea that LAN exposure leads to a decrease in melatonin is widely accepted. However, until the mechanism of this effect is clearly elucidated, it is not recommended to take melatonin supplements for breast cancer prevention without medical advice. We hope to conduct more high-quality research, especially concerning the investigation of other environmental confounding factors, to further advance this field.

Access to Care and Healthcare Quality Metrics for Patients with Advanced Genitourinary Cancers in Urban versus Rural Areas.

Compared to the urban population, patients in rural areas face healthcare disparities and experience inferior healthcare-related outcomes. To compare the healthcare quality metrics and outcomes between patients with advanced genitourinary cancers from rural versus urban areas treated at a tertiary cancer hospital, in this retrospective study, eligible patients with advanced genitourinary cancers were treated at Huntsman Cancer Institute, an NCI-Designated Comprehensive Cancer Center in Utah. Rural-urban commuting area codes were used to classify the patients' residences as being in urban (1-3) or rural (4-10) areas. The straight line distances of the patients' residences from the cancer center were also calculated and included in the analysis. The median household income data were obtained and calculated from "The Michigan Population Studies Center", based on individual zip codes. In this study, 2312 patients were screened, and 1025 eligible patients were included for further analysis (metastatic prostate cancer (n = 679), metastatic bladder cancer (n = 184), and metastatic renal cell carcinoma (n = 162). Most patients (83.9%) came from urban areas, while the remainder were from rural areas. Both groups had comparable demographic profiles and tumor characteristics at baseline. The annual median household income of urban patients was $8604 higher than that of rural patients (p < 0.001). There were fewer urban patients with Medicare (44.9% vs. 50.9%) and more urban patients with private insurance (40.4% vs. 35.1%). There was no difference between the urban and rural patients regarding receiving systemic therapies, enrollment in clinical trials, or tumor genomic profiling. The overall survival rate was not significantly different between the two populations in metastatic prostate, bladder, and kidney cancer, respectively. As available in a tertiary cancer hospital, access to care can mitigate the difference in the quality of healthcare and clinical outcomes in urban versus rural patients.

Comparison of Therapeutic Effects Between Arthroscopic Debridement and Olecranon Fossa Augmentation Plasty for Elbow Osteoarthritis.

Aim: To compare the efficacy of arthroscopic debridement and olecranon fossa augmentation plasty in patients with elbow osteoarthritis. Methods: Eighty-four patients with elbow osteoarthritis admitted to our hospital were randomly divided into two groups with 42 cases in each group. Patients in the control group received expanded olecranon fossa plasty, while those in the observation group underwent arthroscopic debridement. Then the elbow joint function, VAS score, stress level, and incidence of complications were compared between the two groups. Results: The MEPS score, ROM level, and VAS score, as well as the expression of TNF-α, IL-6, and ACTH between the two groups, were significantly different before and after surgery (P < .05). Moreover, compared to patients in the control group, the MEPS score and ROM level of patients in the observation group were higher than those in the control group after six months since surgery, while VAS score, the levels of TNF-α, IL-6, and ACTH were lower on the second day after surgery (P < .05). Conclusion: Arthroscopic cleaning is more helpful in improving elbow joint function and alleviating pain in patients with osteoarthritis of the elbow compared to olecranon fossa augmentation and reconstruction surgery.

Identification and quantification of compounds with Angiotensin-converting enzyme inhibitory activity in licorice by UPLC-MS.

Licorice is a famous medicine-food herb for treating cardiovascular diseases in many compound prescriptions. Angiotensin-converting enzyme (ACE) is a key target of cardiovascular diseases. Despite its significance, there is limited scientific investigation regarding the ACE inhibitory effects of licorice. In this study, we used an activity-guided approach with an aggregation-induced emission (AIE) fluorescent probe to identify compounds with ACE-inhibitory activity in licorice. Nine components of licorice were found to have ACE inhibitory activity, in which 46 compounds were identified by using UPLC-QTOF-MS. Seven active compounds were found in this study. Among them, licochalcone B had best ACE inhibitory activity (IC50 = 0.24 µM). Finally, an UPLC-Q-MS method was established to quantify the five major active compounds in three batches of licorice. The findings of this study offer valuable insights into the potential of licorice as a source of ACE inhibitors and its relevance in the development of related products.

The protective effects of Zhi-Gan-Cao-Tang against diabetic myocardial infarction injury and identification of its effective constituents.

ETHNOPHARMACOLOGICAL RELEVANCE: Cardiovascular complications are highly prevalent in patients with diabetes. Zhi-Gan-Cao-Tang (ZGCT), a famous traditional Chinese medicine (TCM) prescription, can be used for the treatment of diabetes with cardiovascular disease complications. ZGCT is composed of nine Chinese herbs: the radix and rhizoma of Glycyrrhiza uralensis Fisch. (Gancao in Chinese, 12 g), the radix of Rehmannia glutinosa Libosch. (Dihuang in Chinese, 50 g), the radix and rhizoma of Panax ginseng C. A. Mey. (Renshen in Chinese, 6 g), the radix of Ophiopogon japonicus (L. f.) Ker-Gawl. (Maidong in Chinese, 10 g), the fructus of Ziziphus jujuba Mill. (Dazao in Chinese, 18 g), the fructus of Cannabis sativa L. (Maren in Chinese, 10 g), Donkey-hide gelatine (Ejiao in Chinese, 6 g), the ramulus of Cinnamomum cassia Presl (Guizhi in Chinese, 9 g), and the fresh rhizoma of Zingiber officinale Rosc. (Shengjiang in Chinese, 9 g). Many of these Chinese herbs are also used in other systems of medicine (Japan, India, European, etc.). However, the effects and effective constituents of ZGCT against diabetic cardiovascular disease remain unclear. AIM OF THE STUDY: This study aimed to investigate the protective effect of ZGCT against diabetic myocardial infarction (DMI) injury in vivo and in vitro and to identify the effective constituents of ZGCT. MATERIALS AND METHODS: The in vivo effect on DMI injury was evaluated in a DMI mouse model. The in vitro effect and effective constituent screening experiments were conducted in an H9c2 cardiomyocyte injury model induced by high glucose and hypoxia. RESULTS: It was found that ZGCT significantly reduced myocardial infarction size and serum lactate dehydrogenase (LDH) levels in DMI mice. Myocardial histopathological experiments showed that ZGCT alleviated the disordered arrangement and fracture of muscle fibers and cell disappearance and reduced inflammatory cell infiltration. Cellular experiments showed that ZGCT inhibited cardiomyocyte apoptosis by decreasing the expression of the proapoptotic factor Bax. In addition, it inhibited inflammatory reactions by suppressing the activation of the IκBα/NF-κB pathway and the expression of iNOS. Eight constituents from six Chinese herbs in the recipe of ZGCT were found to enhance the viability of injured cardiomyocytes, and six effective constituents played protective roles through anti-apoptotic and/or anti-inflammatory activities. In addition, one of the effective constituents, glycyrrhizic acid, was verified in vivo to have cardioprotective effect on DMI mice. CONCLUSIONS: The TCM prescription ZGCT protects against DMI by inhibiting cardiomyocyte apoptosis and reducing inflammatory reactions. Eight effective constituents of ZGCT were identified. This study provides a scientific basis for the clinical application of ZGCT and is valuable for quality marker research on this prescription.

Adsorption and immobilization of phosphorus from eutrophic seawater and sediment using attapulgite - Behavior and mechanism.

The adsorption behavior of phosphorus on raw sediment (RS), attapulgite (AT), purified attapulgite (PAT) and AT/PAT-amended sediments conforms to the Langmuir, pseudo first-order kinetics and liquid film diffusion model. The adsorption process is spontaneous and monolayer adsorption, and the adsorption rate is mainly controlled by liquid film diffusion. The addition of attapulgite improved the adsorption capacity of phosphorus in the sediments of mariculture ponds. The results of long-term sediment core incubation showed that the average reduction rates of total phosphorus (TP) and soluble reactive phosphorus (SRP) in overlying water and SRP in pore water by adding 20% purified attapulgite (S/PAT20) were 62.11%, 70.83% and 56.32% respectively, and the phosphorus flux in sediments decreased by 53.81%. The addition of attapulgite reduces the risk of phosphorus release in sediments, and changes sediments from "source" to "pool". The specific surface area and pore volume of PAT increased to 203.254 cm2/g and 0.395 cm3/g respectively, but the phosphorus adsorption capacity was only increased by 2 times compared with AT (1431.3-2671.8 mg P/kg), indicating that the changes of mineral structure and chemical composition jointly determine the phosphorus adsorption effect. Adsorption mechanisms include physical adsorption, surface chemical precipitation, ligand effects, electrostatic attraction and ion exchange. Therefore, seeking modification methods with low energy consumption, low production cost, no damage to rod crystal, expansion of pore volume, increase of hydroxyl and other functional groups, and great retention of effective components are issues that need to be considered to improve the phosphorus adsorption capacity of attapulgite.

Cinobufagin restrains the growth and triggers DNA damage of human hepatocellular carcinoma cells via proteasome-dependent degradation of thymidylate synthase.

Anti-tumor candidate drugs from natural products have gained increasing attention. Cinobufagin is a natural product isolated from the traditional chinese medicine Chansu. Herein, we find that cinobufagin inhibits the proliferation and colony-forming ability of human hepatoma HepG2 and SK-HEP-1 cells. Furthermore, cinobufagin induces G2-phase cell cycle arrest and DNA damage in cancer cells. Thymidylate synthase (TYMS), the major target of chemotherapeutic drugs 5-FU or other fluoropyrimidines, which catalyzes the conversion of dUMP to dTMP and provides the sole de novo source of thymidylate for DNA synthesis. We demonstrate that cinobufagin suppresses TYMS expression via proteasome-dependent degradation in human hepatoma cells, moreover, depletion of TYMS restrains the proliferation and colony formation of tumor cells, and the results of western blotting and immunofluorescence assay indicate DNA damage is induced in tumor cells transfected with TYMS-targeting siRNA (siTYMS), additionally, knockdown of TYMS enhances the inhibitory effect of cinobufagin on the proliferative potential of HepG2 and SK-HEP-1 cells. It is worth noting that cinobufagin in combination with 5-FU exhibits antagonism or synergism combined effects on the proliferation of human hepatoma cells, indicating that Chansu-related preparations such as cinobufacini injection and Huachansu capsules applied to clinical practice should be used with caution in combination with 5-FU for the treatment of liver cancer. Collectively, cinobufagin exerts good anti-hepatoma activity through inhibition of growth and induction of DNA damage by promoting the degradation of TYMS. Our results provide evidence that cinobufagin might be a potential agent for the treatment of cancers such as hepatocellular carcinoma. It can also promote the scientific development of Chansu, and has great significance for enriching the application of TCM in the development of new anti-tumor drugs.

Manual Lymphatic Drainage for Breast Cancer-related Lymphedema: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: The purpose of this systematic review was to meta-analyze the effectiveness of manual lymphatic drainage (MLD) in breast cancer-related lymphedema (BCRL) patients. METHODS: The following databases: the Cochrane Library, the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, Web of Science, ClinicalTrials.gov were systematically searched. All English publications before April 2021 have been retrieved without any restrictions of countries, time, or article type. We included randomized controlled trials (RCTs) examining the effectiveness of MLD versus control group without MLD of women with BCRL. The outcomes were (1) the incidence of lymphedema, (2) volumetric changes of lymphedema, (3) pain, (4) quality of life. Review Manager 5.3 was used to perform statistical analysis. RESULTS: In total, 11 RCTs involving 1564 patients were included, in which 10 trials were deemed viable for inclusion in the meta-analysis. Due to the effects of MLD for BCRL, statistically significant improvements were found on the incidence of lymphedema (RR = 0.58, 95% CI [0.37, 0.93], P =.02) and pain intensity (SMD = -0.72, 95% CI [-1.34, -0.09], P = .02). Besides, the meta-analysis carried out implied that the effects that MLD had on volumetric changes of lymphedema and quality of life, were not statistically significant. CONCLUSION: The current evidence based on the RCTs shows that pain of BCRL patients undergoing MLD is significantly improved, while our findings do not support the use of MLD in improving volumetric of lymphedema and quality of life. Note that the effect of MLD for preventing BCRL is worthy of discussion.

[UHPLC-Q-Exactive Orbitrap MS/MS-based rapid identification of chemical components in substance benchmark of Kaixin San].

Ultra-performance liquid chromatography-quadrupole-electrostatic field Orbitrap mass spectrometry(UHPLC-Q-Exactive Orbitrap MS/MS) was used for rapid identification of the chemical components in Kaixin San substance benchmark. The gradient elution was performed through a Waters ACQUITY~(TM) BEH C_(18) column(2.1 mm×150 mm, 1.7 µm) with water-acetonitrile as mobile phase, a column temperature of 30 ℃, a flow rate of 0.3 mL·min~(-1), and a sample size of 1 µL. The scanning was performed in the negative ion mode. The complex component groups in Kaixin San substance benchmark were quickly and accurately identified and clearly assigned based on the comparison of the retention time and MS data with those of the reference substance as well as the relative molecular weight of the same or similar components in the mass spectrum database and literature. A total of 77 compounds were identified, including 26 saponins, 13 triterpenoid acids, 20 oligosaccharide esters, 5 xanthones, and 13 other compounds. The qualitative method established in this study can systematically, accurately, and quickly identify the chemical components in Kaixin San substance benchmark, which can provide a basis for the further analysis of its active components in vivo and the establishment of its quality control system.

Stability evaluation of gardenia yellow pigment in presence of different phenolic compounds.

Gardenia yellow pigment (GYP) may undergo chemical degradation under different conditions resulting in color fading. This study investigated the effects of different phenolic compounds (caffeic acid, rosmarinic acid, tannic acid, epicatechin, chlorogenic acid, epigallocatechin, and epigallocatechin gallate) on the physical and chemical stability of GYP under light and different temperatures. Furthermore, food models with GYP/phenolic compounds were simulated to evaluate the GYP stability under different cooking methods. The addition of phenolic compounds, especially tannic acid, epigallocatechin gallate, epigallocatechin, and rosmarinic acid, significantly improved the GYP stability during light and thermal treatments. Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopy confirmed that the formation of hydrogen bonds between GYP and selected phenolic compounds (tannic acid, epigallocatechin gallate, epigallocatechin, and rosmarinic acid), which may lead to the enhancement of GYP stability. Moreover, these selected phenolic compounds provided potent protective effects on GYP under different cooking methods.

A new iron supplement: The chelate of pig skin collagen peptide and Fe2+ can treat iron-deficiency anemia by modulating intestinal flora.

Introduction: Iron deficiency anemia (IDA) is one of the most common nutritional diseases encountered all over the world. Nowadays, oral iron supplementation is still the mainstay of IDA treatment. Methods: In this study, a new iron nutritional supplement named pig skin collagen peptides ferrous chelates (PSCP-Fe) was prepared, and its structure was characterized by the scanning electron microscopy, sykam amino acid analyzer and Fourier transform infrared spectroscopy (FTIR). The anti-IDA activity of PSCP-Fe was evaluated in low-Fe2+ diet-induced IDA in rats. 16S amplicon sequencing technology was then used to reveal the mechanism of PSCP-Fe against IDA. Results: The results of amino acid analysis and FTIR showed that aspartic acid (Asp), arginine (Arg), histidine (His), glutamic acid (Glu), cystine (Cys), and lysine (Lys) residued in PSCP chelated readily with Fe2+ through their functional groups. PSCP-Fe treated reversed the hematology-related indexes, such as red blood cells (RBC), hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentrate (MCHC), serum ferritin (SF), serum hepcidin (HEPC) and serum transferrin receptor (TFR). And its regulatory action was better than that of FeSO4. Moreover, PSCP-Fe alleviated the hepatocyte apoptosis and necrosis, Fe2+ loss, and injury in IDA rats. In addition, PSCP-Fe could significantly retrace the disturbed profile of gut microbiota in IDA rats (p < 0.05) and significantly up-regulated the relative abundances of nine bacterial genus, including Lactobacillus, Alloprevotella, unclassified_of_Oscillospiraceae, and NK4A214_group (p < 0.05). It could also downgrade the relative abundances of Subdoligranulum and Coriobacteriaceae_UCG-002 (p < 0.05). The results of Spearman's correlation analysis and distance-based redundancy analysis (db-RDA) revealed that Subdoligranulum and Christensenellaceae_R-7_group may be potential microbial markers for effective PSCP-Fe action in the treatment of IDA. Discussion: Overall, our results elucidate the interactions between gut bacteria and related cytokines and reveal the mechanisms underlying the anti-IDA effect of PSCP-Fe. They will thus provide a theoretical foundation for PSCP-Fe as a new iron nutritional supplement.

Cancer drug screening with an on-chip multi-drug dispenser in digital microfluidics.

Microfluidics has been the most promising platform for drug screening with a limited number of cells. However, convenient on-chip preparation of a wide range of drug concentrations remains a large challenge and has restricted wide acceptance of microfluidics in precision medicine. In this paper, we report a digital microfluidic system with an innovative control structure and chip design for on-chip drug dispensing to generate concentrations that span three to four orders of magnitude, enabling single drug or combinatorial multi-drug screening with simple electronic control. Specifically, we utilize droplet ejection from a drug drop sitting on a special electrode, named a drug dispenser, under high-voltage pulse actuation to deliver the desired amount of drugs to be picked up by a cell suspension drop driven by low-voltage sine wave actuation. Our proof-of-principle validation for this technique as a convenient single and multi-drug screening involved testing of the drug toxicity of two chemotherapeutics, cisplatin (Cis) and epirubicin (EP), towards MDA-MB-231 breast cancer cells and MCF-10A normal breast cells. The results are consistent with those screened based on traditional 96-well plates. These findings demonstrate the reliability of the drug screening system with an on-chip drug dispenser. This system with fewer cancer cells, less drug consumption, a small footprint, and high scalability with regard to concentration could pave the way for drug screening on biopsied primary tumor cells for precision medicine or any concentration-related research.

Acupuncture for retinitis pigmentosa: study protocol for a randomised, sham-controlled trial.

INTRODUCTION: Primary retinitis pigmentosa (RP) is a common hereditary retinal disease in ophthalmology that has a considerable impact on quality of life, but there are few effective therapeutic strategies. This trial aims to determine the efficacy and safety of acupuncture versus sham acupuncture (SA) for RP. METHODS AND ANALYSIS: This is a study protocol for a randomised, participant-blind, sham-controlled trial. 64 eligible patients with RP will randomly be divided into acupuncture group and SA group. All groups will receive 48 sessions over 3 months. Participants will complete the trial by visiting the research centre in month 6/9 for a follow-up assessment. The primary outcome is visual field mean sensitivity and visual field mean deviation at month 3/6/9 compared with baseline. Secondary outcomes include the best-corrected visual acuity, central macular thickness, subfoveal choroidal thicknes, traditional Chinese medicine syndrome score and the scale of life quality for diseases with visual impairment at month 3/6/9 compared with baseline. Adverse events and safety indexes will be recorded throughout the study. SPSS V.25.0 statistical software was used for analysis, and measurement data were expressed as mean±SD. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Ethics Committee of the Chinese Clinical Trial Registry (approval no: ChiECRCT20200460). The results of this study will be published in a peer-reviewed journal, and trial participants will be informed via email and/or phone calls. TRIAL REGISTRATION NUMBER: ChiCTR2000041090.

Integrative analysis of TNFRSF6B as a potential therapeutic target for pancreatic cancer.

BACKGROUND: Pancreatic cancer is one of the most lethal malignant tumors worldwide with poor outcomes. Previous studies have shown that tumor necrosis factor receptor superfamily member 6b (TNFRSF6B) plays an important role in cancer progression and immunosuppression. However, the mechanisms by which TNFRSF6B influence pancreatic cancer, and the regulatory networks involved remain to be further studied. METHODS: This study analyzed the mRNA information and clinical data of patients from The Cancer Genome Atlas (TCGA) and the ONCOMINE databases. The gene co-expression data regarding TNFRSF6B was obtained from the c-BioPortal and used to explore the functional network of TNFRSF6B in pancreatic cancer, as well as its function in tumor immunity. Short hairpin (sh) RNA knock-down experiments were performed to examine the functional roles of TNFRSF6B in pancreatic cancer cell lines. RESULTS: The expression of TNFRSF6B was elevated in pancreatic cancer tissues compared to normal pancreatic tissues, and its high expression was associated with poor prognosis of patients with pancreatic cancer. TNFRSF6B was found to be widely involved in cell cycle processes, apoptosis, apoptosis signaling pathways, immune responses, and responses to interferon. Knock-down of TNFRSF6B expression inhibited pancreatic cancer cell proliferation and invasion in vitro. Moreover, carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) was found to be co-expressed with TNFRSF6B, and there was a positive correlation between these molecules in pancreatic cancer cells. CONCLUSIONS: This report suggested that TNFRSF6B has a critical role in the progression and metastasis of pancreatic cancer. These findings provide novel insights into the role of TNFRSF6B in the functional network of pancreatic cancer, and suggest that TNFRSF6B may be a potential therapeutic target.

Electrochemical Palladium-Catalyzed Oxidative Sonogashira Carbonylation of Arylhydrazines and Alkynes to Ynones.

Oxidative carbonylation using carbon monoxide has evolved as an attractive tool to valuable carbonyl-containing compounds, while mixing CO with a stoichiometric amount of a chemical oxidant especially oxygen is hazardous and limits its application in scale-up synthesis. By employing anodic oxidation, we developed an electrochemical palladium-catalyzed oxidative carbonylation of arylhydrazines with alkynes, which is regarded as an alternative supplement of the carbonylative Sonogashira reaction. Combining an undivided cell with constant current mode, oxygen-free conditions avoids the explosion hazard of CO. A diversity of ynones are efficiently obtained using accessible arylhydrazines and alkynes under copper-free conditions. A possible mechanism of the electrochemical Pd(0)/Pd(II) cycle is rationalized based upon cyclic voltammetry, kinetic studies, and intermediates experiments.

Comprehensive Identification of Astilbin Metabolites in Rats Based on Multiple Metabolite Templates Combined with UHPLC-Q-Exactive Mass Spectrometry.

BACKGROUND: Astilbin, a dihydroflavonoid compound widely found in plants, exhibits a variety of pharmacological activities and biological effects. However, little is known about the metabolism of this active compound in vivo, which is very helpful for elucidating the pharmacodynamic material basis and application of astilbin. OBJECTIVE: To establish a rapid profiling and identification method for metabolites in rat urine, faeces and plasma using a UHPLC-Q-Exactive mass spectrometer in negative ion mode. METHODS: In this study, a simple and rapid systematic strategy and 7 metabolite templates, which were established based on previous reports, were utilized to screen and identify astilbin metabolites. RESULTS: As a result, a total of 71 metabolites were detected and characterized, among which 32 metabolites were found in rat urine, while 27 and 38 metabolites were characterized from rat plasma and faeces, respectively. These metabolites were presumed to be generated through ring cleavage, sulfation, dehydrogenation, methylation, hydroxylation, glucuronidation, dehydroxylation and their composite reactions. CONCLUSION: This study illustrated the capacity of the sensitive UHPLC-Q-Exactive mass spectrometer analytical system combined with the data-mining methods to rapidly elucidate the unknown metabolism. Moreover, the comprehensive metabolism study of astilbin provided an overall metabolic profile, which will be of great help in predicting the in vivo pharmacokinetic profiles and understanding the action mechanism of this active ingredient.

Ganoderma lucidum polysaccharides ameliorated depression-like behaviors in the chronic social defeat stress depression model via modulation of Dectin-1 and the innate immune system.

Major depressive disorder (MDD) is a prevalent, chronic, and recurrent disease. At least one-third of patients have treatment-resistant depression; therefore, there is an urgent need for novel drug development. Cumulative studies have suggested an inflammatory mechanism for the pathophysiology of MDD. Ganoderma lucidum polysaccharides (GLP) is an anti-inflammatory and immunomodulatory agent. Here, we found that an injection of GLP led to a rapid and robust antidepressant effect after 60 min in the tail suspension test. This antidepressant effect remained after 5 days of treatment with GLP in the forced swim test. Unlike psychostimulants, GLP did not show a hyperactive effect in the open field test. After 60 min or 5 days of treatment, GLP exhibited an antidepressant effect in a chronic social defeat stress (CSDS) depression animal model. Moreover, after 5 days of treatment, GLP attenuated the expression of the proinflammatory cytokines IL-1ß and TNF-α, enhanced the expression of the anti-inflammatory cytokine IL-10 and the neurotrophic factor BDNF, and inhibited the activation of microglia and proliferation of astrocytes in the hippocampus of CSDS mice. In addition, after 5 days of treatment, GLP significantly enhanced GluA1 S845 phosphorylation as well as GluA1 and GluA2 expression levels in the hippocampus of CSDS mice. To determine whether the antidepressant effect was mediated by Dectin-1, we found that GLP treatment enhanced Dectin-1 expression in the hippocampus in CSDS mice, and the Dectin-1-specific inhibitor laminarin almost completely blocked the antidepressant effect of GLP. This study identified GLP, an agonist of Dectin-1, as a novel and rapid antidepressant with clinical potential and multiple beneficial mechanisms, particularly in regulating the neuroimmune system and, subsequently, AMPA receptor function.

Comparative metabolism study on chlorogenic acid, cryptochlorogenic acid and neochlorogenic acid using UHPLC-Q-TOF MS coupled with network pharmacology.

Chlorogenic acid (5-CQA), neochlorogenic acid (3-CQA), and cryptochlorogenic acid (4-CQA), usually simultaneously exist in many traditional Chinese medicines (TCMs). However, insufficient attentions have been paid to the comparative metabolism study on these three isomeric constituents with similar effects on anti-inflammation until now. In this study, a novel strategy was established to perform comparative analysis of their metabolic fates in rats and elucidate the pharmacological mechanism of anti-inflammation. Firstly, diagnostic product ions (DPIs) deduced from the representative reference standards were adopted to rapidly screen and characterize the metabolites in rat plasma, urine and faeces using UHPLC-Q-TOF MS. Subsequently, Network pharmacology was utilized to elucidate their anti-inflammatory mechanism. Consequently, a total of 73 metabolites were detected and characterized, including 50, 47 and 43 metabolites for 5-CQA, 4-CQA and 3-CQA, orderly. Moreover, the network pharmacology study indicated that these three isomeric constituents and their major metabolites with similar in vivo metabolic pathways exerted anti-inflammatory effects through co-owned 20 biological processes, which involved 10 major signal pathways and 159 potential targets. Our study shed light on the similarities and differences of the metabolic profiling and anti-inflammatory activity among these three isomeric constituents and set an example for the further researches on the active mechanism of isomeric constituents existing in TCMs based on comparative metabolism study.