Age-related decline in melatonin contributes to enhanced osteoclastogenesis via disruption of redox homeostasis.

BACKGROUND: Increased oxidative stress contributes to enhanced osteoclastogenesis and age-related bone loss. Melatonin (MT) is an endogenous antioxidant and declines with aging. However, it was unclear whether the decline of MT was involved in the enhanced osteoclastogenesis during the aging process. METHODS: The plasma level of MT, oxidative stress status, bone mass, the number of bone marrow-derived monocytes (BMMs) and its osteoclastogenesis were analyzed in young (3-month old) and old (18-month old) mice (n = 6 per group). In vitro, BMMs isolated from aged mice were treated with or without MT, followed by detecting the change of osteoclastogenesis and intracellular reactive oxygen species (ROS) level. Furthermore, old mice were treated with MT for 2 months to investigate the therapeutic effect. RESULTS: The plasma level of MT was markedly lower in aged mice compared with young mice. Age-related decline in MT was accompanied by enhanced oxidative stress, osteoclastogenic potential and bone loss. MT intervention significantly suppressed the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis, decreased intracellular ROS and enhanced antioxidant capacity of BMMs from aged mice. MT supplementation significantly attenuated oxidative stress, osteoclastogenesis, bone loss and deterioration of bone microstructure in aged mice. CONCLUSIONS: These results suggest that age-related decline of MT enhanced osteoclastogenesis via disruption of redox homeostasis. MT may serve as a key regulator in osteoclastogenesis and bone homeostasis, thereby highlighting its potential as a preventive agent for age-related bone loss.

Porous Titanium Scaffolds with Mechanoelectrical Conversion and Photothermal Function: A Win-Win Strategy for Bone Reconstruction of Tumor-Resected Defects.

Bone metastases severely threaten the lives of patients. Although surgical treatment combined with adjuvant chemotherapy significantly improves the survival rate of patients, tumor recurrence, or metastasis after surgical resection and bone defects caused by surgical treatment remain major challenges for clinicians. Given the abovementioned clinical requirements, barium titanate-containing iron-coated porous titanium alloy scaffolds have been proposed to promote bone defect repair and inhibit tumor recurrence. Fortunately, in vitro and in vivo experimental research confirms that barium titanate containing iron-coated porous titanium alloy scaffolds promote osteogenesis and bone reconstruction in defect repair via mechanoelectric conversion and inhibit tumor recurrence via photothermal effects. Furthermore, the underlying and intricate mechanisms of bone defect repair and tumor recurrence prevention of barium titanate-containing iron-coated porous titanium alloy scaffolds are explored. A win-win strategy for mechanoelectrical conversion and photothermal functionalization provides promising insights into bone reconstruction of tumor-resected defects.

Residue Effect-Guided Design: Engineering of S. Solfataricus ß-Glycosidase to Enhance Its Thermostability and Bioproduction of Ginsenoside Compound K.

ß-Glycosidase from Sulfolobus solfataricus (SS-BGL) is a highly effective biocatalyst for the synthesis of compound K (CK) from glycosylated protopanaxadiol ginsenosides. In order to improve the thermal stability of SS-BGL, molecular dynamics simulations were used to determine the residue-level binding energetics of ginsenoside Rd in the SS-BGL-Rd docked complex and to identify the top ten critical contributors. Target sites for mutations were determined using dynamic cross-correlation mapping of residues via the Ohm server to identify networks of distal residues that interact with the key binding residues. Target mutations were determined rationally based on site characteristics. Single mutants and then recombination of top hits led to the two most promising variants SS-BGL-Q96E/N97D/N302D and SS-BGL-Q96E/N97D/N128D/N302D with 2.5-fold and 3.3-fold increased half-lives at 95 °C, respectively. The enzyme activities relative to those of wild-type for ginsenoside conversion were 161 and 116%, respectively..

Marsdenia tenacissima extract induces endoplasmic reticulum stress-associated immunogenic cell death in non-small cell lung cancer cells through targeting AXL.

ETHNOPHARMACOLOGICAL RELEVANCE: Marsdenia Tenacissima (Roxb.) Wight et Arn. is a traditional Chinese medicine. Its standardized extract (MTE), with the trade name Xiao-Ai-Ping injection, is widely used for cancer treatment. The pharmacological effects of MTE-inducing cancer cell death have been primarily explored. However, whether MTE triggers tumor endoplasmic reticulum stress (ERS)-associated immunogenic cell death (ICD) is unknown. AIM OF THE STUDY: To determine the potential role of endoplasmic reticulum stress in the anti-cancer effects of MTE, and uncover the possible mechanisms of endoplasmic reticulum stress-associated immunogenic cell death induced by MTE. MATERIAL AND METHODS: The anti-tumor effects of MTE on non-small cell lung cancer (NSCLC) were examined through CCK-8 and wound healing assay. Network pharmacology analysis and RNA-sequencing (RNA seq) were performed to confirm the biological changes of NSCLCs after MTE treatment. Western blot, qRT-PCR, reactive oxygen species (ROS) assay, and mitochondrial membrane potential (MMP) assay were used to explore the occurrence of endoplasmic reticulum stress. Immunogenic cell death-related markers were tested by ELISA and ATP release assay. Salubrinal was used to inhibit the endoplasmic reticulum stress response. SiRNA and bemcentinib (R428) were used to impede the function of AXL. AXL phosphorylation was regained by recombinant human Gas6 protein (rhGas6). The effects of MTE on endoplasmic reticulum stress and immunogenic cell death response were also proved in vivo. The AXL inhibiting compound in MTE was explored by molecular docking and confirmed by Western blot. RESULTS: MTE inhibited cell viability and migration of PC-9 and H1975 cells. Enrichment analysis identified that differential genes after MTE treatment were significantly enriched in endoplasmic reticulum stress-related biological processes. MTE decreased mitochondrial membrane potential (MMP) and increased ROS production. Meanwhile, endoplasmic reticulum stress-related proteins (ATF6, GRP-78, ATF4, XBP1s, and CHOP) and immunogenic cell death-related markers (ATP, HMGB1) were upregulated, and the AXL phosphorylation level was suppressed after MTE treatment. However, when salubrinal (an endoplasmic reticulum stress inhibitor) and MTE were co-treated cells, the inhibitory effects of MTE on PC-9 and H1975 cells were impaired. Importantly, inhibition of AXL expression or activity also promotes the expression of endoplasmic reticulum stress and immunogenic cell death-related markers. Mechanistically, MTE induced endoplasmic reticulum stress and immunogenic cell death by suppressing AXL activity, and these effects were attenuated when AXL activity recovered. Moreover, MTE significantly increased the expression of endoplasmic reticulum stress-related markers in LLC tumor-bearing mouse tumor tissues and plasma levels of ATP and HMGB1. Molecular docking illustrated that kaempferol has the strongest binding energy with AXL and suppresses AXL phosphorylation. CONCLUSION: MTE induces endoplasmic reticulum stress-associated immunogenic cell death in NSCLC cells. The anti-tumor effects of MTE are dependent upon endoplasmic reticulum stress. MTE triggers endoplasmic reticulum stress-associated immunogenic cell death by inhibiting AXL activity. Kaempferol is an active component that inhibits AXL activity in MTE. The present research revealed the role of AXL in regulating endoplasmic reticulum stress and enriched the anti-tumor mechanisms of MTE. Moreover, kaempferol may be considered a novel AXL inhibitor.

Natural Geranylated Sulfur-Containing Amides with Inhibitory Effect on Th17 Differentiation.

Chemical investigation of medicinal plant Glycosmis lucida Wall. ex C. C. Huang leaves led to the production of ten compounds (1-10), including two previously unreported geranylated sulfur-containing amides (1 and 2) and eight known ones (3-10). Structural characterization was carried out using comprehensive spectroscopic methods including NMR, MS and CD. The inhibitory effects of all isolates on Th17 differentiation were evaluated, of which compounds 1 and 6 significantly inhibited Th17 differentiation with IC50 values of 0.36 and 1.30 µM, respectively, while both 1 and 6 failed to bind to retinoic acid-related orphan receptor gamma t (RORγt), suggesting that their inhibition of Th17 differentiation is independent of RORγt.

Efficacy and safety of Jinhua Qinggan granules in the treatment of coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis.

OBJECTIVE: To evaluate, using meta-analysis, the efficacy and safety profile of Jinhua Qinggan granules (JHQG) in the treatment of novel coronavirus pneumonia. METHODS: We screened multiple publication databases (PubMed, Embase, The Cochrane Library, Web of Science, CNKI, WanFang, and VIP), using parameters designed to identify articles detailing randomized controlled trials relating to the treatment of novel coronavirus pneumonia with JHQG. The inclusion period for each search was the point of database inception to November 2022. Each piece of literature identified in our initial screening was independently reviewed by 2 researchers, who extracted the relevant data and evaluated the bias risk associated with the study. The data was split in 2: the control group (containing patients who had received routine treatment or placebo) and the experimental group (containing patients treated with JHQG). The meta-analysis was performed using Revman 5.4 software. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Four articles were selected for this study and combined included a total of 582 patients, which were subdivided into experimental (n = 347) and control (n = 235) groups. The results showed that treatment with JHQG could significantly: enhance the improvement rate of primary symptoms [relative ratio (RR) = 1.26,95% confidence interval (CI) (1.07, 1.49), P = .007] and fever [RR = 1.48, 95% CI (1.07, 2.04), P = .02]; decrease the viral nucleic acid in patients with coronavirus disease 2019 (COVID-19) [RR = 2.04, 95% CI (1.15, 3.62), P = .02] and reduce the progression of pneumonia [RR = 0.34, 95% CI (0.17, 0.67), P = .002]. However, there was no significant difference between the 2 groups with regards to: the improvement rate of cough, nausea and vomiting, fatigue, computed tomography, or frequency of adverse reactions. CONCLUSIONS: Current evidence indicates that JHQG is effective in treating COVID-19, increasing the rate of improvement for fever, increasing the negative rate of viral nucleic acid in patients with COVID-19 and reducing the aggravation rate of pneumonia. These conclusions need to be verified by further rigorous studies, as the existing results were limited by the number and quality of the included studies.

Scenario analysis of phosphorus flow in food production and consumption system in the Mwanza region, Tanzania.

Since the mineral, phosphorus (P), has dual properties of being limited resources for use, and being a pollutant for studying sustainable management of anthropogenic P flows in wetlands and soils, currently P receives the highest interests among researchers around the world. This study has successfully mapped P flows for a reference year (2017) and a future year (2030) using different scenarios of food production and consumption system (hereafter 'system') in the Mwanza region (Tanzania). The results showed that the total P input and output for 2017 alone were 9770 t and 7989 t, respectively. However, as high as 1781 tP accumulated in the system and the potentially recyclable P found, is yet to be recovered due to economic reasons and the lack of market. The main anthropogenic P input to the system occurred via imported feed, fertilizer, and crop food, accounting for about 99.72 % of the total input flow. The output was comprised of animal products exported with 3428 tP, and various P-contained wastes which were lost to water bodies with 4561tP. Analysis of the 2030 scenario showed that setting P management objectives from different perspectives such as the total P budget balance, potential recyclable P, and P emission, can help develop differentially preferred management strategies and measures in the Mwanza region. The combination of diet change, precision feeding, and integrated waste management practices presents the best prospects for decreasing P budget and losses, and the amount of P that can be potentially recovered from the system. We propose a package of integrated P management measures for the Mwanza region. Given the similarity of regional socio-economic development background around the Lake Victoria basin, the model can be used to guide the study of anthropogenic P flow analysis in other areas along the shore of Lake Victoria (Africa).

The effects of music therapy on peripherally inserted central catheter in hospitalized children with leukemia.

To explore the effect of music therapy on children with leukemia who have peripherally inserted central catheters (PICC).In this study, we divided 107 patients undergoing PICC into music group (47 cases) and control group (60 cases). The music group received music therapy during PICC, while the control group was given no complementary treatment. The total length of catheterization, the use of sedatives and the changes of pain level and emotion level before and after PICC placement were compared between two groups.Compared with the control group, the total PICC placement time of the music group was significantly shorter (35(30-40) vs. 60(60-60); Z = -8.307; p < 0.001), and the use of sedative medications was also significantly reduced (4.35% (n = 2) vs. 91.84% (n = 45); p < 0.001). Moreover, the pain of catheterization was significantly alleviated. The median difference of pain scores of the music group was significantly less (2(1-3) vs. 5(5-5); p < 0.001). The mood of patients was also improved. The median difference of emotional scores of the music group was significantly more (5(4.75-6) vs. 3(3-3); p < 0.001) than the control group.Music therapy is effective to use in PICC. It can shorten the treatment time, reduce the use of sedative medications, and improve the children's emotion and pain response significantly, which is worth clinical application.

Chinese herbal bath therapy for the treatment of Atopic dermatitis in children: A meta-analysis and systematic review.

BACKGROUND: To conduct a systematic review of the efficacy of Chinese herbal bath therapy on children with Atopic dermatitis. METHODS: We searched Chinese databases (CNKI, VIP, and Wanfang) and English databases (PubMed, Embase, Web of science, Cochrane library) for studies from the establishment of the database to September 2022. The included literature was randomized control studies investigating the treatment of Atopic dermatitis in children by Chinese herbal bath therapy. The outcomes included the cure rate, scoring atopic dermatitis (SCORAD) index, adverse reactions and recurrence rate. RevMan 5.4 was used to analyze the extracted data. RESULTS: A total of 8 related studies were included containing 854 cases. The meta-analysis showed that Chinese herbal bath therapy group was superior to control group in terms of cure rate, SCORAD index, adverse reactions and recurrence rate in children with Atopic dermatitis [RR = 1.11, 95%(1.02, 1.21), P = .01; SMD = -0.77, 95%(-0.99, -0.55), P < .00001; RR = 0.44, 95%CI(0.28,0.67), P = .0002; RR = 0.25, 95%CI(0.10, 0.59), P = .0002]. CONCLUSION: The present study shows that Chinese herbal bath therapy is an effective treatment for children with Atopic dermatitis in China.

Dandelion extract inhibits triple-negative breast cancer cell proliferation by interfering with glycerophospholipids and unsaturated fatty acids metabolism.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with limited treatment options and a poor prognosis. TNBC exists widely reprogrammed lipid metabolism, and its metabolic-associated proteins and oncometabolites are promising as potential therapeutic targets. Dandelion (Taraxacum mongolicum) is a classical herbal medicine used to treat breast diseases based on traditional Chinese medicine theory and was reported to have antitumor effects and lipid regulatory capacities. Our previous study showed that dandelion extract was effective against TNBC. However, whether dandelion extract could regulate the lipid metabolisms of TNBC and exert its antitumor effects via interfering with lipids metabolism remained unclear. In this study, an integrated approach combined with network pharmacology and multi-omics techniques (including proteomics, metabolomics, and lipidomics) was performed to investigate the potential regulatory mechanisms of dandelion extract against TNBC. We first determined the antitumor effects of dandelion extract in vitro and in vivo. Then, network pharmacology analysis speculated the antitumor effects involving various metabolic processes, and the multi-omics results of the cells, tumor tissues, and plasma revealed the changes in the metabolites and metabolic-associated proteins after dandelion extract treatment. The alteration of glycerophospholipids and unsaturated fatty acids were the most remarkable types of metabolites. Therefore, the metabolism of glycerophospholipids and unsaturated fatty acids, and their corresponding proteins CHKA and FADS2, were considered the primary regulatory pathways and biomarkers of dandelion extract against TNBC. Subsequently, experimental validation showed that dandelion extract decreased CHKA expression, leading to the inhibition of the PI3K/AKT pathway and its downstream targets, SREBP and FADS2. Finally, the molecular docking simulation suggested that picrasinoside F and luteolin in dandelion extract had the most highly binding scores with CHKA, indicating they may be the potential CHKA inhibitors to regulate glycerophospholipids metabolisms of TNBC. In conclusion, we confirmed the antitumor effects of dandelion extract against TNBC cells in vitro and demonstrated that dandelion extract could interfere with glycerophospholipids and unsaturated fatty acids metabolism via downregulating the CHKA expression and inhibiting PI3K/AKT/SREBP/FADS2 axis.

Innovative ochre processing and tool use in China 40,000 years ago.

Homo sapiens was present in northern Asia by around 40,000 years ago, having replaced archaic populations across Eurasia after episodes of earlier population expansions and interbreeding1-4. Cultural adaptations of the last Neanderthals, the Denisovans and the incoming populations of H. sapiens into Asia remain unknown1,5-7. Here we describe Xiamabei, a well-preserved, approximately 40,000-year-old archaeological site in northern China, which includes the earliest known ochre-processing feature in east Asia, a distinctive miniaturized lithic assemblage with bladelet-like tools bearing traces of hafting, and a bone tool. The cultural assembly of traits at Xiamabei is unique for Eastern Asia and does not correspond with those found at other archaeological site assemblages inhabited by archaic populations or those generally associated with the expansion of H. sapiens, such as the Initial Upper Palaeolithic8-10. The record of northern Asia supports a process of technological innovations and cultural diversification emerging in a period of hominin hybridization and admixture2,3,6,11.

Leveraging a Joint learning Model to Extract Mixture Symptom Mentions from Traditional Chinese Medicine Clinical Notes.

This paper addresses the mixture symptom mention problem which appears in the structuring of Traditional Chinese Medicine (TCM). We accomplished this by disassembling mixture symptom mentions with entity relation extraction. Over 2,200 clinical notes were annotated to construct the training set. Then, an end-to-end joint learning model was established to extract the entity relations. A joint model leveraging a multihead mechanism was proposed to deal with the problem of relation overlapping. A pretrained transformer encoder was adopted to capture context information. Compared with the entity extraction pipeline, the constructed joint learning model was superior in recall, precision, and F1 measures, at 0.822, 0.825, and 0.818, respectively, 14% higher than the baseline model. The joint learning model could automatically extract features without any extra natural language processing tools. This is efficient in the disassembling of mixture symptom mentions. Furthermore, this superior performance at identifying overlapping relations could benefit the reassembling of separated symptom entities downstream.

Question Answering System Based on Knowledge Graph in Traditional Chinese Medicine Diagnosis and Treatment of Viral Hepatitis B.

This article uses the real medical records and web pages of Chinese medicine diagnosis and treatment of hepatitis B to extract structured medical knowledge, and obtains a total of 8,563 entities, 96,896 relationships, 32 entity types, and 40 relationship types. The structured data was stored in the Neo4j graph structure database, and a knowledge graph of Chinese medical diagnosis and treatment of hepatitis B was constructed. The knowledge map is used as a structured data source to provide high-quality knowledge information for the medical question and answer system based on hepatitis B disease. Applying the deep learning method to the question identification and knowledge response of the question answering system makes the hepatitis B medical intelligent question answering system has important research and application significance. The question-and-answer system takes aim at hepatitis B, a public health problem in the world and leverages the advantages of traditional Chinese medicine for diagnosis and treatment. It provides a reference for doctors' disease diagnosis, treatment, and patient self-care. Its value is important for the treatment of hepatitis B disease.

[Xianfang Huoming Decoction improves sperm quality in asthenospermia mice: An investigation based on the detoxification and sperm-nourishing method].

OBJECTIVE: To investigate the mechanism of Xianfang Huoming Decoction (XHD) improving sperm motility in mice with asthenospermia (AS). METHODS: Thirty normal BALB/c mice were randomly divided into six groups, blank control, AS model control, low-dose XHD, medium-dose XHD, high-dose XHD and levocarnitine + vitamin E (LC+VE). The AS model was established in the latter five groups by injection of methotrexate at 0.5 mg/kg once a week, and the mice in the blank control group were injected with the same volume of normal saline, all for 8 weeks. From the ninth week, the animals in the blank control and AS model control groups were treated with PBS at 0.1 ml/d, those in the low-, medium- and high-dose XHD groups with XHD at 7.13, 14,2 and 28.52 g/kg/ d respectively, and those in the LC+VE group with LC+VE (30:1) at 0.55 g/kg/d, all for 4 weeks. Then, the bilateral epididymides were harvested from all the mice for preparation of a sperm suspension and observation of the total numbers of sperm and motile sperm. The testis tissues were obtained for to determination of the expressions of Nrf-2- and HO-1-related mRNA and proteins by fluorescence staining, RT-PCR and Western blot. RESULTS: Compared with the AS model controls, the mice treated with low-, medium- and high-dose XHD showed dramatically increased sperm concentration (ï¼»22.36 ± 16.02ï¼½ vs ï¼»39.04 ± 4.50ï¼½, ï¼»40.76 ± 6.57ï¼½ and ï¼»41.04 ± 8.39ï¼½ ×106/ml, P < 0.01) and motility (ï¼»22.89 ± 14.96ï¼½% vs ï¼»47.98 ± 4.74ï¼½%, ï¼»48.53 ± 6.03ï¼½% and ï¼»49.31 ± 6.24ï¼½%, P< 0.01), decreased level of reactive oxygen species (ROS) (ï¼»16.82 ± 14.96ï¼½% vs ï¼»12.08 ± 3.26ï¼½%, ï¼»10.77 ± 2.21ï¼½% and ï¼»9.56 ± 2.08ï¼½%, P< 0.01), and up-regulated expressions of Nrf-2- and HO-1-related mRNA and proteins in the testis tissue (P < 0.05 or P < 0.01). CONCLUSION: Xianfang Huoming Decoction inhibits the development of oxidative stress by up-regulating the expressions of Nrf-2- and HO-1-related mRNA and proteins in the testis tissue, which has provided theoretical evidence for its clinical application in the treatment of asthenospermia.

Modified Tuoli Xiaodusan-assisted Treatment of Hp-positive Peptic Ulcer / 中国实验方剂学杂志

ObjectiveTo observe the clinical efficacy of modified Tuoli Xiaodusan （TLXDS） in adjuvant treatment of Helicobacter pylori （Hp）-positive peptic ulcer （PU） with cold-heat complex syndrome and explore its regulating effect on invasive/protective factors. MethodA total of 136 patients were randomly assigned into the control group （68 cases， including 4 cases missing， 3 cases eliminated， and 61 cases completed） and the TLXDS group （68 cases， including 4 cases missing， 1 case eliminated， and 63 cases completed）. Both groups adopted the quadruple therapy of acid suppression and Hp eradication. The patients in the control group received Weinai'an capsules orally at 4 capsules/time and 3 times/day， and those in the TLXDS group took modified TLXDS orally at 1 dose/day. The administration of both groups lasted for 8 consecutive weeks and the follow-up lasted for 12 months. Electronic gastroscopy was carried out before and after treatment for evaluating the healing of ulcer， the score of mucosal morphology， and the maturity of regenerated mucosa. The Hp infection and the score of cold-heat complex syndrome were evaluated before and after treatment. The serum levels of gastrin （GAS）， prostaglandin E2 （PGE2）， pepsinogen （PG）-Ⅰ， PG-Ⅱ， epidermal growth factor （EGF）， and trefoil factor 2 （TFF-2） were determined before and after therapy. The recurrence of Hp and PU was recorded， and the drug safety was evaluated. ResultAfter treatment， the mucosal morphology score and the traditional Chinese medicine （TCM） syndrome score in the TLXDS group were lower than those in the control group （P<0.01）. The levels of GAS， PG-Ⅰ， and PG-Ⅱ in the TLXDS group were lower than those in the control group （P<0.01）， whereas those of PGE2， EGF， and TFF-2 showed an opposite trend （P<0.01）. After treatment， the Hp eradication rate in the TLXDS group was 95.24% （60/63）， higher than that （83.61%， 51/61） in the control group （χ2=4.467， P<0.05）. The total effective rate of TCM syndromes in the TLXDS group was 98.41% （62/63）， higher than that （81.97%， 50/61） in the control group （χ2=9.589， P<0.01）. The total effective rate of the TLXDS group under gastroscopy was 98.41% （62/63）， higher than that （86.89%， 53/61） in the control group （χ2=4.525， P<0.05）. The excellent and good rate of regenerated mucosal maturity in the TLXDS group was 92.06% （58/63）， also higher than that （73.77%， 45/61） in the control group （χ2=7.372， P<0.01）. After 12 months of follow-up， the TLXDS group had lower PU recurrence rate ［19.05% （12/63） vs 37.70% （23/61）， χ2=5.325， P<0.05］ and lower Hp recurrence rate ［15.00% （9/60） vs 33.33% （17/51）， χ2=5.165， P<0.05） than the control group. No adverse reactions related to TLXDS were detected. ConclusionModified TLXDS-assisted quadruple therapy demonstrates significant short-term clinical efficacy and high Hp eradication rate for Hp-positive PU （cold-heat complex syndrome） patients. Moreover， it can adjust the levels of invasive/protective factors to facilitate ulcer healing and reduce the recurrence rates of Hp and PU in a long term， with good clinical safety.

[Danhong Tongjing Prescription improves sperm quality in patients with bilateral varicocele after varicocelectomy].

OBJECTIVE: To investigate the effect of Danhong Tongjing Prescription (DTP) on sperm quality in patients with bilateral varicocele (VC) after microsurgical varicocelectomy. METHODS: We randomly assigned 68 patients with bilateral VC to receive microsurgical varicocelectomy (the control group, n = 34) or microsurgical varicocelectomy followed by oral administration of DTP for a course of 90 days (the DTP group, n = 34). Before and after treatment, we obtained the sperm concentration, total sperm count, total sperm motility, the percentage of progressively motile sperm (PMS), sperm acrosomal enzyme activity, inhibin B (Inh-B) level, and sperm DNA fragmentation index (DFI) from the patients and compared the parameters between the two groups. RESULTS: There were no statistically significant differences in sperm concentration, PMS, acrosomal enzyme activity or sperm DFI among the patients with different degrees of VC preoperatively. After 3 months of medication, sperm concentration, total sperm count, total sperm motility, PMS and acrosomal enzyme activity were all increased while DFI decreased in both the control and DTP groups, even more significantly in the DTP group than in the control, and the Inh-B level was also markedly elevated in the DTP group in comparison with the baseline. CONCLUSIONS: The severity of bilateral VC is not correlated with the reduction of semen quality. DTP can improve sperm quality by improving total sperm count, PMS and acrosomal enzyme activity and reducing DFI in VC patients after varicocelectomy. The underlying mechanisms of the prescription may be related to its anti-oxidative stress action and abilities of improving reproductive hypoxia, spermatogenic environment and the function of Sertoli cells, but the specific signaling pathway involved is not yet clear.

The Synergistic Reducing Drug Resistance Effect of Cisplatin and Ursolic Acid on Osteosarcoma through a Multistep Mechanism Involving Ferritinophagy.

Increasing evidence suggests that traditional Chinese medicine strategies are obviously beneficial for cancer treatment, but scientific research on the underlying molecular mechanisms is lacking. We report that ursolic acid, a bioactive ingredient isolated from Radix Actinidiae chinensis, has strong antitumour effects on osteosarcoma cells. Functional studies showed that ursolic acid inhibited tumour cell proliferation and promoted the apoptosis of a variety of osteosarcoma cells. Ursolic acid had a synergistic cytotoxic effect with cisplatin on osteosarcoma cells. In a mouse osteosarcoma xenograft model, low-dose cisplatin combined with ursolic acid significantly reduced tumour growth. Notably, ursolic acid reversed weight loss in mice treated with cisplatin. Mechanistic studies showed that ursolic acid degraded ferritin by activating autophagy and induced intracellular overload of ferrous ions, leading to ferroptosis. In addition, ursolic acid enhanced the DNA-damaging effect of cisplatin on osteosarcoma cells. Taken together, these findings suggest that ursolic acid is a nontoxic adjuvant that may enhance the effectiveness of chemotherapy in osteosarcoma.

All around suboptimal health - a joint position paper of the Suboptimal Health Study Consortium and European Association for Predictive, Preventive and Personalised Medicine.

First two decades of the twenty-first century are characterised by epidemics of non-communicable diseases such as many hundreds of millions of patients diagnosed with cardiovascular diseases and the type 2 diabetes mellitus, breast, lung, liver and prostate malignancies, neurological, sleep, mood and eye disorders, amongst others. Consequent socio-economic burden is tremendous. Unprecedented decrease in age of maladaptive individuals has been reported. The absolute majority of expanding non-communicable disorders carry a chronic character, over a couple of years progressing from reversible suboptimal health conditions to irreversible severe pathologies and cascading collateral complications. The time-frame between onset of SHS and clinical manifestation of associated disorders is the operational area for an application of reliable risk assessment tools and predictive diagnostics followed by the cost-effective targeted prevention and treatments tailored to the person. This article demonstrates advanced strategies in bio/medical sciences and healthcare focused on suboptimal health conditions in the frame-work of Predictive, Preventive and Personalised Medicine (3PM/PPPM). Potential benefits in healthcare systems and for society at large include but are not restricted to an improved life-quality of major populations and socio-economical groups, advanced professionalism of healthcare-givers and sustainable healthcare economy. Amongst others, following medical areas are proposed to strongly benefit from PPPM strategies applied to the identification and treatment of suboptimal health conditions:Stress overload associated pathologiesMale and female healthPlanned pregnanciesPeriodontal healthEye disordersInflammatory disorders, wound healing and pain management with associated complicationsMetabolic disorders and suboptimal body weightCardiovascular pathologiesCancersStroke, particularly of unknown aetiology and in young individualsSleep medicineSports medicineImproved individual outcomes under pandemic conditions such as COVID-19.

A qualitative classification signature for post-surgery 5-fluorouracil-based adjuvant chemoradiotherapy in gastric cancer.

BACKGROUND AND PURPOSE: Currently, 5-fluorouracil (5-FU)-based adjuvant chemoradiotherapy (ACRT) is a preferred regimen for post-surgery gastric cancer (GC). However, the survival outcome of 5-FU-based ACRT varies greatly among different GC patients. Thus, it is necessary to classify which patients may benefit from 5-FU-based ACRT. MATERIALS AND METHODS: We collected 577 GC and 84 adjacent normal samples for training and 675 GC samples for validation. Based on the within-sample relative expression orderings (REOs) of gene expression levels, reversal gene pairs were selected, and the pairs correlating with overall survival (OS) of GC patients receiving 5-FU-based ACRT were identified as candidates. Finally, an optimized set of candidate gene pairs was selected as a classification signature in training data and validated in validation data. RESULTS: A signature consisting of 34 gene pairs was identified in training data and validated in three independent datasets. The classified low-risk group had better OS than the classified high-risk group. We also analyzed the recurrent free survival or disease free survival (RFS/DFS) of the validation datasets, and the similar results were shown. Furthermore, although the signature was identified based on the OS of GC patients receiving ACRT, it was not a prognostic signature for patients treated with surgery alone, but may be a potential signature for 5-FU-based chemotherapy alone. CONCLUSIONS: The signature can accurately classify GC patients who may benefit from 5-FU-based ACRT, which could aid clinicians in tailoring more effective GC treatments.

Kinetic Study and Degradation Mechanism of Glycidyl Esters in both Palm Oil and Chemical Models during High-Temperature Heating.

A kinetic model for glycidyl ester (GE) formation in both palm oil and chemical models during high-temperature heating was built to investigate the formation and degradation mechanisms of GEs in refined palm oil. The results showed that the formation and degradation of GEs followed pseudo-first-order reactions, and the rate constants of reaction kinetics followed the Arrhenius equation. The estimated activation energy of the GE degradation reaction (12.87 kJ/mol) was significantly lower than that of the GE formation reaction (34.58 kJ/mol), suggesting that GE degradation occurred more readily than formation. The Fourier transform infrared (FTIR) band intensities of epoxy and ester carboxyl groups decreased over heating time, while no band assigned to the cyclic acyloxonium group was found. Furthermore, no 5,5-dimethyl-1-pyrroline N-oxide (DMPO)-cyclic acyloxonium radical adduct was detected by quadrupole time-of-flight mass spectrometry (Q-TOF-MS). The above findings indicated that GEs were decomposed, fatty acid was also liberated, and GE degradation did not involve a cyclic acyloxonium intermediate. GEs were primarily decomposed into monoacylglycerol via ring-opening reaction during heating followed by fatty acid and glycerol via hydrolysis reaction.