TRIM52 knockdown inhibits proliferation, inflammatory responses and oxidative stress in IL-1ß-induced synovial fibroblasts to alleviate temporomandibular joint osteoarthritis.

To explore the mechanism of tripartite motif 52 (TRIM52) in the progression of temporomandibular joint osteoarthritis (TMJOA). Gene and protein expression were tested by quantitative real-time polymerase chain reaction and western blot, respectively. The levels of pro-inflammatory cytokines and oxidative stress factors were evaluated using enzyme-linked immunosorbent assay and biochemical kit, respectively. Cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays were carried out to assess cell proliferation. Immunofluorescence was used to detect the expression of CD68 and Vimentin in primary synovial fibroblasts (SFs). Haematoxylin and eosin staining and Safranin O/Fast green were used to evaluate the pathological damage of synovial and cartilage tissue in rats. TRIM52 was upregulated in the synovial tissue and SFs in patients with TMJOA. Interleukin (IL)-1ß treatment upregulated TRIM52 expression in TMJOA SFs and normal SF (NSF), promoting cell proliferation, inflammatory response and oxidative stress in NSF, SFs. Silence of TRIM52 relieved the cell proliferation, inflammatory response and oxidative stress induced by IL-1ß in SFs, while overexpression of TRIM52 enhanced IL-1ß induction. Meanwhile, IL-1ß induction activated toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB pathway, which was augmented by upregulation of TRIM52 in NSF, and was attenuated by TRIM52 knockdown in SFs. Besides, pyrrolidinedithiocarbamic acid ameliorated IL-1ß-induced proliferation and inflammatory response by inhibiting TLR4/NF-κB signalling. Meanwhile, TRIM52 knockdown inhibited cell proliferation, oxidative stress and inflammatory response in IL-1ß-induced SFs through downregulation of TLR4. TRIM52 promoted cell proliferation, inflammatory response, and oxidative stress in IL-1ß-induced SFs. The above functions were mediated by the activation of TLR4/NF- κB signal pathway.

TRA2: The dominant power of alternative splicing in tumors.

The dysregulation of alternative splicing (AS) is frequently found in cancer and considered as key markers for cancer progression and therapy. Transformer 2 (TRA2), a nuclear RNA binding protein, consists of transformer 2 alpha homolog (TRA2A) and transformer 2 beta homolog (TRA2B), and plays a role in the regulation of pre-mRNA splicing. Growing evidence has been provided that TRA2A and TRA2B are dysregulated in several types of tumors, and participate in the regulation of proliferation, migration, invasion, and chemotherapy resistance in cancer cells through alteration of AS of cancer-related genes. In this review, we highlight the role of TRA2 in tumorigenesis and metastasis, and discuss potential molecular mechanisms how TRA2 influences tumorigenesis and metastasis via controlling AS of pre-mRNA. We propose that TRA2Ais a novel biomarker and therapeutic target for cancer progression and therapy.

[Effect of acupuncture pretreatment of "Quchi"(LI11) and "Xuehai" (SP10) on mast cells and IL-33/ST2 in rats with urticaria].

OBJECTIVE: To observe the effect of electroacupuncture (EA) pretreatment at "Quchi "(LI11) and "Xuehai "(SP10) on expression of interleukin (IL)-33, suppression of tumorigenicity 2 (ST2) and mast cell degranulation in sensitive area of skin tissue in rats with urticaria, so as to explore its mechanisms underlying prevention of urticaria. METHODS: A total of 32 male SD rats were randomly divided into blank control, model, EA preconditioning and medication groups, with 8 rats in each group. The urticaria model was established by topical injection of the prepared anti-ovalbumin serum (foreign serum, 0.1 mL/spot) along the bilateral sides of the spinal column on the back, followed by injection of mixture solution of ovalbumin, 0.5% evans blue and normal saline via the tail vein 48 h later. EA intervention (2 Hz/15 Hz, 1 mA) was applied to bilateral LI11 and SP10 for 20 min, once daily for 7 d before modeling.Back sensitization was started from the 5th day on. Rats of the medication group received gavage of loratadine, and those of the model group received gavage of the same volume of normal saline. The diameter of evans blue spots at the back skin tissue was measured; the histopathological changes of the blue spot tissues were observed by light microscope after H.E. staining. The state of degranulation of mast cells in the subcutaneous loose connective tissue was observed by using toluidine blue staining. Serum IgE and histamine contents were detected by ELISA, and the immunoactivity of IL-33 and ST2 in the skin and subcutaneous tissues of the sensitized spots (evans blue exudation spots) was observed by immunohistochemistry. RESULTS: Compared with the blank control group, the diameter of evans blue spot, degranulation rate of mast cells, serum IgE and histamine contents, and the immunoactivity of IL-33 and ST2 in the evans blue exudation spot tissues were significantly increased in the model group (P<0.01). In comparison with the model group, the increase of the above-mentioned indexes was reversed in both EA and medication groups (P<0.01，P<0.05). No significant differences were found between the EA and medication groups in down-regulating the levels of the 6 indexes. H.E. staining of the blue spot tissues of rats in the model group showed incomplete structure of the epidermal layer of the skin, unclear interface of tissues, incomplete keratinization, chaotic epidermal cells, disorderly arrangement of fibers in the dermis, and infiltration of inflammatory cells and edema, which was relatively milder in the EA and medication groups. CONCLUSION: EA preconditioning can prevent urticaria (reduce size and sensitive reactions) in rats, which may be associated with its functions in lowering the level of IgE through inhibiting IL-33 and ST2.

Safety, immunogenicity, and efficacy of the mRNA vaccine CS-2034 as a heterologous booster versus homologous booster with BBIBP-CorV in adults aged ≥18 years: a randomised, double-blind, phase 2b trial.

BACKGROUND: Heterologous boosting is suggested to be of use in populations who have received inactivated COVID-19 vaccines. We aimed to assess the safety and immunogenicity of a heterologous vaccination with the mRNA vaccine CS-2034 versus the inactivated BBIBP-CorV as a fourth dose, as well as the efficacy against the SARS-CoV-2 omicron (BA.5) variant. METHODS: This trial contains a randomised, double-blind, parallel-controlled study in healthy participants aged 18 years or older (group A) and an open-label cohort in participants 60 years and older (group B), who had received three doses of inactivated whole-virion vaccines at least 6 months before enrolment. Pregnant women and people with major chronic illnesses or a history of allergies were excluded. Eligible participants in group A were stratified by age (18-59 years and ≥60 years) and then randomised by SAS 9.4 in a ratio of 3:1 to receive a dose of the mRNA vaccine (CS-2034, CanSino, Shanghai, China) or inactivated vaccine (BBIBP-CorV, Sinopharm, Beijing, China). Safety and immunogenicity against omicron variants of the fourth dose were evaluated in group A. Participants 60 years and older were involved in group B for safety observations. The primary outcome was geometric mean titres (GMTs) of the neutralising antibodies against omicron and seroconversion rates against BA.5 variant 28 days after the boosting, and incidence of adverse reactions within 28 days. The intention-to-treat group was involved in the safety analysis, while all patients in group A who had blood samples taken before and after the booster were involved in the immunogenicity analysis. This trial was registered at the Chinese Clinical Trial Registry Centre (ChiCTR2200064575). FINDINGS: Between Oct 13, and Nov 22, 2022, 320 participants were enrolled in group A (240 in the CS-2034 group and 80 in the BBIBP-CorV group) and 113 in group B. Adverse reactions after vaccination were more frequent in CS-2034 recipients (158 [44·8%]) than BBIBP-CorV recipients (17 [21·3%], p<0·0001). However, most adverse reactions were mild or moderate, with grade 3 adverse reactions only reported by eight (2%) of 353 participants receiving CS-2034. Heterologous boosting with CS-2034 elicited 14·4-fold (GMT 229·3, 95% CI 202·7-259·4 vs 15·9, 13·1-19·4) higher concentration of neutralising antibodies to SARS-CoV-2 omicron variant BA.5 than did homologous boosting with BBIBP-CorV. The seroconversion rates of SARS-CoV-2-specific neutralising antibody responses were much higher in the mRNA heterologous booster regimen compared with BBIBP-CorV homologous booster regimen (original strain 47 [100%] of 47 vs three [18·8%] of 16; BA.1 45 [95·8%] of 48 vs two [12·5%] 16; and BA.5 233 [98·3%] of 240 vs 15 [18·8%] of 80 by day 28). INTERPRETATION: Both the administration of mRNA vaccine CS-2034 and inactivated vaccine BBIBP-CorV as a fourth dose were well tolerated. Heterologous boosting with mRNA vaccine CS-2034 induced higher immune responses and protection against symptomatic SARS-CoV-2 omicron infections compared with homologous boosting, which could support the emergency use authorisation of CS-2034 in adults. FUNDING: Science and Technology Commission of Shanghai, National Natural Science Foundation of China, Jiangsu Provincial Science Fund for Distinguished Young Scholars, and Jiangsu Provincial Key Project of Science and Technology Plan. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

[Electroacupuncture preconditioning relieves cutaneous passive anaphylaxis by down-regulating IP3 mediated ROS/TRPM2 signaling pathway and inhibiting mast cell degranulation in rats with urticaria].

OBJECTIVE: To observe the effect of electroacupuncture (EA) preconditioning of "Quchi" (LI11) and "Xuehai" (SP10) on mast cell (MC) degranulation, and expressions of inositol triphosphate(IP3), reactive oxygen species (ROS), transient receptor potential (TRP) M2, calmodulin (CaM) in rats with urticaria, so as to reveal its molecular mechanism under-lying improving urticaria. METHODS: Thirty-two male SD rats were randomly divided into blank control, model, preconditioning of EA (Pre-EA) and medication groups (n=8 rats/group). The urticaria model was established by intradermal injection of dilute allogeneic antioalbumin serum at the spots of the bilateral symmetry of the spine on the back, and followed by tail venous injection of mixture solution of egg albumin diluent, plus 0.5% Evans blue and normal saline. Ten days before the end of modeling, rats of the pre-EA group received EA stimulation of LI11 and SP10 for 20 min, once a day for 10 consecutive days, and those of the medication group received gavage of loratadine tablets diluted solution (1 mg/kg) once a day for 10 days. The times of rat's scratching the sensitized skin were recorded, the diameter of the sensitized blue spots was measured and the degranulation rate of skin MCs was counted under microscope after toluidine blue staining. The expression levels of IP3, ROS, TRPM2 and CaM in the skin tissue were measured by immunohistochemistry and western blot, respectively. RESULTS: Compared with the blank control group, the scratching times, diameter of the sensitized blue spots, degranulation rate of MCs, and the expression levels of ion channel related proteins (IP3, ROS, TRPM2 and CaM) were significantly increased (P<0.01) in the model group. In comparison with the model group, the scratching times, diameter of sensitized blue spot, degranulation rate of MCs, and the expression levels of IP3, ROS, TRPM2 and CaM in both pre-EA and medication groups were significantly down-regulated (P<0.01, P<0.05). No significant differences were found between Pre-EA and medication groups in down-regulating the levels of the above-mentioned 7 indexes. CONCLUSION: EA-LI11 and SP10 preconditioning can reduce the cutaneous anaphylaxis in urticaria rats, which may be related to its effects in inhibiting the degranulation of MCs, and the expression of TRP channel related proteins.

[Current status, challenges and countermeasures of acupuncture data mining literature researches].

Data mining is an analytical method for revealing the implicit internal relations among the data elements, and is also widely used in the field of acupuncture and moxibustion of traditional Chinese medicine. However, there exist some significant deficits in the rationality of design and implementation, preciseness, repeatability, comprehensiveness, objectivity and depth of insights in some current acupuncture data mining researches. In the present paper, we summarized the literature on acupuncture data mining published in the past five years, and analyzed their common shortcomings in the design, implementation and reporting process, including too broad research scope, fuzzy and limited descriptions about the inclusion criteria, not definite retrieval scope and strategy, rarely seen original researches about the assessment of the report quality, lack of detailed descriptions about the literature screening and data processing procedure, incomplete narration about the research outcomes and their clinical significance, and lack of comprehensiveness and subjectiveness and available coping strategies in the discussion of the research papers, etc., in order to promote the improvement of literature methodology and quality of acupuncture data mining research, and then improve the reliability and clinical reference value of such research results.

Youjing granules ameliorate spermatogenesis in rats through regulating the prolifereation of spermatogonial stem cells.

Male infertility has evolved from a common reproductive system disease to a major social issue. Youjing granule (YG) is a Chinese medicinal material used as a therapy method for tonifying the kidneys and removing dampness due to its pathogenic characteristics. YG has been shown to regulate sperm quality in clinical trials, but the underlying mechanism is not fully understood. The present study was aimed to explore the protective effects and mechanism of action of YG on male reproductive system damage caused by methyl methane sulfonate (MMS). We first established an infertility model of rats through oral administration of MMS and then treated with YG. To determine the effect of YG, spermatogenesis, microvascular density, and secretory function of Leydig cells and Sertoli cells in rats were assessed. Spermatogonial stem cells (SSCs) were co-cultured with mouse embryo fibroblast (MEF) cells as an in vitro cell model before exposure to serum containing YG. Furthermore, the proliferation and apoptosis of SSCs were measured. Results indicated that YG increased the expression of self-renewal and proliferation-related molecules such as glial cell line derived neurotrophic factor (GDNF) and fibroblast growth factor-2 (FGF2), and improved the quality of sperm and the proliferation of SSCs. In conclusion, YG may protect spermatogenetic function of rats through regulating the proliferation and self-renewal of SSCs.

The effect of aerobic exercise on the lipophagy of adipose tissue in obese male mice.

This article explores the obesity state and the changes in the level of lipophagy in adipose tissue after exercise to lose weight, so as to provide direction and basis for theoretical research on obesity prevention and control. We established a high-fat diet model of obese mice, and applied exercise intervention and intraperitoneal injection of chloroquine to inhibit autophagy. Long-term high-fat diet can cause obesity in mice, and the process of lipophagy is inhibited, which may be one of the reasons for fat accumulation. Eight weeks of aerobic exercise can effectively reduce the weight of obese mice and promote lipolysis; this process is mainly completed by lipase decomposition, in addition to require the participation of the lipophagy process.

[Influence of electroacupuncture of"Zusanli"(ST36)on mast cells/TRPV1 signaling pathway in visceral hypersensitivity rats with functional dyspepsia].

OBJECTIVE: To explore the interventional mechanism of electroacupuncture (EA) of "Zusanli"(ST36)based on the involvement of mast cells/ transient receptor potential vanilloid type1 (TRPV1) signaling pathway in relieving visceral hypersensitivity in functional dyspepsia (FD) rats. METHODS: Sixty SD rats (half male and half female, 10 days in age) were randomly divided into normal control, model, medication (ketotifen) and EA groups, with 15 rats in each group. The FD model was established by gavage of iodoacetamide combined with tail clamping (stress stimulation). Rats of the medication group received intraperitoneal injection of ketotifen (1 mg·kg-1·d-1) for 14 d, and those of the EA group received EA of ST36 for 20 min, once a day for 14 d. An air-balloon was inserted into the rat's stomach for recording changes of the intragastric pressure (mL/mm Hg) via a pressure transducer. The visceral hypersensitivity was assessed using abdominal withdrawal reflex (AWR) score and the number and degranulation of mast cells of gastric mucosa were observed using toluidine blue staining. The expression levels of TRPV1 and proteinase activated receptor 2 (PAR2) in the stomach were observed using immunofluorescence histochemistry and Western blot, separately, and the contents of SP and CGRP in the stomach detected using ELISA. RESULTS: When the intragastric pressure was at 50, 60 and 70 mm Hg, the gastric compliance was significantly decreased (P<0.01), and the levels of visceral sensitivity increased in the model group （P<0.01）。 TRPV1 immunofluorescence tensity, expression of PAR2 and TRPV1 proteins, and contents of SP and CGRP in the stomach were considerably up-regulated in the model group compared with the normal control group (P<0.01). In comparison with the model group, under intragastric pressure of 50，60 and 70 mm Hg, the gastric compliance was obviously increased, and the visceral hypersensitivity decreased in the EA group （P<0.01,P<0.05）. TRPV1 immunofluorescence intensity, expression levels of PAR2 and TRPV1 proteins, and the contents of SP and CGRP in the stomach were considerably down-regulated in both medication and EA groups compared with the model group (P<0.01, P<0.05). The therapeutic effect of EA was significantly superior to that of medication in up-regulating the gastric compliance （at 70 mm Hg）, and down-regulating the contents of SP and CGRP (P<0.05). No significant differences were found between the EA and medication groups in up-regulating gastric compliance at intragastric pressure of 50 and 60 mm Hg, and in down-regulating the visceral sensitivity, TRPV1 fluorescence intensity, and expression of PAR2 and TRPV1 proteins (P>0.05). Toluidine blue staining showed an apparent increase of mast cell number with obvious degranulation in the gastric mucosa of rats in the model group, which was milder in the EA and medication groups. CONCLUSION: EA of ST36 can suppress visceral hypersensitivity and increase the gastric compliance in FD rats, which may be related with its effects in inhibiting the activation of gastric mast cells, and down-regulating the expression of gastric PAR2 and TRPV1 proteins and SP and CGRP contents.

Piezo1 Affects Temporomandibular Joint Osteoarthritis by Influencing pSmad3.

Objective: The aim of this research was to study the expression of Piezo1 in a rat temporomandibular joint osteoarthritis animal model and to explore its mechanism for inducing inflammatory changes. Methods: A total of 24male SD rats aged approximately 8 weeks were randomly divided into three groups: the blank control group, complete Freund's adjuvant group (CFA), and CFA + inhibitor (GsMTx4) group. After 3 weeks, the condylar heads of the rats were evaluated by micro-CT, HE, immunohistochemistry, safranin O staining, and other experimental techniques. Protein was extracted from the subchondral bone, and the changes in Piezo1, Smad3, and pSmad3 levels in each group were detected by Western blotting. p < 0.05 was considered to indicate statistical significance. Results: The degree of damage to the cartilage and subchondral bone in the Piezo1 inhibitor group was smaller than that in the CFA group. The expression level of Piezo1 in the CFA group was higher than that in the other groups, and the difference was statistically significant. The expression of pSmad3 in the CFA group was also higher than that in the other groups (p < 0.05). Conclusion: Piezo1 is expressed in the condylar cartilage and subchondral bone of rats, and the degree of condylar destruction can be improved by influencing the pSmad3 expression.

Structural and mechanistic insights into starch microgel/anthocyanin complex assembly and controlled release performance.

We report a self-assembly method for the fabrication of multilayer-starch-based microgels used for anthocyanin encapsulation. Alcohol-heating treatment and ionization reactions were employed to reduce the crystallinity of starch and introduce ionic groups on the molecule to further cross-link it with sodium trimetaphosphate and produce a starch microgel. The molecular interactions between the starch and the anthocyanins facilitated the anthocyanin encapsulation and the starch-microgel/anthocyanin complexes with one, two, and three self-assembled layers were obtained. The Lay-1 microgel exhibited an encapsulation efficiency of 50.1% when the anthocyanin concentration, cross-linking starch concentration, contact time, and temperature were 0.25 mg/mL, 1.5 mg/mL, 3 h, and 40 °C, respectively. An increase in the number of layers resulted in a more compact microgel structure with the zeta potential presenting variations upon structural changes. Furthermore, the encapsulated anthocyanins presented a slow release from Lay-1, while the multilayered microgels (Lay-2 and Lay-3) displayed outstanding encapsulation stability. This study gives an insight on the encapsulation and release of anthocyanins by starch microgels, and provides a novel strategy for the design of starch-based encapsulation materials presenting great stability.

Stem Cell-Based Therapy for Diabetic Foot Ulcers.

Diabetic foot ulcer has become a worldwide clinical medical challenge as traditional treatments are not effective enough to reduce the amputation rate. Therefore, it is of great social significance to deeply study the pathogenesis and biological characteristics of the diabetic foot, explore new treatment strategies and promote their application. Stem cell-based therapy holds tremendous promise in the field of regenerative medicine, and its mechanisms include promoting angiogenesis, ameliorating neuroischemia and inflammation, and promoting collagen deposition. Studying the specific molecular mechanisms of stem cell therapy for diabetic foot has an important role and practical clinical significance in maximizing the repair properties of stem cells. In addition, effective application modalities are also crucial in order to improve the survival and viability of stem cells at the wound site. In this paper, we reviewed the specific molecular mechanisms of stem cell therapy for diabetic foot and the extended applications of stem cells in recent years, with the aim of contributing to the development of stem cell-based therapy in the repair of diabetic foot ulcers.

Effectiveness and safety of acupuncture for chronic obstructive pulmonary disease: A protocol for systematic review and meta-analysis.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is the most common respiratory disease in clinic. Traditional Chinese medicine (TCM) lung rehabilitation has gradually been valued in the field of prevention and treatment of COPD. Acupuncture, as an important part of TCM lung rehabilitation, is carried out in clinical extensively and application. It has the advantage of improving the symptoms and quality of life of COPD cases, but the evidence-based proof is limited. METHODS: Eight databases will be systematically retrieved from their inceptions to December 2021. This study will include randomized controlled trials of acupuncture in the treatment of COPD with stable stage. The main outcome will include clinical effective rate, TCM symptom score, quality of life, dyspnea, exercise capacity, lung function, frequency of acute exacerbation, adverse events. Literature screening, quality evaluation and information extraction will be completed by two independent researchers. Revman 5.3 software will be used to perform meta-analysis. Assessment of multiple systematic reviews-2 tool will be used for evaluating the methodological quality of systematic review (SR), grading of recommendations assessment will for rating the quality of evidence, and consolidated standards of reporting trials and Standards for Reporting Interventions in Clinical Trials of Acupuncture tool will for assessing the reporting quality of randomized controlled trials. RESULTS: The findings of this SR will be presented at relevant conferences and submitted for peer-review publication. CONCLUSIONS: The findings of this SR will provide up-to-date summary proof for evaluating the effectiveness and safety of acupuncture for COPD.

[Effect of moxibustion on the expression of microglia and brain-derived neurotrophic factor protein in the spinal cord of rats with myofascial pain syndrome].

OBJECTIVE: To observe the effect of moxibustion at myofascial trigger points on microglia activation and the expression of brain-derived neurotrophic factor (BDNF) in the spinal cord of rats with myofascial pain syndrome (MPS), so as to explore the central mechanism of the analgesic effect of moxibustion. METHODS: Twenty-four male SD rats were randomly divi-ded into control, model and moxibustion groups (n=8 in each group). The MPS model was established by strinking on fascia musculares and eccentric exercise. Rats in the moxibustion group were treated with mild moxibustion at myofascial trigger point for 15 min, once daily for 7 days. The thermal withdrawal latency (TWL) of rats was measured with a hot stabbing instrument. The pathological changes of the rat medial femoris muscle were observed after H.E. staining. The expressions of microglia marker (OX-42) and BDNF in the spinal dorsal horn were detected by immunohistochemistry and Western blot, separately. RESULTS: After modeling, the TWL of both the model and the moxibustion groups were significantly down-regulated (P<0.01)，and were significantly decreased in contrast to that of the control group (P<0.01). After treatment and compared with the model group, the TWL of the moxibustion group was significantly increased (P<0.01) in the moxibustion group. Rat's muscle fibers of the control group were uniform in thickness and arranged tightly and regularly. While in the model group, some fractures and connective structure tissue renewal, irregular arrangement, and inflammatory cell infiltration were seen. The morphology of muscle fibers in the moxibustion group was close to normal, and the arrangement was neat and orderly, with a small amount of inflammatory cell infiltration. Compared with the control group, the expression of OX-42 and BDNF in the spinal dorsal horn of rats in the model group was increased(P<0.01). Following the treatment, and in comparison with the model group, the expression of OX-42 and BDNF of moxibustion group was down-regulated(P<0.05). CONCLUSION: Moxibustion can significantly improve the injury of the medial femoral muscle and the TWL in MPS rats，which may be related to its effects in inhibiting the activation of spinal dorsal horn microglia and reducing the expression of BDNF.

Markers of Prognosis for Early Stage Cervical Cancer Patients (Stage IB1, IB2) Undergoing Surgical Treatment.

BACKGROUND: For individuals with cervical cancer, large tumor volume, lymph node metastasis, distant metastasis, and parauterine infiltration are usually associated with a poor prognosis. Individuals with stage 1B1 and 1B2 cervical cancer usually do not have these unfavorable prognostic factors. Once the disease progresses, the prognosis becomes extremely poor. Therefore, investigating the prognostic markers of these cervical cancer patients is necessary for treatment. METHODS: This retrospective study included 95 cervical cancer patients treated with surgery. The patients were divided into progressor and non-progressor groups according to postoperative follow-up results. T-test (or Mann-Whitney U test), chi-squared test (or Fisher's exact test) and receiver operating characteristic (ROC) curves were used to evaluate imaging, hematology, and clinicopathological index differences between the two groups. Cox analysis was performed to select the independent markers of progression-free survival (PFS) when developing the nomogram. Validation of the nomogram was performed with 1000 bootstrapped samples. The performance of the nomogram was validated with ROC curves, generated calibration curves, and Kaplan-Meier and decision curve analysis (DCA). RESULTS: Cervical stromal invasion depth, lymphovascular space invasion (LVSI), human papilloma virus (HPV-16), Glut1, D-dimer, SUVmax and SUVpeak showed significant differences between the two groups. Multivariate Cox proportional hazard model showed SUVpeak (p = 0.012), and HPV-16 (p = 0.007) were independent risk factors and were used to develop the nomogram for predicting PFS. The ROC curves, Kaplan-Meier method, calibration curves and DCA indicated satisfactory accuracy, agreement, and clinical usefulness, respectively. CONCLUSIONS: SUVpeak level (≥7.63 g/cm3) and HPV-16 negative status before surgery were associated with worse PFS for patients with cervical cancer. Based on this result, we constructed the nomogram and showed satisfactory performance. Clinically, individualized clinical decision-making can be performed on patients based on this result.

The effectiveness and safety of Chinese herbal formulas on skin photoaging: A protocol for systematic review and meta-analysis.

BACKGROUND: Skin photoaging (SP) is a complex and complicated process of skin characteristic changes caused by excessive sunlight. Wrinkles, looseness, coarseness, and increase or loss of pigment are the main clinical manifestations of the disease. The pathogenesis of SP mainly involving oxidative stress, inflammatory reaction, immune dysregulation and DNA damage, and so on. In recent years, traditional Chinese medicine, as an significant form of complementary and alternative medicine, has attracted the more and more attention within the field of health care and indicated a desirable effect on SP. Chinese herbal formula (CHF) is an essential part of traditional Chinese medicine interventions, and the number of clinical trails on SP treated by CHFs have shown a growing trend. Therefore, we developed this systematic review and meta-analysis protocol to assess the effectiveness and safety of CHFs in the therapy of SP, so as to provide reliable evidence-based evidence for clinical decision-making. METHODS: A overall literature retrieval will be carried out in 9 electronic journal database. We will include randomized controlled trials (RCTs) on CHFs alone or combined with routine western medicine measures in the treatment of SP. The outcomes we focused on are consists of symptom score (skin relaxation, telangiectasia, pore coarseness, pigmentation, etc), total effective rate, and adverse reactions. Meta-analysis will be performed using Stata 13.0 software. Literature retrieval and screening, data extraction, risk of bias assessment of RCTs, evidence confidence rating by grading of recommendations assessment, development, and evaluation method and methodological quality assessment of systematic review by assessment of multiple systematic reviews-2 will be conducted independently by 2 reviewers, and disagreements will be resolved through discussion or judged by a third senior reviewer. RESULTS: This systematic review and meta-analysis will pool the proof of RCTs on SP treated by CHFs alone or combined with conventional western medicine treatments. The findings of this study will be presented at relevant conferences and submitted to peer-reviewed journals for publication. CONCLUSION: We expect that the results of this systematic review will provide comprehensive and reliable evidence for clinicians and policy makers. REGISTRATION NUMBER: INPLASY 2020120005.

Leptin and inflammatory factors play a synergistic role in the regulation of reproduction in male mice through hypothalamic kisspeptin-mediated energy balance.

BACKGROUND: Energy balance is closely related to reproductive function, wherein hypothalamic kisspeptin mediates regulation of the energy balance. However, the central mechanism of kisspeptin in the regulation of male reproductive function under different energy balance states is unclear. Here, high-fat diet (HFD) and exercise were used to change the energy balance to explore the role of leptin and inflammation in the regulation of kisspeptin and the hypothalamic-pituitary-testis (HPT) axis. METHODS: Four-week-old male C57BL/6 J mice were randomly assigned to a normal control group (n = 16) or an HFD (n = 49) group. After 10 weeks of HFD feeding, obese mice were randomly divided into obesity control (n = 16), obesity moderate-load exercise (n = 16), or obesity high-load exercise (n = 17) groups. The obesity moderate-load exercise and obesity high-load exercise groups performed exercise (swimming) for 120 min/day and 120 min × 2 times/day (6 h interval), 5 days/week for 8 weeks, respectively. RESULTS: Compared to the mice in the normal group, in obese mice, the mRNA and protein expression of the leptin receptor, kiss, interleukin-10 (IL-10), and gonadotropin-releasing hormone (GnRH) decreased in the hypothalamus; serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels and sperm quality decreased; and serum leptin, estradiol, and tumor necrosis factor-α (TNF-α) levels and sperm apoptosis increased. Moderate- and high-load exercise effectively reduced body fat and serum leptin levels but had the opposite effects on the hypothalamus and serum IL-10 and TNF-α levels. Moderate-load exercise had anti-inflammatory effects accompanied by increased mRNA and protein expression of kiss and GnRH in the hypothalamus and increased serum FSH, LH, and testosterone levels and improved sperm quality. High-load exercise also promoted inflammation, with no significant effect on the mRNA and protein expression of kiss and GnRH in the hypothalamus, serum sex hormone level, or sperm quality. Moderate-load exercise improved leptin resistance and inflammation and reduced the inhibition of kisspeptin and the HPT axis in obese mice. The inflammatory response induced by high-load exercise may counteract the positive effect of improving leptin resistance on kisspeptin and HPT. CONCLUSION: During changes in energy balance, leptin and inflammation jointly regulate kisspeptin expression on the HPT axis.

A tree shrew model for steroid-associated osteonecrosis.

Osteonecrosis is a common human disease in orthopedics. It is difficult to treat, and half of patients may need artificial joint replacement, resulting in a considerable economic burden and a reduction in quality of life. Hormones are one of the major causes of osteonecrosis and high doses of corticosteroids are considered the most dangerous factor. Because of the complexity of treatment, we still need a better animal model that can be widely used in drug development and testing. Tree shrews are more closely related to primates than rodents. As such, we constructed a successful tree shrew model to establish and evaluate steroid-associated osteonecrosis (SAON). We found that low-dose lipopolysaccharide (LPS) combined with high-dose methylprednisolone (MPS) over 12 weeks could be used to establish a tree shrew model with femoral head necrosis. Serum biochemical and histological analyses showed that an ideal model was obtained. Thus, this work provides a useful animal model for the study of SAON and for the optimization of treatment methods.

[Effect of electroacupuncture on expressions of Lyn and Syk in mast cells of subcutaneous loose connective tissue in rats with urticarial].

OBJECTIVE: To observe the effect of electroacupuncture (EA) preconditioning on the expressions of tyrosine kinase Lyn and spleen tyrosine kinase (Syk) in mast cells of subcutaneous loose connective tissue in the rats with urticaria and explore the potential biological mechanism of EA in the intervention of urticaria. METHODS: A total of 32 SD rats were randomized into a blank group, a model group, an EA group and a positive medication group, 8 rats in each one. Except of the blank group, the passive cutaneous anaphylaxis (PCA) was adopted to prepare the model of urticaria in the rats of the rest three groups. In the EA group, EA was applied to bilateral "Quchi" (LI 11), "Xuehai" (SP 10) and "Zusanli" (ST 36), with disperse-dense wave, 2 Hz/15 Hz in frequency and 1 mA in current intensity, once daily, for 20 min each time, consecutively for 7 days. In the positive medication group, loratadine (1 mg•kg-1•d-1) was for intragastric administration, once daily, consecutively for 7 days. The samples were collected for index detection 30 min after PCA antigen challenge in the rats of each group. Spectrophotometer was adopted to determine the effusion quantity of Evans blue in the allergized site of skin. HE staining was used to observe the morphological changes in the allergized site of skin. Toluidine blue staining was provided to observe mast cell degranulation in subcutaneous loose connective tissue in the allergized site of skin. Immunohistochemistry was applied to determine the protein expressions of Lyn and Syk during degranulation of mast cells. RESULTS: In the rats of the odel group, the eipdermis of allergized site was thickening, cells were disorganized in hierarchy and inflammatory cells were infiltrated largely in the dermis. In the positive medication group and the EA group, the epidermis was getting thin, cell arrangement was clear and the inflammatory cell infiltration was obviously alleviated as compared with the model group. Compared with the blank group, the OD value of skin dye effusion quantity, the degranulation rate of mast cells and the positive expressions of Lyn and Syk were all increased in the model group (P<0.01). Compared with the model group, the OD value of skin dye effusion quantity, the degranulation rate of mast cells and the positive expressions of Lyn and Syk were all reduced in the EA group and the positive medication group (P<0.01). Compared with the positive medication group, the degranulation rate of mast cells was increased significantly in the EA group (P<0.01). CONCLUSION: Electroacupuncture at "Quchi" (LI 11), "Xuehai" (SP 10) and "Zusanli" (ST 36) reduces vascular permeability and gives play to the role of anti-allergy by the way of regulating and controlling the degranulation of mast cells in the rats with urticaria and the effect mechanism of electroacupuncture may be related to the inhibition of protein expressions of Lyn and Syk in mast cells.

Sectoral-based CO2 emissions of Pakistan: a novel Grey Relation Analysis (GRA) approach.

Global warming regarded as the major global issue over the past few decades, whereas carbon dioxide (CO2) emissions have been cited as one of the main causes of this problem. Therefore, this study aims to investigate the effect of energy consumption, economic development, and population growth on high CO2 emitting sectors of Pakistan such as transportation, industrial, and household. The data used in this study was taken from multiple databases from 2000 to 2018. We employed novel grey relational analysis (GRA) models to assess the connection between gross domestic product (GDP) per capita, population, energy consumption, and CO2 emission. Furthermore, the Hurwicz method was used to analyze which factor contributing more to CO2 emission. Result reveals that CO2 emission, gross domestic product per capita, population, and energy consumption showed a strong association among all sectors. Whereas, population contributes more to intensifying CO2 emissions in the transportation sector of Pakistan. This study provides useful insights for policymakers to take preventive and corrective measures to overcome CO2 emissions as well as sustainable development.