Sleep is an instinctive behavior alternating awakening state, sleep entails many active processes occurring at the cellular, circuit and organismal levels. The function of sleep is to restore cellular energy, enhance immunity, promote growth and development, consolidate learning and memory to ensure normal life activities. However, with the increasing of social pressure involved in work and life, the incidence of sleep disorders (SD) is increasing year by year. In the short term, sleep disorders lead to impaired memory and attention; in the longer term, it produces neurological dysfunction or even death. There are many ways to directly or indirectly contribute to sleep disorder and keep the hormones, including pharmacological alternative treatments, light therapy and stimulus control therapy. Exercise is also an effective and healthy therapeutic strategy for improving sleep. The intensities, time periods, and different types of exercise have different health benefits for sleep, which can be found through indicators such as sleep quality, sleep efficiency and total sleep time. So it is more and more important to analyze the mechanism and find effective regulation targets during sleep disorder through exercise. Dopamine (DA) is an important neurotransmitter in the nervous system, which not only participates in action initiation, movement regulation and emotion regulation, but also plays a key role in the steady-state remodeling of sleep-awakening state transition. Appreciable evidence shows that sleep disorder on humans and rodents evokes anomalies in the dopaminergic signaling, which are also implicated in the development of psychiatric illnesses such as schizophrenia or substance abuse. Experiments have shown that DA in different neural pathways plays different regulatory roles in sleep behavior, we found that increasing evidence from rodent studies revealed a role for ventral tegmental area DA neurons in regulating sleep-wake patterns. DA signal transduction and neurotransmitter release patterns have complex interactions with behavioral regulation. In addition, experiments have shown that exercise causes changes in DA homeostasis in the brain, which may regulate sleep through different mechanisms, including cAMP response element binding protein signal transduction, changes in the circadian rhythm of biological clock genes, and interactions with endogenous substances such as adenosine, which affect neuronal structure and play a neuroprotective role. This review aims to introduce the regulatory effects of exercise on sleep disorder, especially the regulatory mechanism of DA in this process. The analysis of intracerebral DA signals also requires support from neurophysiological and chemical techniques. Our laboratory has established and developed an in vivo brain neurochemical analysis platform, which provides support for future research on the regulation of sleep-wake cycles by movement. We hope it can provide theoretical reference for the formulation of exercise prescription for clinical sleep disorder and give some advice to the combined intervention of drugs and exercise.

This study aims to reveal the effect and mechanism of Gentianella turkestanorum total extract(GTI) in ameliorating non-alcoholic steatohepatitis(NASH). UPLC-Q-TOF-MS was employed to identify the chemical components in GTI. SwissTarget-Prediction, GeneCards, OMIM, and TTD were utilized to screen the targets of GTI components and NASH. The common targets shared by GTI components and NASH were filtered through the STRING database and Cytoscape 3.9.0 to identify core targets, followed by GO and KEGG enrichment analysis. AutoDock was used for molecular docking of key components with core targets. A mouse model of NASH was established with a methionine-choline-deficient high-fat diet. A 4-week drug intervention was conducted, during which mouse weight was monitored, and the liver-to-brain ratio was measured at the end. Hematoxylin-eosin staining, Sirius red staining, and oil red O staining were employed to observe the pathological changes in the liver tissue. The levels of various biomarkers, including aspartate aminotransferase(AST), alanine aminotransferase(ALT), hydroxyproline(HYP), total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), malondialdehyde(MDA), superoxide dismutase(SOD), and glutathione(GSH), in the serum and liver tissue were determined. RT-qPCR was conducted to measure the mRNA levels of interleukin 1β(IL-1β), interleukin 6(IL-6), tumor necrosis factor α(TNF-α), collagen type I α1 chain(COL1A1), and α-smooth muscle actin(α-SMA). Western blotting was conducted to determine the protein levels of IL-1β, IL-6, TNF-α, and potential drug targets identified through network pharmacology. UPLC-Q-TOF/MS identified 581 chemical components of GTI, and 534 targets of GTI and 1 157 targets of NASH were screened out. The topological analysis of the common targets shared by GTI and NASH identified core targets such as IL-1β, IL-6, protein kinase B(AKT), TNF, and peroxisome proliferator activated receptor gamma(PPARG). GO and KEGG analyses indicated that the ameliorating effect of GTI on NASH was related to inflammatory responses and the phosphoinositide 3-kinase(PI3K)/AKT pathway. The staining results demonstrated that GTI ameliorated hepatocyte vacuolation, swelling, ballooning, and lipid accumulation in NASH mice. Compared with the model group, high doses of GTI reduced the AST, ALT, HYP, TC, and TG levels(P<0.01) while increasing the HDL-C, SOD, and GSH levels(P<0.01). RT-qPCR results showed that GTI down-regulated the mRNA levels of IL-1β, IL-6, TNF-α, COL1A1, and α-SMA(P<0.01). Western blot results indicated that GTI down-regulated the protein levels of IL-1β, IL-6, TNF-α, phosphorylated PI3K(p-PI3K), phosphorylated AKT(p-AKT), phosphorylated inhibitor of nuclear factor kappa B alpha(p-IκBα), and nuclear factor kappa B(NF-κB)(P<0.01). In summary, GTI ameliorates inflammation, dyslipidemia, and oxidative stress associated with NASH by regulating the PI3K/AKT/NF-κB signaling pathway.
Animals ; Non-alcoholic Fatty Liver Disease/genetics* ; Mice ; Network Pharmacology ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Chromatography, High Pressure Liquid ; Liver/metabolism* ; Mice, Inbred C57BL ; Humans ; Mass Spectrometry ; Tumor Necrosis Factor-alpha/metabolism* ; Disease Models, Animal ; Molecular Docking Simulation

OBJECTIVES: To investigate the protective effect of Yiqi Yangyin Huazhuo Tongluo Formula (YYHT) against high glucose-induced injury in mouse renal podocytes (MPC5 cells) and the possible mechanism. METHODS: Adult Wistar rats were treated with 19, 38, and 76 g/kg YYHT or saline via gavage for 7 days to prepare YYHT-medicated or blank sera for treatment of MPC5 cells cultured in high glucose (30 mmol/L) prior to transfection with a miR-21a-5p inhibitor or a miR-21a-5p mimic. The changes in miR-21a-5p expressions and the mRNA levels of FoxO1, PINK1, and Parkin in the treated cells were detected with qRT-PCR, and the protein levels of nephrin, podocin, FoxO1, PINK1, and Parkin were detected with Western blotting. Autophagic activity in the cells were evaluated with MDC staining. The effect of miR-21a-5p mimic on FoxO1 transcription and the binding of miR-21a-5p to FoxO1 were examined with luciferase reporter gene assay and radioimmunoprecipitation assay. RESULTS: MPC5 cells exposed to high glucose showed significantly increased miR-21a-5p expression, lowered expressions of FoxO1, PINK1, and Parkin1 mRNAs, and reduced levels of FoxO1, PINK1, parkin, nephrin, and podocin proteins and autophagic activity. Treatment of the exposed cells with YYHT-medicated sera and miR-21a-5p inhibitor both significantly enhanced the protein expressions of nephrin and podocin, inhibited the expression of miR-21a-5p, increased the mRNA and protein expressions of FoxO1, PINK1 and Parkin, and upregulated autophagic activity of the cells. Transfection with miR-21a-5p mimic effectively inhibited the transcription of FoxO1 and promoted the binding of miR-21a-5p to FoxO1 in MPC5 cells, and these effects were obviously attenuated by treatment with YYHT-medicated sera. CONCLUSIONS YYHT-medicated sera alleviate high glucose-induced injury in MPC5 cells by regulating miR-21a-5p/FoxO1/PINK1-mediated mitochondrial autophagy.
Animals ; MicroRNAs/genetics* ; Podocytes/pathology* ; Drugs, Chinese Herbal/pharmacology* ; Autophagy/drug effects* ; Rats, Wistar ; Protein Kinases/metabolism* ; Rats ; Forkhead Box Protein O1 ; Mice ; Mitochondria/drug effects* ; Ubiquitin-Protein Ligases/metabolism* ; Glucose ; Diabetic Nephropathies ; Male ; Membrane Proteins/metabolism* ; Intracellular Signaling Peptides and Proteins

Objective:To understand the baseline viral load (VL) of newly reported HIV- infected patients before antiretroviral therapy and related factors in Tianjin.Methods:Data were obtained from the China Disease Control and Prevention Information System, and the study subjects were HIV-infected patients before the first antiretroviral therapy in Tianjin from 2019 to 2022, and the information about their socio-demographic characteristics, baseline CD4 +T lymphocyte (CD4) counts before antiretroviral therapy and baseline VL test results were collected, the baseline high VL was defined as ≥100 000 copies/ml. The effect of different factors on viral load were analyzed. Software SPSS 24.0 was used for statistical analysis. Results:A total of 1 296 newly reported HIV-infected patients were included in the study, in whom 15.89% (206/1 296) had high baseline VL, and multifactorial logistic regression analysis showed that those with history of STD (a OR=1.45, 95% CI:1.00-2.08) were more likely to have high baseline VL. Compared with those with baseline CD4 counts <200 cells/μl, those with baseline CD4 counts 200-350 cells/μl (a OR=0.40, 95% CI: 0.27-0.57), 351-500 cells/μl (a OR=0.32, 95% CI: 0.20-0.49), and >500 cells/μl (a OR=0.30, 95% CI: 0.18-0.49) were less likely to have high baseline VL. Conclusions:The proportion of HIV-infected patients with high baseline VL before antiretroviral therapy was low in Tianjin during 2019-2022. History of STD and baseline CD4 counts <200 cells/μl were associated with high baseline VL in HIV-infected patients, to which close attention needs to be paid in AIDS prevention and control.

To analyze the factors associated with infection and death of carbapenem-resistant Klebsiella pneumoniae (CRKP) in patients. Using a case-control study method, patients with CRKP infection from January 2019 to December 2021 in the 3201 Hospital were selected as the case group, and patients with carbapenem-susceptible Klebsiella pneumoniae (CSKP) infection in the same period were selected as the control group in a ratio of 1∶1. The study subjects were followed up for 30 days. The two groups of patients were categorized into survival and death groups based on whether they died or not, respectively, and the 30-day morbidity and mortality rates of the CRKP case group and the CSKP control group were compared. The logistic regression model was used to analyze the factors associated with CRKP infection and death after CRKP infection. This study included 59 cases in the CRKP case group and 59 in the CSKP control group. The 30-day mortality rate of CRKP-infected patients and CSKP-infected patients were 30.5% (18/59) and 5.1% (3/59), with statistically significant differences ( P<0.001). Surgery within three months prior to KP infection ( OR=17.285, P=0.001), use of carbapenems within three months prior to KP infection ( OR=11.235, P=0.002), use of more than three types of antibiotics ( OR=7.993, P=0.016), albumin<30 g/L in patients prior to KP infection ( OR=10.463, P=0.002), sex ( OR=0.078, P<0.001), and diabetes ( OR=0.076, P=0.011) were associated factors of CRKP infection. Higher age-corrected Charlson Comorbidity Index scores of patients ( OR=1.522, P=0.024) and use of carbapenems by the patients with in the first three months prior to the KP infection ( OR=4.902, P=0.029) were associated factors for the deaths of patients with CRKP. In conclusion, medical personnel should be cautious in performing invasive procedures, strictly control the use of antibiotics, and provide targeted protection and treatment for high-risk patients as soon as possible.

To analyze the factors associated with infection and death of carbapenem-resistant Klebsiella pneumoniae (CRKP) in patients. Using a case-control study method, patients with CRKP infection from January 2019 to December 2021 in the 3201 Hospital were selected as the case group, and patients with carbapenem-susceptible Klebsiella pneumoniae (CSKP) infection in the same period were selected as the control group in a ratio of 1∶1. The study subjects were followed up for 30 days. The two groups of patients were categorized into survival and death groups based on whether they died or not, respectively, and the 30-day morbidity and mortality rates of the CRKP case group and the CSKP control group were compared. The logistic regression model was used to analyze the factors associated with CRKP infection and death after CRKP infection. This study included 59 cases in the CRKP case group and 59 in the CSKP control group. The 30-day mortality rate of CRKP-infected patients and CSKP-infected patients were 30.5% (18/59) and 5.1% (3/59), with statistically significant differences ( P<0.001). Surgery within three months prior to KP infection ( OR=17.285, P=0.001), use of carbapenems within three months prior to KP infection ( OR=11.235, P=0.002), use of more than three types of antibiotics ( OR=7.993, P=0.016), albumin<30 g/L in patients prior to KP infection ( OR=10.463, P=0.002), sex ( OR=0.078, P<0.001), and diabetes ( OR=0.076, P=0.011) were associated factors of CRKP infection. Higher age-corrected Charlson Comorbidity Index scores of patients ( OR=1.522, P=0.024) and use of carbapenems by the patients with in the first three months prior to the KP infection ( OR=4.902, P=0.029) were associated factors for the deaths of patients with CRKP. In conclusion, medical personnel should be cautious in performing invasive procedures, strictly control the use of antibiotics, and provide targeted protection and treatment for high-risk patients as soon as possible.

Background::Lymph node staging of prostate cancer (PCa) is important for planning and monitoring of treatment. 18F-prostate specific membrane antigen positron emission tomography/computerized tomography ( 18F-PSMA PET/CT) has several advantages over 68Ga-PSMA PET/CT, but its diagnostic value requires further investigation. This meta-analysis focused on establishing the diagnostic utility of 18F-PSMA PET/CT for lymph node staging in medium/high-risk PCa. Methods::We searched the EMBASE, PubMed, Cochrane library, and Web of Science databases from inception to October 1, 2022. Prostate cancer, 18F, lymph node, PSMA, and PET/CT were used as search terms and the language was limited to English. We additionally performed a manual search using the reference lists of key articles. Patients and study characteristics were extracted and the QUADAS-2 tool was employed to evaluate the quality of included studies. Sensitivity, specificity, the positive and negative likelihood ratio (PLR and NLR), diagnostic odds ratio (DOR), area under the curve (AUC), and 95% confidence interval (CI) were used to evaluate the diagnostic value of 18F-PSMA PET/CT. Stata 17 software was employed for calculation and statistical analyses. Results::A total of eight diagnostic tests including 734 individual samples and 6346 lymph nodes were included in this meta-analysis. At the patient level, the results of each consolidated summary were as follows: sensitivity of 0.57 (95% CI 0.39-0.73), specificity of 0.95 (95% CI 0.92-0.97), PLR of 11.2 (95% CI 6.6-19.0), NLR of 0.46 (95% CI 0.31-0.68), DOR of 25 (95% CI 11-54), and AUC of 0.94 (95% CI 0.92-0.96). At the lesion level, the results of each consolidated summary were as follows: sensitivity of 0.40 (95% CI 0.21-0.62), specificity of 0.99 (95% CI 0.95-1.00), PLR of 40.0 (95% CI 9.1-176.3), NLR of 0.61 (95% CI 0.42-0.87), DOR of 66 (95% CI 14-311), and AUC of 0.86 (95% CI 0.83-0.89).Conclusions::18F-PSMA PET/CT showed moderate sensitivity but high specificity in lymph node staging of medium/high-risk PCa. The diagnostic efficacy was almost equivalent to that reported for 68Ga-PSMA PET/CT. Registration::International Prospective Register of Systematic Reviews (PROSPERO), No. CRD42023391101.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

Objective To compare the clinical effects of total hip arthroplasty(THA)with and without femoral osteotomy in Crowe Ⅳ developmental hip dislocation(DDH).Methods The data on 46 patients who underwent THA for unilateral Crowe ⅣDDH between 2012 and 2017 were analyzed retrospectively.They were divided into two groups according to the different surgical methods.There were 24 patients in the osteotomy group,3 males and 21 females,with an average age of(47.3±9.0)years old ranged from 34 to 57 years old;and 22 patients in the non-osteotomy group,2 males and 20 females,with an average age of(51.6±8.3)years old ranged from 40 to 61 years old.The operative time,bleed loss,postoperative drainage volume,postoperative com-plications,ROM of hip,Harris hip score,limb length discrepancy(LLD),and radiological data were recorded.The femoral dislo-cation height and the implantation depth of sleeve were measured.Results All patients were followed up.The mean follow-up time was(3.8±1.2)years ranged from 2 to 6 years in the osteotomy group and(3.2±0.9)years ranged from 1 to 5 years in the non-os-teotomy group.The operative time(136.8±18.9)min,bleed loss(709.8±89.4)ml,postoperative drainage volume(308.8±98.2)ml of osteotomy group were all significantly greater than those of non-osteotomy group(100.7±15.8)min,(516.5±103.3)ml,(245.3±79.3)ml(P＜0.05).The Harris score at the latest follow up was significantly increased compared with preoperative score in two groups(P＜0.05),but there was no significant difference between two groups(P＞0.05).The LLD at last follow up was sig-nificantly increased compared with preoperative LLD in two groups,the LLD in non-osteotomy group(0.7±0.2)cm showed signif-cant smaller than the two osteotomy group(1.2±0.4)cm.Between osteotomy and non-osteotomy groups,the preoperative range of motion of hip joint[(89.5±19.7)°vs(102.5±16.8)°],the preoperative height of dislocation of femoral head[(4.56±0.61)cm vs(3.10±0.73)cm],the proximal implant depth of S-ROM[(0.93±0.36)cm vs(1.67±0.28)cm]was significantly different(P＜0.05).Eleven patients in the osteotomy group still had claudication,and 4 patients in the non-osteotomy group had mild claudica-tion(P＜0.05).In non-osteotomy group,3 patients developed nerve injury(1 patient of sciatic nerve,2 patients of femoral nerve)and 1 case developed periprosthetic fracture.In osteotomy group,2 case of dislocation and 2 cases of periprosthetic fractures.Conclusion Whether osteotomy or not can achieve satisfactory results for treating Crowe type Ⅳ DDH and significantly improve LLD.However,osteotomy is more complex and time-consuming,limb length difference is greater,and the incidence of claudica-tion is higher.Furthermore,patients with smaller preoperative hip mobility,higher femoral dislocation,limb lengthening≥4 cm and severely narrow femoral proximal canals are prone to be peformed with subtrochanteric osteotomy.

Objective To investigate the feasibility of translocation of pedicled buccal fat pad in the treatment of the temporomandibular joint ankylosis(TMJA)by measuring the diameter of buccal fat pad and related anatomical structures of the transverse blood vessels,nerves and temporomandibular joint.Methods A total of 40 adult head and neck specimens were randomly divided into group A and group B,with 20 cases in each group.The morphology of the buccal fat pad in group A was observed,and its size and compression diameter through blood vessels and nerves were measured.The anatomical structures of the temporomandibular joint in group B were observed and measured.Results The volume of buccal fat pad in group A was(10.10±1.10)mL on the left side and(9.70±1.50)mL on the right side.The longitudinal axis length of buccal fat pad was(28.18±1.35)mm on the left side and(29.47±1.12)mm on the right side;Transverse axis length of buccal fat pad was(18.56±1.67)mm on the left side and(18.97±1.73)mm on the right side;There are facial artery,facial vein,maxillary artery branch,facial nerve buccal branch and so on through the buccal fat pad.In group B,the sagittal section of the temporomandibular joint disc presented S-type in 15 cases(75.0%),L-type in 3 cases(15.0%),and transitional type in 2 cases(10.0%).Anterior and posterior diameter of the articular disc was(14.42±1.94)mm on the left side and(15.34±1.37)mm on the right side;inside and outside diameter of the articular disc was(20.18±1.77)mm on the left side and(19.57±1.32)mm on the right side.Branches of maxillary artery and superficial temporal artery were respectively distributed within and outside the joint.Conclusion The pedicled buccal fat pad has a constant anatomical position,abundant blood supply,strong tissue repair,anti-infection ability and"buffer pad"function,which can reduce the formation of scar after surgery for TMJA,reduce the postoperative recurrence rate,and contribute to the recovery of joint function after surgery.