Aim To study the effect of menthol on hypobaric hypoxia-induced pulmonary arterial hypertension and explore the underlying mechanism in mice. Methods 10 to 12 weeks old wild type (WT) mice and TRPM8 gene knockout (TRPM8

ObjectiveTo investigate the effects of Jiaohong pills （JHP） and its prescription， Pericarpium Zanthoxyli （PZ） and Rehmanniae Radix （RR） cognitive dysfunction in scopolamine-induced Alzheimer's disease （AD） mice and its mechanism through pharmacodynamic and metabolomics study. MethodThe animal model of AD induced by scopolamine was established and treated with PZ， RG and JHP， respectively. The effects of JHP and its formulations were investigated by open field test， water maze test， object recognition test， avoidance test， cholinergic system and oxidative stress related biochemical test. Untargeted metabolomics analysis of cerebral cortex was performed by ultra-performance liquid chromatography-Quadrupole/Orbitrap high resolution mass spectrometry （UPLC Q-Exactive Orbitrap MS）. ResultThe behavioral data showed that， compared with the model group， the discrimination indexes of the high dose of JHP， PZ and RR groups was significantly increased （P<0.05）. The staging rate of Morris water maze test in the PZ， RR， high and low dose groups of JHP was significantly increased （P<0.05， P<0.01）， the crossing numbers in the PZ， JHP high and low dose groups were significantly increased （P<0.05， P<0.01）； the number of errors in the avoidance test were significantly reduced in the PZ and high-dose JHP groups （P<0.01）， and the error latencies were significantly increased in the JHP and its prescription drug groups （P<0.01）. Compared with the model group， the activities of acetylcholinesterase in the cerebral cortex of the two doses of JHP group and the PZ group were significantly increased （P<0.05， P<0.01）， and the activity of acetylcholinesterase in the high-dose JHP group was significantly decreased （P<0.05）， and the level of acetylcholine was significantly increased （P<0.01）. At the same time， the contents of malondialdehyde in the serum of the two dose groups of JHP decreased significantly （P<0.05， P<0.01）. The results of metabolomics study of cerebral cortex showed that 149 differential metabolites were identified between the JHP group and the model group， which were involved in neurotransmitter metabolism， energy metabolism， oxidative stress and amino acid metabolism. ConclusionJHP and its prescription can antagonize scopolamine-induced cognitive dysfunction， regulate cholinergic system， and reduce oxidative stress damage. The mechanism of its therapeutic effect on AD is related to the regulation of neurotransmitter， energy， amino acid metabolism， and improvement of oxidative stress.

Objective To analyze the epidemic characteristics of varicella in Chongqing from 2014 to 2020, and to provide evidence for the development of scientific and effective varicella control strategies. Methods Data on the outbreak of varicella and vaccination in Chongqing from 2014 to 2020 were collected through the China Disease Prevention and Control Information System, and descriptive epidemiological methods were used for statistical analysis. Results A total of 181 551 cases of varicella were reported in Chongqing from 2014 to 2020, with an average annual incidence rate of 83.79 per 100 000. The incidence rate of varicella increased from 39.95 per 100 000 in 2014 to 81.88 per 100 000 in 2020 (P < 0.001). The incidence of varicella was seasonal, with the peak periods occurring from May to June and from October to December each year. The average annual incidence rate in municipal districts was 88.90/100 000, higher than 67.42/100 000 in counties and 82.50/100 000 in autonomous counties. The average annual incidence rate of varicella in males (87.13/100 000) was higher than that in females (80.38/100 000). The incidence of varicella was mainly distributed in people under 15 years old, with 143 508 cases (79.10%) reported, and the highest incidence age was 5-9 years old (37.00%). Among the affected occupations , 133 733 cases (62.6%) were students , 39 274 cases (18.40%) were children in nursery care, and 17 963 cases (8.4%) were scattered children. The actual number of doses of varicella vaccine from 2014 to 2020 was 2 302 522 doses, with the coverage rates of one-dose and two-dose vaccines being 75.56% and 32.17%, respectively. ARIMA predicted that there would be 2 604, 811, 756, 1 226, 2 405, 3 904, 2 410, 1 211, 2 034, 6 878, 10 887, and 8 955 cases of varicella from January to December 2021. Conclusion The incidence of varicella in Chongqing is on the rise, with obvious seasonal, regional and population distribution characteristics. It is necessary to strengthen the prevention and control of varicella epidemic, strengthen the prevention and control measures of key groups and key institutions in the high incidence season, strengthen the publicity of varicella vaccine, and improve the vaccination rate of two-doses of varicella vaccine for eligible children.

The outer membrane composed predominantly of lipopolysaccharide (LPS) is an essential biological barrier for most Gram-negative (G^-) bacteria. Lipopolysaccharide transport protein (Lpt) complex LptDE is responsible for the critical final stage of LPS transport and outer membrane assembly. The structure and function of LptDE are highly conserved in most G^- bacteria but absent in mammalian cells, and thus LptDE complex is regarded as an attractive antibacterial target. In recent 10 years, the deciphering of the three-dimensional structure of LptDE protein facilities the drug discovery based on such "non-enzyme" proteins. Murepavadin, a peptidomimetic compound, was reported to be the first compound able to target LptD, enlightening a new class of antibacterial molecules with novel mechanisms of action. This article is devoted to summarize the molecular characteristics, structure-function of LptDE protein complex and review the development of murepavadin and related peptidomimetic compounds, in order to provide references for relevant researches.

Objective:To discuss the distinctive sonographic feature and the biological behavior of renal angiomyolipoma(RAML),and to provide the reference for the clinicians to make the accurate diagnosis of RAML.Methods:The clinical data of one patient with invasive classical RAML combined with pseudaneurysm formation were collected.The sonographic appearances were analyzed in conjunction with the pathological characteristics to clarify the biological behavior of RAML,and the relevant literatures were reviewed.Results:The patient,a 60-year-old female,visited the local hospital due to discomfort in the lumbar area,and received CT examination,and the CT examination results revealed a left renal mass,so the patient came to our hospital.The specialist clinical examinations and laboratory investigations were unremarkable.The ultrasound results indicated an enlarged left kidney with a cystic and solid mass at the upper pole,which featured pseudaneurysm formation(originating from the interlobar arteries);the enhanced CT image results suggested a high probability of upper pole renal carcinoma combined with aneurysmal formation within the tumor,alongside invasion into the left adrenal gland.The patient underwent laparoscopic radical left nephrectomy,and the postoperative pathology confirmed the diagnosis of invasive classical RAML.Conclusion:The classical RAML can exhibit the invasive biological behavior.The pseudaneurysm formation is a special sonographic manifestation of RAML,which can be challenging to differentiate from the other renal tumors.

Objective To establish the methods of galvanic vestibular stimulation-vestibular evoked myogenic potentials(GVS-VEMPs)in healthy children and to obtain the normal value of GVS-cVEMP and GVS-oVEMP in these children in China.Methods Twenty(3～14 years)healthy children and 24 healthy adults(18～30 years)were enrolled for conventional examinations of GVS-cVEMP and GVS-oVEMP.Using the galvanic stimulation in-tensity under 3 mA/1 ms for children and 5 mA/1 ms for adults.The characteristics of elicitation and parameter re-sults of GVS-cVEMP and GVS-oVEMP in children and adults,as well as the pain scores and the elicitation of differ-ent stimulus intensities in the two age groups were recorded.Results The elicitation of GVS-cVEMP and GVS-oVEMP were both 100.0％in children and adult groups.The p1 latency,n1 latency and p1-n1 interval latency of GVS-cVEMP were 10.46±1.84 ms,16.98±2.12 ms and 6.52±1.42 ms respectively in children group,the n1 la-tency and p1-n1 interval latency were significantly shorter than the adult group(P＜0.05).The n1 latency,p1 la-tency and p1-n1 interval latency of GVS-oVEMP were 8.87±1.40 ms,12.25±1.80 ms and 3.39±1.07 ms re-spectively in children group with no significant difference between the two groups.The thresholds of GVS-cVEMP and GVS-oVEMP in children group were significantly lower than adult group(P＜0.01),but no differences were found in adult group regarding on the amplitude and interaural amplitude asymmetry ratio.In addition,with the in-crease of the intensity of galvanic stimulation,the correlation between pain scores and the elicitation rates of GVS-cVEMP and GVS-oVEMP also increased.Conclusion Using appropriate stimulus intensity and recording methods,GVS-cVEMP and GVS-oVEMP could be successfully assessed and detected in healthy children over 3 years old and adolescents.The latency of GVS-cVEMP in children is slightly shorter than that in adults,therefore we recommend selecting the matched age group for assessment in the children group.

BACKGROUND:Cadmium is a common environmental pollutant,which can damage multiple organs and tissues,such as the kidney and bone,but its effect on annulus fibrosus cells in the intervertebral disc has been less reported. OBJECTIVE:To investigate the effect of cadmium chloride on the senescence of annulus fibrosus cells and the role of PI3K/Akt signaling pathway. METHODS:Annulus fibrosus cells from Sprague-Dawley rat intervertebral discs were harvested and passage 3 cells were intervened with different concentrations of cadmium chloride(0,1,5,10,20 μmol/L).Cell viability and proliferation were detected by cell counting kit-8 assay.Transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis were performed on annulus fibrosus cells with or without cadmium chloride addition.Passage 3 annulus fibrosus cells were divided into control group,cadmium chloride group and LY294002 group.Cell proliferation rate was detected by EdU method,positive cell rate was detected by senescence-associated β-galactosidase staining,and expressions of senescence-associated proteins(p16,p21 and p53)and p-Akt at protein and mRNA levels were measured by western blot,RT-PCR and immunofluorescence. RESULTS AND CONCLUSION:5 μmol/L cadmium chloride could inhibit the proliferation of annulus fibrosus cells.Results from the Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis showed that the main signal transduction pathways included PI3K/Akt,cell cycle and p53 signaling pathways,which were related to cell senescence and proliferation.PI3K/Akt signaling pathways with significant differential expression were selected for validation.Compared with the control group,the EdU-positive rate was significantly decreased in the cadmium chloride group(P<0.05),while the β-galactosidase-positive rate,the expression of senescence-associated proteins(p16,p21 and p53)and p-Akt significantly increased(P<0.05).Compared with the cadmium chloride group,the EdU-positive rate and p-Akt expression were significantly decreased in the LY294002 group(P<0.05),while the β-galactosidase-positive rate and the expression of senescence-associated proteins(p16,p21 and p53)significantly increased(P<0.05).To conclude,cadmium chloride can regulate the senescence of annulus fibrosus cells by activating the PI3K/Akt signaling pathway,thereby inducing the occurrence and progression of intervertebral disc degeneration.

Objective To explore the application effect of new improved 3D printing individualized guidance(3D psi)in total knee arthroplasty(TKA)for knee osteoarthritis(KOA).Methods A total of 100 patients with KOA in 920th Hospital of Joint Logistics Support Force,PLA from January 2021 to January 2022 were selected,and were divided into 2 groups of 50 patients each using the randomized numerical table method.The control group was treated with conventional TKA,and the study group was treated with new improved 3D psi assisted TKA.The operation conditions,postoperative rehabilitation,complications,prosthesis component position deviation,knee range of motion(ROM),lower limb force line parameters[coronal distal femoral mechanical axis lateral angle(mldfa),lower limb mechanical axis angle(HKA)],gait parameters(percentage of support time,stride,pace),knee function(HSS score),quality of life(AIMS2 score)were observed.Results Com-pared with control group,the amount of intraoperative and postoperative blood loss and drainage volume 2 days after operation were less in the study group,and the operation time and hospital stay were shorter(P<0.05).The deviations of LTC Angle,FFC Angle,HKA Angle,LFC Angle and FTC Angle in the study group were smaller than those in the control group(P<0.05).At 3 months,6 months and 12 months after surgery,the percentage of knee ROM,supporting time,stride length and walking speed of the research group were higher than those of the control group,while the coronal-position mLDFA and HKA were lower than those of the control group(P<0.05).The proportion of WBC and PMN in joint fluid at 3 months,6 months and 12 months after surgery was lower than that in control group(P<0.05).The HSS score of the study group was higher than that of the control group at 3 months,6 months and 12 months after operation,and the AIMS2 score was lower than that of the control group(P<0.05).There was no statistically significant difference in the incidence of complications between the study group and the control group(P>0.05).Conclusion The new improved 3D PSI-assisted TKA treatment of KOA can optimize the surgical situation,improve operating accuracy,improve the patient's lower limb alignment,promote limb function recovery,help improve the quality of life,and has high safety.

ObjectiveAlthough expression of the TEAD1 protein in preadipocytes has been established, its function remains unclear. In this study, we sought to detect transcripts of TEAD1 in chicken and to examine the effects of this protein on the proliferation, migration, apoptosis, and differentiation of immortalized chicken preadipocyte cell lines (ICP1). MethodsThe full-length sequence of the TEAD1 gene was cloned and the two transcripts were subjected to bioinformatics analysis. The subcellsular localization of TEAD1 transcripts was determined based on indirect immunofluorescence. The effects of TEAD1 transcripts overexpression on the proliferation of ICP1 cells were examined by RT-qPCR, CCK-8, and EdU assays; the effects of TEAD1 transcripts on ICP1 cells migration were examined based on the scratch test; and the effects of TEAD1 transcripts overexpression on ICP1 cells apoptosis were analyzed using apoptosis-Hoechst staining and RT-qPCR. The expression of TEAD1 transcripts in different tissues, cells lines, and ICP1 at different periods of differentiation was analyzed by RT-qPCR. The effects of TEAD1 transcripts overexpression on lipid droplet accumulation and adipogenic-related gene expression in ICP1 cells were analyzed based on Oil Red O and BODIPY staining, RT-qPCR, Western blot, and dual-luciferase reporter gene assays. Finally, the content of triglyceride (TG) was measured in TEAD1 overexpressed ICP1 cells. ResultsThe full-length TEAD1 was cloned and two TEAD1 transcripts were identified. The TEAD1-V1 protein was found to be localized primarily in the cell nucleus, whereas the TEAD1-V2 protein is localized in the cell cytoplasm and nucleus. The overexpression of both TEAD1-V1 and TEAD1-V2 significantly inhibited the proliferation of ICP1 cells. Whereas the overexpression of TEAD1-V1 promoted ICP1 cell migration, the overexpression of TEAD1-V2 had no significant effects on ICP1 migration; the overexpression of both TEAD1-V1 and TEAD1-V2 significantly promoted the apoptosis of ICP1 cells. We found that the different transcripts of TEAD1 have similar expression pattern in different tissues and cells lines. During induced preadipocyte differentiation, the expression of these genes initially declined, although subsequently increased. Overexpression of TEAD1-V1 promoted a significant reduction in lipid droplet formation and inhibited C/EBPα expression during the differentiation of ICP1 cells (P<0.05). However, the overexpression of TEAD1-V2 had no significant effect on lipid droplet accumulation or the expression of adipogenic-related proteins (P>0.05). Overexpression of TEAD1-V1 significantly decreased triglyceride content in ICP1 cells (P<0.05), while overexpression of TEAD1-V2 had no effect on triglyceride content in ICP1 cells (P>0.05). ConclusionIn this study, for the first time, identified two TEAD1 transcripts. Overexpressed transcripts TEAD1-V1 and TEAD1-V2 both inhibited the proliferation of chicken preadipocytes and promoted apoptosis of chicken preadipocytes. TEAD1-V1 inhibited the differentiation of preadipocytes and promoted the migration of preadipocytes, while TEAD1-V2 had no effect on the differentiation and migration of preadipocytes.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.