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Lei Gao,1,2 Ruo-Wen Chen,2 John P Williams,3 Tong Li,4 Wei-Jiang Han,5 Qian-Nan Zhao,2 Yong Wang,2 Jian-Xiong An1,2 1Department of Anesthesiology, Weifang Medical University, Weifang City 261000, Shangdong, People’s Republic of China; 2Department of Anesthesiology, Pain and Sleep Medicine, Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine, Chinese Academy of Sciences, Beijing, 100012, People’s Republic of China; 3Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; 4Department of Pain, Lanzhou Maternity and Child Healthcare Hospital, Lanzhou, 730030, People’s Republic of China; 5Department of Pain, Xishuangbanna Dai Nationality Autonomous Prefecture People’s Hospital, Xishuangbanna, 666100, People’s Republic of ChinaCorrespondence: Jian-Xiong AnDepartment of Anesthesiology, Pain and Sleep Medicine, Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine, Chinese Academy of Sciences, Beiyuan Road 3, Beijing 100012, People’s Republic of ChinaTel +86 138 0128 1750Fax +86 10 5952 0393Email anjianxiong@yeah.netBackground: Ozone injection around Gasserian ganglion (OIAGG) has been reported to be an effective treatment for trigeminal neuralgia (TN); however, there remain areas for improvement. To overcome one of these limitations, a multicenter examination of application would be extremely helpful.Objective: The goal of this report was to assess the efficacy of OIAGG for refractory TN across multiple centers and to explore factors predictive of successful treatment.Design: A multicenter, retrospective study.Setting: The study was conducted across 3 pain centers across China.Patients and Methods: A total of 103 subjects from 3 pain centers were enrolled in the study. An ozone-oxygen mixture gas at a concentration of 30 μg/mL was injected into the area around the Gasserian ganglion performed under C-arm X-ray guidance. Primary outcome measures included a pain assessment using a visual analog scale (VAS) and the Barrow Neurological Institute (BNI) pain intensity scale. Clinical assessment of patients for these outcome measures was performed at pretreatment, post-treatment, 6 months, 1 year and 2 years after the OIAGG.Results: Successful pain relief was defined as a score within BNI grades I–IIIa. The pain relief rates at post-treatment, 6 months, 1 year and 2 years after the procedure were 88.35%, 86.87%, 84.46% and 83.30%, respectively. The VAS at each observation time point was significantly different from the preoperative levels (P< 0.05). Logistic regression analysis showed that previous nerve damage had a significant effect on the treatment results. No significant complications or side effects were found during or after treatment.Conclusion: This multicenter research confirms our previous single center results that OIAGG is both effective and safe for patients with TN.Keywords: trigeminal neuralgia, trigeminal post-herpetic neuralgia, ozone therapy, Gasserian ganglion

Patients with tissue inflammation or injury often experience aberrant mechanical pain hypersensitivity, one of leading symptoms in clinic. Despite this, the molecular mechanisms underlying mechanical distortion are poorly understood. Canonical transient receptor potential (TRPC) channels confer sensitivity to mechanical stimulation. TRPC3 and TRPC6 proteins, coassembling as heterotetrameric channels, are highly expressed in sensory neurons. However, how these channels mediate mechanical pain hypersensitivity has remained elusive. It is shown that in mice and human, TRPC3 and TRPC6 are upregulated in DRG and spinal dorsal horn under pathological states. Double knockout of TRPC3/6 blunts mechanical pain hypersensitivity, largely by decreasing nociceptor hyperexcitability and spinal synaptic potentiation via presynaptic mechanism. In corroboration with this, nociceptor-specific ablation of TRPC3/6 produces comparable pain relief. Mechanistic analysis reveals that upon peripheral inflammation, TRPC3/6 in primary sensory neurons get recruited via released bradykinin acting on B1/B2 receptors, facilitating BDNF secretion from spinal nociceptor terminals, which in turn potentiates synaptic transmission through TRPC3/6 and eventually results in mechanical pain hypersensitivity. Antagonizing TRPC3/6 in DRG relieves mechanical pain hypersensitivity in mice and nociceptor hyperexcitability in human. Thus, TRPC3/6 in nociceptors is crucially involved in pain plasticity and constitutes a promising therapeutic target against mechanical pain hypersensitivity with minor side effects., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Recent labor market transformations brought on by digital and technological advances, together with the rise of the service economy since the 1980s, have subjected more workers to precarious conditions, such as irregular work hours and low or unpredictable wages, threatening their economic well-being and health. This study advances our understanding of the critical role employment plays in our health by examining how employment patterns throughout our working lives, based on work schedules, may shape our health at age 50, paying particular attention to the moderating role of social position. The National Longitudinal Survey of Youth-1979 (NLSY79), which has collected 30+ years of longitudinal information, was used to examine how employment patterns starting at ages 22 (n ≈ 7,336) might be associated with sleep hours and quality, physical and mental functions, and the likelihood of reporting poor health and depressive symptoms at age 50. Sequence analysis found five dominant employment patterns between ages 22 and 49: "mostly not working" (10%), "early standard hours before transitioning into mostly variable hours" (12%), "early standard hours before transitioning into volatile schedules" (early ST-volatile, 17%), "mostly standard hours with some variable hours" (35%), and "stable standard hours" (26%). The multiple regression analyses indicate that having the "early ST-volatile" schedule pattern between ages 22 and 49 was consistently, significantly associated with the poorest health, including the fewest hours of sleep per day, the lowest sleep quality, the lowest physical and mental functions, and the highest likelihood of reporting poor health and depressive symptoms at age 50. In addition, social position plays a significant role in these adverse health consequences. For example, whereas non-Hispanic White women reported the most hours of sleep and non-Hispanic Black men reported the fewest, the opposite was true for sleep quality. In addition, non-Hispanic Black men with less than a high school education had the highest likelihood of reporting poor health at age 50 if they engaged in an employment pattern of "early ST-volatile" between ages 22 and 49. In comparison, non-Hispanic White men with a college degree or above education had the lowest likelihood of reporting poor health if they engaged in an employment pattern of stable standard hours. This analysis underscores the critical role of employment patterns in shaping our daily routines, which matter to sleep and physical and mental health as we approach middle adulthood. Notably, the groups with relatively disadvantaged social positions are also likely to be subject to nonstandard work schedules, including non-Hispanic Blacks and people with low education; hence, they were more likely than others to shoulder the harmful links between nonstandard work schedules and sleep and health, worsening their probability of maintaining and nurturing their health as they approach middle adulthood., Competing Interests: The author has declared that no competing interests exist., (Copyright: © 2024 Wen-Jui Han. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To evaluate the efficacy of Dongbai Tonglin Mixture (DTM) in the treatment of chronic prostatitis (CP) with the damp-heat downward diffusion syndrome., Methods: We randomly selected 76 cases of CP with the damp-heat downward diffusion syndrome, equally divided them into a DTM and a control group, and treated them by oral administration of DTM and Qianlie Tai Tablets, respectively, both for 8 weeks. We obtained the NIH-CPSI and TCM Syndrome Scores of the patients, recorded the counts of white blood cells (WBC) and small particles of lecithin (SPL) in the prostate fluid, and compared them between the two groups before and after treatment., Results: Compared with the baseline, the total NIH-CPSI scores were significantly reduced in both groups after treatment (P<0.05), particularly the scores on urination symptoms, pain / discomfort and quality of life (P<0.05), even more significantly in the DTM than in the control group (P<0.05), and so were the TCM Syndrome Scores (P<0.05), especially the scores on urinary incontinence, abdominal pain, perineal pain, and scrotal dampness (P<0.05), even more significantly in the former than in the latter group (P<0.05). The count of WBC in the prostate fluid was remarkably decreased (P<0.05), while that of SPL markedly increased in both groups after treatment (P<0.05), with an even more significant improvement in the DTM than in the control group (P<0.05), and the overall effectiveness rate of treatment was significantly higher in the former group than in the latter (88.89% vs 70.27%, P<0.05)., Conclusion: Dongbai Tonglin Mixture is effective for the treatment of CP with the damp-heat downward diffusion syndrome.

The colloidal borescope, using colloidal particle motion, is used to monitor the flow velocities and directions of groundwater. It integrates advanced techniques such as microscopy, high-speed photography, and big data computing and enjoys high sensitivity at the micron level. However, In the same well, the groundwater flow velocity monitored by colloidal hole mirror is varies greatly from that obtained by conventional hydrogeological monitoring, such as pumping test. In order to solve this problem, the stability catcher and stratified packer are designed to control the interference of the vertical flow in drilling, and to monitor the flow velocity and direction of groundwater velocity at the target aquifer and target fracture. Five wells with different aquifers and different groundwater types were selected for monitoring in south-central China. The instantaneous velocity and direction are converted into east-west component and north-south component, the average velocity and direction is calculated according to the time of 10 min, and the particle trajectory diagram is established. Based on these results, it proposed a concept of cumulative flow velocity. Using curve-fitting equations, the limits of cumulative flow velocities as the monitoring time tends to infinity were then calculated as the actual flow velocities of the groundwater. The permeability coefficient of aquifer is calculated by using the fissure ratio of aquifer, hydraulic slope and flow velocity, and compared with the permeability coefficient obtained by pumping test. The results are as follows: (1) The variation coefficient of the instantaneous flow velocity measured at the same depth in the same well at different times is greater than that of the time average flow velocity and greater than that of the cumulative flow velocity. The variation coefficient of the actual velocity is the smallest, indicating that the risk of using the actual flow velocity is lower. (2) The variation coefficient of the flow rate monitored at different depths in the same well is mainly controlled by the properties of the aquifer. The more uniform water storage space in the aquifer, the smaller the variation coefficient. (3) The comparison between the permeability coefficient obtained by monitoring and the permeability coefficient obtained by pumping test shows that the flow of structural fissure water controlled by planar fissure is more surface flow, and the results are consistent. When the groundwater flow is controlled by pores and solution gaps, the flow channel is complicated, which is easy to produce turbulent flow, and the result consistency is poor. (4) According to different research accuracy requirements, different monitoring and calculation methods can be selected for different aquifers and groundwater types. Researches show that, the permeability coefficient calculated for the actual flow velocity in well DR01 is the same as that calculated for the pumping test. The aquifer characteristics reflected by the coefficient of variation of the actual flow velocity in the same aquifer are more realistic. The pumping test method obtains the comprehensive parameters of a certain aquifer, and this method can be used to monitor a certain fissure. In this paper, the new technology developed for monitoring, and the new algorithm established for data processing, can accurately obtain the flow velocity and direction of groundwater, using capsule hole mirror monitoring method. The key parameters of hydrogeology can be obtained by using one well, which can reduce the time and cost input and improve the work efficiency., (© 2024. The Author(s).)

Aim: To explore whether and to what extent, nurse-patient assessment differences mediate the association between nurse-to-patient ratios and readiness for hospital discharge, and examine whether nurse-patient characteristics moderate the indirect and/or direct effect of mediation model., Design: A cross-sectional study was carried out from March 2021 to December 2022., Methods: A total of 523 pairs of gastrointestinal cancer patients with PICC and their nurses were recruited. All the participants were invited to complete the general information questionnaire and the Readiness for Hospital Discharge Scale. Outcome measure was patient-reported readiness for hospital discharge. This study was reported according to the STROBE checklist., Results: The patients reported a low level of readiness for hospital discharge. Nurse-patient assessment differences were positively associated with nurse-to-patient ratios but negatively associated with readiness for hospital discharge. Furthermore, nurse-patient assessment differences fully mediated the effect of nurse-to-patient ratios on readiness for hospital discharge, and age and gender of patients only moderated the indirect path of mediation model., (© 2023 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

Whole-brain genome editing to correct single-base mutations and reduce or reverse behavioral changes in animal models of autism spectrum disorder (ASD) has not yet been achieved. We developed an apolipoprotein B messenger RNA-editing enzyme, catalytic polypeptide-embedded cytosine base editor (AeCBE) system for converting C·G to T·A base pairs. We demonstrate its effectiveness by targeting AeCBE to an ASD-associated mutation of the MEF2C gene (c.104T>C, p.L35P) in vivo in mice. We first constructed Mef2cL35P heterozygous mice. Male heterozygous mice exhibited hyperactivity, repetitive behavior and social abnormalities. We then programmed AeCBE to edit the mutated C·G base pairs of Mef2c in the mouse brain through the intravenous injection of blood-brain barrier-crossing adeno-associated virus. This treatment successfully restored Mef2c protein levels in several brain regions and reversed the behavioral abnormalities in Mef2c-mutant mice. Our work presents an in vivo base-editing paradigm that could potentially correct single-base genetic mutations in the brain., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

A metal-free and efficient approach for the synthesis of structurally important nicotinates through 4-HO-TEMPO-mediated [3 + 3] annulation of cyclopropanols with β-enamine esters is presented. This protocol features high atom efficiency, green waste, simple operation and broad substrate scope. Moreover, the experiments of gram-scale synthesis and recovery of oxidants make this strategy more sustainable and practical.

Purpose: Lung squamous cell carcinoma (LUSC) is an aggressive subset of non-small-cell lung cancer (NSCLC). The tumor microenvironment (TME) plays an important role in the development of LUSC. We aim to identify potential therapeutic targets and a TME-related prognostic signature and for LUSC., Methods: TME-related genes were obtained from TCGA-LUSC dataset. LUSC samples were clustered by the non-negative matrix clustering algorithm (NMF). The prognostic signature was constructed through univariate Cox regression, multivariate Cox regression, and the least absolute shrinkage and selection operator (LASSO) analyses. Gene set enrichment analysis (GSEA) was carried out to explore the enrichment pathways., Results: This study constructed a prognostic signature which contained 12 genes: HHIPL2, PLK4, SLC6A4, LSM1, TSLP, P4HA1, AMH, CLDN5, NRTN, CDH2, PTGIS, and STX1A. Patients were classified into high-risk and low-risk groups according to the median risk score of this signature. Compared with low-risk group patients, patients in high-risk group patients had poorer overall survival, which demonstrated this signature was an independent prognostic factor. Besides, correlation analysis and GSEA results revealed that genes of this signature were correlated with immune cells and drug response., Conclusion: Our novel signature based on 12 TME-related genes might be applied as an independent prognostic indicator. Importantly, the signature could be a promising biomarker and accurately predict the prognosis of LUSC patients., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To explore the diagnosis, surgical management and outcome of jugular foramen chondrosarcoma (CSA). Methods: Fifteen patients with jugular foramen CSA hospitalized in the Department of Otorhinolaryngology Head and Neck Surgery of Chinese PLA General Hospital from December 2002 to February 2020 were retrospectively collected,of whom 2 were male and 13 were female, aging from 22 to 61 years old. The clinical symptoms and signs, imaging features, differential diagnosis, surgical approaches, function of facial nerve and cranial nerves IX to XII, and surgical outcomes were analyzed. Results: Patients with jugular foramen CSA mainly presented with facial paralysis, hearing loss, hoarseness, cough, tinnitus and local mass. Computed tomography (CT) and magnetic resonance (MR) could provide important information for diagnosis. CT showed irregular destruction on bone margin of the jugular foramen. MR demonstrated iso or hypointense on T1WI, hyperintense on T2WI and heterogeneous contrast-enhancement. Surgical approaches were chosen upon the sizes and scopes of the tumors. Inferior temporal fossa A approach was adopted in 12 cases, inferior temporal fossa B approach in 2 cases and mastoid combined parotid approach in 1 case. Five patients with facial nerve involved received great auricular nerve graft. The House Brackmann (H-B) grading scale was used to evaluate the facial nerve function. Preoperative facial nerve function ranked grade Ⅴ in 4 cases and grade Ⅵ in 1 case. Postoperative facial nerve function improved to grade Ⅲ in 2 cases and grade Ⅵ in 3 cases. Five patients presented with cranial nerves Ⅸ and Ⅹ palsies. Hoarseness and cough of 2 cases improved after operation, while the other 3 cases did not. All the patients were diagnosed CSA by histopathology and immunohistochemistry, with immunohistochemical staining showing vimentin and S-100 positive, but cytokeratin negative in tumor cells. All patients survived during 28 to 234 months' follow-up. Two patients suffered from tumor recurrence 7 years after surgery and received revision surgery. No complications such as cerebrospinal fluid leakage and intracranial infection occurred after operation. Conclusions: Jugular foramen CSA lacks characteristic symptoms or signs. Imaging is helpful to differential diagnosis. Surgery is the primary treatment of jugular foramen CSA. Patients with facial paralysis should receive surgery in time as to restore the facial nerve. Long-term follow-up is necessary after surgery in case of recurrence.

Objective: This study compared the clinical usefulness of structured reports (SRs) and free-text reports (FTRs) of lesions depicted on cone beam computed tomography (CBCT) images from the perspectives of report providers and receivers., Study Design: In total, 36 CBCT images of jaw lesions obtained between February 2020 and August 2020 were evaluated. A working group of 3 oral and maxillofacial radiologists (OMRs) established a reporting system and prepared reports. Evaluation group I (2 OMRs) wrote SRs and FTRs for each case and assessed the reporting process for the criteria of convenience and organization. Evaluation group II (3 general practitioners [GPs] and 3 oral and maxillofacial surgeons [OMSs]) assessed the reports for the criteria of productivity, consistency, and organization. A 5-point Likert scale was used to assess the usefulness of each report. Scores were statistically compared according to report type with the paired Wilcoxon signed-rank test., Results: The SRs scored significantly higher for all criteria as assessed by evaluation group I and the GPs of group II (P < .001). The FTRs scored significantly higher for productivity and organization as assessed by the OMSs of group II (P = .005 for both criteria)., Conclusions: The clinical usefulness of reports may differ according to roles of the report recipients in diagnosis and treatment., (Copyright © 2022 Elsevier Inc. All rights reserved.)

We report a templated reaction for the facile translation of nucleic acid cues into signals of universal rhodamine derivatives based on the riboflavin-catalyzed oxidation of dihydrorhodamine compounds. The rhodamine-signaling operation enabled us to design a highly sequence-selective fluorescent sensor that can detect as little as 500 pM of the target nucleic acid in 90 min or to present a rhodamine antibody that can be further applied to immunoassays.

The inflammasome is a multiprotein oligomer in the cell cytoplasm and is part of the innate immune system. It plays a crucial role in the pathological process of noise-induced hearing loss (NIHL). However, the mechanisms of NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in NIHL have not been clearly demonstrated. In this study, miniature pigs were exposed to white noise at 120 dB(A) and auditory brainstem response measurements were used to measure their hearing function. Immunofluorescence staining, confocal laser scanning microscopy, western blot assay, and quantitative reverse transcription-polymerase chain reaction were used to analyze inflammasome-related protein distribution and expression. NLRP3, interleukin-1β, interleukin-18, and cleaved-caspase-1 were highly expressed in the cochlea after 120 dB(A) white noise exposure. Our findings suggest that NLRP3-inflammasomes in the cochlea may be activated after acoustic trauma, which may be an important mechanism of noise-induced hearing loss., Competing Interests: None

Objective: To observe the effect of electroacupuncture (EA) at "Ciliao" (BL 32) and "Huiyang" (BL 35) on the pain, urodynamic and the expressions of transient receptor poteintial vanilloid 1 (TRPV1) and P2X3 receptors in bladder of rats with interstitial bladder (IC), and to explore the possible mechanism on EA for IC., Methods: A total of 24 Wistar female rats were randomly divided into a blank group, a model group and an EA group, 8 rats in each group. In the model group and the EA group, IC model was established by intraperitoneal injection of cyclophosphamide by 150 mg/kg at once. EA was applied at "Ciliao" (BL 32) and "Huiyang" (BL 35) in the EA group for 20 min, with continuous wave, 30 Hz in frequency, once a day for 3 consecutive days. Mechanical pain threshold of bladder and urodynamic indexes (first urination time, bladder effective volume and urination pressure) were observed after model establishment and after intervention, the expressions of TRPV1 and P2X3 receptors in the bladder were detected by Western blot., Results: After model establishment, the mechanical pain threshold of bladder was decreased in the model group and the EA group compared with that in the blank group ( P <0.01). After intervention, the mechanical pain threshold of bladder in the model group was lower than the blank group ( P <0.01), and that in the EA group was higher than the model group ( P <0.01). The urodynamic of the rats in the blank group was normal, obvious abnormal contraction during the filling period of bladder was found in the rats of the model group, while no abnormal contraction during the filling period was found in the rats of the EA group. After model establishment, in the model group and the EA group, the first urination time was earlier than the blank group ( P <0.01), while bladder effective volume and urination pressure were lower than the blank group ( P <0.01). After intervention, in the model group, the first urination time was earlier than the blank group ( P <0.01), while bladder effective volume and urination pressure were lower than the blank group ( P <0.05); in the EA group, the first urination time was later than the model group ( P <0.05), while bladder effective volume and urination pressure were higher than the model group ( P <0.05). Compared with the blank group, the protein expressions of TRPV1 and P2X3 receptors in bladder were up-regulated in the model group ( P <0.01); compared with the model group, the protein expressions of TRPV1 and P2X3 receptors in bladder were down-regulated in the EA group ( P <0.05)., Conclusion: EA can relieve bladder pain and improve urodynamic in IC rats. The mechanism may be related to the down-regulation on the expressions of TRPV1 and P2X3 receptors and the further inhibition on the abnormal input of bladder signal.

Objective: As labor markets have become increasingly volatile and precarious since 1980s, more workers are susceptible to working conditions such as unpredictable and unstable hours, threatening their economic security. However, our understanding of employment patterns regarding the changes in work schedules over our working lives has yet been established. This study builds our knowledge in this area by paying attention to how social positions may shape the specific work schedule patterns over our working lives., Methods: We used the National Longitudinal Survey of Youth-1979 (NLSY79) to examine our research questions. NLSY79 follows a nationally representative sample of United States men and women between the ages of 14 and 22 when first interviewed in 1979. The participants were then interviewed annually until 1994 and then biennially thereafter. We first conducted a sequence analysis to examine work schedule patterns between ages 22 and 53 ( n = 7987). We then used a multinomial logit regression to examine the factors contributing to specific work schedule patterns, with attention to social position., Results: Our sequence analysis results suggest five work schedule patterns during 31 years of adult life: working only standard hours (25%), mainly standard hours with some portions of nonstandard hours (38%), standard hours during early working years but transitioning to either largely variable or mainly evening or night hours (14% and 13%), and mostly not working (10%). Our multinomial logit analysis indicates that being non-Hispanic Black, having a high school degree or below, or having ever experienced poverty or welfare by age 23 were more likely to have a nonstandard work schedule pattern than their counterparts., Conclusions: Our analysis underscores the dynamic employment patterns over our working lives, with some groups more likely than others to be engaged in nonstandard or volatile work schedules. Importantly, the groups likely to be subject to nonstandard work schedules also tend to have relatively disadvantaged social positions, thus worsening their vulnerability in securing work characterized by stability and economic security.

Background: The human leukocyte antigen (HLA) susceptibility gene is the main genetic risk factor for primary biliary cholangitis (PBC). The prognosis of patients with PBC is linked to gut microbiota dysbiosis. However, whether the HLA alleles are associated with the gut microbiota distribution and disease severity remains unknown., Methods: A cohort of 964 Chinese patients with PBC was enrolled at Beijing YouAn Hospital, Beijing, China. High-resolution genotyping of the HLA class I and class II loci from 151 of these patients was performed using sequence-based PCR. Stool samples were collected from 43 of the 151 fully HLA-typed patients to analyze their microbiota compositions via 16S RNA gene sequencing., Results: Of the 964 patients, the male:female ratio was 114:850, and 342 of these patients (35.5%) had already developed liver cirrhosis (LC) before enrollment. Patients with PBC showed a significantly higher frequency of HLA DRB1*08:03 than did the controls (21.2% vs. 9.0%, P =0.0001). HLA- DRB1*03:01 , DRB1*07:01 , DRB1*14:05 , and DRB1*14:54 frequencies were also increased but did not reach significance after Bonferroni's correction. Conversely, the DQB1*03:01 frequency was significantly lower in patients with PBC than in the controls (24.5% vs. 39.2%, P =0.0010). The patients' gut microbiota were analyzed from four perspectives. The microbial community abundances were significantly lower in FHRAC-positive patients (patients with a combination of five HLA DRB1 high-risk alleles) than in FHRAC-negative patients ( P <0.05). Of the top 10 microbial genera, Lachnospiraceae&#95;incertae&#95;sedis was higher in the FHRAC-positive patients than in the FHRAC-negative patients ( P <0.05). linear discriminant analysis (LDA) effect-size (LEfSe) analysis showed different microbes at different levels in the FHRAC-negative patients but not in the FHRAC-positive patients. DQB1*03:01 -positive patients contained mostly Lactobacillaceae at the family level. A comparison of the FHRAC-positive patients with and without liver cirrhosis showed that the abundances of Veillonella were significantly higher in patients with cirrhosis and FHRAC than in those without cirrhosis and are FHRAC-negative., Conclusion: The HLA class II genes may influence the gut microbiota compositions in patients with PBC. Differential gut microbiota were expressed at different taxonomic levels. Some bacterial abundances may be increased in FHRAC-positive patients with PBC and cirrhosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer JJ declared a shared parent affiliation with the authors C-YH, H-PZ, D-TZ, H-YL, Y-XM, BX, L-JL, YH, X-HL, QW, J-LL, X-DZ, JZ, W-JL, Y-ML, and H-PY to the handling editor at the time of review., (Copyright © 2022 Huang, Zhang, Han, Zhao, Liao, Ma, Xu, Li, Han, Liu, Wang, Lou, Zhang, Zhao, Li, Liu and Yan.)

STIP1 Homology and U-Box Containing Protein 1 (STUB1), a ubiquitin E3 ligase initially involved in immune responses, has recently emerged as a pleiotropic regulator of different biological systems, including skeletal and male reproduction systems. On the latter, a homozygous mutation in the STUB1 gene has been identified in patients with hypogonadism. However, the pattern of expression and biological actions of STUB1 in testis remains so far unexplored. Herein, we report analyses on the testicular expression of STUB1 in human testes with impaired spermatogenesis and paracrine regulation of STUB1 expression in mouse testis development and the direct effects of ablation STUB1 on Sertoli cell (SC) functions. STUB1 was expressed abundantly in pachytene spermatocytes and SCs, and weakly in spermatogonia and differentiating spermatids in normal human testis. In contrast, Sertoli-specific expression of STUB1 was significantly decreased in the human testes with impaired spermatogenesis. Throughout postnatal development of mouse testis, however, STUB1 was expressed exclusively in the nuclei of the functionally mature SCs. The adjacent germ cell (GC)-derived IL-1α overtly regulated STUB1 expression through promoting the ETS domain transcription factor Elk-1 (ELK1)-mediated transactivation. Importantly, ablation of endogenous STUB1 caused lipid accumulation and senescence in GC co-incubated SCs. Together with previous reports on the stimulatory effects of IL-1α on cell senescence, our findings suggest that STUB1 may serve as an important negative feedback signaling to modulate the magnitude of GCs-derived IL-1α, which is normally maintained at low levels within testis.

A challenging but critical question is that new foot-and-mouth disease (FMD) vaccines should be to induce B cell memory to provide antibodies for long-term protection. The maintenance of B cell memory is dependent on long-lived plasma cells (LLPCs) and memory B cells. We developed a chimeric FMDV virus-like particles (FMDV-VLPs), fusing VP1-VP4 into HBcAg. In our study, we investigated if or how long B cell memory was induced by FMDV-VLPs in mice. The data showed that FMDV-VLPs can induce memory humoral responses with a high level of total IgG1, IgG2a, IgA, and FMDV-specific IgG antibodies in serum. The persistence of antibody levels in serum could depend on LLPCs. The proportion of LLPCs in CD19 + cells in bone marrow exhibited a dynamic trend with two peaks at 28 days post-immunization (dpi) and 72 dpi, respectively. Additionally, the proportion of memory B cells in CD19 + cells in the spleen increased significantly both at 7 days post primary immunization and at 7 days post -boost immunization. Of note, LLPCs together with memory B cells contribute to the production of FMDV-specific IgG and IgG1. The changes of LLPCs and memory B cells may be related to TNF-α, IL-6 and, CXCL12. Taken together, FMDV-VLPs could induce B cells memory responses. A further understanding of the mechanisms that FMDV-VLPs how we can manipulate the induction and maintenance of memory B cells and LLPCs will promote vaccine design and likely address several challenges to develop FMDV new vaccines in the future., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Since the mid-1990s, information technology, particularly the diffusion of the internet, has brought tremendous changes to communication and social participation for people in China, including older adults. At the same time, modernisation and urbanisation have transformed the way many people in China live. The traditional multigenerational household-older adults living with adult children and grandchildren-is giving way to other living arrangements, such as living alone or with a spouse only. Using wave 1 of the World Health Organization Study on Global AGEing and Adult Health collected between 2007 and 2010, we examined the extent to which home internet access might be associated with cognitive function in older adults aged 50 or over in urban China (N = 5,898), paying attention to the moderating role of living arrangements. We found that home internet access was associated with better cognitive function, and living arrangements played an essential role in such an association for different age groups. Specifically, older adults living alone benefited cognitively from internet access, particularly among those aged 50-64 and 65-74. Those living with a spouse only and those in two-generation households benefited cognitively from internet access, particularly among those aged 50-64 and 75+. Older adults age 75+ in skip-generation households benefited cognitively from internet access. Considering the trend of older adults living apart from their children, our research suggests that providing internet access to older adults in urban China, especially those living alone, could help protect their cognitive function., (© 2021 John Wiley & Sons Ltd.)

Tumor necrosis factor-α-induced protein-8 like-2 (TIPE2) as a novel negative immune regulator plays an important role in several human diseases. However, its influences in cervical cancer and preeclampsia (PE) remain unclear. This study aims to explore the important role of TIPE2 in cervical cancer and PE via regulating cell invasion. TIPE2 expression in the cervical cancer tissues or the placenta of PE patients was detected. Human cervical cancer cell lines and trophoblasts were transfected with adenovirus expressing human TIPE2 and green fluorescent protein (GFP) (Ad-TIPE2), or the control adenovirus expressing GFP (Ad-GFP). Xenograft models were also constructed on nude mice, aiming to clarify how TIPE2 affects in vivo growth of cervical cancer cells. TIPE2 was down-regulated in the tumor tissues or placenta of patients with cervical cancer or PE. As a result, CaSKi and Hela cells in the Ad-TIPE2 group had decreased migration and invasion, with significant up-regulations of TIPE2 and E-cadherin, but down-regulations of β-catenin and N-cadherin. Ad-TIPE2 decreased the volume and weight of xenograft tumors in the nude mice, with the down-regulation of Ki67. The quantity of cells (HTR8/SVneo and JEG3 cells) transfected with Ad-TIPE2 had increased, with up-regulations of TIPE2, matrix metalloproteinase (MMP)-2 and MMP-9. TIPE2 overexpression could reduce the invasion and migration of cervical cancer cells via inhibiting the epithelial-mesenchymal transition (EMT) process, and promote trophocyte invasion via upregulating the expression of MMPs, and it may be used as a potential therapeutic target for cervical cancer and PE.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common disease in men, which has a high incidence and seriously affects the quality of life of the patients. The possible pathogenic factors of the disease include urine reflux, hidden infection, central sensitization, oxidative stress, and abnormal immune response, among which abnormal immune response plays a significant role in its development and progression. Immune response involves innate immunity and adaptive immunity, and most previous studies focused on adaptive immunity. In recent years, more and more attention has been paid to the role of the innate immune system in the pathogenesis of CP/CPPS. Studies show that mast cells, macrophages, Toll-like receptors and related cytokines in the innate immune system are all involved in the development and progression of CP/CPPS. As the innate immune system is the first barrier of the immune response of the body, studies on innate immunity will provide some new ideas for the diagnosis and treatment of CP/CPPS.

Slow development has been shown to be a general mechanism to restore the fertility of thermo-sensitive and photoperiod-sensitive genic male sterile (TGMS and PGMS) lines in Arabidopsis. rpg1 is a TGMS line defective in primexine, which is essential for pollen wall pattern formation. Here, we showed that RPG1-GFP was highly expressed in microsporocytes, microspores, and pollen grains but not in the tapetum in the complemented transgenic line, suggesting that microsporocytes are the main sporophytic cells for primexine formation. Further cytological observations showed that primexine formation in rpg1 was partially restored under slow growth conditions, leading to its fertility restoration. RPG2 is the homolog of RPG1 in Arabidopsis. We revealed that the fertility recovery of rpg1 rpg2 was significantly reduced compared with that of rpg1 under low temperature. The RPG2-GFP protein was also expressed in microsporocytes in the RPG2-GFP (WT) transgenic line. These results suggest that RPG2 plays a redundant role in rpg1 fertility restoration. rpg1 plants were male sterile at the early growth stage, while their fertility was partially restored at the late developmental stage. The fertility of the rpg1 lateral branches was also partially restored. Further growth analysis showed that slow growth at the late reproductive stage or on the lateral branches led to fertility restoration. This work reveals the importance of gene redundancy in fertility restoration for TGMS lines and provides further insight into pollen wall pattern formation., (© 2021 Society for Experimental Biology and John Wiley & Sons Ltd.)

Postsynaptic NMDARs at spinal synapses are required for postsynaptic long-term potentiation and chronic pain. However, how presynaptic NMDARs (PreNMDARs) in spinal nociceptor terminals control presynaptic plasticity and pain hypersensitivity has remained unclear. Here we report that PreNMDARs in spinal nociceptor terminals modulate synaptic transmission in a nociceptive tone-dependent manner. PreNMDARs depresses presynaptic transmission in basal state, while paradoxically causing presynaptic potentiation upon injury. This state-dependent modulation is dependent on Ca 2+ influx via PreNMDARs. Small conductance Ca 2+ -activated K + (SK) channels are responsible for PreNMDARs-mediated synaptic depression. Rather, tissue inflammation induces PreNMDARs-PKG-I-dependent BDNF secretion from spinal nociceptor terminals, leading to SK channels downregulation, which in turn converts presynaptic depression to potentiation. Our findings shed light on the state-dependent characteristics of PreNMDARs in spinal nociceptor terminals on modulating nociceptive transmission and revealed a mechanism underlying state-dependent transition. Moreover, we identify PreNMDARs in spinal nociceptor terminals as key constituents of activity-dependent pain sensitization., (© 2022. The Author(s).)

A radical [1,4]-oxygen-atom transfer has been realized by the reaction of linear alkyne-tethered ketoximes and ethynylbenziodoxolones (EBX) under sequential catalytic conditions. Mechanism studies indicate that the O atom transfer experiences a cascade O atom radical cyclization/alkynylation/N-O bond photocleavage and subsequent N,O-diradical rearrangement. By the diversification of catalytic sequences, a series of structurally important 3 H -pyrrol-3-ones and chlorinated furo[3,2- b ]pyrroles are divergently synthesized along with an O atom shift under the catalysis of Cu/Ir photosensitization and Cu/Ir photosensitization/AlCl 3 , respectively.

Background: Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 technology is widely used in disease treatment and medicinal plant improvements due to its advantages, such as easy operation, low time consumption, and high efficiency. However, potential off-target risks still exist in practical applications and need to be solved urgently., Objectives: This study aimed to review the application progress of CRISPR/Cas9 technology in the field of disease treatment and medicinal agriculture in recent years. Furthermore, the study discusses the ways to reduce the off-target effect of CRISPR/Cas9 technology, providing a reference for the further application of this technology., Methods: CiteSpace software was used to analyze relevant literature data from 2013 to August 2021, and search results were retrieved from Web of Science, PubMed, and CNKI databases., Results: In the field of disease treatment, CRISPR/Cas9 technology has great potential to cure challenging human diseases and has been widely used in drug target development, drug design, and screening. In crop breeding, CRISPR/Cas9 accelerates the improvement of crop varieties and shortens the number of years of crop breeding. By adjusting the length and GC content of sgRNA and changing the concentration of Cas9/sgRNA complex to reduce the off-target effect of CRISPR/Cas9 technology, the target genes can be manipulated more accurately., Conclusion: CRISPR/Cas9 technology is an indispensable and key technology in the field of disease treatment and medicinal plants. With the in-depth study of the off-target effect, CRISPR/Cas9 technology can have broader application prospects in the fields of medicine and medicinal agriculture., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Diabetes is one of the common chronic diseases in which susceptibility is determined by a combination of genetic and environmental factors, and more than 90% of diabetic patients are diabetes mellitus type 2 (T2DM). The existing studies on the association between CDKAL1 rs10946398 gene polymorphism and susceptibility to type 2 diabetes are inconsistent across populations., Aim: We aim to explore the association between CDKAL1 rs10946398 gene polymorphism and susceptibility to type 2 diabetes in different populations., Methods: We examined all studies before June 12, 2021, that associated CDKAL1 rs10946398 with T2DM. Heterogeneity was assessed by meta-analysis of allelic inheritance models (A vs. C), dominant inheritance models (AA vs. AC+CC), and recessive inheritance model (AA+AC vs. CC); I 2 was used to assess the heterogeneity (if I 2 < 50%, the fixed-effects model was used; if I 2 ≥ 50%, the random-effects model was used for data consolidation); correlation was judged by a forest map; potential publication bias was tested by the Egger test ( p > 0.05 indicates that there is no publication bias)., Results: Fourteen data totaling 30288 subjects, including 19272 controls and 11016 patients with T2DM, met our inclusion criteria. In the Asian population, the differences were statistically significant ( p < 0.01) for dominant genetic model (OR = 0.75, 95%CI = 0.64-0.88, p = 0.0003). But the allelic effect model (OR = 0.87, 95%CI = 0.75-1.02, p = 0.08) and the recessive genetic model (OR = 0.85, 95%CI = 0.66-1.10, p = 0.23) were not statistically significant ( p > 0.01). In the non-Asian population, the differences were statistically significant ( p < 0.01) for the allelic effect model (OR = 0.83, 95%CI = 0.77-0.88, p < 0.00001), the dominant model (OR = 0.79, 95%CI = 0.72-0.87, p < 0.00001), and the recessive model (OR = 0.78, 95%CI = 0.70-0.87, p < 0.0001)., Conclusion: In this study, CDKAL1 RS10946398 was positively associated with T2DM, but the association was different in Asian populations., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Ning Xu et al.)

To date, the use of biomarkers for assessing individual severity of osteoarthritis (OA) is limited, and the correlation of histological scores with biomarkers for individual animals in the destabilization of the medial meniscus (DMM) model of OA has not been well investigated. Accordingly, this study investigated how well representative biomarkers in the DMM model reflected specific changes in individual animals. Rats were randomly divided into the OA group and the sham group. OA model was established by destabilization of the medial meniscus (DMM). After 2,4,6,8,10 and 12 weeks (n=14, each week), the concentrations of CTXII, COMP, C2C, and OC in serum were measured, and cartilage degeneration, osteophytes, and synovial membrane inflammation, typical of OA, were scored using Osteoarthritis Research Society International (OARSI) scoring system. Additionally, the correlation between each biomarker and the specific changes in osteoarthritis was analyzed for individual animals using the Generalized Estimating Equation (GEE). Statistical analysis showed a low correlation between CTXII and osteophyte score of the medial femur (coefficient = -0.0088, p= 0.0103), COMP and osteophyte score of the medial tibia (coefficient = -0.0911, p= 0.0003), and C2C and synovial membrane inflammation scores of the medial femoral (coefficient = 0.054, p= 0.0131). These results suggest that representative OA bio- markers in individual animals in the DMM model did not reflect histological scores well.

Background: Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases in adults, causing high morbidity and mortality worldwide. In recent years, the prevalence of T2DM has been increasing significantly, and genome-wide association studies (GWAS) have shown that KCNQ1 significantly increases the risk of T2DM., Objective: To find large-scale evidence on whether the KCNQ1rs2237892C⟶T gene polymorphism is associated with T2DM susceptibility., Methods: A comprehensive review of the Chinese and English literature on the association of T2DM with KCNQ1rs2237892 is published by PubMed and Baidu Academic. The included literature was part or all of the studied loci which were evaluated for association with T2DM. Forest plots were made of the included literature to analyze the association of KCNQ1 with polymorphisms of the studied loci, and funnel plots and Egger's test were used to evaluate the publication bias of the selected included literature., Results: Ten case-control studies including a total of 7027 cases and 8208 controls met our inclusion criteria. Allele (C allele frequency distribution) (OR: 1.19; 95% CI: 0.87,1.62; P < 0.00001), recessive (OR: 0.73; 95% CI: 0.45,1.18; P < 0.00001) genetic model under the full population was observed between KCNQ1rs2237892C⟶T gene polymorphism and T2DM without a significant relationship. In a stratified analysis by race, a meaningful association was found in non-Asian populations under the allelic genetic model, but no association was found in Asian populations., Conclusion: This meta-analysis showed no significant association between the rs2237892 polymorphism of the KCNQ1 gene and the risk of T2DM., Competing Interests: The authors state that the study was conducted without any commercial or financial relationship., (Copyright © 2021 Wen-Jia Han et al.)

The quiescence, activation, and subsequent neurogenesis of neural stem cells (NSCs) play essential roles in the physiological homeostasis and pathological repair of the central nervous system. Previous studies indicate that transmembrane protein Ttyh1 is required for the stemness of NSCs, whereas the exact functions in vivo and precise mechanisms are still waiting to be elucidated. By constructing Ttyh1-promoter driven reporter mice, we determined the specific expression of Ttyh1 in quiescent NSCs and niche astrocytes. Further evaluations on Ttyh1 knockout mice revealed that Ttyh1 ablation leads to activated neurogenesis and enhanced spatial learning and memory in adult mice (6-8 weeks). Correspondingly, Ttyh1 deficiency results in accelerated exhaustion of NSC pool and impaired neurogenesis in aged mice (12 months). By RNA-sequencing, bioinformatics and molecular biological analysis, we found that Ttyh1 is involved in the regulation of calcium signaling in NSCs, and transcription factor NFATc3 is a critical effector in quiescence versus cell cycle entry regulated by Ttyh1. Our research uncovered new endogenous mechanisms that regulate quiescence versus activation of NSCs, therefore provide novel targets for the intervention to activate quiescent NSCs to participate in injury repair during pathology and aging., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cao, Wu, Cao, Yue, Han, Cao, Zhang, Gao, Luo, Jiang, Han and Zheng.)

Injectable hydrogel systems are a facile approach to apply to the damaged meniscus in a minimally invasive way. We herein developed a clinically applicable and injectable semi-interpenetrated network (semi-IPN) hydrogel system based on fibrin (Fb), reinforced with Pluronic F127 (F127) and polymethyl methacrylate (PMMA), to improve the intrinsic weak mechanical properties. Through the dual-syringe device system, the hydrogel could form a gel state within about 50 s, and the increment of compressive modulus of Fb hydrogels was achieved by adding F127 from 3.0% (72.0 ± 4.3 kPa) to 10.0% (156.0 ± 9.8 kPa). The shear modulus was enhanced by adding PMMA microbeads (26.0 ± 1.1 kPa), which was higher than Fb (13.5 ± 0.5 kPa) and Fb/F127 (21.7 ± 0.8 kPa). Moreover, the addition of F127 and PMMA also delayed the rate of enzymatic biodegradation of Fb hydrogel. Finally, we confirmed that both Fb/F127 and Fb/F127/PMMA hydrogels showed accelerated tissue repair in the in vivo segmental defect of the rabbit meniscus model. In addition, the histological analysis showed that the quality of the regenerated tissues healed by Fb/F127 was particularly comparable to that of healthy tissue. The biomechanical strength of the regenerated tissues of Fb/F127 (3.50 ± 0.35 MPa) and Fb/F127/PMMA (3.59 ± 0.89 MPa) was much higher than that of Fb (0.82 ± 0.05 MPa) but inferior to that of healthy tissue (6.63 ± 1.12 MPa). These results suggest that the reinforcement of Fb hydrogel using FDA-approved synthetic biomaterials has great potential to be used clinically., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Using a sample of Chinese adults over the age of 50 from wave 1 of the WHO Study on Global Ageing and Adult Health (n = 13,367), we investigated the relationship between living arrangements and subjective well-being (SWB) in regard to life satisfaction, happiness, and control. We also looked at the moderating role of resources, proxied by income and hukou status. Multivariate regression results indicate that living only with a spouse was significantly associated with better SWB. Multigenerational living arrangements may not always promote SWB, particularly when resources are constrained. Yet, results also underscore the importance of daughters and daughters-in-law in promoting SWB among older adults. Older adults in rural areas had better SWB, including greater life satisfaction if living with grandchildren only, compared to their urban peers living with a spouse only. Findings suggest that context matters in the association between living arrangements and older adults' SWB.

Hemostasis has critical significance during surgical procedures. Bone Wax has traditionally been commonly used for bone hemostasis despite well-documented undesirable side effects: hindering osteogenesis and induction of inflammatory reactions with consequent increase in infection rates. A later developed formulation, Ostene, offers an alternative to Bone Wax with lesser undesired effects. In this study, BoneStat, a newly developed bone hemostatic formulation comprising water-soluble alkylene oxide co-polymers, was evaluated for water solubility, hemostatic efficacy, ease of handling, bone healing efficacy, and inflammatory reactions compared with Bone Wax and Ostene in a rat calvarial defect model. More than 95% of BoneStat was dissolved in water within 48 h, as was Ostene, but not Bone Wax. The time to hemostasis using BoneStat was significantly faster than with Ostene or Bone Wax. BoneStat also improved ease of handling compared to Ostene or BoneWax. BoneStat- and Ostene-treated groups constantly showed better bone healing than with Bone Wax. The BoneStat and Ostene groups presented no evidence of chronic inflammation reaction contrary to Bone Wax. These results suggest improved hemostasis, ease of handling, non-hindering bone healing, and unnoticeable chronic inflammatory reactions with BoneStat. Thus, Bonestat is a useful and reliable formulation for mechanical hemostasis.

Objective: As labor markets in recent decades have become increasingly volatile and precarious, more workers are susceptible to working conditions threatening their economic security. COVID-19 has further laid bare such economic insecurity from holding a precarious job. We examined the association between precarious employment and the probability of losing income or a job during COVID-19 pandemic., Methods: A multivariate regression analysis was conducted using a cross-sectional data set collected in May 2020 in the United States., Results: Our results confirm a strong positive association between precarious employment and losing work or income. Specifically, holding part-time work in the service sector, and feeling disempowered in the workplace, receiving low material rewards, having few benefits, and experiencing obstacles in exercising rights all significantly doubled the probability of losing income or jobs., Conclusion: Our analysis underscores the increasing vulnerability faced by our workforce and how a public health crisis magnifies the dire consequences of a precarious job., (© 2021 by the Southwestern Social Science Association.)

Patients with neuropathic pain often experience comorbid psychiatric disorders. Cellular plasticity in the anterior cingulate cortex (ACC) is assumed to be a critical interface for pain perception and emotion. However, substantial efforts have thus far been focused on the intracellular mechanisms of plasticity rather than the extracellular alterations that might trigger and facilitate intracellular changes. Laminin, a key element of the extracellular matrix (ECM), consists of one α-, one β-, and one γ-chain and is implicated in several pathophysiological processes. Here, we showed in mice that laminin β1 (LAMB1) in the ACC was significantly downregulated upon peripheral neuropathy. Knockdown of LAMB1 in the ACC exacerbated pain sensitivity and induced anxiety and depression. Mechanistic analysis revealed that loss of LAMB1 caused actin dysregulation via interaction with integrin β1 and the subsequent Src-dependent RhoA/LIMK/cofilin pathway, leading to increased presynaptic transmitter release probability and abnormal postsynaptic spine remodeling, which in turn orchestrated the structural and functional plasticity of pyramidal neurons and eventually resulted in pain hypersensitivity and anxiodepression. This study sheds new light on the functional capability of ECM LAMB1 in modulating pain plasticity and identifies a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified cingulate LAMB1/integrin β1 signaling as a promising therapeutic target for the treatment of neuropathic pain and associated anxiodepression.

Background: Meniscal deficiency from meniscectomy is a common situation in clinical practices. Regeneration of the deficient meniscal portion, however, is still not feasible., Purpose: To develop an injectable hydrogel system consisting of fibrin (Fb) and polyethylene oxide (PEO) and to estimate its clinical potential for treating a segmental defect of the meniscus in a rabbit meniscal defect model., Study Design: Controlled laboratory study., Methods: The Fb/PEO hydrogel was fabricated by extruding 100 mg·mL -1 of fibrinogen solution and 2,500 U·mL -1 of thrombin solution containing 100 mg·mL -1 of PEO through a dual-syringe system. The hydrogels were characterized by rheological analysis and biodegradation tests. The meniscal defects of New Zealand White male rabbits were generated by removing 60% of the medial meniscus from the anterior side. The removed portion included the central portion. The Fb/PEO hydrogel was injected into the meniscal defect of the experimental knee through the joint space between the femoral condyle and tibial plateau at the anterior knee without a skin incision. The entire medial menisci from both knees of each rabbit were collected and photographed before placement in formalin for histological processing. Hematoxylin and eosin, safranin O, and immunohistochemical staining for type II collagen was performed. The biomechanical property of the regenerated meniscus was evaluated using a universal tensile machine., Results: The Fb/PEO hydrogel was fabricated by an in situ gelation process, and the hydrogel displayed a semi-interpenetrating polymer network structure. We demonstrated that the mechanical properties of Fb-based hydrogels increased in a PEO-dependent manner. Furthermore, the addition of PEO delayed the biodegradation of the hydrogel. Our in vivo data demonstrated that, as compared with Fb hydrogel, Fb/PEO hydrogel injection into the meniscectomy model showed improved tissue regeneration. The regenerated meniscal tissue by Fb/PEO hydrogel showed enhanced tissue quality, which was supported by the histological and biomechanical properties., Conclusion: The Fb/PEO hydrogel had an effective tissue-regenerative ability through injection into the in vivo rabbit meniscal defect model., Clinical Relevance: This injectable hydrogel system can promote meniscal repair and be readily utilized in clinical application.

Tweety-homolog 1 (Ttyh1) is expressed in neural tissue and has been implicated in the generation of several brain diseases. However, its functional significance in pain processing is not understood. By disrupting the gene encoding Ttyh1, we found a loss of Ttyh1 in nociceptors and their central terminals in Ttyh1-deficient mice, along with a reduction in nociceptor excitability and synaptic transmission at identified synapses between nociceptors and spinal neurons projecting to the periaqueductal grey (PAG) in the basal state. More importantly, the peripheral inflammation-evoked nociceptor hyperexcitability and spinal synaptic potentiation recorded in spinal-PAG projection neurons were compromised in Ttyh1-deficient mice. Analysis of the paired-pulse ratio and miniature excitatory postsynaptic currents indicated a role of presynaptic Ttyh1 from spinal nociceptor terminals in the regulation of neurotransmitter release. Interfering with Ttyh1 specifically in nociceptors produces a comparable pain relief. Thus, in this study we demonstrated that Ttyh1 is a critical determinant of acute nociception and pain sensitization caused by peripheral inflammation.

Objective: The purpose of this study was to evaluate the relationship between rotational disk displacement (DD) of the temporomandibular joint (TMJ) and the dentoskeletal morphology., Methods: Women aged > 17 years were included in this study. Each subject had a primary complaint of malocclusion and underwent routine cephalometric examinations. They were divided into five groups according to the findings on sagittal and coronal magnetic resonance images of their TMJs: bilateral normal disk position, bilateral anterior DD with reduction (ADDR), bilateral rotational DD with reduction (RDDR), bilateral anterior DD without reduction (ADDNR), and bilateral rotational DD without reduction (RDDNR). Twenty-three cephalometric variables were analyzed, and the Kruskal-Wallis test was used to evaluate differences in the dentoskeletal morphology among the five groups., Results: Patients with TMJ DD exhibited a hyperdivergent pattern with a retrognathic mandible, unlike those with a normal disk position. These specific skeletal characteristics were more severe in patients exhibiting DD without reduction than in those with reduction, regardless of the presence of rotational DD. Rotational DD significantly influenced horizontal and vertical skeletal patterns only in the stage of DD with reduction, and the mandible exhibited a more backward position and rotation in patients with RDDR than in those with ADDR. However, there were no significant dentoskeletal differences between ADDNR and RDDNR., Conclusions: The results of this study suggest that rotational DD of TMJ plays an important role in the dentoskeletal morphology, particularly in patients showing DD with reduction.

Objective: To explore the clinical characteristics, intervention and treatment of tympanic osteoma at different locations. Methods: The medical history, audiological and imaging examination, operation and follow-up results of two patients with tympanic osteoma at different sites were reviewed and summarized. Furthermore, the clinical characteristics and interventions of 36 patients reported in literatures with tympanic osteomas were also summarized and analyzed. Results: Osteoma of the two patients collected in this study located at promontory and incus respectively;both of them presented with intact tympanum and conductive deafness, without obvious etiology or predisposing factor. Both of them underwent surgeries and the hearing improved significantly. For patient one, the ossicular chain was intact and restored to activity after removed the osteoma. For patient two, an artificial ossicle was implanted after removed the osteoma and incus. In the 36 patients reported in literatures, the average age was 26.5 years, and 39.47% of them located at promontory; in addition, the main symptoms of them were progressive hearing loss, tinnitus and ear stuffy. Conclusions: Patients with tympanic osteoma are characterized by conduction deafness with intact tympanic membrane, and the most common lesion is promontory. Hearing can be restored by excision of the osteoma and maintenance or reconstruction of the ossicle chain.

Using the ECLS-K, a dataset following a nationally representative cohort of children from kindergarten through 8th grade in the United States (N ≈ 9,250), this study fills the following knowledge gaps. We captured childhood economic experiences by incorporating multiple forms of exposures to income-based deprivation-poverty depth (i.e., the severity of deprivation), spells (i.e., length of time in poverty), and income volatility (i.e., fluctuations in family income)-with a latent class analysis. We also examined how different patterns of economic experiences shaped adolescents' socioemotional functioning through family stress (parental depressive symptoms and punitive parenting) and family investment (provision of stimulating materials and parental school involvement) pathways via structural equation modeling. Our analysis indicated 6 classes of deprivation, and these deprivation patterns had both direct and indirect significant associations with children's locus of control and internalizing behaviors. Our structural equation modeling results further indicated that deprivation was associated with parental depressive symptoms, which were, in turn, associated with parents providing less cognitively stimulating materials to children and engaging less in children's school activities. These disadvantages were associated with unfavorable socioemotional functioning in 8th grade. The findings highlight the importance of family practitioners and psychologists recognizing and acting on the interconnections among deprivation, inequity, and child well-being. Our results also suggest considering variations in economic experiences and mechanisms when developing informed policies and programs. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Background: Chaihu is a popular traditional Chinese medicine that has been used for centuries. It is traditionally used to treat cold fever and liver-related diseases. Saikosaponins (SSs) are one of the main active components of chaihu, in addition to essential oils, flavonoids, and polysaccharides. Considerable effort is needed to reveal the biosynthesis and regulation of SSs on the basis of current progress., Objective: The aim of this study is to provide a reference for further studies and arouse attention by summarizing the recent achievements of SS biosynthesis., Methods: All the data compiled and presented here were obtained from various online resources, such as PubMed Scopus and Baidu Scholar in Chinese, up to October 2019., Results: A few genes of the enzymes of SSs participating in the biosynthesis of SSs were isolated. Among these genes, only the P450 gene was verified to catalyze the SS skeleton β-amyrin synthase. Several UDP-glycosyltransferase genes were predicted to be involved in the biosynthesis of SSs. SSs could be largely biosynthesized in the phloem and then transported from the protoplasm, which is the biosynthetic site, to the vacuoles to avoid self-poisoning. As for the other secondary metabolites, the biosynthesis of SSs was strongly affected by environmental factors and the different species belonging to the genus of Bupleurum. Transcriptional regulation was studied at the molecular level., Conclusion: Profound discoveries in SSs may elucidate the mechanism of diverse the monomer formation of SSs and provide a reference for maintaining the stability of SS content in Radix Bupleuri., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Patients with neuropathic pain often experience exaggerated pain and anxiety. Central sensitization has been linked with the maintenance of neuropathic pain and may become an autonomous pain generator. Conversely, emerging evidence accumulated that central sensitization is initiated and maintained by ongoing nociceptive primary afferent inputs. However, it remains elusive what mechanisms underlie this phenomenon and which peripheral candidate contributes to central sensitization that accounts for pain hypersensitivity and pain-related anxiety. Previous studies have implicated peripherally localized cGMP-dependent protein kinase I (PKG-I) in plasticity of nociceptors and spinal synaptic transmission as well as inflammatory hyperalgesia. However, whether peripheral PKG-I contributes to cortical plasticity and hence maintains nerve injury-induced pain hypersensitivity and anxiety is unknown. Here, we demonstrated significant upregulation of PKG-I in ipsilateral L3 dorsal root ganglia (DRG), no change in L4 DRG, and downregulation in L5 DRG upon spared nerve injury. Genetic ablation of PKG-I specifically in nociceptors or post-treatment with intervertebral foramen injection of PKG-I antagonist, KT5823, attenuated the development and maintenance of spared nerve injury-induced bilateral pain hypersensitivity and anxiety. Mechanistic analysis revealed that activation of PKG-I in nociceptors is responsible for synaptic potentiation in the anterior cingulate cortex upon peripheral neuropathy through presynaptic mechanisms involving brain-derived neurotropic factor signaling. Our results revealed that PKG-I expressed in nociceptors is a key determinant for cingulate synaptic plasticity after nerve injury, which contributes to the maintenance of pain hypersensitivity and anxiety. Thereby, this study presents a strong basis for opening up a novel therapeutic target, PKG-I, in nociceptors for treatment of comorbidity of neuropathic pain and anxiety with least side effects.

The maxillary sinus is the largest of the four paranasal sinuses in humans, and its close proximity to the teeth means that caution is required during dental treatment. In particular, implant surgeries involving the maxillary posterior teeth should include evaluating the inferior part of the maxillary sinus. The purpose of this study is to evaluate the differences by comparing the inferior part of the maxillary sinus based on the nasal cavity floor (NCF) between patients (male 30, female 30) genders through the use of the three-dimensional (3-D) program that can facilitate 3-D visualizations. The present study results obtained from 3-D visualizations using cone beam computed tomography (CBCT) data showed that the inferior part of the maxillary sinus was mostly larger in males than in females. In addition, the utilization of 3-D visualization data was more likely to assure accuracy than when using data obtained by two-dimensional (2-D) imaging. Therefore, 3-D visualizations of the inferior part of the maxillary sinus will contribute to accurate analyses of its anatomical structure during implant surgery and other operations. Further studies utilizing 3-D visualization will yield useful fundamental data and guidelines for future research.

Surgical pleth index (SPI) has been widely investigated in assessing the nociceptive level. The aim of this study was to investigate the relationship between SPI level and patient responses to trachea intubation and skin incision. A total of 40 patients undergoing open abdominal general surgery were recruited for analyses. The patients were monitored with electrocardiogram, non-invasive blood pressure, SpO 2 , invasive blood pressure and SPI before anesthesia induction. Anesthesia was induced with midazolam, propofol, sufentanil and rocuronium and maintained with sufentanil and sevoflurane. Blood pressure, heart rate and SPI were recorded for analyses during the peri-intubation and peri-incision periods. A receiver operating characteristic (ROC) curve analysis was performed to analyze the predictive value of blood pressure, heart rate (HR) and SPI for hemodynamic responses for trachea intubation and skin incision. SPI had a similar changing trend to systolic blood pressure (SBP) and diastolic blood pressure (DBP). The SPI level was linearly correlated with SBP, DBP and HR. SPI increased significantly after intubation and incision in patients with positive but not negative responses to intubation and incision. The ROC analysis showed that only SBP level is predictive of intubation responses. These data suggested that SPI elevated under the noxious stimulation by intubation and incision, but it was not predictive of the hemodynamic responses to intubation and incision.