Overexpression of EphB2 in the basolateral amygdala is crucial for inducing visceral pain sensitization in rats subjected to water avoidance stress.

AIMS: Basolateral amygdala (BLA), as a center for stress responses and emotional regulation, is involved in visceral hypersensitivity of irritable bowel syndrome (IBS) induced by stress. In the present study, we aimed to investigate the role of EphB2 receptor (EphB2) in BLA and explore the underlying mechanisms in this process. METHODS: Visceral hypersensitivity was induced by water avoidance stress (WAS). Elevated plus maze test, forced swimming test, and sucrose preference test were applied to assess anxiety- and depression-like behaviors. Ibotenic acid or lentivirus was used to inactivate BLA in either the induction or maintenance stage of visceral hypersensitivity. The expression of protein was determined by quantitative PCR, immunofluorescence, and western blot. RESULTS: EphB2 expression was increased in BLA in WAS rats. Inactivation of BLA or downregulation of EphB2 in BLA failed to induce visceral hypersensitivity as well as anxiety-like behaviors. However, during the maintenance stage of visceral pain, visceral hypersensitivity was only partially relieved but anxiety-like behaviors were abolished by inactivation of BLA or downregulation of EphB2 in BLA. Chronic WAS increased the expression of EphB2, N-methyl-D-aspartate receptors (NMDARs), and postsynaptic density protein (PSD95) in BLA. Downregulation of EphB2 in BLA reduced NMDARs and PSD95 expression in WAS rats. However, activation of NMDARs after the knockdown of EphB2 expression still triggered visceral hypersensitivity and anxiety-like behaviors. CONCLUSIONS: Taken together, the results suggest that EphB2 in BLA plays an essential role in inducing visceral hypersensitivity. In the maintenance stage, the involvement of EphB2 is crucial but not sufficient. The increase in EphB2 induced by WAS may enhance synaptic plasticity in BLA through upregulating NMDARs, which results in IBS-like symptoms. These findings may give insight into the treatment of IBS and related psychological distress.

Are Sandwich Vertebrae Prone to Refracture After Percutaneous Vertebroplasty or Kyphoplasty? A Meta-Analysis.

BACKGROUND: The formation of sandwiched vertebrae (SDVs) after percutaneous vertebroplasty (PVP) or percutaneous kyphoplasty (PKP) has become a common phenomenon. Whether SDVs are more likely to fracture is still controversial. Therefore, we conducted a meta-analysis to provide medical evidence for whether SDVs are more prone to refracture than non-SDVs (NSDVs) after PVP or PKP. METHODS: This study was conducted in accordance with the criteria of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Several databases, including PubMed, Embase, Medline databases, China National Knowledge Infrastructure, Wanfang, and Weipu, were thoroughly searched for relevant studies included from any point up until June 2022. Statistical analyses were performed using Revman 5.4. RESULTS: A total of 4052 individuals from 9 studies were enrolled. Overall, patients with SDV presented more risk to have refracture than patients with NSDV (OR = 1.57, P = 0.04). The incidences of refracture were comparable between the 2 cohorts in studies with a follow-up time less than 3 years (OR = 1.28, P = 0.49). However, patients with SDV were more prone to have refracture than patients with NSDV in studies with a follow-up time longer than 3 years (OR = 1.92, P = 0.009). Moreover, patients with SDV were more likely to have refracture than patients with NSDV in studies that involved both PVP and PKP (OR = 1.62, P = 0.002). In addition, age, low bone density, and postoperative kyphosis angle of sandwich fracture segments >10° were independent factors to predict refracture. CONCLUSIONS: Patients with SDV were more likely to have refracture after PVP or PKP, especially when the follow-up time was longer than 3 years.

Short-chain fatty acids in diseases.

Short-chain fatty acids (SCFAs) are the main metabolites produced by bacterial fermentation of dietary fibre in the gastrointestinal tract. The absorption of SCFAs is mediated by substrate transporters, such as monocarboxylate transporter 1 and sodium-coupled monocarboxylate transporter 1, which promote cellular metabolism. An increasing number of studies have implicated metabolites produced by microorganisms as crucial executors of diet-based microbial influence on the host. SCFAs are important fuels for intestinal epithelial cells (IECs) and represent a major carbon flux from the diet, that is decomposed by the gut microbiota. SCFAs play a vital role in multiple molecular biological processes, such as promoting the secretion of glucagon-like peptide-1 by IECs to inhibit the elevation of blood glucose, increasing the expression of G protein-coupled receptors such as GPR41 and GPR43, and inhibiting histone deacetylases, which participate in the regulation of the proliferation, differentiation, and function of IECs. SCFAs affect intestinal motility, barrier function, and host metabolism. Furthermore, SCFAs play important regulatory roles in local, intermediate, and peripheral metabolisms. Acetate, propionate, and butyrate are the major SCFAs, they are involved in the regulation of immunity, apoptosis, inflammation, and lipid metabolism. Herein, we review the diverse functional roles of this major class of bacterial metabolites and reflect on their ability to affect intestine, metabolic, and other diseases. Video Abstract.

Incidence of Spontaneous Resorption of Lumbar Disc Herniation: A Meta-analysis.

STUDY DESIGN: A meta-analysis. OBJECTIVE: This study aimed to analyze the incidence of spontaneous resorption of lumbar disk herniation (LDH) after conservative treatment. SUMMARY OF BACKGROUND DATA: The resorption of intervertebral disks has been more frequently reported, but there is a lack of reference to the probability of resorption. METHODS: We strictly refer to the standard established in the PRISMA (Preferred Reporting Items for a Systematic Review and Meta-analysis) statement, comprehensively searched electronic databases using the terms related to the spontaneous resorption of LDH. Two reviewers independently evaluated the potential studies, extracted, and analyzed the enrolled data. RESULTS: Thirty-one studies with 2233 patients who received conservative treatment were included for this analysis. We found that the pooled overall incidence of disk resorption was 70.39%, 87.77% for disk sequestration, 66.91% for disk extrusion, 37.53% for disk protrusion, and 13.33% for disk bugle, respectively. The resorption incidence in of 25%≤ reduction of disk herniation (RDH) 50%, RDH≥50%, and RDH=100% were 40.19%, 43.62, and 36.89%. The resorption incidence was 66.98% in Japan, 61.66% in the United States, 83.52% in Korea, 60.68% in China, 78.30% in the UK, 56.70% in Italy, and 83.68% in Turkey, respectively. Subgroup analysis showed that there was no significant difference in resorption incidence among prospective, retrospective studies and randomized controlled trials (P=0.77), and there was no significant difference in evaluation method among qualitative and quantitative studies (P=0.05). CONCLUSIONS: The existing evidence shows that the overall resorption incidence of LDH was 70.39%, the resorption incidence of ruptured LDH is higher than that of contained LDH. There are significant differences in the resorption incidence among countries. The resorption process mainly occurred within 6 months of conservative treatment.

Gradually Tuning the Flexibility of Two-Dimensional Covalent Organic Frameworks via Stepwise Structural Transformation and Their Flexibility-Dependent Properties.

Flexible covalent organic frameworks (COFs) are intriguing for their dynamic properties distinctive from rigid counterparts but still suffer from limited accessibility. Especially, controlling flexibility of COFs is challenging and the impact of different flexibility on properties of COFs has rarely been unveiled. This article reports stepwise adjustment on flexibility of two-dimensional COFs, which is realized by the designed synthesis of rigid COF (R-COF), semi-flexible COF (SF-COF), and flexible COF (F-COF) through polymerization, linker exchange, and linkage conversion with a newly developed method for reduction of hydrazone, respectively. Significant difference in breathing behavior and self-adaptive capability of the three COFs are uncovered through vapor response and iodine capture experiments. Gas sorption experiments indicate that the porosity of F-COF could switch from "close" state in nitrogen to "open" state in carbon dioxide, which are not observed for R-COF and SF-COF. This study not only develops a strategy to adjust the flexibility of COFs by tuning their linkers and linkages, but also provides a deep insight into the impact of different flexibility on properties of COFs, which lays a foundation for the development of this new class of dynamic porous materials.

[Acupuncture combined with auricular point sticking for girls aged 3-8 years with incomplete precocious puberty: a randomized controlled trial].

OBJECTIVE: To observe the efficacy and safety of acupuncture combined with auricular point sticking for girls aged 3-8 years with incomplete precocious puberty (IPP). METHODS: Sixty girls with IPP were randomly divided into an observation group (30 cases, 2 cases dropped off) and a control group (30 cases, 2 cases were eliminated). The girls in the control group were treated with healthy diet and proper exercise for 12 weeks. On the basis of the treatment in the control group, the girls in the observation group were treated with acupuncture combined with auricular point sticking. The acupuncture was applied at Sanyinjiao (SP 6), Guanyuan (CV 4), Guilai (ST 29), etc., the needles were retained for 20 min, acupuncture was given twice a week (once every 3 days). The auricular point sticking was applied at Luanchao (TF2), Neishengzhiqi (TF2), Neifenmi (CO18), Yuanzhong (AT2,3,4i), etc., twice a week. The treatment was given for 12 weeks. Before treatment, after treatment and in follow-up after 12 weeks of treatment completion, the Tanner stage of breast, serum contents of sex hormone (luteinizing hormone [LH], follicle-stimulating hormone [FSH], estradiol [E2]) were observed. The ovarian volume, the number of follicles with diameter>4 mm, and the uterine volume were measured by abdominal color Doppler ultrasound. In addition, the safety of the observation group was evaluated. RESULTS: Compared with before treatment, the Tanner stage of breast in the observation group was improved after treatment and in follow-up (P<0.05); after treatment and in follow-up, the Tanner stage of breast in the observation group was better than that in the control group (P<0.05). Compared with before treatment, the serum levels of LH and E2 in the observation group were increased (P<0.05), and the volume of bilateral ovaries was larger (P<0.05) in follow-up. Compared with before treatment, the serum contents of LH, FSH and E2 in the control group were increased (P<0.05), the volume of bilateral ovaries was larger (P<0.05), and the number of follicles was increased (P<0.05) after treatment and in follow-up. The serum levels of LH, FSH and E2 in the observation group were lower than those in the control group (P<0.05), the volume of bilateral ovaries was smaller than that in the control group (P<0.05), and the number of follicles was lower than that in the control group (P<0.05). Compared with before treatment, the uterine volume in the two groups was larger in follow-up (P<0.05). There was no statistically significant difference between the two groups after treatment and in follow-up (P>0.05). During the treatment, 3 cases in the observation group had slight abdominal pain and subcutaneous blood stasis, without serious adverse reactions. CONCLUSION: Acupuncture combined with auricular point sticking could improve the Tanner stage of breast, reduce the level of sex hormone, slow down the development and maturation of ovary and follicle, and control the degree and speed of sexual development in girls aged 3-8 years with IPP.

[Effect of posture on total hip arthroplasty through direct anterior approach].

OBJECTIVE: To investigate the effect of different postures on direct anterior approach(DAA) total hip arthroplasty. METHODS: Total of 94 patients who underwent DAA total hip arthroplasty from July 2016 to June 2020 were retrospectively analyzed. They were divided into two groups according to different positions during the operation, including 45 cases in lateral position and 49 cases in supine position (with the aid of stent). The general data such as gender, affected limb, body mass index(BMI), incision length, operation time, intraoperative bleeding volume, drainage volume 24 hours after operation, hemoglobin difference before and after operation, first landing time after operation, postoperative hospitalization time, postoperative complications, visual analogue scale(VAS) at 1 day, 1, 2 weeks, 1, 3 and 6 months after operation, Harris score at 1, 2 weeks, 1, 3 and 6 months after operation were observed and compared between the two groups. RESULTS: Patients in both groups were followed up for 6 to 12 months with an average of (8.31±2.22) months. There was no significant difference between two groups in gender, affected limb, age, height, weight, body mass index(BMI), preoperative VAS score and preoperative Harris score(P>0.05). The incision length, operation time, intraoperative bleeding volume, 24-hour drainage volume, hemoglobin difference before and after operation, first time to the ground and postoperative hospitalization time of patients in supine position (assisted by stent) group were all better than those in lateral position group(P<0.05);There was no significant difference in the number of blood transfusions during and after operation(P=0.550). There was no significant difference in anteversion angle and abduction angle in the supine position(with the aid of stent) group during and after operation (P=0.825, P=0.066);There was significant difference in anteversion angle and abduction angle in the lateral position group during and after operation(P<0.05). VAS of patients in supine position (assisted by stent) group were lower than those in lateral position group at 1 day, 1, 2 weeks and 1 month after operation(P<0.05), and there was no statistical difference between two groups at 3 and 6 months after operation(P>0.05). Harris scores of patients in supine position(assisted by stent) group were higher than those in lateral position group at 1 week, 1 month and 3 months after operation(P<0.05), and there was no significant difference between two groups at 6 months after operation(P>0.05). CONCLUSION: Compared with the lateral position, the supine position DAA total hip arthroplasty has the advantages of small incision, short operation time, less bleeding, early landing time, short hospitalization time, and small intraoperative acetabular cup position judgment error. It has the advantage of fast postoperative recovery, but the recovery of hip joint function is the same after 6 months.

ARF6 plays a general role in targeting palmitoylated proteins from the Golgi to the plasma membrane.

Protein palmitoylation is a post-translational lipid modification of proteins. Accumulating evidence reveals that palmitoylation functions as a sorting signal to direct proteins to destinations; however, the sorting mechanism remains largely unknown. Here, we show that ARF6 plays a general role in targeting palmitoylated proteins from the Golgi to the plasma membrane (PM). Through shRNA screening, we identified ARF6 as the key small GTPase in targeting CD36, a palmitoylated protein, from the Golgi to the PM. We found that the N-terminal myristoylation of ARF6 is required for its binding with palmitoylated CD36, and the GTP-bound form of ARF6 facilitates the delivery of CD36 to the PM. Analysis of stable isotope labeling by amino acids in cell culture revealed that ARF6 might facilitate the sorting of 359 of the 531 palmitoylated PM proteins, indicating a general role of ARF6. Our study has thus identified a sorting mechanism for targeting palmitoylated proteins from the Golgi to the PM.

Nucleus Pulposus Cells Induce M2 Polarization of RAW264.7 via CX3CL1/CX3CR1 Pathway and M2 Macrophages Promote Proliferation and Anabolism of Nucleus Pulposus Cells.

Background: The mechanisms underlying M2 macrophage polarization induced by nucleus pulposus (NP) cells are unclear. The effects that M2-polarized macrophages have on NP cells are also controversial. Methods: Transcriptome sequencing was performed to detect the gene change profiles between NP cells from ruptured intervertebral disc (IVD) and normal IVD. The main difference on biological activities between the two cell groups were analyzed by GO analysis and KEGG analysis. Virus transduction, flow cytometry, immunofluorescence, RT-PCR, western blot, CCK-8, TUNEL staining, and AO/EB staining were performed to explore the interactions between NP cells and RAW264.7 macrophages. Statistics were performed using SPSS26. Results: 801 upregulated and 276 downregulated genes were identified in NP cells from ruptured IVD in mouse models. According to GO and KEGG analysis, we found that the differentially expressed genes (DEG) were dominantly enriched in inflammatory response, extracellular matrix degradation, blood vessel morphogenesis, immune effector process, ossification, chemokine signaling pathway, macrophage activation, etc. CX3CL1 was one of the top 20% DEG, and we confirmed that both NP tissue and cells expressed remarkably higher level of CX3CL1 in mouse models (p < 0.001∗). Besides, we further revealed that both the recombinant CX3CL1 and NP cells remarkably induced M2 polarization of RAW264.7 (p < 0.001∗), respectively, while this effect was significantly reversed by si-CX3CL1 or JMS-17-2 (p < 0.001∗). Furthermore, we found that M2 macrophages significantly decreased the apoptosis rate (p < 0.001∗) and the catabolic gene levels (p < 0.001∗) of NP cells, while increased the viability, proliferation as well as the anabolic gene levels of NP cells (p < 0.01∗). Conclusions: Via regulating CX3CL1/CX3CR1 pathway, NP cells can induce the M2 macrophage polarization. M2 polarized macrophages can further promote NP cell viability, proliferation, and anabolism, while inhibit NP cell apoptosis and catabolism.

[Effect of transcutaneous electrical acupoint stimulation combined with auricular acupressure on sexual hormone level and gonadal development in girls with precocious puberty].

OBJECTIVE: To explore the effect of transcutaneous electrical acupoint stimulation (TEAS) combined with auricular acupressure on serum sexual hormone level, and the ovarian, follicular and uterine development in the girls with precocious puberty. METHODS: Sixty girls with precocious puberty were randomly divided into a control group (30 cases, 2 cases dropped off) and a treatment group (30 cases, 3 cases dropped off). In both the control group and the treatment group, the healthy life-style intervention was provided for 12 weeks. Besides, in the treatment group, TEAS was delivered for 20 minutes each time, twice a week; and bilateral auricular acupressure was combined. The duration of treatment was 12 weeks. The levels of serum luteinizing hormone (LH), follicle stimulating hormone (FSH) and estradiol (E2), as well as ovarian volume, maximum follicular diameter and uterine volume before and after treatment were detected, and the safety was evaluated separately. RESULTS: Compared with before treatment, the contents of serum LH and FSH were increased (P<0.05), and the ovarian volume and the maximum follicle diameter were increased (P<0.05) in the control group after treatment; the contents of serum FSH and E2 were decresed (P<0.05), and the maximum follicular diameter was reduced significantly (P<0.05) in the treatment group after treatment. Compared with the control group, the contents of serum LH, FSH and E2 were decreased (P<0.05), while the ovarian volume and the maximum follicle diameter were decreased (P<0.05) in the treatment group after treatment. CONCLUSION: TEAS combined with auricular acupressure can effectively decrease the level of sex hormone, improve the ovarian and uterine development and retard the gonadal development. Such combined therapy is of high safety and conductive to regulating the development for the girls with precocious puberty.

On-Site Assessment of a Cryogenic Disinfectant for the Alpine Environment and Outer Packaging of Frozen Items.

Objective: To study the effectiveness and feasibility of cryogenic disinfectants in different cold scenarios and analyze the key points of on-site cryogenic disinfection. Methods: Qingdao and Suifenhe were selected as application sites for the manual or mechanical spraying of cryogenic disinfectants. The same amount of disinfectant (3,000 mg/L) was applied on cold chain food packaging, cold chain containers, transport vehicles, alpine environments, and article surfaces. The killing log value of the cryogenic disinfectant against the indicator microorganisms ( Staphylococcus aureus and Escherichia coli) was used to evaluate the on-site disinfection effect. Results: When using 3,000 mg/L with an action time of 10 min on the ground in alpine regions, the surface of frozen items, cold-chain containers, and cold chain food packaging in supermarkets, all external surfaces were successfully disinfected, with a pass rate of 100%. The disinfection pass rates for cold chain food packaging and cold chain transport vehicles of centralized supervised warehouses and food processing enterprises were 12.5% (15/120), 81.67% (49/60), and 93.33% (14/15), respectively; yet, the surfaces were not fully sprayed. Conclusion: Cryogenic disinfectants are effective in disinfecting alpine environments and the outer packaging of frozen items. The application of cryogenic disinfectants should be regulated to ensure that they cover all surfaces of the disinfected object, thus ensuring effective cryogenic disinfection.

Update on the roles of macrophages in the degeneration and repair process of intervertebral discs.

Intervertebral disc (IVD) degeneration is the common cause of lumbar degenerative diseases, causing severe social and economic burden. The process of IVD degeneration involves a complex of pathologic changes on both extracellular matrix degradation and resident cell apoptosis. In recent years, there is increasing evidence that macrophages play vital roles during the damage and repair process of IVD degeneration. Nevertheless, the interactions between macrophages and IVD are not well understood, even if the IVD has long been regarded as the immune privileged site. Therefore, this review mainly focuses on the progress and obstacles of studies investigating the blood supply, immune response and especially macrophages during the IVD degeneration process.

Targeting EGFR-dependent tumors by disrupting an ARF6-mediated sorting system.

Aberrant activation of EGFR due to overexpression or mutation is associated with poor prognosis in many types of tumors. Here we show that blocking the sorting system that directs EGFR to plasma membrane is a potent strategy to treat EGFR-dependent tumors. We find that EGFR palmitoylation by DHHC13 is critical for its plasma membrane localization and identify ARF6 as a key factor in this process. N-myristoylated ARF6 recognizes palmitoylated EGFR via lipid-lipid interaction, recruits the exocyst complex to promote EGFR budding from Golgi, and facilitates EGFR transporting to plasma membrane in a GTP-bound form. To evaluate the therapeutic potential of this sorting system, we design a cell-permeable peptide, N-myristoylated GKVL-TAT, and find it effectively disrupts plasma membrane localization of EGFR and significantly inhibits progression of EGFR-dependent tumors. Our findings shed lights on the underlying mechanism of how palmitoylation directs protein sorting and provide an potential strategy to manage EGFR-dependent tumors.

Predictive factors for residual leg numbness after decompression surgery for lumbar degenerative diseases.

BACKGROUND: The purpose of this study is to evaluate the change patterns of leg numbness (LN) after lumbar decompression surgery (LDS), and to find the predictive factors that affect the recovery of numbness. METHODS: Patients who underwent LDS in our institution between August 2020 and July 2021 were prospectively enrolled in this study, and were followed by a 12-month follow-up. The degree of LN, leg pain (LP) and the disability were assessed using the visual analog scale (VAS) and oswestry disability index (ODI). RESULTS: A total of 314 patients finished the 12-month follow-up. The preoperative mean VAS-LN score was 3.49 ± 2.44, which decreased to 1.91 ± 1.30 at 3 months, to 1.29 ± 0.97 at 6 months and to 1.26 ± 0.96 at 12 months after surgery. The preoperative mean VAS-LP score was 6.05 ± 1.30, which decreased to 2.00 ± 0.86 at 3 months, to 1.02 ± 0.80 at 6 months, and to 0.49 ± 0.71 at 12 months after surgery. The preoperative mean ODI score was 27.90 ± 7.08, which decreased to 9.73 ± 3.09 at 3 months, to 6.72 ± 2.98 at 6 months, and to 4.57 ± 2.76 at 12 months after surgery. Via multivariate logistic regression analysis, only preoperative VAS-LN score (p < 0.001*) was identified as a significantly independent predictive factor for residual LN after operation. CONCLUSION: Clinically significant improvement in LN was observed in the majority of patients within 6 months after LDS, and the improvement of VAS-LN was slower than the VAS-LP. High pre-operative VAS-LN score can independently predict the presence of residual LN after surgery at 12-month follow up.

Minimally invasive posterior cervical foraminotomy versus anterior cervical discectomy and fusion for cervical radiculopathy: a meta-analysis.

With the recent development of minimally invasive techniques, minimally invasive posterior cervical foraminotomy (MIS-PCF) has become increasingly popular as a minimally invasive method to treat cervical radiculopathy. However, there are still controversies about whether MIS-PCF is superior to anterior cervical discectomy and fusion (ACDF). The purpose of this study is to evaluate the therapeutic effects of MIS-PCF and ACDF on unilateral cervical radiculopathy without myelopathy. We searched PubMed, Embase, the Cochrane Library, and Scopus comprehensively using the terms related to MIS-PCF. Two reviewers independently evaluated the potential studies, and extracted and analyzed the data of operation time, hospital stay, neck disability index (NDI) score, visual analog scale for neck pain (VAS-neck) and arm pain (VAS-arm) scores, reoperation rate, and complications. Seven studies with 1175 patients were included. The study population was 53.5% male, with a mean age of 48.9. MIS-PCF presented a significantly shorter postoperative hospitalization time compared to ACDF, while the operation time, complication/reoperation rate, and VAS-arm, VAS-neck, and NDI scores were comparable between the two cohorts. In North America, the average cost of MIS-PCF is lower than ACDF. Thus, we suggest that MIS-PCF is an alternative to ACDF for selected patients.

A novel mutation of RPGR in a Chinese family with X-linked retinitis pigmentosa.

AIM: To identify potential mutations and elucidate the clinical findings of male patients and female carriers of X-linked retinitis pigmentosa (XLRP) in a Chinese family. METHODS: A four generation pedigree was collected that consisted of 20 individuals. Genomic DNA was extracted from peripheral blood, and then the target fragments were amplified by PCR and sequenced directly. In addition, all affected patients and female carriers underwent comprehensively ophthalmic evaluation. RESULTS: A novel mutation c.2865G>A p.W955X in RPGR gene was identified of this family, including four affected individuals and eight carriers. All male patients, aging from 7 to 31y, tended to have more various, even potentially deleterious clinical features of RP. At the same time, individuals with heterozygous mutations (carriers) manifested a wide spectrum of clinical features. Herein, only two male patients and three female carriers manifested pathological myopia (PM). Among the female carriers, half of subjects who harbor poor visual acuity suffered esotropia or exotropia. Additionally, 16.7% and 66.7% of carriers had abnormal electroretinogram (ERG) and fundus, respectively. CONCLUSION: In this study, a novel mutation of the RPGR gene is identified, which broadens the spectrum of RPGR mutations, and elaborates the relationship between genotype and phenotype.

Tandospirone prevents stress-induced anxiety-like behavior and visceral hypersensitivity by suppressing theta oscillation enhancement via 5-HT1A receptors in the anterior cingulate cortex in rats.

Tandospirone, a third-generation of antianxiety agent with fewer side effects, has been widely used in the treatment of anxiety. Moreover, it is interesting that tandospirone has been found to relieve gastrointestinal symptoms in patients with refractory irritable bowel syndrome who also have psychological dysfunctions. However, the underlying mechanism remains unclear. In this study, using a visceral hypersensitivity rat model induced by chronic water avoidance stress to mimic the symptoms of irritable bowel syndrome, we found that tandospirone relieved anxiety-like behavior and visceral hypersensitivity induced by stress. Meanwhile, stressed rats had increased 5-HT concentration, less 5-HT1A receptor expression, and enhanced theta oscillations in the anterior cingulate cortex (ACC). Furthermore, the power of the theta band in ACC is positively correlated with the level of visceral sensitivity. Activation of 5-HT1A receptors by its agonist, 8-OH-DPAT, to compensate for their effect in ACC reduced the enhancement of theta oscillations in ACC slices in stressed rats, whereas 5-HT1A receptor antagonist, WAY100135, facilitates theta oscillations in slices of normal rats. Tandospirone reduced the enhancement of theta band power in ACC in vitro and in vivo, thus alleviating anxiety-like behavior and visceral hypersensitivity through 5-HT1A receptors in stressed rats. These results suggest a novel mechanism by which tandospirone activates 5-HT1A receptors to relieve stress-induced anxiety and visceral hypersensitivity by suppressing theta oscillation enhancement in ACC.

Hu'po Anshen Decoction Accelerated Fracture-Healing in a Rat Model of Traumatic Brain Injury Through Activation of PI3K/AKT Pathway.

Hu'po Anshen decoction (HPASD) is a traditional Chinese medicine formula comprising five herbal medicines for the treatment of concussion and fracture healing, but its pharmacological mechanism is still unclear. Ultra-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC/Q-TOF MS) was used to analyze the main active components of HPASD. Rats were randomly assigned to fracture group, fracture combined with traumatic brain injury (TBI) group (FBI) and FBI combined with HPASD treatment group (FBIH). Rats in the FBIH group were given oral doses of HPASD (2.4 g/kg, 4.8 g/kg and 9.6 g/kg) for 14 or 21 consecutive days. The fracture callus formation and fracture sites were determined by radiographic analysis and micron-scale computed tomography (micro-CT) analysis. Hematoxylin and eosin (H&E) staining and a three-point bending test were applied to assess histological lesions and biomechanical properties, respectively. The levels of cytokines-/protein-related to bone formation and differentiation as well as PI3K/AKT pathway-related proteins were determined by Enzyme-linked immunosorbent assay (ELISA), quantitative reverse transcription-polymerase chain reaction (qRT-PCR), or western blot assays, respectively. UPLC-Q/TOF-MS-based serum metabolomic analysis was also performed to investigate the therapeutic effects of HPASD in the treatment of FBI. UPLC/Q-TOF MS analysis showed the chemical components in HPASD, including flavonoids, amino acids, saponins, and phenylpropanoid constituents, etc. HPASD dose-dependently promoted callus formation, increased bone density, improved mechanical parameters and morphological scores, and facilitated the expressions of VEGF, PDGF, bFGF, VEGFA, CoL1A1, RUNX2, BMP2, and Aggrecan, inhibited the expression of MMP13, and activated PI3K/AKT pathway. Metabolomics analysis revealed abnormalities of malate-aspartate shuttle and glucose-alanine. HPASD accelerates fracture healing by promoting bone formation and regulating the malate-aspartate shuttle and glucose-alanine cycle, which might be associated with the activation of the PI3K/AKT pathway.

Effects of Cyclooxygenase-2 Inhibitors on Gastrointestinal Malignancies: a Systematic Review and Meta-analysis.

Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with a reduced risk of gastrointestinal malignancies, which is thought to be mediated mainly through the inhibition of cyclooxygenases-2 (COX-2). Due to the severe side effects of aspirin/NSAIDs, selective COX-2 inhibitors may be a more ideal choice. The objective is to evaluate the association of selective COX-2 inhibitors with gastrointestinal (GI) malignancies and premalignant lesions. We searched for published manuscripts evaluating the association between COX-2 inhibitors and GI malignancies or precancerous lesion. Two investigators independently abstracted the data; then, we conducted the analysis by Review Manager V.5.0; evaluation of effectiveness was performed by an intention to treat (ITT) method. Selective COX-2 inhibitors had no beneficial effects on the progression or regression of esophageal and gastric dysplasia (OR = 1.06, 95% CI 0.63-1.78, P = 0.83 for regression of esophageal dysplasia; OR = 1.06, 95% CI 0.58-1.91, P = 0.86 for progression of esophageal dysplasia; OR = 1.95, 95%CI 0.92-4.17, P = 0.08 for regression of gastric dysplasia; and OR = 0.99, 95%CI 0.68-1.43, P = 0.94 for progression of gastric dysplasia). There is no protective effect on colorectal cancer (OR = 0.89, 95% CI 0.77-1.03, P = 0.11), and the use could not improve the effect of chemoradiation (OR = 1.20, 95% CI 0.46-3.19, P = 0.71). This pooled analysis indicates no meaningful association between selective COX-2 inhibitors and GI malignancies.

Melanosis coli: A factor not associated with histological progression of colorectal polyps.

OBJECTIVE: In this study we aimed to investigate the association of melanosis coli (MC) and the colorectal polyp detection rate (PDR). METHODS: In all, 1104 MC patients and 62 181 non-MC participants were enrolled. And 2208 controls were matched by participants' age and gender, and quality of bowel preparation using the propensity score matching (PSM) method. Additionally, 490 polyps in MC and 980 in controls matched by age and gender, and size and location of polyps were analyzed. The association of PDR and pathological features of polyps with MC were also analyzed. RESULTS: MC patients showed a higher PDR (44.3% vs 39.3%, P = 0.006) and detection rate of low-grade adenoma (45.4% vs 36.7%, P = 0.002) but fewer large polyps (≥10 mm) (18.8% vs 26.9%, P = 0.001), fewer polyps in the left colon (33.5% vs 40.0%, P = 0.018), and a lower detection rate of advanced adenoma/adenocarcinoma (17.4% vs 24.3%, P = 0.003) than the matched controls. On multivariate logistic regression analysis, MC was independently associated with an increased PDR (odds ratio 1.184, 95% confidence interval 1.045-1.343, P = 0.008). Analysis targeting polyps showed that there were significant differences in age, gender, location, and pathology (P < 0.001) between polyps with and without MC. However, after adjusting for participants' age and gender, size and location of polyps, there was no difference between the two groups in pathology (P = 0.635). CONCLUSION: MC is independently associated with increased colorectal PDR, but not with histological progression of polyps.