Malvidin attenuates trauma-induced heterotopic ossification of tendon in rats by targeting Rheb for degradation via the ubiquitin-proteasome pathway.

The pathogenesis of trauma-induced heterotopic ossification (HO) in the tendon remains unclear, posing a challenging hurdle in treatment. Recognizing inflammation as the root cause of HO, anti-inflammatory agents hold promise for its management. Malvidin (MA), possessing anti-inflammatory properties, emerges as a potential agent to impede HO progression. This study aimed to investigate the effect of MA in treating trauma-induced HO and unravel its underlying mechanisms. Herein, the effectiveness of MA in preventing HO formation was assessed through local injection in a rat model. The potential mechanism underlying MA's treatment was investigated in the tendon-resident progenitor cells of tendon-derived stem cells (TDSCs), exploring its pathway in HO formation. The findings demonstrated that MA effectively hindered the osteogenic differentiation of TDSCs by inhibiting the mTORC1 signalling pathway, consequently impeding the progression of trauma-induced HO of Achilles tendon in rats. Specifically, MA facilitated the degradation of Rheb through the K48-linked ubiquitination-proteasome pathway by modulating USP4 and intercepted the interaction between Rheb and the mTORC1 complex, thus inhibiting the mTORC1 signalling pathway. Hence, MA presents itself as a promising candidate for treating trauma-induced HO in the Achilles tendon, acting by targeting Rheb for degradation through the ubiquitin-proteasome pathway.

Association of serum uric acid to serum creatinine ratio with 1-year stroke outcomes in patients with acute ischemic stroke: A multicenter observational cohort study.

BACKGROUND AND PURPOSE: Considering the reliance of serum uric acid (SUA) levels on renal clearance function, its role in stroke outcomes remains controversial. This study investigated the association of renal function-normalized SUA (SUA to serum creatinine ratio, SUA/SCr), a novel renal function index, with the 1-year outcomes in patients with acute ischemic stroke (AIS). METHODS: This is a prospective, multicenter observational study. Renal function-normalized SUA levels were determined by calculating the ratio of SUA to SCr. One-year outcomes included stroke recurrence, all-cause mortality, and poor prognosis. Multivariable Cox regression analyses and restriction cubic splines for curve fitting were used to evaluate SUA/SCr's association with 1-year stroke outcomes. RESULTS: Among 2294 enrolled patients, after adjustment for potential confounders, multivariable Cox regression analyses showed that each one-unit increase in SUA/SCr corresponded to a 19% decrease in 1-year stroke recurrence in patients with AIS. SUA/SCr was analyzed as a continuous variable and categorized into quartiles (Q1-Q4). Compared with the Q1 reference group, Q2, Q3, and Q4 showed significantly lower 1-year stroke recurrence risks. The trend test indicated significant differences in the 1-year stroke recurrence trend from Q1 to Q4. In these patients, SUA/SCr did not show a significant association with poor prognosis or all-cause mortality. Curve fitting revealed SUA/SCr had a negative but nonlinear association with 1-year stroke recurrence. CONCLUSIONS: In patients with AIS, low SUA/SCr may be an independent risk factor for 1-year stroke recurrence. Changes in SUA/SCr had no significant impact on 1-year poor prognosis and all-cause mortality.

Impact of age on clinical characteristics and 1-year outcomes of non-disabling ischemic cerebrovascular events: A multicenter prospective cohort study.

BACKGROUND: The exploration of age-related clinical features and adverse outcomes of non-disabling ischemic cerebrovascular disease (NICE) has been largely unaddressed in current research. This study aimed to analyze the differences in clinical characteristics and prognostic outcomes of NICE across various age groups, utilizing data from the Xi'an Stroke Registry Study in China. METHODS: The age distribution of NICE was categorized into four groups: age ≤ 54 years, age 55-64 years, age 65-74 years, and age ≥ 75 years. Multivariate Cox logistic regression analysis was employed to evaluate the 1-year risk of outcome events in each age group of patients with NICE. A subgroup analysis was conducted to explore interaction factors influencing age-dependent outcomes in patients with NICE. RESULTS: This study included 1,121 patients with NICE aged between 23 and 96 years, with an average age of 63.7 ± 12.2 years. Patients aged ≥ 75 years had a higher proportion of women, lower education levels, and a greater likelihood of having urban employee medical insurance. Those aged < 55 years had a higher prevalence of smoking, while individuals aged > 65 years showed a higher prevalence of comorbidities. Furthermore, there was a significant decrease in body mass index among patients aged ≥ 75 years. Laboratory tests indicated well-controlled blood lipids, liver function, and inflammation across all age groups, but renal function was notably reduced in patients with NICE aged ≥ 75 years. Adjusting for potential confounding factors revealed a significant increase in the one-year risk of all-cause mortality and poor prognosis among patients aged ≥ 75 years compared to those aged < 55 years, with no significant gender difference observed. Subgroup analysis indicated that patients with NICE who consumed alcohol were more prone to experience all-cause mortality with advancing age. CONCLUSIONS: Age significantly influences the clinical characteristics and prognostic outcomes of NICE patients. Clinicians should consider age-specific characteristics when diagnosing, treating, and developing prevention strategies. Tailored prevention and treatment strategies for different age groups can enhance prognosis and reduce adverse outcomes in NICE patients.

Effect of graphene oxide/ poly-L-lactic acid composite scaffold on the biological properties of human dental pulp stem cells.

BACKGROUND: Tissue engineering has attracted recent attention as a promising bone repair and reconstruction approach. Dental pulp stem cells (DPSCs) are pluripotent and can differentiate into bone cells with the correct environment and substrate. Therefore, suitable scaffold materials are essential for fabricating functional three-dimensional (3D) tissue and tissue regeneration. Composite scaffolds consisting of biodegradable polymers are very promising constructs. This study aims to verify the biological function of human DPSCs seeded onto composite scaffolds based on graphene oxide (GO) and poly-L-lactic acid (PLLA). METHODS: The surface morphology was observed under scanning electron microscopy (SEM). Chemical composition was evaluated with Fourier transform infrared (FTIR) spectroscopy. The biocompatibility of GO/PLLA scaffolds was assessed using phalloidin staining of cytoskeletal actin filaments, live/dead staining, and a CCK-8 assay. The effect of GO/PLLA scaffolds on cell osteogenic differentiation was detected through ALP staining, ALP activity assays, and alizarin red S staining, complemented by quantitative real-time PCR (qRT-PCR) analysis. RESULTS: Our data showed that GO and PLLA are successfully integrated and the GO/PLLA scaffolds exhibit favorable bioactivity and biocompatibility towards DPSCs. Additionally, it was observed that the 0.15% GO/PLLA scaffold group promoted DPSC proliferation and osteogenic differentiation by forming more calcium nodules, showing a higher intensity of ALP staining and ALP activity, and enhancing the expression levels of differentiation marker genes RUNX2 and COL1. CONCLUSIONS: These results demonstrate that the GO/PLLA scaffold is a feasible composite material suitable for cell culture and holds promising applications for oral bone tissue engineering.

Dynamic changes in intestinal microbiota and metabolite composition of pre-weaned beef calves.

Gut microbes and their metabolites are essential for maintaining host health and production. The intestinal microflora of pre-weaned calves gradually tends to mature with growth and development and has high plasticity, but few studies have explored the dynamic changes of intestinal microbiota and metabolites in pre-weaned beef calves. In this study, we tracked the dynamics of faecal microbiota in 13 new-born calves by 16S rRNA gene sequencing and analysed changes in faecal amino acid levels using metabolomics. Calves were divided into the relatively high average daily gain group (HA) and the relatively low average daily gain group (LA) for comparison. The results demonstrated that the alpha diversity of the faecal microbiota increased with calf growth and development. The abundance of Porphyromonadaceae bacterium DJF B175 increased in the HA group, while that of Lactobacillus reuteri decreased. The results of the LEfSe analysis showed that the microbiota of faeces of HA calves at eight weeks of age was enriched with P. bacterium DJF B175, while Escherichia coli and L. reuteri were enriched in the microbiota of faeces of LA calves. Besides, the total amino acid concentration decreased significantly in the eighth week compared with that in the first week (P < 0.05). Overall, even under the same management conditions, microorganisms and their metabolites interact to play different dynamic regulatory roles. Our results provide new insights into changes in the gut microbiota and metabolites of pre-weaned calves.

Association between Triglyceride-Glucose Index and 1-year Recurrent Stroke after Acute Ischemic Stroke: Results from the Xi'an Stroke Registry Study of China.

INTRODUCTION: The triglyceride-glucose (TyG) index is reported to be related to poor functional outcomes and all-cause mortality post-stroke. However, the association between TyG index and recurrent stroke after acute ischemic stroke (AIS) has not been well described. We aimed to identify whether the TyG index was associated with 1-year recurrent stroke after AIS. METHODS: Baseline patient information was collected at admission, and the TyG index was calculated. Recurrent stroke events were followed up at 1, 3, 6, and 12 months after diagnosis. We then examined the association between the TyG index and risk of 1-year recurrent stroke using multivariable Cox regression models and restricted cubic spline analyses. RESULTS: Among 2,288 participants, the mean TyG index was 8.8  0.7. Those in the fourth quartile (Q4) demonstrated higher recurrent stroke risk than those in Q1 (adjusted hazard ratio [HR] = 1.63; 95% confidence interval [CI], 0.98-2.72; p = 0.059). Subgroup analysis revealed a sex-specific association between TyG index and recurrent stroke (p for interaction = 0.022). Additionally, restricted cubic splines analyses showed a non-linear association between the TyG index and 1-year recurrent stroke. In females, patients in the Q4 had a 2.95-fold increased recurrent stroke risk than did patients in the Q1 (adjusted HR =2.95; 95% CI, 1.09-7.94; p = 0.032); the risk increased when the TyG index was > 8.73. However, no significant correlation was observed in males. CONCLUSION: A non-linear association was found between the TyG index and 1-year recurrent stroke risk. Subsequently, a high TyG index could predict an increased 1-year recurrent stroke risk in female AIS patients.

Elevated non-HDL-C/HDL-C ratio increases the 1-year risk of recurrent stroke in older patients with non-disabling ischemic cerebrovascular events: results from the Xi'an Stroke Registry Study of China.

BACKGROUND: Few studies have explored the prognostic role of nontraditional lipid-related indicators in non-disabling ischemic cerebrovascular events (NICE). In this study, we aimed to investigate the relationship between the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (non-HDL-C/HDL-C) and the1-year risk of recurrent stroke in patients with NICE. METHODS: Total cholesterol (TC), HDL-C, and patient information were collected at admission. Recurrent stroke events were followed up 3, 6, and 12 months after onset. Non-HDL-C levels were calculated by subtracting HDL-C from TC. The non-HDL-C/HDL-C ratio was treated as a continuous variable and in quartiles (Q1-Q4). Stratified multivariate Cox regression was used to investigate the relationship between the non-HDL-C/HDL-C ratio and the 1-year risk of recurrent stroke in patients with NICE. RESULTS: Overall, 1,659 patients with NICE were enrolled. For each unit increase in the non-HDL-C/HDL-C ratio, the 1-year risk of recurrent stroke in patients aged ≥ 65 years (older patients) with NICE increased by 64% in the adjusted model (hazard ratio [HR]: 1.64, 95%confidence interval [CI]:1.18-2.27, P = 0.003), and the HRs were 3.21 and 4.24 times higher in the Q3 and Q4 groups than that in the Q1 group, which was considered to be the reference (adjusted model Q3: HR: 3.21, 95%CI: 1.05-9.83, P = 0.041; adjusted model Q4: HR: 4.24, 95%CI: 1.30-13.85, P = 0.017). However, there was no significant difference in patients younger than 65 years. Both curve fitting and Kaplan-Meier cumulative risk analysis showed that an elevated non-HDL-C/HDL-C ratio significantly increased the 1-year risk of recurrent stroke in older patients with NICE. The optimal range for the non-HDL-C/HDL-C ratio should be no higher than the Q2 group (2.256-2.939). Stratified Cox regression analysis showed that these results tended to be stable for different comorbidities (all P for interaction > 0.05). CONCLUSIONS: Elevated non-HDL-C/HDL-C ratios significantly increased the 1-year risk of recurrent stroke in older patients with NICE. Therefore, clinicians need to pay more attention to this indicator when managing older patients with NICE.

Pulmonary recruitment maneuver reduces the intensity of post-laparoscopic shoulder pain: a systematic review and meta-analysis.

BACKGROUND: Post-laparoscopic shoulder pain (PLSP) is a common complication following laparoscopic surgeries. This meta-analysis aimed to investigate whether pulmonary recruitment maneuver (PRM) was beneficial to alleviated shoulder pain after laparoscopic procedures. METHODS: We reviewed existing literature in the electronic database from the date of inception to January 31, 2022. The relevant RCTs were independently selected by two authors, after which data extraction, assessment of the risk of bias, and comparison of results. RESULTS: This meta-analysis included 14 studies involving 1504 patients, among which 607 patients were offered pulmonary recruitment maneuver (PRM) alone or in combination with intraperitoneal saline instillation (IPSI), while 573 patients were treated with passive abdominal compression. The administration of PRM significantly decreased the post-laparoscopic shoulder pain score at 12 h (MD (95%CI) - 1.12(-1.57, - 0.66), n = 801, P < 0.001, I2 = 88%); 24 h (MD (95%CI) - 1.45(-1.74, - 1.16), n = 1180, P < 0.001, I2 = 78%) and at 48 h (MD (95%CI) - 0.97(-1.57, - 0.36), n = 780, P < 0.001, I2 = 85%). We observed high heterogeneity in the study and analyzed the sensitivity but failed to identify the cause of the heterogeneity, which may have resulted from the different methodologies and clinical factors in the included studies. CONCLUSION: This systematic review and meta-analysis indicate that PRM can reduce the intensity of PLSP. More studies may be needed to explore the usefulness of PRM in more laparoscopic operations besides gynecological surgeries and determine the optimal pressure of PRM or its appropriate combination with other measures. The results of this meta-analysis should be interpreted with caution owing to the high heterogeneity between the analyzed studies.

Efficacy and safety of ciprofol vs. propofol for the induction and maintenance of general anaesthesia: A multicentre, single-blind, randomised, parallel-group, phase 3 clinical trial.

BACKGROUND: HSK3486 (ciprofol) is a 2,6-disubstituted phenol derivative that acts like propofol as an agonist at the gamma-aminobutyric acid-A (GABA A ) receptor. OBJECTIVE: To investigate the efficacy and safety of HSK3486 for general anaesthesia induction and maintenance. DESIGN: A single-blinded, randomised, parallel-group, phase 3 trial. SETTING: Involving 10 study centres, from November 24, 2020 to January 25, 2021. PATIENTS: A total of 129 patients undergoing nonemergency, noncardiothoracic, and nonneurosurgical elective surgery. INTERVENTION: Patients were randomly assigned at a 2:1 ratio into HSK3486 or propofol groups, to receive HSK3486 (0.4 mg kg -1 ) or propofol (2.0 mg kg -1 ) for induction before a maintenance infusion at initial rates of 0.8 and 5.0 mg kg -1 h -1 , and were adjusted to maintain a bispectral index (BIS) of 40-60 until the end of surgery. MAIN OUTCOME MEASURES: Noninferiority between the drugs was evaluated as the lower limit of the 95% confidence interval (CI) for the between-group difference in the success rate of anesthetic maintenance (primary outcome) >-8%. Secondary outcomes included successful anaesthetic induction, full alertness and spontaneous breathing recovery, time until leaving the postanaesthesia care unit and changes in BIS. Safety profiles were also measured. RESULTS: Of 129 enrolled patients, 128 completed the trial, with 86 in the HSK3486 group and 42 in the propofol group. The success rate for the maintenance of general anaesthesia was 100% for both groups, and noninferiority of HSK3486 was confirmed (95% CI -4.28% to 8.38%). No significant differences were found between the two groups of patients with regard to secondary outcomes (all P  > 0.05). There appeared to be a comparable incidence of treatment for emergency adverse events (TEAEs) (80.2% vs. 81.0%, P  = 1.000) and drug-related TEAEs (57.0% vs. 64.3%, P  = 0.451) in the HSK3486 and propofol groups. CONCLUSION: HSK3486 had a noninferior efficacy profile compared to propofol, exhibiting excellent tolerance. TRIAL REGISTRATION: Clinicaltrials.gov, identifier: NCT04511728.

Amplicon-based sequencing and co-occurence network analysis reveals notable differences of microbial community structure in healthy and dandruff scalps.

BACKGROUND: Dandruff is a chronic, recurring, and common scalp problem that is caused by several etiopathogeneses with complex mechanisms. Management of this condition is typically achieved via antifungal therapies. However, the precise roles played by microbiota in the development of the condition have not been elucidated. Despite their omnipresence on human scalp little is known about the co-occurrence/co-exclusion network of cutaneous microbiota. RESULTS: We characterized the scalp and hair surface bacterial and fungal communities of 95 dandruff-afflicted and healthy individuals residing in China. The degree distributions of co-occurrence/co-exclusion network in fungi-bacteria and bacteria-bacteria were higher in the healthy group (P < 0.0001), whereas the betweenness values are higher in the dandruff group (P < 0.01). Meanwhile, the co-occurrence/co-exclusion network among fungi-fungi and fungi-bacteria showed that compared to the healthy group, the dandruff group had more positive links (P < 0.0001). In addition, we observed that Malassezia slooffiae, Malassezia japonica and Malassezia furfur, were more abundant in the dandruff group than in the healthy group. These microbiota were co-exclusion by either multiple bacterial genera or Malassezia sp. in healthy group. The lactic acid bacteria on the scalp and hair surface, especially the genera Lactobacillus and Lactococcus, exhibit a negative correlation with multiple bacterial genera on the scalp and hair surface. Lactobacillus plantarum and Pediococcus lactis isolated on the healthy human scalp can inhibit the growth of Staphylococcus epidermidis in vitro. CONCLUSIONS: We showed that microbial networks on scalp and hair surface with dandruff were less integrated than their healthy counterparts, with lower node degree and more positive and stronger links which were deemed to be unstable and may be more susceptible to environmental fluctuations. Lactobacillus bacteria have extensive interactions with other bacteria or fungi in the scalp and hair surface micro-ecological network and can be used as targets for improving scalp health.

RAC1 is involved in uterine myometrium contraction in the inflammation-associated preterm birth.

In brief: Various etiologies can cause uterine myometrium contraction, which leads to preterm birth. This study demonstrates a new functional relationship between the Ras-related C3 botulinum toxin substrate 1 (RAC1) and uterine myometrium contraction in preterm birth. Abstract: Preterm birth (PTB) is a public health issue. The World Health Organization has recommended the use of tocolytic treatment to inhibit preterm labour and improve pregnancy outcomes. Intrauterine inflammation is associated with preterm birth. RAC1 can modulate inflammation in different experimental settings. In the current study, we explored whether RAC1 can modulate spontaneous uterine myometrium contraction in a mouse model of lipopolysaccharide (LPS)-induced intrauterine inflammation. Subsequently, we recorded uterine myometrium contraction and examined uterine Rac1 expression in a mouse model of preterm birth and a case in pregnant women by Western blotting analysis. We also measured progesterone levels in the blood serum of mice. Murine myometrium was obtained 12 h post LPS treatment. Human myometrium was obtained at the time of caesarean section. We found that in the LPS-treated group of mice, uterine myometrium contraction was enhanced, protein levels and activation of RAC1 were increased and serum progesterone levels were decreased. The protein levels of RAC1 were also increased in preterm birth and in pregnant women. NSC23766, a RAC1 inhibitor, attenuated uterine myometrium contraction and diminished RAC1 activation and COX-2 expression. Furthermore, silencing of RAC1 suppressed cell contraction and COX-2 expression in vitro. In conclusion, our results suggested that RAC1 may play an important role in modulating uterine myometrium contraction. Consequently, intervening with RAC1 represents a novel strategy for the treatment of preterm birth.

Relationship between serum alkaline phosphatase and poor 3-month prognosis in acute ischemic stroke patients with preserved renal function: results from Xi'an Stroke Registry Study of China.

BACKGROUND: In recent years, alkaline phosphatase (ALP) has been considered as one of the independent risk factors of acute ischemic stroke (AIS) and leads to worse clinical outcomes in patients with renal failure. In this study, we aim to investigate whether serum ALP level is associated with poor early-term prognosis in relationship of AIS patients with preserved renal function. METHODS: A prospectively collected database of AIS patients hospitalized in the Xi'an district of China from January to December, 2015 was analyzed. The demographics, serum ALP levels and stroke outcomes of all patients at 3 months were reviewed. Patients were routinely followed-up for 3 months. Serum ALP level was analyzed as a continuous variable and quintiles (Q1-Q5). Multivariate logistic regression model and a two-piecewise linear regression model were used to investigate the relationship and to determine the threshold effect regarding serum ALP levels and poor 3-month prognosis of AIS patients with preserved renal function. RESULTS: Overall, 1922 AIS patients were enrolled with 62.3% of them being men. The risk of having a poor 3-month prognosis was significantly increased in Q1, Q2, Q3 and Q5, when compared to that in Q4 being as the reference. The highest risk was noted in Q5 (odds ratio 2.21, 95% confidence interval: 1.32-3.73, P = 0.003) after being adjusted for confounders. Further analysis revealed a J-shaped curvilinear relationship between ALP levels and a poor 3-month prognosis of strokes (optimal threshold ALP level = 90 U/L). The relationship between both parameters was not significantly affected by age, sex, drinking, hypertension and leukocyte count (stratified by 10 × 109/L) (P for interaction > 0.05). CONCLUSIONS: Serum ALP was noted as an independent risk factor for a poor 3-month prognosis of AIS patients with preserved renal function. ALP levels higher than 90 U/L could cause an increased risk of a poor 3-month prognosis.

Cephalosporins as key lead generation beta-lactam antibiotics.

Antibiotics are antibacterial compounds that interfere with bacterial growth, without harming the infected eukaryotic host. Among the clinical agents, beta-lactams play a major role in treating infected humans and animals. However, the ever-increasing antibiotic resistance crisis is forcing the pharmaceutical industry to search for new antibacterial drugs to combat a range of current and potential multi-resistant bacterial pathogens. In this review, we provide an overview of the development, innovation, and current status of therapeutic applications for beta-lactams with a focus on semi-synthetic cephalosporins. Cephalosporin C (CPC), which is a natural secondary metabolite from the filamentous fungus Acremonium chrysogenum, plays a major and demanding role in both producing modern antibiotics and developing new ones. CPC serves as a core compound for producing semi-synthetic cephalosporins that can control infections with different resistance mechanisms. We therefore summarize our latest knowledge about the CPC biosynthetic pathway and its regulation in the fungal host. Finally, we describe how CPC serves as a key lead generation source for the in vitro and better, in vivo synthesis of 7-aminocephalosporanic acid (7-ACA), the major core compound for the pharmaceutical synthesis of current and future semi-synthetic cephalosporins. KEY POINTS: • Latest literature on cephalosporin generations • Biotechnical production of cephalosporins • In vivo production of 7-ACA.

How do maternal emotion and sleep conditions affect infant sleep: a prospective cohort study.

BACKGROUND: Recent studies suggest that the incidence of infant sleep disorder is related to maternal emotional and sleep conditions, but how they influence each other is not fully understood. METHODS: A total of 513 pairs of parents and infants were enrolled in this prospective cohort study. Maternal emotional and sleep conditions were assessed using a self-rating depression scale, self-rating anxiety scale, and Pittsburgh Sleep Quality Index at the third trimester and within 3 months after delivery. Infant sleep was assessed by the Brief Screening Questionnaire for Infant Sleep Problems within 3 months after birth. Expression of the glucocorticoid receptor (GR), melatonin receptors (MR), exchange proteins directly activated by cAMP (EPAC) receptors, and dopamine receptor (DR) in the placenta was detected by immunohistochemistry. Methylation of the promoter regions for the GR (NR3C1 and NR3C2), MR (MTNR1A and MTNR1B), EPAC (RASGRF1 and RASGRF2), and DR (DRD1 and DRD2) genes was assessed by next generation sequencing-based bisulfite sequencing PCR. RESULTS: The incidence of sleep disorders in infants 0-3 months of age in this cohort was 40.5%. Risk factors for infant sleep disorder were low education level of the father, depression of father, maternal postpartum depression, postpartum anxiety, postpartum sleep disorder, and maternal sleep disorder extend from the third trimester to postpartum. There was no difference in expression of placental DR, GR, MR, and EPAC between mothers whose infants were with and without sleep disorders. Methylation of MTNR1B was higher and expression of MR was lower in the placenta of mothers with sleep disorder in the third trimester than in mothers without sleep disorder. Level of NR3C2 methylation was lower and GR expression was higher in the placenta of mothers with sleep disorder extend from the third trimester to postpartum than in mothers without sleep disorder. CONCLUSION: Maternal sleep disorders in the third trimester could lead to decreased MR expression by up-regulating MTNR1B methylation, and then resulting in elevated cortisol and increased GR expression by down-regulating NR3C2 methylation, which could increase the incidence of maternal postpartum sleep disorders, finally, the maternal postpartum sleep disorder could result in the high incidence of infant sleep disorder.

Promoter methylation changes in the placenta involved in the relationship between prenatal depression and small for gestational age.

BACKGROUND: Recent studies suggest that the incidence of small for gestational age (SGA) birth related to maternal depression, but the mechanism is unclear. The aim of this study was to explore the changes of promoter methylation in the placenta which may be involved in the relationship between prenatal depression and SGA. METHODS: Three hundred forty-five pregnant women were enrolled in this prospective cohort study. Perinatal emotion and sleep quality in the second and third trimesters were assessed using self-rating depression scale, self-rating anxiety scale, and Pittsburgh sleep quality index. According to the exposure (depressed emotion of mother) and outcome (SGA), the placentas were divided into four groups. Methylation of the promoter regions of the placental CRH, HSD11ß2, SLA16A10, DIO3, and MTNR1B genes was determined using next generation sequencing based on bisulfite sequencing PCR. RESULTS: There were 97 (28.1%) and 95 (27.5%) pregnant women who had depression in the second trimester and third trimester, respectively. Thirty-five pregnant women had an SGA birth. The incidence of SGA births in this prospective cohort was 10.1%. The risk factors of SGA birth were low BMI of pregnancy women (RR = 0.71, 95%CI = 0.54 ~ 0.92), hypertensive disorder complicating pregnancy (HDCP, RR = 4.7, 95%CI = 1.18 ~ 18.72), and maternal depression in the second trimester (RR = 3.71, 95%CI = 1.31 ~ 12.16). We found that the CRH and HSD11ß2 methylation levels were higher in the depression group than those in the non-depression group. Methylation levels of DIO3 were higher in SGA group than that in the non-SGA group. Higher methylation levels of CRH correlated with higher methylation levels of DIO3 in the placenta. CONCLUSIONS: Maternal depression in the second trimester may lead to the changes of methylation levels in the promoter region of CRH and HSD11ß2 gene, while the changes of methylation of DIO3 in subsequent could related to SGA. This study suggests that maternal depressed emotion during pregnancy may result in SGA due to the epigenetic changes of placenta.

Modified Radiographic Classification System for Congenital Thumb Duplication: An Analysis of 2,300 Thumbs in 2,108 Children.

PURPOSE: The objectives of this study were to (1) evaluate the radiographic characteristics of children with congenital thumb duplication (CTD) seen in our institution between August 2015 and April 2021; (2) introduce a modified radiographic classification system (MCS) capable of including all cases of CTD based on their radiographic pathoanatomy; and (3) evaluate the inter- and intrarater reliability of the new classification system. METHODS: We retrospectively reviewed 2,108 patients with 2,300 CTDs. The MCS is based on the Wassel-Flatt and Chung et al classification systems and includes specific subtypes from the Rotterdam and modified Wassel-Flatt classifications. The MCS is characterized by 4 groups according to the anatomical morphology of the duplication: A (joint), B (epiphysis), C (bone), and D (soft tissues). Each group includes 4 subtypes according to the location of the CTD, with subtypes 1-3 extending from the distal phalanx to the metacarpal or interphalangeal joints, then to the carpometacarpal joint, and with subtype 4 only including the triphalangia of the main thumb. RESULTS: Among the 2,300 fingers, 360 (15.7%), 2 (0.1%), and 3 (0.1%) CTDs could not be classified according to the Wassel-Flatt, Chung et al, and Rotterdam classifications, respectively. According to the MCS, the 2 most common forms of CTD were A2 (680/2,300; 29.6%) and D2 (308/2,300; 13.4%). All cases could be classified according to this classification system. The MCS showed excellent intrarater (0.875) and interrater (0.851) reliability relative to the Wassel-Flatt (0.863 and 0.820, respectively), Chung et al (0.793 and 0.822, respectively), and Rotterdam (0.873 and 0.836, respectively) systems. CONCLUSIONS: The MCS is a potential radiographic classification for CTD that enables the classification of all patients and has excellent inter- and intrarater reliability. CLINICAL RELEVANCE: Existing classification systems do not allow classification of the full spectrum of CTD and are not always related to surgery, and some existing systems are complex, with many categories that are rarely encountered, or are difficult to use widely in clinical practice.

Gastric foveolar elongation causes invisibility of regular arrangement of collecting venules in chronic active and inactive gastritis.

OBJECTIVES: Helicobacter pylori (H pylori) infection is the most common cause of gastritis. The disappearance of regular arrangement of collecting venules (RAC) is well known as one of the main manifestations of H pylori-affected gastritis while the reason behind it remains obscure. The aim of this study was to investigate the relationship between invisibility of RAC and the length of gastric foveolae. METHODS: 43 RAC-positive and 118 RAC-negative patients were enrolled. Gastric biopsy specimens were obtained from lesser and greater curvature of the corpus with RAC-positive or RAC-negative pattern. Histopathological evaluation was performed based on the updated Sydney System, and foveolar length was derived by a morphometric technique. RESULTS: The median gastric foveolar length in RAC-positive group (median [IQR], 138.54 µm [120.50, 159.09]) was significantly shorter than that in the RAC-negative group (median [IQR], 260.96 µm [217.40, 315.23], P < .05). The length of gastric foveolae in chronic active gastritis (RAC-negative, activity grades 1, 2, and 3) and inactive gastritis (RAC-negative, activity grade 0) was longer than that in normal group (RAC-positive, activity grade 0) (P < .05). The optimal cutoff value for gastric foveolae length of the corpus mucosa showing RAC-negative pattern was more than 181.53 µm. The sensitivity and specificity of more than cutoff value for predicting the invisibility of RAC were 93.03% and 91.78%, respectively. CONCLUSIONS: The elongation of gastric foveolae caused the invisibility of RAC in gastric corpus mucosa in chronic active and inactive gastritis on gastroendoscopy.

Dorsolateral medullary infarction registry: a study protocol for a prospective, multicentric registry.

BACKGROUND: Dorsolateral medullary infarction is a typical cerebral infarction which is characterized by Wallenberg's syndrome. Neurotrophic keratopathy is an uncommon consequence of dorsolateral medullary infarction. At present, the protocol is aimed to study the dynamic changes in corneal innervation and the ocular surface environment after dorsolateral medullary infarction. METHODS: This study will involve consecutive data from all medical records of patients within 7 days of acute dorsolateral medullary infarction onset at the Departments of Neurology from 10 collaborating stroke centers. Eligible patients will mainly be characterized based on detailed physical examinations, multimodal imaging, and corneal related examinations and patients will be followed-up for 2 years. Neurotrophic keratopathy after dorsolateral medullary infarction is the primary endpoint. The dynamic histological corneal innervation and ocular surface environment after dorsolateral medullary infarction will be observed during the follow-up period. DISCUSSION: This multicentric, prospective registry is the first to identify and characterize the dynamic changes of corneal innervation and the ocular surface environment after acute dorsolateral medullary infarction. The significance of the study is to emphasize that the curative effect is based on the doctors' identification of the disease in the earliest stage before irreversible damage occurs to the cornea. TRIAL REGISTRATION: The registry was registered ( ChiCTR-OPC-17,011,625 ) on June 11, 2017.

Association between regular arrangement of collecting venules and Helicobacter pylori status in routine endoscopy.

BACKGROUND: The sensitivity of regular arrangement of collecting venules (RAC)-positive pattern for predicting Helicobacter pylori (H. pylori)-negative status greatly altered from 93.8 to 48.0% in recent two decades of various studies, while the reason behind it remained obscure. The aim of this study was to investigate the value of RAC as an endoscopic feature for judging H. pylori status in routine endoscopy and reviewed the underlying mechanism. METHODS: A prospective study with high-definition non-magnifying endoscopy was performed. RAC-positive and RAC-negative patients were classified according to the collecting venules morphology of the lesser curvature in gastric corpus. Gastric biopsy specimens were obtained from the lesser and greater curvature of corpus with normal RAC-positive or abnormal RAC-negative mucosal patterns. Helicobacter pylori status was established by hematoxylin and eosin staining and immunohistochemistry. RESULTS: 41 RAC-positive and 124 RAC-negative patients were enrolled from June 2020 to September 2020. The prevalence of H. pylori infection in patients with RAC-positive pattern and RAC-negative pattern was 7.3% (3/41) and 71.0% (88/124), respectively. Among all 124 RAC-negative patients, 36 (29.0%) patients were H. pylori-negative status. Ten patients (32.3%) demonstrated RAC-positive pattern in 31 H. pylori-eradicated cases. The sensitivity, specificity, positive predictive value, and negative predictive value of RAC-positive pattern for predicting H. pylori-negative status were 51.4% (95% CI, 0.395-0.630), 96.7% (95% CI, 0.900-0.991), 92.7% (95% CI, 0.790-0.981), and 71.0% (95% CI, 0.620-0.786), respectively. CONCLUSIONS: RAC presence can accurately rule out H. pylori infection of gastric corpus, and H. pylori-positive status cannot be predicted only by RAC absence in routine endoscopy. Trial registration The present study is a non-interventional trial.

Risk factors affecting the 1-year outcomes of minor ischemic stroke: results from Xi'an stroke registry study of China.

BACKGROUND: The prevalence of stroke recurrence, disability, and all-cause mortality of patients with minor ischemic stroke (MIS) remains problematic. The aim of the present study was to identify risk factors associated with adverse outcomes at 1 year after MIS in the Xi'an region of China. METHODS: This prospective cohort study included MIS patients above 18 years old with National Institutes of Health Stroke Scale (NIHSS) score ≤ 3 who were treated in any of four hospitals in Xi'an region of China between January and December 2015. The 1-year prevalence of stroke recurrence, disability, and all-cause mortality were evaluated, respectively. Multivariate logistic regression analysis was performed to assess the association between the identified risk factors and clinical outcomes. RESULTS: In this study, 131(10.5%, 131/1252) patients were lost to follow-up at 1 year. A total of 1121 patients were included for analysis, the prevalence of stroke recurrence, disability, and all-cause mortality at 1 year after MIS were 3.4% (38/1121), 9.3% (104/1121), and 3.3% (37/1121), respectively. Multivariate logistic regression analysis identified age, current smoking, and pneumonia as independent risk factors for stroke recurrence. Age, pneumonia, and alkaline phosphatase were independent risk factors for all-cause mortality. Independent risk factors for disability were age, pneumonia, NIHSS score on admission, and leukocyte count. CONCLUSIONS: The 1-year outcomes of MIS in Xi'an region of China were not optimistic, especially with a high prevalence of disability. The present study indicated that age and pneumonia were the common independent risk factors affecting the 1-year outcomes of MIS in Xi'an region of China.