NLRP3/miR-223-3p axis attenuates neuroinflammation induced by chronic intermittent hypoxia.

Obstructive sleep apnea (OSA) is mainly characterized by chronic intermittent hypoxia (CIH) with multiple brain injuries. Nucleotide oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome is considered the most important factor inducing and maintaining inflammation. However, the role of NLRP3 and its underlying mechanism in CIH-elicited neuroinflammation remains unclear. We constructed an OSA-related CIH in vivo model and assessed the rats' cognitive behavior in the Morris water maze. The combination of miR-223-3p and NLRP3 was confirmed by the TargetScan database, double luciferase reporter gene experiment, and RNA immunoprecipitation (RIP) experiment. Western blot and ELISA assay were used to analyze the effects of miR-223-3p targeting NLRP3 on the expression of pyroptotic or inflammatory factors in vivo in CIH rats. Severe cognitive impairment was observed in rats at week 6 post-treatment, with increased inflammatory factors in the blood and hippocampus, heightened NLRP3 expression, and low miR-223-3p levels. And the good binding activity of the two was confirmed by dual luciferase reporter and RIP experiments. Next, we found that silencing NLRP3 or overexpression of miR-223-3p in the CIH model could improve cognitive deficits and reduce the level of proinflammatory factors and pyroptosis factors in rats. Finally, based on silencing NLRP3 or overexpression miR-223-3p, we confirmed that there was a regulatory relationship between miR-223-3p and NLRP3. Our results suggested that the NLRP3/ miR-223-3p axis played a role in attenuating CIH-induced neuroinflammation.

The H3K27 demethylase controls the lateral line embryogenesis of zebrafish.

BACKGROUND: Kdm6b, a specific histone 3 lysine 27 (H3K27) demethylase, has been reported to be implicated in a variety of developmental processes including cell differentiation and cell fate determination and multiple organogenesis. Here, we regulated the transcript level of kdm6bb to study the potential role in controlling the hearing organ development of zebrafish. METHODS: A morpholino antisense oligonucleotide (MO) strategy was used to induce Kdm6b deficiency; immunohistochemical staining and in situ hybridization analysis were conducted to figure out the morphologic alterations and embryonic mechanisms. RESULTS: Kdm6bb is expressed in the primordium and neuromasts at the early stage of zebrafish embryogenesis, suggesting a potential function of Kdm6b in the development of mechanosensory organs. Knockdown of kdm6bb severely influences the cell migration and proliferation in posterior lateral line primordium, abates the number of neuromasts along the trunk, and mRNA-mediated rescue test can partially renew the neuromasts. Loss of kdm6bb might be related to aberrant expressions of chemokine genes encompassing cxcl12a and cxcr4b/cxcr7b in the migrating primordium. Moreover, inhibition of kdm6bb reduces the expression of genes in Fgf signaling pathway, while it increases the axin2 and lef1 expression level of Wnt/ß-catenin signaling during the migrating stage. CONCLUSIONS: Collectively, our results revealed that Kdm6b plays an essential role in guiding the migration of primordium and in regulating the deposition of zebrafish neuromasts by mediating the gene expression of chemokines and Wnt and Fgf signaling pathway. Since histone methylation and demethylation are reversible, targeting Kdm6b may present as a novel therapeutic regimen for hearing disorders.

A novel ADGRG2 truncating variant associated with X-linked obstructive azoospermia in a large Chinese pedigree.

PURPOSE: In this study, we aimed to identify sterility-related variants in a Chinese pedigree with male infertility and to reveal the different phenotypes and intracytoplasmic sperm injection (ICSI) outcomes of the affected members. METHODS: Physical examinations were performed on male patients. G-band karyotype analysis, copy number variation sequencing, and quantitative fluorescent PCR were conducted to detect common chromosomal disorders in the probands. Whole-exome sequencing and Sanger sequencing were applied to identify the pathogenic genes and the protein expression changes caused by the very mutation were identified by Western Blot in vitro. RESULTS: A novel nonsense mutation (c.908C > G: p.S303*) in the ADGRG2 was identified in all infertile male patients of the pedigree, which was inherited from their mothers. This variant was absent from the human genome databases. This mutation was also unexpectedly found in a male member with normal reproductive capability. Members with the mutation had different genitalia phenotypes, ranging from normal to dilated phenotypes of the vas deferens, spermatic veins and epididymis. There was a truncated ADGRG2 protein in vitro after mutation. Of the three patients' wives treated with ICSI, only one successfully gave birth. CONCLUSIONS: Our study is the first to report the c.908C > G: p.S303* mutation in the ADGRG2 in an X-linked azoospermia pedigree and is the first to report normal fertility in a member with this mutation, expanding the mutation spectrum and phenotype spectrum of this gene. In our study, ISCI had a success rate of only one-third in couples including men with azoospermia with this mutation.

Thioredoxin interacting protein drives astrocytic glucose hypometabolism in corticosterone-induced depressive state.

Brain energetics disturbance is a hypothesized cause of depression. Glucose is the predominant fuel of brain energy metabolism; however, the cell-specific change of glucose metabolism and underlying molecular mechanism in depression remains unclear. In this study, we firstly applied 18 F-FDG PET and observed brain glucose hypometabolism in the prefrontal cortex (PFC) of corticosterone-induced depression of rats. Next, astrocytic glucose hypometabolism was identified in PFC slices in both corticosterone-induced depression of rats and cultured primary astrocytes from newborn rat PFC after stress-level corticosterone (100 nM) stimulation. Furthermore, we found the blockage of glucose uptake and the decrease of plasma membrane (PM) translocation of glucose transporter 1 (GLUT1) in astrocytic glucose hypometabolism under depressive condition. Interestingly, thioredoxin interacting protein (TXNIP), a glucose metabolism sensor and controller, was found to be over-expressed in corticosterone-stimulated astrocytes in vivo and in vitro. High TXNIP level could restrict GLUT1-mediated glucose uptake in primary astrocytes in vitro. Adeno-associated virus vector-mediated astrocytic TXNIP over-expression in rat medial PFC suppressed GLUT1 PM translocation, consequently developed depressive-like behavior. Conversely, TXNIP siRNA facilitated GLUT1 PM translocation to recover glucose hypometabolism in corticosterone-exposed cultured astrocytes. Notably, astrocyte-specific knockdown of TXNIP in medial PFC of rats facilitated astrocytic GLUT1 PM translocation, showing obvious antidepressant activity. These findings provide a new astrocytic energetic perspective in the pathogenesis of depression and, more importantly, provide TXNIP as a promising molecular target for novel depression therapy.

Kinesin spindle protein inhibitor exacerbates cisplatin-induced hair cell damage.

There is emerging evidence indicating that Kinesin family, plays vital roles in influencing the growth of axons, interference with the progression of tumor. However, the function of Kinesin member in the auditory organs remains unknown. SB743921, a kinesin spindle protein (KSP) inhibitor, was applied in mouse organ of Corti and House Ear Institute-Organ of Corti 1 (HEI-OC1) cell line to examine the role of KSP in auditory system with and without cisplatin damage. Cell Counting Kit-8 (CCK-8) and Lactase dehydrogenase (LDH) release assay were conducted to evaluate cell activity and toxicity. Pretreatment with SB743921 increased the sensitivity of HEI-OC1 cells to cisplatin ototoxicity through promoting cell apoptosis and deteriorating superoxide generation mediated damage from cisplatin. SB743921 also enhanced cisplatin induced hair cell damage in explants of mouse cochleae in vitro. Furthermore, the combined N-acetylcysteine (NAC) treatment with cisplatin or with cisplatin and SB743921 both completely rescued the reduced number of hair cells impaired by cisplatin, confirming the strengthening function of superoxide accumulation by SB743921 after cisplatin treatment. Inhibition of kinesin spindle protein enhanced the susceptibility of hair cells to cisplatin induced damage in mouse cochlear explants and HEI-OC1 cells, indicating that kinesin spindle protein might be an unprecedented target to weaken the ototoxicity of platinum medicaments.

Inspection depth of uterine lumen measured by transvaginal ultrasound is associated with the success of IVF: a prospective longitudinal cohort study in China.

OBJECTIVE: To measure the inspection depth of uterine lumen by transvaginal ultrasound and assess the association between the inspection depth and pregnancy outcomes in IVF-ET. METHODS: This prospective longitudinal cohort study was conducted from June 2018 to December 2020. We enrolled patients aged 20-45 years who underwent frozen embryo transfer cycle. We calculated the average distance from the uterine lumen to the ultrasound probe (inspection depth) using transvaginal ultrasonography and divided the entire cohort into four groups according to the quartiles of the overall inspection depth distribution. The chi-square test was used to compare the pregnancy outcomes of the four groups. Univariate and multivariate regression analyses were performed to assess the association between the inspection depth and pregnancy outcomes. RESULTS: Seven hundred forty-two patients were finally enrolled, and they were grouped according to the inspection depth quartiles. There were significant decrease in the clinical pregnancy, implantation, and live birth rates among the four groups (P < 0.05); however, there was no significant difference in the miscarriage rate. Multivariable logistic regression analysis with the inspection depth as a continuous variable demonstrated that the inspection depth was associated with clinical pregnancy, implantation, and live birth rates (clinical pregnancy rate, adjusted odds ratio, 0.549; 95% confidence interval, 0.380-0.793; implantation rate, adjusted odds ratio, 0.680; 95% confidence interval, 0.496-0.931; live birth rate, adjusted odds ratio, 0.602; 95% confidence interval, 0.420-0.863), but not with the miscarriage rate. CONCLUSIONS: The inspection depth of the uterine lumen measured by transvaginal ultrasound was associated with IVF success. TRIAL REGISTRATION: This prospective observational study was registered at the Chinese Clinical Trial Registry ( www.chictr.org.cn ) (ChiCTR2200057977) on March 24, 2022, retrospectively registered.

Effects of immediate versus delayed frozen embryo transfer in high responder patients undergoing freeze-all cycles.

BACKGROUND: Frozen embryo transfer (FET) can greatly improve the pregnancy outcomes for high responder patients. However, it is not known whether the timing of FET is a risk factor on pregnancy outcomes in high responder patients undergoing freeze-all cycles. METHODS: A retrospective cohort study to compare the pregnancy outcomes of the immediate and delayed FET groups in high responder patients undergoing freeze-all cycles. The two groups were defined as that FET took place either within the first menstrual cycle following oocyte retrieval or afterwards. Propensity score matching was used to make the potential risk factors of the two groups comparable. Multivariable regression analysis was used to study the effect of the timing of FET on pregnancy outcomes in the entire cohort and propensity score-matched cohort, even in different controlled ovarian hyperstimulation protocol cohorts as subgroup analysis. RESULTS: We obtained 1130 patients in immediate FET group and 998 patients in delayed FET group, and the average age of the two groups were 30.30 and 30.63. We showed that the immediate FET group were equivalent to delayed FET group in the entire cohort [clinical pregnancy rate (CPR), 61.0% versus 63.4%, adjusted odd ratio (OR), 0.939, 95% confidence interval (CI), 0.781-1.129; spontaneous abortion rate (SAR), 10.1% versus 12.6%, adjusted OR, 0.831, 95% Cl (0.628-1.098); live birth rate (LBR), 49.9% versus 49.2%, adjusted OR, 1.056, 95% Cl (0.883-1.263)]. The same results were obtained by χ2 test in the propensity score-matched cohort (CPR, 60.5% versus 63.5%; SAR, 11.6% versus 12.3%; LBR, 48% versus 49.3%) (P > 0.05). Subgroup analysis indicated that pregnancy outcomes of immediate FET were no difference to delayed FET in gonadotropin-releasing hormone agonist (GnRH-a) protocol (P > 0.05). The SAR of the immediate FET group were lower than that of the delayed FET group in GnRH antagonist protocol (adjusted OR, 0.645, 95% CI, 0.430-0.966) (P < 0.05), no differences were observed in CPR and LBR (P > 0.05). CONCLUSIONS: The pregnancy outcomes of immediate FET were no difference to delayed FET in high responder population undergoing freeze-all cycles.

Novel laparoscopic surgery for the repair of cesarean scar defect without processing scar resection.

BACKGROUND: Cesarean scar defect (CSD), especially CSD with residual myometrium less than 3 mm is reported to be the highest risk agent associated with uterine rupture for subsequent pregnancy. Currently, laparoscopic resection and suture was the mainstay therapy method for CSD with a residual myometrium less than 3 mm in women with a desire to conceive. Besides, the women have CSD related symptoms, especially postmenstrual bleeding, should be recommended for CSD treatment. This study is to investigate the efficiency of this novel laparoscopic surgery for the repair of cesarean scar defect (CSD) without scar resection for residual myometrium thickening. METHOD: This retrospective clinical study enrolled 76 women diagnosed with CSD who had a residual myometrium thickness less than 3 mm and also had a desire to conceive, had undergone laparoscopic surgery for the repair of CSD in the time period March 2016 to March 2018. Two study cohorts were created among the 76 patients: 40 patients had undergone the novel laparoscopic repair of CSD without processing scar resection (Group A), whereas 36 patients had undergone the traditional laparoscopic resection and suture of CSD (Group B). RESULTS: Residual myometrium thickening occurred among all the 76 patients and the average residual myometrium thickness was increased to almost 6 mm, presenting no between-group difference. In Group A, all the CSD-related postmenstrual bleeding was resolved or improved, but one patient in Group B has no obvious change to postmenstrual bleeding. After CSD repair, 20 patients got pregnant naturally in Group A, and there was no cesarean scar pregnancy and uterine rupture. While, there were 9 cases of natural pregnancy in Group B. No uterine rupture occurred among these 9 pregnant women of Group B, but 1 case of pregnancy was terminated due to cesarean scar pregnancy. CONCLUSION: Laparoscopic repair without processing scar resection seems to be a feasible, safe and simple operative approach for CSD treatment, which can thicken residual myometrium and improve postmenstrual bleeding.

Effect of Anti-Hp treatment on nutritional status of children with Helicobacter Pylori-Positive Gastritis and its clinical significance.

OBJECTIVES: To evaluate the outcome of anti-HP treatment on the nutritional status of children with Helicobacter pylori-positive gastritis. METHODS: Sixty children with Helicobacter pylori-positive gastritis admitted to our hospital from June 2018 to June 2020 were selected as the experimental group, and 60 healthy normal people (Hp negative) were selected as the control group. The experimental group were given anti-HP treatment, and the improvement of their clinical symptoms after treatment and the changes of nutritional indexes such as hemoglobin and serum ferritin were observed one year after treatment. Gastroscopy was performed before treatment and four weeks after treatment, and the improvement of gastric inflammation and the positive rate of Hp were compared and analyzed before and after treatment. RESULTS: The nutritional indicators of the children in experimental group were inferior compared with those in the control group (p<0.05). The clinical symptoms and signs of the experimental group were significantly alleviated after anti-Hp treatment, and the biochemical indicators were significantly improved after one Year of follow-up compared with those before treatment (p<0.05). The incidence of moderate and severe gastric mucosal inflammation in the experimental group decreased from 70% before treatment to 17% (p<0.05). The HP infection decreased from 100% before treatment to 13% (p<0.05). CONCLUSION: Helicobacter pylori infection has a negative impact on the nutritional status of children. Anti-HP therapy can improve the gastrointestinal symptoms and nutritional status of children, which plays an important role in the growth and development of children.

An Effective Method Combining Various Endoscopes in the Treatment of Intravesical Migrated Intrauterine Device.

OBJECTIVE: To introduce an effective method combining various endoscopes in the treatment of intravesical migrated intrauterine device (IUD). DESIGN: A step-by-step explanation of the surgery using video, approved by the Shengjing Hospital of China Medical University. SETTING: Shengjing Hospital of China Medical University. INTERVENTIONS: A 39-year-old young woman, in whom an IUD was inserted 2 months prior, presented with frequent urination after IUD insertion. Cystoscope and pelvic computed tomography were performed, and the results showed an IUD in the bladder. The migrated IUD was found partly in the uterus and partly in the bladder by hysteroscope and cystoscope. Management of the migrated IUD consists of 4 steps: (1) lysing the adhesion between the bladder and uterus, (2) suturing the bladder and taking the IUD part out of the bladder, (3) removing the IUD part in the uterus, and (4) suturing the bladder again to reinforce it and suturing the uterus. CONCLUSION: The migrated IUD in the bladder was successfully and completely extracted by the method combining various endoscopes; operative time was 56 minutes. In the follow-up period the patient did not report any symptoms of frequency urination. This surgical process has the following characteristics: Preoperative examination should be performed to clarify the ectopic site of the IUD, various endoscopes should be combined for diagnosis and treatment, and endoscopic surgery is an effective treatment method for migrated IUD.

Relationship between myocardial enzyme levels, hepatic function and metabolic acidosis in children with rotavirus infection diarrhea.

OBJECTIVE: To investigate the relationship between myocardial enzymes, liver function and metabolic acidosis in children with rotavirus infection diarrhea. METHODS: The data of 70 children with infectious diarrhea treated in Baoding Children's Hospital, China, from October 2017 to April 2018 were retrospectively studied. The antigen of rotavirus in feces was positive by colloidal gold method. According to the clinical features of biochemical indicators and mental status, the patients were divided into four groups, an acidosis-free group, a mild acidosis group, a moderate acidosis group and a severe acidosis group, in line with acidosis severity. In addition to detecting the hepatic functions of the pediatric patients in the four groups, including aspartate aminotransferase (AST), alanine aminotransfer (ALT) levels, and myocardial enzyme levels (e.g., creatine kinase, or CK, and creatine kinase isoenzyme, or CK-MB), the relationships of hepatic function, myocardial enzyme levels and acidosis severity of the patients with infectious diarrhea caused by rotavirus infection were also analyzed. RESULTS: There was no significant difference in sex and age among the four groups (P>0.05). However, there was a significant difference in the frequency of diarrhea and vomiting (p<0.05). In addition, there were significant differences in creatine kinase, CK-MB, AST and ALT levels in children with metabolic acidosis of different severities. CONCLUSION: With the aggravation of metabolic acidosis, infectious diarrhea caused by rotavirus is characterized by the aggravation of hepatic function and myocardial cells.

Inhibition of myeloid differentiation 1 specifically in colon with antisense oligonucleotide exacerbates dextran sodium sulfate-induced colitis.

Myeloid differentiation 1 (MD-1), also known as lymphocyte antigen 86 (Ly86), is a soluble protein homologous to MD-2 and forms a complex with radioprotective 105 (RP105). RP105/MD-1 complex negatively regulates toll-like receptor 4 (TLR4) signaling and is involved in several immune disorders. However, the precise role of MD-1 in inflammatory bowel diseases (IBD) remains poorly understood. To further investigate the involvement of MD-1 in IBD, we inhibited MD-1 in colon with antisense oligonucleotide (AS-ODN) and assessed the effect of MD-1 inhibition on dextran sodium sulfate (DSS)-induced colitis. We discovered that MD-1 protein expression was remarkably decreased in both patients with ulcerative colitis and mice with DSS-induced colitis. For the first time, we showed that oral administration of MD-1 AS-ODN to mice significantly suppressed the MD-1 protein levels in colon rather than systemic tissues. Subsequently, we found that MD-1 AS-ODN treated mice were more susceptible to DSS-induced colitis based on loss of body weight, colon length, histological scores, and disease activity index. MD-1 inhibition also significantly enhanced inflammatory cytokines production such as IL-6 and IL-1ß in colons. Finally, mice treated with MD-1 AS-ODN exhibited increased messenger RNA levels of TLR4 and MyD88 after DSS exposure and showed enhanced nuclear factor (NF)-κB activation compared with the control. Taken together, specifically suppression of MD-1 in colon tissues with AS-ODN exacerbates DSS-induced experimental colitis in mice, which is possibly related to activation of TLR4/NF-κB signaling.

Prevalence and type-specific distribution of human papillomavirus infection among women in mid-western rural, Nepal- A population-based study.

BACKGROUND: Cervical cancer is the most common cancer among women in Nepal. The prevalence of human papillomavirus (HPV) 16 and or HPV 18 among women with cervical pre-cancer and cancer is higher than the incidence of HPV in the world population. The population-based epidemiological data of HPV in the general population in most parts of the country remains unknown. The objective of this study was to assess the prevalence and type distribution of HPV infection and association of abnormal cytology with high risk HPV infection among women in mid-western rural, Nepal. METHODS: A population-based cross sectional study was conducted in Jumla, one of the most remote districts in Nepal. A total of 1050 cervical samples were collected from married and non- pregnant women aged 20-65 years during mobile Cervical Cancer Screening Clinics conducted from May 2016 to January 2017. The presence of HPV DNA was firstly confirmed by HPV consensus PCR using PGMY09/PGMY11 designed primers, then HPV positive samples were further genotyped by the membrane hybridization method to detect the 21 high-risk HPV (HR-HPV) and low-risk HPV types. The prevalence of HR-HPV among women with normal and abnormal cytology was calculated. Data were analyzed using SPSS software for Windows. P < 0.05 was considered statistically significant. RESULTS: A total of 998 women were eligible for this study with the mean age 32.6 ± 8.6 years, and the mean marital age was 16.7 ± 3.8 years. The overall prevalence of HPV infections was 19.7%. HR-HPV and low-risk HPV were 11.7 and 8.7% respectively. The six most common HR-HPV types were HPV16, 39, 58, 33, 51 and 18. HR-HPV infection among the women with abnormal and normal cytology was of 27.3 and 10.8% respectively. CONCLUSIONS: There was a higher prevalence of HR-HPV infection among women living in Jumla than other parts of Nepal. This study provides preliminary information on overall HPV and type-specific HR-HPV prevalence, HR-HPV 16, 39, 58, 33, 51, and 18 are the most prevalent genotypes in this region. The data contribute to the epidemiological knowledge about HPV and type-specific HR-HPV genotypes prevalence in mid-Western Nepal.

Low functional programming of renal AT2R mediates the developmental origin of glomerulosclerosis in adult offspring induced by prenatal caffeine exposure.

Our previous study has indicated that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR) of offspring. Recent research suggested that IUGR is a risk factor for glomerulosclerosis. However, whether PCE could induce glomerulosclerosis and its underlying mechanisms remain unknown. This study aimed to demonstrate the induction to glomerulosclerosis in adult offspring by PCE and its intrauterine programming mechanisms. A rat model of IUGR was established by PCE, male fetuses and adult offspring at the age of postnatal week 24 were euthanized. The results revealed that the adult offspring kidneys in the PCE group exhibited glomerulosclerosis as well as interstitial fibrosis, accompanied by elevated levels of serum creatinine and urine protein. Renal angiotensin II receptor type 2 (AT2R) gene expression in adult offspring was reduced by PCE, whereas the renal angiotensin II receptor type 1a (AT1aR)/AT2R expression ratio was increased. The fetal kidneys in the PCE group displayed an enlarged Bowman's space and a shrunken glomerular tuft, accompanied by a reduced cortex width and an increase in the nephrogenic zone/cortical zone ratio. Observation by electronic microscope revealed structural damage of podocytes; the reduced expression level of podocyte marker genes, nephrin and podocin, was also detected by q-PCR. Moreover, AT2R gene and protein expressions in fetal kidneys were inhibited by PCE, associated with the repression of the gene expression of glial-cell-line-derived neurotrophic factor (GDNF)/tyrosine kinase receptor (c-Ret) signaling pathway. These results demonstrated that PCE could induce dysplasia of fetal kidneys as well as glomerulosclerosis of adult offspring, and the low functional programming of renal AT2R might mediate the developmental origin of adult glomerulosclerosis.

Reconstruction of lower limb defect with a variant sural neuro-fasciocutaneous flap: A case report.

INTRODUCTION: The sural neuro-fasciocutaneous flap is widely used for reconstructing skin defects in the lower calf. Variations of the sural nerve in the calf are infrequent, which may require a variation in the traditional surgical procedure. CASE PRESENTATION: A 76-year-old male patient had soft tissue defect of the right lateral ankle and lower leg caused by an accident 18 years ago. He had exposed bones and had osteomyelitis. He underwent two primary operations, and finally, we used a sural neuro-fasciocutaneous flap to effectively cover the defect. We observed that the course of the sural nerve was atypical during the surgery, and we adjusted the flap axis laterally to bring the lateral sural cutaneous nerve inside the flap to improve the success rate of the surgery. The flap entirely survived, and there was no sensory impairment in the calf. The patient was discharged from the hospital after 10 days. CLINICAL DISCUSSION: Some type of variant of the sural nerve makes the flap harvest without the neurovascular component of the sural nerve and the cutaneous chain, which might decrease flap survival. Moving the flap axis laterally and bringing in the lateral sural nerve or peroneal communicating nerve offers an adequate blood supply to the vascular territory and the flap region. CONCLUSION: In patients with sural nerve variants, the procedure does not have to follow the traditional theory of the sural neuro-fasciocutaneous flap. Preoperative and intraoperative protection of the sural nerve variant should also be considered.

Limited ability of increased sequencing depth in detecting cases missed by noninvasive prenatal testing: a comparative analysis of 3 clinical cases.

Increased sequencing depth can improve the detection rate of noninvasive prenatal testing (NIPT) for chromosome aneuploidies and copy number variations (CNVs). However, due to the technical limitations of NIPT, false-positives and false-negatives are inevitable. False-positives for aneuploidy and CNVs have been widely reported, but few missed cases have been reported. In this study, we report 3 patients missed by NIPT, which were still missed after increasing the sequencing depth. To verify the detection efficiency of the platform, the results of NIPT in 32,796 patients treated in Yulin Women and Children Health Care Hospital from 2020 to 2022 were retrospectively analyzed. Data on false-negative cases found by postnatal follow-up or amniocentesis were collected, and the sequencing data, pregnancy examination data, and postnatal follow-up results of these missed patients were summarized. Five patients missed by NIPT were found, and they were missed again by retesting or increasing the sequencing depth. Except for hypospadias found in 1 patient, ultrasonography of the other 4 patients showed no obvious abnormalities during the whole pregnancy. Our results suggest that pregnant women should be fully informed of the benefits and limitations of NIPT before undergoing the examination to avoid unnecessary medical disputes.

The Advantage of Growth Hormone Alone as an Adjuvant Therapy in Advanced Age and BMI ≥ 24 kg/m2 with In Vitro Fertilization Failure Due to Poor Embryo Quality.

This study aimed to assess the effects of GH adjuvant therapy on the cumulative live birth rate in patients with poor embryo quality and to determine the characteristics of patients who are more responsive to GH. A retrospective cohort study was carried out in patients who have suffered from previous IVF failure due to poor embryonic development and underwent IVF with or without a 6-week pretreatment with GH in the subsequent cycle from January 2018 to December 2020. Clinical parameters including the cumulative live birth rate between the (-) GH and (+) GH groups were compared. Multivariate analysis was performed to ascertain associations between clinical parameters and cumulative live birth rate. Upon analysis of the clinical data from 236 IVF cycles, 84 patients received GH and 152 did not receive GH. In frozen embryo transfer cycles, compared with the (-) GH group, the implantation rate and live birth rate were significantly higher in the (+) GH group (p < 0.05). After adjusting for possible confounding factors, GH improved cumulative live birth per oocyte retrieval cycle by 1.96 folds (p = 0.032). Furthermore, when patients were subdivided based on age and BMI, a significant increase in the cumulative live birth rate was found in the (+) GH group of patients between 35 and 42 years old and BMI ≥ 24 kg/m2, respectively (p < 0.05). GH may increase the live birth rate in women who experienced IVF failure because of poor embryonic development, particularly in obese patients and women with advanced age.

miR-1246 Promotes Laryngeal Squamous Cell Carcinoma Progression by Interacting with THBS1.

MicroRNAs (miRNAs) have been confirmed to be related to the occurrence and progress of multiple cancers, including laryngeal squamous cell carcinoma (LSCC). The present work focused on exploring the role of miR-1246 in LSCC and investigating the possible mechanisms. miR-1246 expression levels within clinical LSCC tissues and cell lines (TU212 and AMC-HN-8) were detected through quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay. Then the overall survival (OS) rates of LSCC patients with different miR-1246 expressions were assessed by the Kaplan-Meier method. In addition, the roles of miR-1246 in the proliferation, apoptosis and migration of TU212 and AMC-HN-8 cells were measured by colony formation, flow cytometry, wound-healing, and Western blot (WB) assays, respectively. Moreover, TargetScan was carried out to predict the miR-1246 targets (thrombospondin-1, THBS1), further confirmed by a dual-luciferase reporter assay. Afterward, the negative relationship between miR-1246 and THBS1 was assessed by qRT-PCR and WB. Furthermore, the restoring effects of THBS1 on TU212 and AMC-HN-8 functional roles transfected with miR-1246 inhibitor were further investigated. miR-1246 expression levels were increased in clinical LSCC tissues and cell lines. Patients with low miR-1246 expression exhibited improved OS rates. In addition, miR-1246 down-regulation notably suppressed cell proliferation and migration and induced cell apoptosis of TU212 and AMC-HN-8 cells. Moreover, THBS1 was predicted and confirmed as a direct target of miR-1246 and negatively related to miR-1246 expression. Mechanically, THBS1 inhibition partially rescued the effects of the miR-1246 inhibitor on proliferation, apoptosis and migration of TU212 and AMC-HN-8 cells. This study provides an experimental basis suggesting the potential of miR-1246/THBS1 as the novel markers for LSCC.

MECOM promotes supporting cell proliferation and differentiation in cochlea.

Permanent damage to hair cells (HCs) is the leading cause of sensory deafness. Supporting cells (SCs) are essential in the restoration of hearing in mammals because they can proliferate and differentiate to HCs. MDS1 and EVI1 complex locus ( MECOM) is vital in early development and cell differentiation and regulates the TGF-ß signaling pathway to adapt to pathophysiological events, such as hematopoietic proliferation, differentiation and cells death. In addition, MECOM plays an essential role in neurogenesis and craniofacial development. However, the role of MECOM in the development of cochlea and its way to regulate related signaling are not fully understood. To address this problem, this study examined the expression of MECOM during the development of cochlea and observed a significant increase of MECOM at the key point of auditory epithelial morphogenesis, indicating that MECOM may have a vital function in the formation of cochlea and regeneration of HCs. Meanwhile, we tried to explore the possible effect and potential mechanism of MECOM in SC proliferation and HC regeneration. Findings from this study indicate that overexpression of MECOM markedly increases the proliferation of SCs in the inner ear, and the expression of Smad3 and Cdkn2b related to TGF signaling is significantly down-regulated, corresponding to the overexpression of MECOM. Collectively, these data may provide an explanation of the vital function of MECOM in SC proliferation and trans-differentiation into HCs, as well as its regulation. The interaction between MECOM, Wnt, Notch and the TGF-ß signaling may provide a feasible approach to induce the regeneration of HCs.

The Effect of Nonpharmacological Integrated Care Protocols on Patients with Fatigue Undergoing Hemodialysis: A Randomized Controlled Trial.

This study was designed to investigate the effects of nonpharmacological integrated care protocols on fatigue in patients with hemodialysis. This parallel randomized controlled trial was conducted on patients undergoing hemodialysis from May to October 2020 at the Dialysis Center of the Fifth Affiliated Hospital of Zunyi Medical University. The patients were randomized into an intervention group (accepting nonpharmacological integrated care protocols and standard care) or a control group (accepting standard care only) using a computer-generated random number. The nonpharmacological holistic care intervention used in this study involved a well-rounded multidisciplinary team that worked together to improve dietary compliance, medication adherence, and self-management to improve patients' care and promote self-management. From the 120 evaluated patients, 116 cases were eligible and analyzed. The results showed that patients from the intervention group had obviously reduced overall fatigue, mental fatigue, and muscular fatigue relative to the control group. The nonpharmacological integrated care protocols were interactive and promotive to each other. Meanwhile, the role and function of nurses in the management of chronic disease were demonstrated to be crucial.