Imputation strategies for low-coverage whole-genome sequencing data and their effects on genomic prediction and genome-wide association studies in pigs.

The uncertainty resulting from missing genotypes in low-coverage whole-genome sequencing (LCWGS) data complicates genotype imputation. The aim of this study is to find out an optimal strategy for accurately imputing LCWGS data and assess its effectiveness for genomic prediction (GP) and genome-wide association study (GWAS) on economically important traits of Large White pigs. The LCWGS data of 1 423 Large White pigs were imputed using three different strategies: (1) using the high-coverage whole-genome sequencing (HCWGS) of 30 key progenitors as the reference panel (Ref_LG); (2) mixing HCWGS of key progenitors with LCWGS (Mix_HLG) and (3) self-imputation in LCWGS (Within_LG). Additionally, to compare the imputation effects of LCWGS, we also imputed SNP chip data of 1 423 Large White pigs to the whole-genome sequencing level using the reference panel consisting of key progenitors (Ref_SNP). To evaluate effects of the imputed sequencing data, we compared the accuracies of GP and statistical power of GWAS for four reproductive traits based on the chip data, sequencing data imputed from chip data and LCWGS data using an optimal strategy. The average imputation accuracies of the Within_LG, Ref_LG and Mix_HLG were 0.9893, 0.9899 and 0.9875, respectively, which were higher than that of the Ref_SNP (0.8522). Using the imputed sequencing data from LCWGS with the Ref_LG imputation strategy, the accuracies of GP for four traits improved by approximately 0.31-1.04% compared to the chip data, and by 0.7-1.05% compared to the imputed sequencing data from chip data. Furthermore, by using the sequence data imputed from LCWGS with the Ref_LG, 18 candidate genes were identified to be associated with the four reproductive traits of interest in Large White pigs: total number of piglets born - EPC2, MBD5, ORC4 and ACVR2A; number of piglets born healthy - IKBKE; total litter weight of piglets born alive - HSPA13 and CPA1; gestation length - GTF2H5, ITGAV, NFE2L2, CALCRL, ITGA4, STAT1, HOXD10, MSTN, COL5A2 and STAT4. With the exception of EPC2, ORC4, ACVR2A and MSTN, others represent novel candidates. Our findings can provide a reference for the application of LCWGS data in livestock and poultry.

[Research progress on the role of adipose-derived stem cell exosomes in skin scar formation].

The adipose-derived stem cell exosomes are subcellular structures of adipose stem cells. They are nano-sized membrane vesicles that can transport various cell components and act on target cells by paracrine, and they play an important role in the exchanges of substance and information between cells. Scar healing is the commonest way of healing after skin tissue injury. Pathological scar can not only cause movement dysfunction, but also lead to deformity, which affects the appearance of patients and brings life and mental pressure to the patients. In recent years, many researches have shown that the adipose-derived stem cell exosomes contain a variety of bioactive molecules, which play an important role in reducing scar formation and scar-free wound healing, by affecting the proliferation and migration of fibroblasts and the composition of extracellular matrix. This article reviewed the recent literature on the roles and mechanisms of adipose-derived stem cell exosomes in scar formation, and prospected the future application and development of adipose-derived stem cell exosomes in scar treatment.

[Curative effects of medial plantar free flap in reconstructing electric burn wound and scar contracture in the palm].

Objective: To explore the curative effects of medial plantar free flap in reconstructing electric burn wound and scar contracture in the palm. Methods: A retrospective observational study was conducted. From January 2020 to January 2023, 6 patients with electric burn wounds or scar contracture in the palm who met the inclusion criteria were admitted to the First Affiliated Hospital of Air Force Medical University, including 5 males and 1 female, aged 35 to 55 years. The wound area was 5.0 cm×3.0 cm-8.0 cm×7.0 cm after the debridement of electric burn wounds or resection of scar in the palm. The medial plantar free flap anastomosed with cutaneous nerve was used for wound reconstruction, with flap area of 5.5 cm×3.5 cm-8.5 cm×7.5 cm. The wound in the donor site was repaired with transplantation of abdominal full-thickness skin graft. After surgery, the survival of flaps and skin grafts were observed, the shape and texture of flap and the recovery of donor site of flap were observed, and the holding function of the affected hand was assessed. At the last follow-up, the two-point discrimination distance of flap was measured, the sensory recovery of flap was evaluated with the trial standard for the evaluation of the functions of the upper limbs of the Hand Surgery Society of the Chinese Medical Association, and the function recovery of flap was evaluated by post-surgery flap function evaluation scale. Results: After surgery, 5 flaps survived well, while the distal part of 1 flap was partially necrotic, which was repaired by medium-thickness skin graft from lateral thigh after debridement. All the skin grafts at the donor sites survived well. During follow-up of 3 to 24 months, the flap was not bloated, the texture and color were good, the match with the surrounding tissue was high, with no obvious scar contracture occurred at the donor site. The affected hand had good holding function. At the last follow-up, the two-point discrimination distance of flap was 6-8 mm, the flap sensation recovery was as follows: 5 flaps recovered to grade S3+, 1 flap recovered to grade S3, and the functional evaluation of flaps was excellent in 5 cases and good in 1 case. The patients basically returned to normal life and work. Conclusions: The medial plantar free flap with cutaneous nerve anastomosis has many advantages, such as high matching degree of appearance, good sensory recovery, and holding function of the affected hand. It is an ideal choice for the reconstruction of the electric burn wound and scar contracture in the palm.

Effects of different stocking densities on organ development, blood biochemical indices, and antioxidative status of breeder pigeons during the rearing period.

The present experiment was conducted to investigate the effect of different stocking densities on the organ development, blood biochemical indices, and antioxidative status of breeder pigeons during the rearing period. A total of 280 (half male and half female) 40-day-old young pigeons were allocated into 4 groups, including 3 experimental groups (in compartments of the flying room): the high stocking density (HSD) (0.308 m3/bird), standard stocking density (SD) (0.616 m3/bird), and low stocking density (LSD) (1.232 m3/bird) and a caged control (0.04125 m3/bird). The results showed that the contents of corticosterone and heat shock protein 70 in males and the corticosterone content in females were higher in the control than in the other groups. The relative weight of liver, lung, and gizzard in males of the HSD group was the highest among the 4 treatments, whereas the abdominal fat index in the control group was higher than those in the other 3 treatments. Body weight and the relative weight of liver and abdominal fat in female pigeons in HSD group increased significantly. The levels of serum urea nitrogen and uric acid in pigeons of LSD group increased significantly, while the concentration of total cholesterol and the activity of alanine aminotransferase were higher in the control group. Ion (K+, Ca2+, and Na+) concentrations in female pigeon serum were also elevated in the control. The activity of antioxidant enzymes, including the total antioxidant capacity, superoxide dismutase, and glutathione peroxidase in pigeon breast muscle and liver had different degrees of inhibition when the space room was crowded. Moreover, the level of malondialdehyde in the liver of male caged pigeons was higher than that in the other treatments. In summary, rearing in cages or at a high density caused stress responses in the breeder pigeons. The stocking density of breeder pigeons during the rearing period should be ranged from 0.616 m3/bird to 1.232 m3/bird.

[Application of two kinds of electrophysiological monitoring techniques for the prediction of facial nerve outcomes after vestibular Schwannoma surgery].

Objective: To investigate the application of transcranial facial nerve motor evoked potential (FNMEP) and direct nerve electrical stimulation (DNES) for the prediction of facial nerve function after vestibular schwannoma surgery. Methods: The clinical data of 106 patients who underwent vestibular schwannoma surgery under electrophysiological monitoring of facial nerve between 2017 and 2021 were retrospectively examined, and there were 57 males and 49 females, with a mean age of (51±11) years. Neuroelectrophysiological monitoring was performed in all patients during the operation. After the tumor was removed, FNMEP and DNES were used for electrophysiological evaluation of facial nerve function. The amplitude ratios of FNMEP to baseline (M1) and the brainstem segment to the internal auditory canal segment of DNES (M2) were recorded after the tumor was removed, respectively. The correlation between these two ratios and facial nerve function at 1 day, 1 month and 3 months after the operation were compared. According to the House-Brackmann (HB) scale, Grade Ⅰ-Ⅱ refers to good facial nerve function, and grade Ⅲ-Ⅵ refers to moderate and severe facial nerve dysfunction. Non-parameter Spearman correlation coefficient was used to evaluate the correlation between M1 and M2 and facial nerve function at 1 day, 1 month and 3 months after operation, and the receiver operating characteristic (ROC) curves were plotted to verify the diagnostic efficacy of M1 and M2 for predicting the prognosis of postoperative facial nerve function. Results: Among 106 patients, 102 cases (96.3%) underwent total tumor resection, 4 patients (3.7%) underwent subtotal resection, 104 patients (98.1%) had anatomical preservation of facial nerves, and there were no deaths reported. All patients could evoke reliable FNMEP and 2 patients could not evoke DNES in the brainstem segment of the facial nerve. There were 81 (76.4%), 99 (93.4%) and 103 patients (97.2%) with satisfactory function of facial nerve at 1 day, 1 month and 3 months after surgery, respectively. M1 had large absolute values of Spearman correlation coefficient at 1 day (ρ=|-0.648|) and 1 month (ρ=|-0.552|) after surgery (both P<0.001), while M2 showed a greater absolute value of Spearman correlation coefficient at 3 months (ρ=|-0.395|) than that of M1 (ρ=|-0.378|) (P<0.001). Cut-off value of M1 was 0.58 (sensitivity=0.92, specificity=0.64), and that of M2 was 0.36 (sensitivity=0.64, specificity=1.00). Meanwhile, M1<0.58 or M2<0.36 suggested moderate and severe impairment of facial nerve function. Conclusions: Both FNMEP and DNES during vestibular schwannoma surgery can effectively evaluate the postoperative facial nerve function. FNMEP is better than DNES in predicting the early postoperative facial nerve function, but DNES is better for predicting the long-term postoperative facial nerve function.

Lipid accumulation and oxidative stress in the crop tissues of male and female pigeons during incubation and chick-rearing periods.

The current study aimed to evaluate the changes in lipid accumulation and oxidative status in pigeon crops during different breeding stages. Forty-two pairs of adult pigeons were randomly assigned to 7 groups. Lipid droplet accumulation in pigeon crops was visualized by using oil red O staining from d 17 of incubation (I17) to d 7 of chick rearing (R7). Transmission electron microscopy analysis showed swollen mitochondria with disintegration of cristae and typical characteristics of endoplasmic reticulum stress in crop tissues at R1 compared with those at I4. During the peak of pigeon milk formation, the concentrations of reactive oxygen species, and oxidative damage markers (advanced oxidation protein products, 8-hydroxy-2 deoxyguanosine, and malondialdehyde) and the enzyme activities of total superoxide dismutase and glutathione peroxidase were all elevated significantly (P < 0.05). The protein concentration of B-cell lymphoma-2 associated X in crop tissues was significantly higher at R1, while the level of B-cell lymphoma-2 protein in males was the highest at I4 (P < 0.05). The ratio of B-cell lymphoma-2 associated X protein (Bax)/B-cell lymphoma-2 (Bcl-2) in both male and female crops peaked at R1 (P < 0.05). Gene expression of the key enzymes involved in mitochondrial and peroxisomal fatty acid ß-oxidation was investigated in crops. In males, the gene expression of carnitine palmitoyltransferase 1a peaked at R15, and that of carnitine palmitoyltransferase 2 increased significantly from R1 to R15 (P < 0.05). The mRNA abundance of long chain 3-hydroxyacyl-CoA dehydrogenase increased to the maximum value at R1 and I17 in males and females, respectively. From I17 to R7, the mRNA levels of acyl-CoA oxidase 1 and acyl-CoA oxidase 2 were decreased in pigeon crops (P < 0.05). Conclusively, lipid droplet accumulation was found in male and female pigeon crops from the end of incubation to the early stage of chick rearing. Although antioxidant defence and mitochondrial fatty acid ß-oxidation were both mobilized, oxidative stress in crop tissues still occurred during the peak of milk formation.

[Clinical effect of laparoscopic transcystic drainage combined with common bile duct exploration for the patients with difficult biliary stones].

OBJECTIVE: To explore the feasibility and efficacy of laparoscopic transcystic drainage and common bile duct exploration in the treatment of patients with difficult biliary stones. METHODS: Between April 2020 and December 2021, eighteen patients with difficult biliary stones received laparoscopic transcystic drainage (C-tube technique) and common bile duct exploration. The clinical characteristics and outcomes were retrospectively collected. The safety and effectiveness of laparoscopic transcystic drainage and common bile duct exploration were analyzed. RESULTS: Among the eighteen patients with difficult biliary stones, thirteen patients received traditional laparoscopic transcystic drainage, and the remaining five received modified laparoscopic transcystic drainage. The mean surgical duration were (161±59) min (82-279 min), no bile duct stenosis or residual stone was observed in the patients receiving postoperative cholangiography via C-tube. The maximum volume of C-tube drainage was (500±163) mL/d (180-820 mL/d). Excluding three patients with early dislodgement of C-tube, among the fifteen patients with C-tube maintained, the median time of C-tube removal was 8 d (5-12 d). The duration of hospital stay was (12±3) d (7-21 d) for the 18 patients. Five C-tube related adverse events were observed, all of which occurred in the patients with traditional laparoscopic transcystic drainage, including two abnormal position of the C-tube, and three early dislocation of the C-tube. All the 5 adverse events caused no complications. Only one grade one complication occurred, which was in a patient with modified laparoscopic transcystic drainage. The patient demonstrated transient fever after C-tube removal, but there was no bile in the drainage tube and the subsequent CT examination confirmed no bile leakage. The fever spontaneously relieved with conservative observation, and the patient recovered uneventfully with discharge the next day. All the 18 patients were followed up for 1-20 months (median: 9 months). Normal liver function and no recurrence of stone were detected with ultrasonography or magnetic resonance cholangiopancreatography (MRCP). CONCLUSION: Laparoscopic transcystic drainage combined with common bile duct exploration is safe and feasible in the treatment of patients with difficult biliary stones. The short-term effect is good. Modified laparoscopic transcystic drainage approach may reduce the incidence of C-tube dislocation and bile leak.

[Factors analysis of worsening renal function in patients with acute right ventricular myocardial infarction during hospitalization].

Objective: To analyze the related factors of worsening renal function (WRF) in patients with acute right ventricular myocardial infarction (RVMI) during hospitalization. Methods: A total of 98 patients with acute RVMI admitted to the emergency comprehensive ward of Beijing Anzhen Hospital from August 2011 to January 2020 were enrolled in this cross-sectional study. According to the situation of WRF, the patients were divided into non-WRF group (76 cases) and WRF group (22 cases). WRF was defined as ≥0.3 mg/dL increase in serum creatinine level from baseline on day 6 of hospitalization (if hospital stay<6 days, it was at discharge). Baseline data, intravenous fluid infusion, diuretic and significant positive balance of patients' intake and output volume [any 24 h intakes and outputs ≥1 000 ml or any consecutive 72 h intakes and outputs ≥2 000 ml within 6 d of hospitalization (if hospitalization<6 d, it was from admission to discharge)] were obtained, and the differences of above indicators between the two groups were analyzed. Multiple logistic regression model was used to analyze the related factors of WRF. Results: The ages of patients in WRF group and non-WRF group were 60 (50, 68) and 63 (52, 72) years, and the male proportions were 63.6% (14 cases) and 76.3% (58 cases), respectively, and there was no significant difference (all P>0.05). The proportion of positive balance was 31.8% (7 cases) in WRF group, which was higher than 14.5% (11 cases) in non-WRF group (P=0.034). The rate of loop diuretic use in WRF group was 4.5% (1 case), lower than that in non-WRF group 10.5% (8 cases) (P=0.027). After adjusting for age, sex, baseline estimated glomerular filtration rate (eGFR), preoperative isoproterenol/temporary pacemaker/atropine use, significant positive balance of intake and output volume, and loop diuretic use, it was found that eGFR≥60 ml·min-1·1.73 m-2 and significant positive balance were associated with WRF, the OR (95%CI) were 0.71 (0.62-0.86) and 1.21 (1.02-1.43) (both P<0.05); After eliminating the variable of significant positive balance in the above model, loop diuretic use was found to be a correlation factor for WRF, with an OR (95%CI) of 0.89 (0.72-0.97) (P<0.05). Conclusions: Significant positive balance of intake and output volume during hospitalization in patients with acute RVMI is a risk factor for WRF on day 6 or at discharge. In the presence of a significant positive balance, loop diuretic use is a protective factor for WRF.

[Mechanism of human airway epithelial cell injury induced by Candida albicans infection].

Objective: To investigate the immune mechanism of human airway epithelial cell injury induced by invasion of Candida albicans with different biofilm formation abilities. Methods: Twenty-five strains of Candida albicans isolated and cultured in General Hospital of Ningxia Medical University from June to December 2019 were selected, and quality control strain SC5314 was used as the standard strain. An in vitro model of Candida albicans biofilm was established, and the biofilm formation ability of different Candida albicans was detected by crystal violet staining and enzyme plate method. The absorbance value at 570 nm (A570) was determined by enzyme plate method. A570≥0.5, 0.250.05). Conclusion: Strong biofilm Candida albican can inhibit cell proliferation, disrupt the integrity of epithelial cells and induce cell damage by down-regulating the expression of cell proliferation-related protein.

Effect of tirofiban in treating patients with progressive ischemic stroke.

OBJECTIVE: Our aim is to investigate the efficacy and safety of tirofiban in the treatment of patients experiencing progressive ischemic stroke (PIS). PATIENTS AND METHODS: A retrospective analysis was performed on the clinical data of 150 patients with ischemic stroke admitted to our hospital from May 2018 to December 2019. All the patients were divided into two groups according to different treatment methods. In Control group, conventional comprehensive treatment and antiplatelet therapy with aspirin + clopidogrel were conducted, while tirofiban was administered in Tirofiban group in addition to the treatments in Control group. Neurological deficits were scored by means of the National Institutes of Health Stroke Scale (NIHSS) at the time of progression and 30 d after treatment, and the modified Rankin Scale (mRS) and Activity of Daily Living (ADL) scale were employed to assess prognosis at 90 d after treatment. Thereafter, the platelet aggregation rate, platelet adhesion rate, plateletcrit (PCT), platelet distribution width (PDW), and platelet inhibition rate were measured before and after treatment. Finally, the patients were followed up, and the occurrence of hemorrhage events during treatment and within 90 d after discharge was recorded. RESULTS: After treatment, all the patients had significantly lower NIHSS and mRS scores and a dramatically higher Barthel index (BI) than those before treatment (p<0.001). At 90 d after treatment, Tirofiban group exhibited significantly higher BI (p<0.001) and lower mRS score than Control group (p=0.011). In addition, at 14 d after treatment, the clinical efficacy was assessed for all the patients. It was found that the overall response rate in Tirofiban group was substantially higher than that in Control group [82.7% (62/75) vs. 64.0% (48/75), p=0.009]. At 7 d after treatment, the PCT and adenosine diphosphate (ADP) platelet inhibition rate in Tirofiban group were markedly higher than those in Control group (p=0.006, p<0.001), and Tirofiban group had remarkably lower measured values of platelet aggregation rate, platelet adhesion rate and PDW than Control group (p=0.007, p=0.021, p<0.001). After treatment, the levels of serum IL-6 and hs-CRP declined notably in the two groups of patients, and the differences in their levels at 2 and 14 d after treatment between the two groups were statistically significant (p<0.05). During treatment and within 90 d after discharge, both groups of patients had no cerebral hemorrhage, gastrointestinal hemorrhage, and severe hemorrhage adverse events requiring blood transfusion, but they experienced subcutaneous ecchymosis, epistaxis, gingival hemorrhage, and hemorrhage around the infarct, which were improved after symptomatic treatment. Moreover, the occurrence rate of hemorrhage in Tirofiban group was higher than that in Control group, showing no statistically significant difference (p>0.05). CONCLUSIONS: Tirofiban combined with conventional basic treatment can greatly improve neurological deficits and disease outcomes, alleviate platelet adhesion, and reduce platelet activation without increasing the risk of hemorrhage in PIS patients.

Dual-energy CT perfusion imaging for differentiating invasive thymomas, thymic carcinomas, and lymphomas in adults.

AIM: To evaluate the role of dual-energy computed tomography perfusion (DECTP) imaging in differentiating invasive thymomas (ITs), thymic cancers (TCs), and lymphomas in adults. MATERIALS AND METHODS: Ninety-five patients with solid masses in the prevascular mediastinum who underwent DECTP examinations were enrolled in this study. The perfusion parameters (blood flow, BF; blood volume, BV; mean transit time, MTT; permeability surface, PS) and spectral parameters (water concentration, WC; iodine concentration, IC; normalised iodine concentration, NIC; the slope of spectral radiodensity [Hounsfield units] curve, λHU) of the lesions were analysed. RESULTS: There were no differences in the MTT or WC values among ITs, TCs, and lymphomas (all p>0.05). The IC, NIC, and λHU values in the optimal arterial and venous phases and PS values of TCs were higher than those of ITs and lymphomas (all p<0.05), and there were no differences between ITs and lymphomas (all p>0.05). The BF and BV values of lymphomas were lower than those of ITs and TCs (all p<0.05), and there were no differences between ITs and TCs (all p>0.05). The cut-off values for BF and BV used to differentiate lymphomas from ITs and TCs were 42.83 ml/min/100 g and 4.66 ml/100 g, respectively (area under the receiver operating characteristic curve: 0.847 and 0.839; sensitivity, 80.6% and 82.1%; specificity, 75% and 71.4%; accuracy, 78.9% and 81.1%). CONCLUSIONS: The perfusion and spectral parameters of DECTP imaging help to identify ITs, TCs, and lymphomas, and BF and BV values help to differentiate lymphomas from ITs and TCs.

[Comparison study for the proportion of underdiagnosed zonulopathy in angle closure glaucoma].

Objective: To analyze the proportion and clinical characteristics of underdiagnosed zonulopathy in angle closure glaucoma (ACG) patients and to explore the related risk factors. Methods: Case-control study. Continuous cases of ACG patients who underwent phacoemulsification combined with intraocular lens implantation and goniosynechialysis surgery [ACG group, including acute angle closure glaucoma (AACG) and chronic angle closure glaucoma (CACG)] from November 1, 2020 to October 31, 2021 and age-related cataract patients who underwent phacoemulsification combined with intraocular lens implantation surgery in the same period (control group) were included. The diagnosis of zonulopathy was determined according to the intraoperative signs such as wrinkles of the anterior capsule during continuous circular capsulorhexis. The proportion of zonulopathy, preoperative diagnosis rate of zonulopathy, demographic characteristics, anterior chamber depth (ACD), axis length, difference of ACD in both eyes (ACD of the contralateral eye minus ACD of the operated eye) were compared between the two groups. The related risk factors were explored. The paired t-test (comparison between two groups of normally distributed data), non-parametric test (comparison between two groups of non-normally distributed data), Chi-square test (categorical variables), univariate and multivariate logistic regression analysis were used. Results: There were 104 ACG patients (104 eyes), including 63 AACG patients (63 eyes) and 41 CACG patients (41 eyes), and 117 controls (117 eyes). There was no significant difference in age (P=0.29) and gender (P=0.07) between the two groups. The ACG group had shallower anterior chamber (P<0.001), shorter axial length (P<0.001) and more ACD difference in both eyes (P<0.001). In the ACG group, the proportion of zonulopathy was 46.2% (48/104), which was significantly higher than that (6.0%, 7/117) in the control group (P<0.001). In the control group, only zonular laxity was found, while in the ACG group, besides the predominant zonular laxity (68.8%, 33/48), there was zonular dehiscence (31.3%, 15/48). The eyes with AACG (57.1%, 36/63) had a higher proportion of zonulopathy than those with CACG (29.3%, 12/41) (P=0.006). In the ACG group, only 14 cases (29.8%) were diagnosed preoperatively according to slit lamp examination and/or ultrasound biomicroscopy. The proportion of underdiagnosed zonulopathy was 70.8% in the ACG group (34/48). A smaller ACD was found to be related to the zonulopathy in the ACG group. All AACG cases with an ACD ≤2.0 mm and CACG cases with an ACD ≤1.9 mm had zonulopathy. Multivariate logistic regression showed that the ACD difference in both eyes (P=0.025) and the diagnosis of ACG (AACG vs. cataract, P<0.001; CACG vs. cataract, P=0.023) were independent risk factors associated with zonulopathy. Conclusions: The proportion of underdiagnosed zonulopathy among ACG patients is high. Better preoperative diagnostic methods for zonulopathy are needed. Zonulopathy is common in ACG patients, especially in AACG patients, suggesting that zonulopathy may be related to the pathogenesis of ACG. The shallower the ACD, the riskier the zonulopathy. ACD differences between two eyes and ACG types (including AACG and CACG) were related risk factors of zonulopathy.(This article was published ahead of print on the Online-First Publishing Platform for Excellent Scientific Researches of Chinese Medical Association Publishing House on March 11, 2022).

Changes of brain-derived neurotrophic factors in rats with generalized anxiety disorder before and after treatment.

OBJECTIVE:   The aim of the current study was to investigate the association between brain-derived neurotrophic factor (BDNF) and generalized anxiety disorder (GAD). MATERIALS AND METHODS: A total of sixty male adult Wistar rats with similar body weight and age were randomly divided into 3 groups the blank control group (CON, n=20), the saline control group (SAL, n=20), and the combined medication group (Deanxit +fluoxetine, DF, n=20), then rats in group SAL and group DF were prepared for model of anxiety disorder for 14 days. The body weight, center-retention time (CRT) and square-crossover number per unit time (SCN) were compared during modeling to define the anxiety of rats on day 1, day 7 and day 14; the BDNF mRNA in brain were detected by RT-PCR and the protein of BDNF in brain were detected by immunohistochemistry before and after intervention. The body weight, CRT and SCN in group SAL and DF after modeling were decreased with time compared with CON (p<0.05). The rats were taken euthanasia after 14 days, the BDNF mRNA showed significant decrease in SAL group (0.58±0.07) compared with group CON (2.87±0.23), while in DF group (1.76±0.21), the BDNF mRNA were higher than SAL group but lower than CON (p<0.05); the BDNF positive cells in group CON was highest (90%), then was group DF (75%) and group SAL was the lowest (35%). RESULTS: The changes in the indexes of the rats among different groups before and after modeling showed that after modeling, the body weights of the rats in group SAL and group DF were lower than group CON, the CRT decreased, and the SCN increased. The differences were statistically significant (p < 0.05), indicating that the combined medication (Qilixin + fluoxetine) can improve anxiety symptoms (body weight, CRT, and SCN). CONCLUSIONS: Anti-anxiety drugs (Deanxit+fluoxetine) can improve anxiety symptoms of rats and increase the expressions of BDNF mRNA and protein in rat brain cells. Anxiolytic drugs (Deanxit+fluoxetine) may achieve the treatment of anxiety disorders through improving the 5-HT nervous system and the expressions of BDNF mRNA and protein. BDNF can be used as a biochemical indicator for the diagnosis and efficacy evaluation of GAD.

Propofol ameliorates acute postoperative fatigue and promotes glucagon-regulated hepatic gluconeogenesis by activating CREB/PGC-1α and accelerating fatty acids beta-oxidation.

Postoperative fatigue (POF) is the most common and long-lasting complication after surgery, which brings heavy burden to individuals and society. Recently, hastening postoperative recovery receives increasing attention, but unfortunately, the mechanisms underlying POF remain unclear. Propofol is a wildly used general anesthetic in clinic, and inspired by the rapid antidepressant effects induced by ketamine at non-anesthetic dose, the present study was undertaken to investigate the anti-fatigue effects and underlying mechanisms of propofol at a non-anesthetic dose in 70% hepatectomy induced POF model in rats. We first showed here that single administration of propofol at 0.1 mg/kg ameliorated acute POF in hepatectomy induced POF rats. Based on metabonomics analysis, we hypothesized that propofol exerted anti-fatigue activity in POF rats by facilitating free fatty acid (FFA) oxidation and gluconeogenesis. We further confirmed that propofol restored the deficit in FFA oxidation and gluconeogenesis in POF rats, as evidenced by the elevated FFA utilization, acetyl coenzyme A content, pyruvic acid content, phosphoenolpyruvic acid content, hepatic glucose output and glycogen storage. Moreover, propofol stimulated glucagon secretion and up-regulated expression of cAMP-response element binding protein (CREB), phosphorylated CREB, peroxlsome prolifeator-activated receptor-γ coactivator-1α (PGC-1α), phosphoenolpyruvate carboxykinade1 and carnitine palmitoltransferase 1A. In summary, our study suggests for the first time that propofol ameliorates acute POF by promoting glucagon-regulated gluconeogenesis via CREB/PGC-1α signaling and accelerating FFA beta-oxidation.

[Diagnostic value of serum amyloid A and C-reactive protein for predicting acute aortic dissection].

Objective: To explore the diagnostic value of serum amyloid A (SAA) and C-reactive protein (CRP) for predicting acute aortic dissection (AAD). Methods: One hundred and seventy-five AAD patients and 160 patients with acute coronary syndrome (disease control group) who were admitted to Cardio-cerebrovascular Disease Hospital of General Hospital of Ningxia Medical University from January 2018 to June 2020 were retrospectively selected. Meanwhile, 148 healthy subjects (healthy control group) who underwent physical examination were also enrolled. The latex-enhanced immunoturbidimetric assay and the latex immunoturbidimetric assay were used to determine the serum SAA and CRP levels of all subjects, and related clinical data were collected and analyzed. Univariate and multivariate logistic regression analyses were performed to analyze the independent risk factors, and the receiver operating characteristic (ROC) curve was drawn to calculate the diagnostic value of SAA and CRP for predicting AAD. Results: The levels of SAA and CRP in the AAD patient group ((165.7±7.4) mg/L and (76.0±4.0)mg/L) were significantly higher than those of the healthy control group ((6.5±0.4) mg/L and (3.9±0.2) mg/L) and the disease control group ((27.2±1.3) mg/L and (9.4±3.2) mg/L), with significant differences (all P<0.05). Compared with patients less than 60 years, levels of SAA and CRP in AAD patients over 60 years old decreased ((150.6±12.7) mg/L and (73.9±7.3) mg/L), and there were significant differences (both P<0.05). Likewise, SAA levels in AAD patients with high-risk pain characteristics over 6 h increased compared to those with pain less than 6 h, and there was a significant difference (P<0.05). SAA was positively correlated with CRP (r=0.053 4, P<0.05). ROC analysis showed that SAA and CRP levels were independently related to the risk of AAD (P=0.001), and the ROC curve of SAA for predicting AAD showed that the area under the curve (AUC) of type A aortic dissection (TAAD) and type B aortic dissection (TBAD) were 0.997 and 0.995, respectively (both P<0.001). And the ROC curve of CRP for predicting AAD demonstrated that the AUC of TAAD and TBAD were 0.998 and 0.991, respectively (both P<0.001). The best cut-off values of SAA and CRP for predicting AAD were 175.17 mg/L and 72.96 mg/L, respectively. Conclusion: Increased levels of SAA and CRP have high predictive value for AAD, and SAA combined with CRP is expected to serve as a laboratory marker to assist the diagnosis of AAD.

[In vivo study of liposome-modified polyetheretherketone implant on bacteriostasis and osseointegration].

OBJECTIVE: To develop dexamethasone plus minocycline-loaded liposomes (Dex/Mino liposomes) and apply them to improve bioinert polyetheretherketone (PEEK) surface, which could prevent post-operative bacterial contamination, enhance ossification for physiologic osseointegration, and finally reduce implant failure rates. METHODS: Dex/Mino liposomes were covalently grafted onto the PEEK surface using polydopamine (pDA) coating as a medium. Confocal laser scanning microscopy was used to confirm the binding of fluorescently labeled liposomes onto the PEEK substrate, and a microplate reader was used to semiquantitatively measure the average fluorescence intensity of fluorescently labeled liposome-decorated PEEK surfaces. Moreover, the mouse subcutaneous infection model and the beagle femur implantation model were respectively conducted to verify the bioactivity of Dex/Mino liposome-modified PEEK in vivo, by means of micro computed tomography (micro-CT) and hematoxylin and eosin (HE) staining analysis. RESULTS: The qualitative and quantitative results of fluorescently labeled liposomes showed that, the red fluorescence intensity of the PEEK-pDA-lipo group was stronger than that of the PEEK-NF-lipo group (P < 0.05); the liposomes were successfully and uniformly decorated on the PEEK surfaces due to the pDA coating. After mouse subcutaneous implantation of PEEKs for 24 hours, HE staining results showed that the number of inflammatory cells in the PEEK-Dex/Mino lipo group were lower than that in the inert PEEK group (P < 0.05), indicating a lower degree of infection in the test group. These results suggested that the Mino released from the liposome-functionalized surface provided an effective bacteriostasis in vivo. After beagle femoral implantation of PEEK for 8 weeks, micro-CT results showed that the PEEK-Dex/Mino lipo group newly formed more continuous bone when compared with the inert PEEK group; HE staining results showed that more new bones were formed in the PEEK-Dex/Mino lipo group than in the inert PEEK group, which were firmly bonded to the functionalized PEEK surface and extended along the PEEK interface. These results suggested that the Dex released from the liposome-functionalized surface induced effective bone regeneration in vivo. CONCLUSION: Dex/Mino liposome modification enhanced the bioactivity of inert PEEK, the functionalized PEEK with enhanced antibacterial and osseointegrative capacity has great potential as an orthopedic/dental implant material for clinical application.

[Effect of androgen replacement therapy on mixed dry eye in a rabbit model].

Objective: To explore the effect of androgen replacement therapy in a rabbit dry eye model characterized by androgen deficiency and meibomian gland dysfunction (MGD). Methods: Thirty 6-month-old male Chinchilla rabbits were randomly divided into the treatment group, model group and control group, with 10 rabbits in each group. In the treatment and model groups, 2/3 of the meibomian gland openings were closed by cauterization with electric coagulation pen, and bilateral testes were removed. One gram gel containing 1% testosterone was applied for 28 days on the skin of rabbits in the treatment group since day 28 after the surgery. The model group and control group received transdermal petrolatum instead. Tear secretion, tear breakup time (TBUT), corneal fluorescein staining, and serum free testosterone level were monitored throughout the study period. The globes and eyelids were collected for hematoxylin-eosin staining and periodic acid-Schiff staining. Conjunctival tissue was tested for the expression of miRNA-744-5p and interleukin-6. Meibum was collected for fatty acid analysis. Results: Animals presented with typical dry eye signs and androgen deficiency. After 28-day androgen replacement therapy, compared with the model group, the treatment group had a significantly higher tear secretion rate [(14.7±5.2) vs (10.3±3.6) mm, P=0.001], higher TBUT [(15.0±4.2) vs (10.2±3.6) s, P=0.003], lower fluorescein staining score [0 (0, 1) vs 2 (1, 4), P<0.001], and higher goblet cell density at conjunctival fornix (27.2±7.6 vs 10.7±4.8, P<0.001). Additionally, compared with the model group, the conjunctiva of the treatment group expressed a significantly lower level of miRNA-744-5p (1.67±0.24 vs 2.63±0.58, P<0.001) and interleukin-6 [2.38 (1.84, 4.61) vs 4.82 (3.99, 6.36), P=0.022]. Meanwhile, the treatment group showed significantly increased level of 16∶1, Δ9 fatty acid [(10.31±1.00)% vs (3.87±0.45)%, P<0.001] and iso-18∶0 fatty acid [(7.09±0.93)% vs (2.44±0.70)%, P<0.001], but decreased level of iso-26∶0 fatty acid [(5.72±1.07)% vs (8.02±0.65)%, P<0.001] in the meibum compared with the model group. Conclusion: Androgen replacement therapy can alleviate dry eye signs in rabbits presented with combined androgen deficiency and MGD.

[Application of BRAF in the diagnosis and treatment of thyroid papillary carcinoma].

Thyroid cancer is the most common endocrine malignancy, and thyroid carcinoma (PTC) has the highest incidence rate, accounts for about 85%~90% of thyroid carcinoma. There are many markers of PTC, such as murine sarcoma viral oncogene homolog B1 (BRAF), telomerase reverse transcriptase, Ki-67, microRNA-146b, PDZ and LIM domain 5 (PDLIM5). Among them, BRAF plays an important role in the carcinogenesis, development and prognosis of PTC. This article summarizes the research progress of BRAF signaling pathway, its role in the carcinogenesis, development and prognosis of PTC, its clinical correlation with the clinical pathological characteristics of PTC, and its application in the diagnosis and treatment of PTC to provide the references to readers.