[Expression changes of RNA m6A regulators in mouse cerebellum affected by hypobaric hypoxia stimulation].

Objective: To investigate the role of RNA m6A methylation in mediating cerebellar dysplasia through analyzing the phenotypes of the mouse cerebella and the expression of several key m6A regulators upon hypobaric hypoxia treatment. Methods: Five-day old C57/BL6 mice were exposed to hypobaric hypoxia for 9 days. The status of mouse cerebellar development was analyzed by comparing the body weights, brain weights and histological features. Immunostaining of cell-type-specific markers was performed to analyze the cerebellar morphology. Real-time PCR, Western blot and immunohistochemical staining were performed to detect the expression of key m6A regulators in the mouse cerebella. Results: Compared with the control, the body weights, brain weights and cerebellar volumes of hypobaric hypoxic mice were significantly reduced (P<0.01). The expression of specific markers in different cells, including NeuN (mature neuron), Calbindin-D28K (Purkinje cell) and GFAP (astrocyte), was decreased in hypobaric hypoxic mouse cerebella (P<0.01), accompanied with disorganized cellular structure. The expression of methyltransferase METTL3 was significantly down-regulated in the cerebella of hypobaric hypoxic mice (P<0.05). Conclusions: Hypobaric hypoxia stimulation causes mouse cerebellar dysplasia, with structural abnormalities in mature granular neurons, Purkinje cells and astrocytes. Expression of METTL3 is decreased in hypobaric hypoxic mice cerebellum compared with that of normobaric normoxic mice, suggesting that its mediated RNA m6A methylation may play an important role in hypobaric hypoxia-induced mouse cerebellar dysplasia.

Myokines and Biomarkers of Frailty in Older Inpatients with Undernutrition: A Prospective Study.

BACKGROUND: Population aging might increase the prevalence of undernutrition in older people, which increases the risk of frailty. Numerous studies have indicated that myokines are released by skeletal myocytes in response to muscular contractions and might be associated with frailty. This study aimed to evaluate whether myokines are biomarkers of frailty in older inpatients with undernutrition. METHODS: The frailty biomarkers were extracted from the Gene Expression Omnibus and Genecards datasets. Relevant myokines and health-related variables were assessed in 55 inpatients aged ≥ 65 years from the Peking Union Medical College Hospital prospective longitudinal frailty study. Serum was prepared for enzyme-linked immunosorbent assay using the appropriate kits. Correlations between biomarkers and frailty status were calculated by Spearman's correlation analysis. Multiple linear regression was performed to investigate the association between factors and frailty scores. RESULTS: The prevalence of frailty was 13.21%. The bioinformatics analysis indicated that leptin, adenosine 5'-monophosphate-activated protein kinase (AMPK), irisin, decorin, and myostatin were potential biomarkers of frailty. The frailty group had significantly higher concentrations of leptin, AMPK, and MSTN than the robust group (p < 0.05). AMPK was significantly positively correlated with frailty (p < 0.05). The pre-frailty and frailty groups had significantly lower concentrations of irisin than the robust group (p < 0.05), whereas the DCN concentration did not differ among the groups. Multiple linear regression suggested that the 15 factors influencing the coefficients of association, the top 50% were the ADL score, MNA-SF score, serum albumin concentration, urination function, hearing function, leptin concentration, GDS-15 score, and MSTN concentration. CONCLUSIONS: Proinflammatory myokines, particularly leptin, myostatin, and AMPK, negatively affect muscle mass and strength in older adults. ADL and nutritional status play major roles in the development of frailty. Our results confirm that identification of frailty relies upon clinical variables, myokine concentrations, and functional parameters, which might enable the identification and monitoring of frailty.

Risk factor analysis and nomogram construction in patients with distant metastatic prostate cancer at different PSA levels: a study based on the SEER database.

OBJECTIVE: Prostate cancer (PCa) is the most common malignant tumor in the male genitourinary system. Once PCa has metastasized, it is very difficult to cure. The purpose of this study was to investigate the prognostic risk factor analysis of patients with different prostate-specific antigen (PSA) levels in distant metastatic PCa. At the same time, we construct effective models for predicting the survival rate of prostate cancer patients. PATIENTS AND METHODS: Data on prostate cancer patients with the presence of distant metastases were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. PCa patients with distant metastases were categorized into two groups based on PSA levels, one with PSA <20 ng/mL and the other with PSA ≥20 ng/mL. Univariate and multivariate COX regression analyses were used to identify independent factors affecting the prognosis of the patients. A nomogram was constructed using the independent prognostic factors, and the results were evaluated using calibration curves, timeROC curves, and Kaplan-Meier curves. RESULTS: In the PSA <20 ng/mL group, there were a total of 1,832 patients. COX regression analysis showed that age, marital status, N stage, grade, Gleason score, and medical household income inflation were independent prognostic factors for overall survival (OS) in patients. In addition, we found that age, marital status, N stage, bone metastasis, grade, and Gleason score were independent prognostic factors for cancer-specific survival (CSS) in patients. In the PSA ≥20 ng/mL group, there were a total of 5,314 patients. It was found that age, ethnicity, marital status, bone metastasis, first malignant primary indicator, grade, Gleason score, and medical household income inflation were patients' independent prognostic factors for OS. For CSS, we found that age, ethnicity, marital status, T stage, radiotherapy, bone metastasis, Gleason score, and Median household income inflation were independent prognostic factors. Constructing a nomogram can accurately predict the prognosis of this group of patients. CONCLUSIONS: We found different independent prognostic factors for different PSA levels in patients with distant metastatic PCa. A new nomogram was constructed to predict OS and CSS in patients, which helps in clinical-assisted decision-making.

[Clinical value of focused ultrasound ablation surgery in the treatment of abdominal wall endometriosis].

Objective: To explore the effectiveness and safety of focused ultrasound ablation surgery (FUAS) for abdominal wall endometriosis. Methods: From November 2019 to October 2022, a total of 34 patients with abdominal wall endometriosis who underwent FUAS were collected, and their clinical features, imaging features, intraoperative treatment and side effects after treatment were analyzed retrospectively, and the improvement of symptoms and re-intervention were followed up. Results: (1) Characteristics of clinical data: the average age of 34 patients with abdominal wall endometriosis was (32.8±3.8) years old. The largest diameter of the lesion was 48 mm, and the median lesion diameter was 24 mm. Thirty cases (88%, 30/34) had moderate to severe periodic pain in abdominal incision before FUAS. All patients were diagnosed by preoperative magnetic resonance imaging, including 19 cases (56%, 19/34) of superficial type, 8 cases (24%, 8/34) of intermediate type and 7 cases (21%, 7/34) of deep type. (2) FUAS treatment parameters: ablation was completed with average operation time of (64±18) minutes, average sonication time was (385±108) s, (103±11) W of average power, (38 819±16 309) J of average total energy, the average treatment area volume of (3.11±1.42) cm3, and (377.79±106.34) s/h of average treatment intensity. (3) Efficiency: the pain of patients after FUAS was significantly relieved, and the pain scores of patients after 1 month, 3 months, 6 months and 1 year after FUAS were significantly decreased (Z=-4.66, -5.13, -5.11 and -4.91, all P<0.01). One year after FUAS, the near relief and effective pain relief rate was 74% (25/34), and the clinical effective rate was 85% (29/34). Five patients recurred after one year, including 3 patients who underwent abdominal wall endometriosis lesion resection and 2 patients who received drug treatment. One month after FUAS, the size of the lesion did not change significantly compared with that before FUAS (P>0.05), and the size of the lesion decreased significantly after FUAS at 3 months, 6 months and 1 year (Z=-2.15, -2.67 and -3.41, all P<0.05). It has no difference in pain relief among different types (P>0.05), but has significant difference in focus reduction among three types (P<0.01). (4) Safety: there were 34 cases (100%, 34/34) of skin burning sensation, 19 cases (56%, 19/34) of pain in the treatment area and 2 cases (6%, 2/34) of hematuria. All patients got better after corresponding treatments. Conclusion: FUAS is safe and effective for the treatment of abdominal wall endometriosis, which has clinical application value.

[Cutting scheme and clinical application effects of ultrathin thoracodorsal artery perforator flap assisted by color Doppler ultrasound].

Objective: To explore the cutting scheme and clinical application effects of ultrathin thoracodorsal artery perforator flap assisted by color Doppler ultrasound. Methods: This study was a retrospective historical control study. From February 2017 to October 2019, 20 patients who were admitted to the Third Department of Orthopedics of Xingtai General Hospital of North China Medical and Health Group (hereinafter referred to as our department), met the inclusion criteria, and underwent repair of skin and soft tissue defects of extremities with ultrathin thoracodorsal artery perforator flap designed and harvested based on the surgeon's clinical experience were selected as control group, including 16 males and 4 females, aged (37±5) years. From November 2019 to December 2022, 21 patients who were admitted to our department, met the inclusion criteria, and underwent repair of skin and soft tissue defects of extremities with ultrathin thoracodorsal artery perforator flap designed and harvested under the assistance of color Doppler ultrasound were selected as ultrasound-assisted group, including 15 males and 6 females, aged (38±6) years. After debridement, the area of skin and soft tissue defects of extremities ranged 5.0 cm×4.0 cm to 19.0 cm×8.0 cm, and the area of thoracodorsal artery perforator flaps ranged 6.0 cm×5.0 cm to 20.0 cm×9.0 cm. The wounds in flap donor sites were closed directly. For patients in ultrasound-assisted group, the time and cost required for color Doppler ultrasound examination were recorded, and the number, type, and location of thoracodorsal artery perforator vessels detected by preoperative color Doppler ultrasound were compared with those of intraoperative actual detection. The time required for complete flap harvest of patients in 2 groups was recorded. On postoperative day (POD) 1, 3, 5, 7, and 14, the blood perfusion of flaps in the 2 groups of patients was assessed using a flap perfusion assessment scale. On POD 14, flap survival of patients in 2 groups was observed, and the percentage of flap survival area was calculated. In postoperative 6 months, satisfaction of patients with the treatment outcome in the 2 groups was assessed using 5-grade Likert scale, and the satisfaction rate was calculated. Results: For patients in ultrasound-assisted group, the time required for preoperative color Doppler ultrasound examination was (10.5±2.3) min, and the cost was 120 yuan; 21 thoracodorsal artery perforator vessels were detected and marked using preoperative color Doppler ultrasound, including 8 (38.10%) type 1 perforator vessels, 10 (47.62%) type 2 perforator vessels, and 3 (14.29%) type 3 perforator vessels; the number, type, and location of thoracodorsal artery perforator vessels detected preoperatively were consistent with those detected intraoperatively. The time required for complete flap harvest of patients in ultrasound-assisted group was (41±10) min, which was significantly shorter than (63±12) min in control group (t=6.32, P<0.05). On POD 1, 3, 5, 7, and 14, the blood perfusion scores of flaps of patients in ultrasound-assisted group were significantly better than those in control group (with t values of 6.67, 7.48, 8.03, 8.75, and 7.99, respectively P<0.05). On POD 14, only one patient in ultrasound-assisted group had partial flap necrosis and 6 patients in control group had complete or partial necrosis of the flap; the percentage of flap survival area of patients in ultrasound-assisted group was (99±8)%, which was significantly higher than (87±8)% in control group (t=4.57, P<0.05). In postoperative 6 months, there was no significant difference in the satisfaction rate of patients with the treatment outcome between the two groups (P>0.05). Conclusions: Preoperative color Doppler ultrasound is highly accurate in detecting the number, type, and location of perforator vessels. The cutting scheme of ultrathin thoracodorsal artery perforator flaps can be designed according to the different types of perforator vessels, with shorted flap cutting time and improved flap survival rate.

Cardiac MRI feature-tracking-derived torsion mechanics in systolic and diastolic dysfunction in systemic light-chain cardiac amyloidosis.

AIM: To describe the myocardial torsion mechanics in cardiac amyloidosis (CA), and evaluate the correlations between left ventricle (LV) torsion mechanics and conventional parameters using cardiac magnetic resonance imaging feature tracking (CMR-FT). MATERIALS AND METHODS: One hundred and thirty-nine patients with light-chain CA (AL-CA) were divided into three groups: group 1 with preserved systolic function (LV ejection fraction [LVEF] ≥50%, n=55), group 2 with mildly reduced systolic function (40% ≤ LVEF <50%, n=51), and group 3 with reduced systolic function (LVEF <40%, n=33), and compared with age- and gender-matched healthy controls (n=26). All patients underwent cine imaging and late gadolinium-enhancement (LGE). Cine images were analysed offline using CMR-FT to estimate torsion parameters. RESULTS: Global torsion, base-mid torsion, and peak diastolic torsion rate (diasTR) were significantly impaired in patients with preserved systolic function (p<0.05 for all), whereas mid-apex torsion and peak systolic torsion rate (sysTR) were preserved (p>0.05 for both) compared with healthy controls. In patients with mildly reduced systolic function, global torsion and base-mid torsion were lower compared to those with preserved systolic function (p<0.05 for both), while mid-apex torsion, sysTR, and diasTR were preserved (p>0.05 for all). In patients with reduced systolic function, only sysTR was significantly worse compared with mildly reduced systolic function (p<0.05). At multivariable analysis, right ventricle (RV) end-systolic volume RVESV index and NYHA class were independently related to global torsion, whereas LVEF was independently related to sysTR. RV ejection fraction (RVEF) was independently related to diasTR. LV global torsion performed well (AUC 0.71; 95% confidence interval [CI]: 0.61, 0.77) in discriminating transmural from non-transmural LGE in AL-CA patients. CONCLUSION: LV torsion mechanics derived by CMR-FT could help to monitor LV systolic and diastolic function in AL-CA patients and function as a new imaging marker for LV dysfunction and LGE transmurality.

[Clinical efficacy of posterior femoral muscle flaps combined with posterior femoral cutaneous nerve nutrient vessel flap and closed lavage in the treatment of stage â £ ischial tuberosity pressure ulcers].

Objective: To explore the clinical efficacy of posterior femoral muscle flaps combined with posterior femoral cutaneous nerve nutrient vessel flap and closed lavage in the treatment of stage Ⅳ ischial tuberosity pressure ulcers. Methods: This study was a retrospective observational study. From March 2021 to March 2022, 15 patients with stage Ⅳ ischial tuberosity pressure ulcers who met the inclusion criteria were admitted to Dezhou Dongcheng Hospital, including 11 males and 4 females, aged 31 to 72 years. The pressure ulcer wound size ranged from 6.0 cm×4.5 cm to 10.0 cm×6.0 cm, with cavity diameters of 10-14 cm. Five cases were complicated with ischial tuberosity bone infection. After clearing the lesion, the biceps femoris long head muscle flap with an area of 10.0 cm×4.0 cm-18.0 cm×5.0 cm and the semitendinosus muscle flap with an area of 8.0 cm×4.0 cm-15.0 cm×5.0 cm combined with the posterior femoral cutaneous nerve nutrient vessel flap with an area of 6.5 cm×5.5 cm-10.5 cm×6.5 cm was transplanted to repair the pressure ulcer wound. The flap donor area was directly sutured, and the closed lavage with tubes inserted into the wound cavity was performed for 2-3 weeks. The postoperative survival of the muscle flaps and skin flaps, the wound healing of the donor and recipient areas were observed. The recurrence of pressure ulcers, the appearance and texture of flaps, and scar conditions of the donor and recipient areas were followed up. Results: All the muscle flaps and skin flaps in the 15 patients successfully survived after surgery. Two patients experienced incisional dehiscence at one week after surgery due to improper turning over, during which the incision in the recipient area was pressed on, and the wounds healed after dressing changes of 3 to 4 weeks; the wounds in the donor and recipient areas healed well in the other patients. All patients received follow-up after surgery. During the follow-up period of 6 to 12 months, none of the patients experienced pressure ulcer recurrence, and the texture, color, and thickness of the skin flaps closely resembled those of the surrounding skin at the recipient site, with only linear scar left in the donor and recipient areas. Conclusions: When using the posterior femoral muscle flaps combined with the posterior femoral cutaneous nerve nutrient vessel flap and closed lavage to treat stage Ⅳ ischial tuberosity pressure ulcers, the tissue flap can be used to fully fill in the dead space of the pressure ulcers. After treatment, the wound heals well, the appearance of the donor and recipient areas is better, and the pressure ulcers are less prone to reoccur.

A comprehensive analysis of essential meiotic endonuclease 1 to prognosis and immune infiltration in kidney renal clear cell carcinoma.

OBJECTIVE: Clear cell renal cell carcinoma (ccRCC) is the most common type of cancer, and its molecular pathogenesis is unclear. In this study, we investigated the prognostic value of essential meiotic endonuclease 1 (EME1) in kidney renal clear cell carcinoma (KIRC). MATERIALS AND METHODS: We downloaded the RNA-Seq expression of 526 KIRC tissues and 72 normal tissues from the TCGA database and the corresponding clinical data. The gene expression profiles associated with four clear cell renal cell carcinomas were downloaded from the GEO database for analysis. The expression of EME1 in clear renal cell carcinoma and its correlation with the clinical baseline data were analyzed. Kaplan-Meier survival curve analysis was performed to assess the relationship between EME1 and patient survival. Enrichment analysis was performed to elucidate the possible functions of EME1. We also analyzed the relationship between the EME1 expression and immune infiltration through TIMER2.0 and TISIDB online databases as well as the relationship between EME1 and common immune checkpoints. RESULTS: EME1 was identified as a risk factor for overall survival in clear cell renal cell carcinoma with a hazard ratio of 3.201 (95% confidence interval: 2.430-4.215; p < 0.001). EME1 was highly expressed in KIRC compared to that in normal tissues (p < 0.001) and in the worse TNM stages and late stages (stage 3/4) (p < 0.001). High EME1 expression was strongly associated with the advanced T stage (p = 0.003), advanced N stage (p = 0.002), and advanced M stage (p = 0.006). Research data on KIRC were simultaneously collected and analyzed from the GEO database, including GSE40435, GSE53000, GSE68417, and GSE53757. EME1 predicted the survival status in KIRC patients (AUC = 0.62). We further established a nomogram including the correlation between the high and low EME1 expression, and EME1 was found to contribute to the prediction of the probability of patient survival with a c-index = 0.796. Kaplan-Meier analysis revealed a lower likelihood of survival with a high EME1 expression (p < 0.001). In addition, further bioinformatics analysis suggested that EME1 may be associated with the extent of immune infiltration in KIRC. CONCLUSIONS: An increased expression of EME1 in KIRC is thus associated with advanced clinicopathological features, possibly acting as a potential biomarker of poor prognosis in KIRC.

An established abdominal wall multidisciplinary team improves patient care and aids surgical decision making with complex ventral hernia patients.

INTRODUCTION: Abdominal wall reconstruction (AWR) is an emerging subspecialty within general surgery. The practice of multidisciplinary team (MDT) meetings to aid decision making and improve patient care has been demonstrated, with widespread acceptance. This study presents our initial experience of over 150 cases of complex hernia patients discussed in a newly established MDT setting. METHODS: From February 2020 to July 2022 (30-month period), abdominal wall MDTs were held bimonthly. Key stakeholders included upper and lower gastrointestinal surgeons, a gastrointestinal specialist radiologist, a plastic surgeon, a high-risk anaesthetist and two junior doctors integrated into the AWR clinical team. Meetings were held online, where patient history, past medical and surgical history, hernia characteristics and up-to-date computed tomography scans were discussed. RESULTS: Some 156 patients were discussed over 18 meetings within the above period. Ninety-five (61%) patients were recommended for surgery, and 61 (39%) patients were recommended for conservative management or referred elsewhere. Seventy-eight (82%) patients were directly waitlisted, whereas seventeen (18%) required preoperative optimisation: three (18%) for smoking cessation, eleven (65%) for weight-loss management and three (18%) for specialist diabetic assessment and management. In total, 92 (59%) patients (including operative and nonoperative management) have been discharged to primary care. DISCUSSION: A multidisciplinary forum for complex abdominal wall patients is a safe process that facilitates decision making, promotes education and improves patient care. As the AWR subspecialty evolves, our view is that the "complex hernia MDT" will become commonplace. We present our experience and share advice for others planning to establish an AWR centre.

[Diagnostic values of conventional tumor markers and their combination with chest CT for patients with stageâ A lung cancer].

Objective: To investigate the diagnostic efficiency of conventional serum tumor markers and their combination with chest CT for stage ⅠA lung cancer. Methods: A total of 1 155 patients with stage ⅠA lung cancer and 200 patients with benign lung lesions (confirmed by surgery) treated at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to October 2020 were retrospectively enrolled in this study. Six conventional serum tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), squamous cell carcinoma associated antigen (SCCA), cytokeratin 19 fragment (CYFRA21-1), neuron-specific enolase (NSE), and gastrin-releasing peptide precursor (ProGRP)] and chest thin-slice CT were performed on all patients one month before surgery. Pathology was taken as the gold standard to analyze the difference of positivity rates of tumor markers between the lung cancer group and the benign group, the moderate/poor differentiation group and the well differentiation group, the adenocarcinoma group and the squamous cell carcinoma group, the lepidic and non-lepidic predominant adenocarcinoma groups, the solid nodule group and the subsolid nodule group based on thin-slice CT, and subgroups of ⅠA1 to ⅠA3 lung cancers. The diagnostic performance of tumor markers and tumor markers combined with chest CT was analyzed using the receiver operating characteristic curve. Results: The positivity rates of six serum tumor markers in the lung cancer group and the benign group were 2.32%-20.08% and 0-13.64%, respectively; only the SCCA positivity rate in the lung cancer group was higher than that in the benign group (10.81% and 0, P=0.022). There were no significant differences in the positivity rates of other serum tumor markers between the two groups (all P>0.05). The combined detection of six tumor markers showed that the positivity rate of the lung cancer group was higher than that of the benign group (40.93% and 18.18%, P=0.004), and the positivity rate of the adenocarcinoma group was lower than that of the squamous cell carcinoma group (35.66% and 47.41%, P=0.045). The positivity rates in the poorly differentiated group and moderately differentiated group were higher than that in the well differentiated group (46.48%, 43.75% and 22.73%, P=0.025). The positivity rate in the non-lepidic adenocarcinoma group was higher than that in lepidic adenocarcinoma group (39.51% and 21.74%, P=0.001). The positivity rate of subsolid nodules was lower than that of solid nodules (30.01% vs 58.71%, P=0.038), and the positivity rates of stageⅠA1, ⅠA2 and ⅠA3 lung cancers were 33.33%, 48.96% and 69.23%, respectively, showing an increasing trend (P=0.005). The sensitivity and specificity of the combined detection of six tumor markers in the diagnosis of stage ⅠA lung cancer were 74.00% and 56.30%, respectively, and the area under the curve (AUC) was 0.541. The sensitivity and specificity of the combined detection of six serum tumor markers with CT in the diagnosis of stage ⅠA lung cancer were 83.0% and 78.3%, respectively, and the AUC was 0.721. Conclusions: For stage ⅠA lung cancer, the positivity rates of commonly used clinical tumor markers are generally low. The combined detection of six markers can increase the positivity rate. The positivity rate of markers tends to be higher in poorly differentiated lung cancer, squamous cell carcinoma, or solid nodules. Tumor markers combined with thin-slice CT showed limited improvement in diagnostic efficiency for early lung cancer.

[A case report of bronchial granular cell tumor].

Granular cell tumor (GCT) is a relatively rare tumor that develops in soft tissues at various sites in the body, and GCT originating in the bronchus is rather rare. Here, we reported a case of primary GCT of the bronchial to improve the understanding of this disease.

[Clinical application of retrosigmoid approach for BONEBRIDGE implantation after auricle reconstruction using expanded postauricular flap].

Objective: To explore the safety and reliability of retrosigmoid approach BONEBRIDGE implantation in patients with auricle reconstruction using skin expansion flap. Methods: A retrospective analysis was conducted on 43 congenital aural atresia cases (43 ears) who underwent BONEBRIDGE implantation from September 2019 to January 2023 in Beijing Tongren Hospital. 30 males and 13 females were included in this work. The implantation age was 9-36 years old (median age=10 y/o). All cases underwent auricle reconstruction surgery using the posterior ear flap expansion method, with 36 cases using the single expanded postauricular flap method and 7 cases using two-flap method. BONEBRIDGE implant surgery was performed during the third stage of auricle reconstruction or after all stages. The hearing improvements were evaluated by comparing the changes in pure tone hearing threshold and speech recognition rate of patients before and after BONEBRIDGE implantation. Routine follow-up was conducted to observe the hearing results and complications. SPSS 14.0 software was applied for data statistical analysis. Results: All 43 patients healed well and had no surgical complications when discharge. The average bone conduction hearing threshold after surgery was (8.2±6.6) dBHL, and there was no statistically significant difference compared to the preoperative [(8.1±5.7) dBHL] (P=0.95). After surgery, the threshold of hearing assistance with power on was significantly lower than that without hearing assistance [(32.8±4.6) dBHL vs (60.5±5.5) dBHL], and the difference was statistically significant (P<0.001). The speech recognition rate of monosyllable words, disyllabic words and short sentences in quiet environment increased to 72%, 84%, and 98% respectively. The differences were statistically significant (P<0.001). The speech recognition rate of monosyllabic words, disyllabic words, and short sentences in noise environment was significantly increased by 70%, 80%, and 92% respectively (P<0.001). After a follow-up of 4 to 47 months (median=24 months), the hearing results were stable and the aesthetic outcomes were satisfying. One patient had delayed hematoma around coil of the implant. After aspiration and compressed dressing for one week, hematoma was not recurrent. Conclusion: For patients after auricle reconstruction using expanded postauricular flap, the preference of retrosigmoid approach is a good choice in terms of safety and reliability of operation, as well as aesthetic appearance.

TNF inhibitors associated with cardiovascular diseases and cardiometabolic risk factors: a Mendelian randomization study.

OBJECTIVE: There is still disagreement about whether anti-tumor necrosis factor (TNF) therapy is beneficial or detrimental to cardiovascular conditions. This two-sample Mendelian randomization (MR) study aimed to evaluate the effects of long-term tumor necrosis factor (TNF) inhibition on cardiovascular diseases (CVDs) and cardiometabolic risk factors via genetically proxied inhibition of tumor necrosis factor receptor 1 (TNFR1) and TNF. MATERIALS AND METHODS: Two genetic instruments were examined to mimic the long-term effect of TNF inhibitors. The first were single-nucleotide polymorphisms (SNPs) within or nearby drug-target genes TNFRSF1A and TNF (encoding TNFR1 and TNF) associated with circulating CRP levels. The other instruments were the expression quantitative trait loci (eQTLs) near the genes. Inverse variance-weighted MR (IVW-MR) and summary-based MR (SMR) methods were employed to estimate causal effects. RESULTS: In IVW-MR analysis, TNF-mediated circulating CRP levels were significantly associated with 4 out of 12 CVDs, including hypertension [odds ratio (OR) = 1.13; 95% CI, 1.09-1.18], coronary artery disease (OR = 3.18; 95% CI, 1.77-5.71), coronary atherosclerosis (OR = 1.05; 95% CI, 1.02-1.08) and type 2 diabetes (OR = 3.48; 95% CI, 1.98-6.10). These findings were also validated in the FinnGen study. Moreover, TNF inhibition was also associated with total cholesterol, triglycerides, apolipoprotein B, systolic blood pressure, serum cystatin C, height, weight, and body mass index. CONCLUSIONS: In this study, the decrease in several CVDs and cardiometabolic risk factors has been found to be causally associated with genetically proxied TNF inhibitors.

[Primary hepatic angiosarcoma: a clinicopathological analysis of nine cases].

Objective: To investigate the clinical manifestations, histomorphology, and differential diagnosis of primary hepatic angiosarcoma. Methods: Nine cases of primary hepatic angiosarcoma diagnosed in the Department of Pathology, the First Affiliated Hospital of Nanjing Medical University from January 2014 to December 2021 were collected, including biopsy and surgical specimens. The histomorphology, clinical, and radiologic findings were analyzed. The relevant literature was also reviewed. Results: There were six males and three females, aged 30 to 73 years (mean 57 years). Grossly, the growth pattern of the tumor was classified as either mass formation or non-mass formation (sinusoidal). Microscopically, the mass-forming primary hepatic angiosarcoma were further subdivided into vasoformative or non-vasoformative growth patterns; and those non-vasoformative tumors had either epithelioid, spindled, or undifferentiated sarcomatoid features. Sinusoidal primary hepatic angiosarcoma on the other hand presented with markedly dilated and congested blood vessels of varying sizes, with mild to moderately atypical endothelial cells. Follow-up in all nine cases revealed 8 mortality ranging from 1 to 18 months (mean 5 months) from initial diagnosis. One patient was alive with disease within a period of 48 months. Conclusions: Primary hepatic angiosarcoma is a rare entity with a wide spectrum of histomorphology, and often misdiagnosed. It should be considered when there are dilated and congested sinusoids, with overt nuclear atypia. The overall biological behavior is aggressive, and the prognosis is worse.

[Y-shaped osteotomy in the apical vertebra for treating congenital complex rigid scoliosis:at least 2-year follow-up].

Objective: To investigate the clinical outcome of the coronal Y-shaped osteotomy in the apical vertebra for treating congenital complex rigid scoliosis. Methods: A retrospective analysis was conducted on 66 cases who underwent Y-shaped osteotomy treatment for congenital complex rigid scoliosis in the uppermost vertebra at the Department of Orthopedics,the Second Hospital of Shanxi Medical University from June 2007 to August 2020. There were 19 males and 47 females,with an age of (13.1±5.3) years(range:2 to 30 years).Classification of congenital scoliosis:25 cases (37.9%) were incomplete,13 cases (19.7%) were dysarthritic,and 28 cases (42.4%) were mixed. There were 25 cases (37.9%) with thoracic or rib malformations. 45 cases (68.2%) were complicated with spinal cord malformation.The main radiological indicators included Cobb angle of the curvature,Cobb angle of the local bend,apical vertebral translation (AVT),trunk shift (TS),thoracic trunk shift (TTS),radiographic shoulder height (RSH),coronal balance and sagittal vertebral axis. The preoperative,postoperative immediate,and last follow-up radiological indicators were collected and the operation time,blood loss,hospitalization time,and operation-related complications were recorded. Data were compared by repeated measure ANOVA and paired-t test. Results: All patients underwent surgery successfully. The duration of the first surgery was (221.4±52.8) minutes,and the blood loss during the first surgery was (273.2±41.8) ml. The length of the first hospital stay was (8.8±1.7) days.Unilateral fixation was performed in 19 cases (28.8%),while bilateral fixation was performed in 47 cases (71.2%). The fused segments were 7.5±2.9,and the vertebral pedicle screw density was (68.5±20.6)%. The follow-up time for the 66 patients was (36.7±17.0) months(range:24 to 102 months).The main curve Cobb Angle was improved from (58.5±18.9)°before surgery to (21.1±11.8)°after surgery,and was (23.6±15.3) ° at the last follow-up(F=273.957,P<0.01),with a correction rate of 66.2%. Segmental curve Cobb Angle was improved from (47.9±18.0)° to (16.0±11.3)° after surgery,and was (16.8±12.8) °at the last follow-up (F=270.483,P<0.01)with a correction rate of 69.2%. The AVT,TS,TTS and RSH values improved significantly at the final follow-up (all P<0.05),while coronal balance and sagittal vertical axis were maintained without significant differences between pre-operation and post-operation(both P>0.05). A total of 5 patients underwent staged operation,all of which were residual scoliosis aggravated after the first stage of orthosis operation and had good prognosis after the second stage of operation. Conclusions: Y-shaped osteotomy for the treatment of congenital rigid scoliosis results in good clinical and radiological outcomes without serious complications. This procedure can be considered as an option for the treatment of congenital complex rigid scoliosis.