Exogenous GDNF promotes peripheral facial nerve regeneration in rats through the PI3K/AKT/mTOR signaling pathway.

Facial nerve regeneration still lacks a well-defined and practical clinical intervention. The survival of central facial motoneuron is a critical component in the successful peripheral facial nerve regeneration. Endogenous GDNF is vital for facial nerve regeneration according to earlier investigations. Nevertheless, the low endogenous GDNF level makes it challenging to achieve therapeutic benefits. Thus, we crushed the main trunk of facial nerve in SD rats to provide a model of peripheral facial paralysis, and we administered exogenous GDNF and Rapa treatments. We observed changes in the animal behavior scores, the morphology of facial nerve and buccinator muscle, the electrophysiological of facial nerve, and the expression of GDNF, GAP-43, and PI3K/AKT/mTOR signaling pathway-related molecules in the facial motoneurons. We discovered that GDNF could boost axon regeneration, hasten the recovery of facial paralysis symptoms and nerve conduction function, and increase the expression of GDNF, GAP-43, and PI3K/AKT/mTOR signaling pathway-related molecules in the central facial motoneurons. Therefore, exogenous GDNF injection into the buccinator muscle can enhance facial nerve regeneration following crushing injury and protect facial neurons via the PI3K/AKT/mTOR signaling pathway. This will offer a fresh perspective and theoretical foundation for the management of clinical facial nerve regeneration.

CCDC88C, an O-GalNAc glycosylation substrate of GALNT6, drives breast cancer metastasis by promoting c-JUN-mediated CEMIP transcription.

Coiled-coil domain containing 88C (CCDC88C) is a component of non-canonical Wnt signaling, and its dysregulation causes colorectal cancer metastasis. Dysregulated expression of CCDC88C was observed in lymph node metastatic tumor tissues of breast cancer. However, the role of CCDC88C in breast cancer metastasis remains unclear. To address this, the stable BT549 and SKBR3 cell lines with CCDC88C overexpression or knockdown were developed. Loss/gain-of-function experiments suggested that CCDC88C drove breast cancer cell motility in vitro and lung and liver metastasis in vivo. We found that CCDC88C led to c-JUN-induced transcription activation. Overlapping genes were identified from the genes modulated by CCDC88C and c-JUN. CEMIP, one of these overlapping genes, has been confirmed to confer breast cancer metastasis. We found that CCDC88C regulated CEMIP mRNA levels via c-JUN and it exerted pro-metastatic capabilities in a CEMIP-dependent manner. Moreover, we identified the CCDC88C as a substrate of polypeptide N-acetylgalactosaminyltransferase 6 (GALNT6). GALNT6 was positively correlated with CCDC88C protein abundance in the normal breast and breast cancer tissues, indicating that GALNT6 might be associated with expression patterns of CCDC88C in breast cancer. Our data demonstrated that GALNT6 maintained CCDC88C stability by promoting its O-linked glycosylation, and the modification was critical for the pro-metastatic potential of CCDC88C. CCDC88C also could mediate the pro-metastatic potential of GALNT6 in breast cancer. Collectively, our findings uncover that CCDC88C may increase the risk of breast cancer metastasis and elucidate the underlying molecular mechanisms.

Research of injury mapping relationship of lumbar spine in reclined occupants between anthropomorphic test devices and human body model.

PURPOSE: To judge the injury mode and injury severity of the real human body through the measured values of anthropomorphic test devices (ATD) injury indices, the mapping relationship of lumbar injury between ATD and human body model (HBM) was explored. METHODS: Through the ATD model and HBM simulation, the mapping relationship of lumbar injury between the 2 subjects was explored. The sled environment consisted of a semi-rigid seat with an adjustable seatback angle and a 3-point seat belt system with a seatback-mounted D-ring. Three seatback recline states of 25°, 45°, and 65° were designed, and the seat pan angle was maintained at 15°. A 23 g, 47 km/h pulse was used. The validity of the finite element model of the sled was verified by the comparison of ATD simulation and test results. ATD model was the test device for human occupant restraint for autonomous vehicles (THOR-AV) dummy model and HBM was the total human model for safety (THUMS) v6.1. The posture of the 2 models was adjusted to adapt to the 3 seat states. The lumbar response of THOR-AV and the mechanical and biomechanical data on L1-L5 vertebrae of THUMS were output, and the response relationship between THOR-AV and THUMS was descriptive statistically analyzed. RESULTS: Both THOR-AV and THUMS were submarined in the 65° seatback angle case. With the change of seatback angle, the lumbar spine axial compression force (Fz) of THOR-AV and THUMS changed in the similar trend. The maximum Fz ratio of THOR-AV to THUMS at 25° and 45° seatback angle cases were 1.6 and 1.7. The flexion moment (My) and the time when the maximum My occurred in the 2 subjects were very different. In particular, the form of moment experienced by the L1 - L5 vertebrae of THUMS also changed. The changing trend of My measured by THOR-AV over time can reflect the changing trend of maximum stress of L1 and L2 of THUMS. CONCLUSION: The Fz of ATD and HBM presents a certain proportional relationship, and there is a mapping relationship between the 2 subjects on Fz. The mapping function can be further clarified by applying more pulses and adopting more seatback angles. It is difficult to map My directly because they are very different in ATD and HBM. The My of ATD and stress of HBM lumbar showed a similar change trend over time, and there may be a hidden mapping relationship.

Research and Development of a Big Data Application Platform for Intelligent Blast Furnace Intensive Management and Control.

The blast furnaces of Anshan Iron and Steel have completed large-scale modernization, and a large amount of information technology has been popularized and applied to the process of blast furnaces. This paper takes the Anshan Iron and Steel blast furnace group as the research background. Based on big data and industrial Internet technology, combining the smelting process mechanism of blast furnace production and using artificial intelligence, cloud analysis, and other technologies, the data management platform was used to effectively integrate the data of each process of the blast furnace and design the data asset catalogue. The big data application platform for the intensive control of the blast furnace was established. The data were in multidimensional in-depth mining, and the intelligent application model of the blast furnace was established. The visual intelligent monitoring of the safe production and operation of the blast furnace was realized, and the production operation of the blast furnace was guided. The overall information and intelligent level of production operation and management of the blast furnace have been improved.

Triage performance of PAX1m/JAM3m in opportunistic cervical cancer screening of non‒16/18 human papillomavirus-positive women: a multicenter prospective study in China.

OBJECTIVES: In this study, we aimed to validate the performance of the PAX1 and JAM3 methylation (PAX1m/JAM3m) test as a triage tool for detecting cervical intraepithelial neoplasia grade 3 or worse (CIN3 +) in non-16/18 high-risk human papillomavirus-positive patients (non-16/18 hrHPV +). METHODS: The triage performance of liquid-based cytology (LBC) and the PAX1m/JAM3m test for detecting CIN3 + were compared. RESULTS: In total, 1851 participants had cervical histological outcomes and were included in the analysis. The sensitivity/specificity of the LBC test results with atypical squamous cells of undetermined significance or worse (LBC ≥ ASCUS) and the PAX1m/JAM3m test were 90.1%/26.7% and 84.8%/88.5%, respectively. PAX1m/JAM3m( +) had the highest diagnostic AUC (0.866, 95% confidence interval (CI) 0.837-0.896) in the whole cohort. All cancers (n = 20) were detected by PAX1m/JAM3m(+). Compared with LBC ≥ ASCUS, PAX1m/JAM3m(+) reduced the number of patients who needed referral for colposcopy by 57.21% (74.66% vs. 17.45%). The odds ratios for detecting CIN3 + by LBC ≥ ASCUS and PAX1m/JAM3m(+) were 3.3 (95% CI 2.0-5.9) and 42.6 (27.1-69.6), respectively (p < 0.001). The combination of LBC ≥ ASCUS or PAX1m/JAM3m(+) slightly increased the diagnostic sensitivity (98.0%, 95% CI: 95.8-100%) and referral rate (77.09%) but reduced the diagnostic specificity (24.8%, 22.7-26.8%). CONCLUSIONS: In non-16/18 hrHPV(+) women, PAX1m/JAM3m was superior to cytology for detecting CIN3 + . Compared with LBC ≥ ASCUS, PAX1m/JAM3m(+) reduced the number of significant referrals to colposcopy without compromising diagnostic sensitivity.

Experience in the management of sigmoid sinus thrombophlebitis secondary to middle ear cholesteatoma.

OBJECTIVE: To discuss the management of sigmoid sinus thrombophlebitis secondary to middle ear cholesteatoma. METHODS: We retrospectively analyzed all cases of sigmoid sinus thrombophlebitis caused by middle ear cholesteatoma over a period of 7 years. 7 male and 2 female patients, ranging in age from 9 to 66 years, were diagnosed with sigmoid sinus thrombophlebitis by clinical presentation and radiological examination. By executing a modified mastoidectomy and tympanoplasty (canal wall-down tympanoplasty) to entirely remove the cholesteatoma-like mastoid epithelium, all patients were effectively treated surgically without opening the sigmoid sinus. All patients were treated with broad-spectrum antibiotics, but no anticoagulants were used. RESULTS: 9 patients had otogenic symptoms such as ear pus, tympanic membrane perforation, and hearing loss. In the initial stage of the surgery, modified mastoidectomy and tympanoplasty were performed on 8 of the 9 patients. 1 patient with a brain abscess underwent puncturing (drainage of the abscess) to relieve cranial pressure, and 4 months later, a modified mastoidectomy and tympanoplasty were carried out. Following surgery and medication, the clinical symptoms of every patient improved. After the follow-up of 6 months to 7 years, 3 patients were re-examined for MRV and showed partial sigmoid sinus recovery with recanalization. 4 months following middle ear surgery, the extent of a patient's brain abscess lesions was significantly reduced. 1 patient experienced facial paralysis after surgery and recovered in 3 months. None of the patients had a secondary illness, an infection, or an abscess in a distant organ. CONCLUSION: The key to a better prognosis is an adequate course of perioperative antibiotic medication coupled with surgical treatment. A stable sigmoid sinus thrombus can remain for a long time after middle ear lesions have been removed, and it is less likely to cause infection and abscesses in the distant organs. The restoration of middle ear ventilation is facilitated by tympanoplasty. It is important to work more closely with multidisciplinary teams such as neurology and neurosurgery when deciding whether to perform lateral sinusotomies to remove thrombus or whether to administer anticoagulation.

Efficacy of Fuzheng Huayu Tablets for Treating Pulmonary Inflammation in COVID-19 Patients / 中国实验方剂学杂志

ObjectiveTo observe the efficacy and safety of Fuzheng Huayu tablets （FHT） for treating pulmonary inflammation in patients with coronavirus disease 2019 （COVID-19）. MethodA total of 70（4 cases were lost to follow-up, and 66 cases were finally completed） COVID-19 patients were recruited from February 1 to April 15 in 2020. They were assigned to a control group （35 patients） and a FHT group （31 patients）. The patients in the control group received routine treatment alone and those in the FHT group received FHT in addition to routine treatment. The primary outcome was the ratio of patients showing improvement in chest computed tomographic manifestations after 14 days. The secondary outcome measures included remission rate or progression rate of critical illness， clinical remission rate of respiratory symptoms， routine blood examination， C-reactive protein （CPR） level， procalcitonin （PCT） level， and blood oxygen saturation （SPO2）. The safety was assessed based on liver and kidney functions and adverse events. ResultAfter the 14-day treatment， the ratio of patients showing improvement in the FHT group （100%） was higher than that in the control group （77.1%） （χ2=8.063，P<0.01）. The ratio of disease stages after treatment showed no significant difference between two groups. In the FHT group， the symptoms including cough， dyspnea， and fatigue were alleviated after treatment （P<0.01）. In the control group， the symptoms including fever， cough， and dyspnea were alleviated （P<0.01）， while the fatigue was not relieved after treatment. No significant difference was observed in the clinical symptoms between the two groups after treatment. After treatment， the FHT group showed decreased white blood cell （WBC） count and neutrophil-to-lymphocyte ratio （NLR） （P<0.01）， elevated platelet （PLT） level （P<0.05）， lowered CRP level （P<0.05）， and no significant difference in lymphocyte （LYM）， hemoglobin （Hb）， SPO2 or PCT level. The control group showed decreased NLR （P<0.05） and WBC count （P<0.01）， elevated PCT level （P<0.05）， and no significant change in LYM， Hb， PLT， SPO2 or CRP level after treatment. Furthermore， the FHT group had higher PLT level than the control group （P<0.05） after treatment， and other indicators had no significant differences between the two groups. The liver and kidney functions had no significant difference between the two groups after treatment. ConclusionFHT can safely promote the absorption of acute pulmonary inflammation in COVID-19 patients.

Correlation between thyroid function and glucolipid metabolism in type 1 diabetic adults / 中华内科杂志

To assess the correlation between thyroid function and glucolipid metabolism in type 1 diabetic adults. A retrospective analysis was conducted in 230 type 1 diabetic adults who were hospitalized in the Department of Endocrinology of Shandong Provincial Hospital Affiliated to Shandong University from January 2008 to January 2020. It showed that thyroid stimulating hormone(TSH) was significantly positively correlated with total cholesterol (TC) ( r=0.239), triglycerides (TG) ( r=0.166) and low-density lipoprotein cholesterol (LDL-C) ( r=0.249), respectively (all P<0.05). Free triiodothyronine (FT 3) was significantly negatively correlated with fasting plasma glucose (FPG) ( r=-0.272), glycated hemoglobin (HbA1c) ( r=-0.240), TC ( r=-0.197) and LDL-C ( r=-0.220), respectively (all P<0.05). Free thyroxine (FT 4) was negatively correlated with TC ( r=-0.171) and LDL-C ( r=-0.170), respectively (all P<0.05). TC was an independent predictor of TSH, FT 3 and FT 4, FT 3 and FT 4 were independent predictors of HbA1c. TSH was an independent predictor of TC, TG and LDL-C. Thyroid function is closely related to glucolipid metabolism in type 1 diabetic adults.

Impacts of treatment modes on the prognosis of Ⅰ B1-Ⅱ A patients with intermediate-risk recurrence factors / 中华放射医学与防护杂志

Objective:To analyze the prognostic factors of patients with Ⅰ B1-Ⅱ A cervical cancers after surgery and to assess the effects and adverse reactions of intensity-modulated radiotherapy(IMRT)combined with concurrent chemotherapy(CCRT). Methods:A retrospective analysis was performed based on the clinical and follow-up data of 362 patients with Ⅰ B1-Ⅱ A cervical cancers who were treated in Changzhou Second People′s Hospital from January 2009 to December 2019. Meanwhile, these patients suffered large primary tumors(LPT; tumors size: ≥4 cm), lymphatic vascular space invasion (LVSI), and deep stromal invasion(DSI; stromal infiltration depth: ≥1/2) after surgery and showed at least one intermediate-risk factor. Among these cases, 161 cases were treated with CCRT, 131 cases under-went single radiotherapy (RT), and 70 cases received unadjuvanted radiotherapy. The Kaplan-Meier method and the logrank test were adopted for univariate survival analysis, the binary logistic regression was used to analyze the recurrence risk, and Cox regression model was used for multivariate survival analysis. Results:The 3 and 5-year overall survival (OS) rates were 94.20% and 88.39%, respectively. The retrospective analysis showed that the risk factors of recurrence included tumor size ≥ 4 cm and poorly differentiated cancers( OR=3.287, 2.870, 95% CI: 1.366-7.905, 1.105-7.457, P<0.05). Compared with the treatment without adjuvant radiotherapy and RT, CCRT reduced the recurrence rate of tumors with tumor size of ≥ 4 cm, adenocarcinomas or adenosquamous carcinomas (pathological types), and poorly differentiated carcinomas( χ2=6.725-7.518, P<0.05). A multivariate analysis showed that the CCRT improved the recurrence-free survival ( HR=0.290, 95% CI: 0.128-0.659, P=0.003) and OS ( HR=0.370, 95% CI: 0.156-0.895, P=0.024). A subgroup analysis indicated that CCRT prolonged the OS of patients with tumor size ≥ 4 cm or poorly differentiated cancers compared to the patients receiving no radiotherapy or those treated with RT (χ 2=7.614, 5.964, P<0.05). Compared with the cases receiving single radiotherapy, those receiving CCRT did not suffer an increase in the incidence of hematology, radiation enteritis, and cystitis above grade 3 according to observation ( P>0.05). Conclusions:Among the intermediate-risk factors leading to the recurrence of postoperative cervical cancers, the factors of large primary tumors or poorly differentiated cancers affect the prognosis of patients.Compared with RT and the treatment without adjuvant radiotherapy, IMRT combined with concurrent chemotherapy can prolong the recurrence-free survival and overall survival of patients with large tumors or poorly differentiated cancers and adverse reactions induced are tolerable.

Prognostic factors assessment of premature detachment of placenta in cesarean section under combined spinal-epidural anesthesia / 中华麻醉学杂志

Seven cases scheduled for cesarean section following combined spinal-epidural anesthesia,complicating the premature detachment of placenta,which occurred in the 2nd Affdiated Hospital of Wenzhou Medical College from January 1997 to December 2006,were analyzed to determine the risk factors.The results showed that the supine hypotensive syndrome after combined spinal-epidural anesthesia and anxiety before cesarean section were closely related to the premature detachment of placenta.The incidence rate of the premature detachment of placenta after combined spinal-epidural anesthesia is low,but the prermature of detachment of placenta is severe if it occurs,and the effectively prophylactic measures should be taken,including premedication with midazolam to eliminate anxiety before cesarean section and prevention of supine hypotensive syndrome after combined spinal-epidural anesthesia.