[Clinical observation on the treatment of ossification of the posterior longitudinal ligament of the cervical spine using 3D printed self-stable zero-profile artificial vertebral body].

Objective: To observe the clinical efficacy of a 3D printed self-stable zero-profile artificial vertebral body for anterior cervical corpectomy decompression and fusion in the treatment of ossification of the posterior longitudinal ligament (OPLL) of the cervical spine. Methods: In this prospective randomized controlled trial, patients diagnosed with OPLL in Luohe Central Hospital from January to July 2022 were divided into a zero-profile group (3D printed self-stable zero-profile artificial vertebral body was used for internal fixation and fusion after anterior cervical subtotal decompression,) and titanium-mesh group (titanium-mesh and titanium plate were used for internal fixation and fusion after anterior cervical subtotal decompression) according to envelope random method. Operation time, intraoperative blood loss, Japanese Orthopaedic Association (JOA) score and improvement rate, incidence of postoperative prosthesis subsidence, and bone graft fusion were recorded and compared between the two groups. Results: Finally, 21 patients in the zero notch group and 20 patients in the titanium mesh group were included in the study and were followed-up. In the zero-profile group, there were 16 males and 5 females, aged (48.0±12.7) years. In the titanium-mesh group, there were 14 males and 6 females, aged (49.8±10.2) years. All the 41 patients successfully completed the operation. In the zero-profile group, the surgical time was (50.04±8.45) minutes, the blood loss was (95.38±26.07) ml and the hospitalization cost was (42.32±6.12) thousand yuan. In the titanium-mesh group, the surgical time was (59.20±11.95) minutes, the blood loss was (93.10±27.86) ml and the hospitalization cost was (42.10±6.71) thousand yuan. The surgical time in the zero-profile group was shorter than that in the titanium-mesh group (P=0.007), and there was no statistically significant difference in blood loss and hospitalization costs between the two groups (both P>0.05). The 41 patients were followed-up for (14.29±1.45) months. Four cases (20.0%) in the titanium mesh group experienced swallowing difficulties and 0 cases in the zero incision group, the difference between the two groups was statistically significant (P=0.048). No intraoperative hematoma, spinal cord nerve recompression, airway crisis, incision infection complications, and no steel plate or screw breakage or displacement occurred after surgery. At the last follow-up, all cases had bone fusion. At the follow-up of 12 months after surgery, the JOA score of the zero incision group increased from preoperative (10.33±1.71) points to (15.47±0.81) points, with an improvement rate of 76.1%±15.7%; the JOA score of the titanium mesh group increased from (10.30±1.75) points to (15.30±0.92) points, with an improvement rate of 73.2%±16.7%; there was no statistically significant difference in improvement rate between the two groups (P=0.580). At the follow-up of 12 months after surgery, 1 case (4.8%) in the zero incision group and 8 cases (40.0%) in the titanium mesh group experienced implant sinking, and the difference between the two groups was statistically significant (P=0.009). Conclusion: Compared with titanium-mesh, 3D printed self-stable zero-profile artificial vertebral body for the treatment of OPLL of the cervical spine can achieve good surgical efficacy, shorter surgical time, lower incidence of postoperative chronic swallowing discomfort, and can provide a better bone material bonding interface and be less prone to prosthesis settlement.

[Analysis of iodine nutritional status of children aged 8-10 years in Zhejiang Province from 2016 to 2021].

Objective: To analyze the iodine nutrition status of children aged 8 to 10 years in Zhejiang Province from 2016 to 2021. Methods: A multi-stage stratified sampling method was used to select non-residential children aged 8 to 10 years from 90 counties in Zhejiang Province. A total of 114 103 children were included in the study from 2016 to 2021. Direct titration method and arsenic-cerium catalytic spectrophotometry were used to detect salt iodine content and urinary iodine level, respectively, to evaluate the iodine nutritional status of children. Ultrasound was used to detect thyroid volume and analyze the current prevalence of goiter in school-age children. Results: The age of 114 103 children was (9.04 ± 0.81) years old, with 50.0% of (57 083) boys. The median of iodine content M (Q1, Q3) in children's household salt was 23.00 (19.80, 25.20) mg/kg, including 17 242 non-iodized salt, 6 173 unqualified iodized salt, and 90 688 qualified iodized salt. The coverage rate of iodized salt was 84.89%, and the coverage rate of qualified iodized salt was 79.48%. The proportion of non-iodized salt increased from 11.85% in 2016 to 16.04% in 2021 (χ2trend=111.427, P<0.001). The median of urinary iodine concentration M (Q1, Q3) in children was 182.50 (121.00, 261.00) µg/L, among which the proportions of iodine deficiency, iodine suitability, iodine over suitability, and iodine excess were 17.25% (19 686 cases), 39.21% (44 745 cases), 26.85% (30 638 cases), and 16.68% (19 034 cases), respectively. The median of urinary iodine concentration in children in inland areas [M (Q1, Q3): 190.90 (128.80, 269.00) µg/L] was significantly higher than that in children in coastal areas [M (Q1, Q3): 173.00 (113.00, 250.30) µg/L] (P<0.001). From 2016 to 2021, a total of 39 134 ultrasound examinations were conducted, and 1 229 cases of thyroid enlargement were detected. The goiter rate was 3.14% (95%CI: 2.97%-3.32%). The incidence of goiter in children in coastal areas [3.45% (95%CI: 3.19%-3.72%), 641/18 604] was higher than that in children in inland areas [2.86% (95%CI: 2.64%-3.10%), 588/20 530] (P=0.001). Conclusion: From 2016 to 2021, the iodine nutrition level of children aged 8-10 years in Zhejiang Province is generally suitable, and the rate of goiter in children meets the limit of iodine deficiency disease elimination standards.

[Progress in the diagnose and treatment of pulmonary arterial thrombosis in situ].

In situ pulmonary arterial thrombosis (ISPAT) refers to the formation of new blood clots in the pulmonary arterial system in the absence of pre-existing clots in the peripheral venous system. With the emergence and prevalence of COVID-19, ISPAT has become an increasingly important cause of pulmonary arterial thrombosis (PAT) alongside thromboembolism. Several factors such as hypoxia, inflammation, endothelial dysfunction, and hypercoagulable state can lead to ISPAT, which is associated with a number of conditions such as thoracic trauma, partial lung resection, pulmonary infectious disease, pulmonary vasculitis, connective tissue diseases, severe pulmonary hypertension, radiation pneumonitis, and acute chest syndrome in sickle cell disease. It is important to differentiate between pulmonary thromboembolism (PTE) and ISPAT for proper disease management and prognosis. In this review, we summarized the characteristics of ISPAT under different disease conditions, the methods to distinguish ISPAT from PTE, and the best treatment strategies. We hoped that this review could improve clinicians' understanding of this independent disease and provide guidance for the refined treatment of patients with PAT.

[A phase I study of subcutaneous envafolimab (KN035) monotherapy in Chinese patients with advanced solid tumors].

Objective: To evaluate the safety and antitumor activity of envafolimab monotherapy in Chinese patients with advanced solid tumors. Methods: This open-label, multicenter phase I trial included dose escalation and dose expansion phases. In the dose escalation phase, patients received subcutaneous 0.1, 0.3, 1.0, 2.5, 5.0 or 10.0 mg/kg envafolimab once weekly (QW) following a modified "3+ 3" design. The dose expansion phase was performed in the 2.5 mg/kg and 5.0 mg/kg (QW) dose cohorts. Results: At November 25, 2019, a total of 287 patients received envafolimab treatment. During the dose escalation phase, no dose-limiting toxicities (DLT) was observed. In all dose cohorts, drug-related treatment-emergent adverse events (TEAEs) for all grades occurred in 75.3% of patients, and grade 3 or 4 occurred in 20.6% of patients. The incidence of immune-related adverse reactions (irAE) was 24.0% for all grades, the most common irAEs (≥2%) included hypothyroidism, hyperthyroidism, immune-associated hepatitis and rash. The incidence of injection site reactions was low (3.8%), all of which were grades 1-2. Among the 216 efficacy evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 11.6% and 43.1%, respectively. Median duration of response was 49.1 weeks (95% CI: 24.0, 49.3). Pharmacokinetic (PK) exposure to envafolimab is proportional to dose and median time to maximum plasma concentration is 72-120 hours based on the PK results from the dose escalation phase of the study. Conclusion: Subcutaneous envafolimab has a favorable safety and promising preliminary anti-tumor activity in Chinese patients with advanced solid tumors.

[The distribution of blood pressure and associated factors of the elderly with type 2 diabetes in Jiangsu Province].

Objective: To investigate the distribution of blood pressure and analyze the associated factors of blood pressure of the elderly with type 2 diabetes in Jiangsu Province. Methods: The elderly over 60 years old participants with type 2 diabetes in the communities of Huai'an City and Changshu City, Jiangsu Province were selected in this study. They were divided into two groups: taking antihypertensive drugs and not taking antihypertensive drugs. The demographic characteristics, such as age and sex, and relevant factors were collected by questionnaire. The systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by physical examination. The percentile of SBP and DBP in each age group of men and women were described. The kernel density estimation curve was used to show the blood pressure distribution. The trend of blood pressure with age was fitted by locally weighted regression. The logistic regression model was used to analyze relevant factors of blood pressure. Results: A total of 12 949 participants were included in this study, including 7 775 patients in the antihypertensive drug group and 5 174 patients in the group without antihypertensive drugs. The SBP of participants was concentrated at 140-160 mmHg, and their DBP was concentrated at 75-85 mmHg. There were significant differences in the distribution of blood pressure among the subgroups of body mass index (BMI) and rural areas whether taking antihypertensive drugs and not. For participants aged under 80 years old, the SBP showed an increasing trend with age and the DBP showed a decreasing trend with age. Age, BMI ≥24 kg/m2, fasting blood glucose ≥7.0 mmol/L, living in rural areas and no smoking were influencing factors of the elevated SBP; BMI ≥24 kg/m2, male, living in rural areas, no smoking, drinking alcohol and not receiving drug hypoglycemic treatment were influencing factors of the elevated DBP. Conclusion: The SBP of older diabetic adults in Jiangsu Province is at a high level, and the distribution of blood pressure is significantly different between men and women in taking antihypertensive drugs group. The SBP presents a rising trend and the DBP is decreasing at the age of 60-80 years. The blood pressure level of this population are mainly affected by age, BMI, urban and rural areas, smoking.

[Rescue balloon pulmonary angioplasty for a patient with acute exacerbation of chronic thromboembolic pulmonary hypertension supported by extracorporeal membrane oxygenation: a case report].

A 33-year-old male patient was admitted to hospital because of "dyspnea after activity for 3 years and aggravation for 15 days". With a history of membranous nephropathy, irregular anticoagulation led to acute exacerbation of Chronic thromboembolic pulmonary hypertension(CTEPH) and acute respiratory failure, and endotracheal intubation and mechanical ventilation was given. Although treated with thrombolysis and adequate anticoagulation, the condition worsened and hemodynamics deteriorated, and then VA-ECMO was performed. Due to severe pulmonary hypertension and right heart failure,ECMO could not be weaned off, and the patient subsequently developed pulmonary infection, right lung hemorrhage, hyperbilirubinemia, coagulation dysfunction and other complications. Then the patient was transferred to our hospital by airplane, and multidisciplinary discussions were quickly arranged after admission. Considering that the patient was critically ill and complicated with multiple organ failure, pulmonary endarterectomy (PEA) could not be tolerated, rescue balloon pulmonary angioplasty (BPA) was recommended and performed on the second day after admission. The mean pulmonary artery pressure was 59 mmHg(1 mmHg=0.133 kPa) measured by right heart catheterization, and pulmonary angiography showed that the main pulmonary artery was dilated, while the right lower pulmonary artery was completely occluded, and there were multiple stenoses in the branches of the right upper lobe, middle lobe pulmonary artery and the left pulmonary artery. BPA was performed on a total of 9 pulmonary arteries. VA-ECMO was weaned off on day 6 after admission, and the mechanical ventilation was weaned off on day 41 after admission. The patient was successfully discharged on day 72 after admission. Rescue BPA was an effective treatment for severe CTEPH patients who could not be treated with PEA.

[Endoscopic resection of type D trigeminal schwannoma through nasal sinus approach].

Objective: To examine the feasibility and surgical approach of removing type D trigeminal schwannoma through nasal cavity and nasal sinus under endoscope. Methods: Eleven patients with trigeminal schwannoma who were treated in the Department of Otorhinolaryngology, Qilu Hospital of Shandong University from December 2014 to August 2021 were analyzed retrospectively in this study. There were 7 males and 4 females, aged (47.5±13.5) years (range: 12 to 64 years). The neoplasm involved the pterygopalatine fossa, infratemporal fossa, ethmoidal sinus, sphenoid sinus, cavernous sinus, and middle cranial fossa. The size of tumors were between 1.6 cm×2.0 cm×2.0 cm and 5.7 cm×6.0 cm×6.0 cm. Under general anesthesia, the tumors were resected through the transpterygoid approach in 4 cases, through the prelacrimal recess approach in 4 cases, through the extended prelacrimal recess approach in 2 cases, and through the endoscopic medial maxillectomy approach in 1 case. The nasal endoscopy and imaging examination were conducted to detect whether neoplasm recurred or not, and the main clinical symptoms during follow-up. Results: All the surgical procedures were performed under endonasal endoscope, including Gross total resection in 10 patients. The tumor of a 12-year-old patient was not resected completely due to huge tumor size and limited operation space. One patient was accompanied by two other schwannomas located in the occipital region and the ipsilateral parotid gland region originating from the zygomatic branch of the facial nerve, both of which were removed concurrently. After tumor resection, the dura mater of middle cranial fossa was directly exposed in the nasal sinus in 2 cases, including 1 case accompanied by cerebrospinal fluid leakage which was reconstructed by a free mucosal flap obtained from the middle turbinate, the other case was packed by the autologous fat to protect the dura mater. The operation time was (M(IQR)) 180 (160) minutes (range: 120 to 485 minutes). No complications and deaths were observed. No recurrence was observed in the 10 patients with total tumor resection during a 58 (68) months' (range: 10 to 90 months) follow-up. No obvious change was observed in the facial appearance of all patients during the follow-up. Conclusion: Type D trigeminal schwannoma involving pterygopalatine fossa and infratemporal fossa can be removed safely through purely endoscopic endonasal approach by selecting the appropriate approach according to the size and involvement of the tumor.

[Characteristics of Guyton's exaggerated forced duction test (FDT) and torsional FDT in congenital superior oblique palsy].

Objective: To investigate the characteristics of Guyton's exaggerated forced duction test (FDT) and torsional FDT in patients with congenital superior oblique palsy (CSOP) and their correlation with clinical features. Methods: This cross-sectional study included single-eye CSOP patients and intermittent exotropia (IXT) patients scheduled for strabismus correction surgery at Tianjin Eye Hospital from September 2021 to March 2022. Prior to surgery, measurements of fovea-disc angle (FDA) and maximum cross-sectional area of the superior oblique muscle (max-CSA) were obtained in both eyes of the patients. The Guyton's exaggerated FDT and torsional FDT were performed intraoperatively to assess the degree of superior oblique muscle relaxation. The characteristics of the two FDT tests and their correlation with vertical strabismus angle, FDA, and max-CSA were analyzed. Statistical analyses were conducted using t-test, ANOVA, Tukey's test, Mann-Whitney U test, and chi-square test. Results: A total of 42 patients (84 eyes) were included in the study, including 19 IXT patients (38 eyes) and 23 CSOP patients (46 eyes, 23 eyes with palsy and 23 eyes without palsy). There were no statistically significant differences in gender composition or age between the IXT and CSOP patients (all P>0.05). The degrees of superior oblique muscle relaxation measured by the Guyton's exaggerated FDT were (-2.52±1.20), (-0.35±0.71), and (-0.03±0.16) for the palsy eye, non-palsy eye, and IXT eyes, respectively, showing significant differences (F=88.10, P<0.001). The torsional FDT measurements yielded external rotation angles of 48.70°±9.67°, 37.39°±5.40°, and 38.95°±2.88° for the palsy eye, non-palsy eye, and IXT eyes, respectively, showing significant differences (F=16.67, P<0.001). There was no statistically significant difference in internal rotation angles (F=2.36, P=0.100). The FDA values were-12.11°±7.42° for IXT patients and-19.02°±4.95° for CSOP patients, while the max-CSA values for the palsy eye and non-palsy eye of CSOP patients were (7.59±4.69) mm² and (11.63±3.64) mm², respectively, all showing significant differences (all P<0.001). The degree of superior oblique muscle tendon relaxation assessed by the Guyton's exaggerated FDT was negatively correlated with the external rotation angle measured by the torsional FDT (r=-0.64, P=0.001). They were positively correlated with max-CSA (r=0.45, P=0.030) and negatively correlated with max-CSA (r=-0.52, P=0.011). However, there was no correlation with vertical and rotational strabismus angle (r=-0.12, P=0.579; r=0.33, P=0.126) and FDA (r=-0.02, P=0.921; r=-0.23, P=0.309). Conclusions: Guyton's exaggerated FDT and torsional FDT can both assess the degree of superior oblique muscle relaxation in patients with CSOP. Furthermore, these two tests are correlated with changes in superior oblique muscle morphology. However, FDT cannot reflect the degree of vertical and rotational strabismus in patients.

Protein kinase C signalling involved in prothoracicotropic hormone-stimulated prothoracic glands in the silkworm, Bombyx mori.

In the present study, the participation of protein kinase C (PKC) signalling in prothoracicotropic hormone (PTTH)-stimulated ecdysteroidogenesis in Bombyx prothoracic glands (PGs) is demonstrated and characterized. PTTH stimulated phosphorylation of a 37-kDa protein in Bombyx PGs both in vitro and in vivo, as recognized by a PKC substrate antibody. Treatment with either A23187 or thapsigargin also stimulated this 37-kDa protein phosphorylation. PTTH-stimulated phosphorylation of the 37-kDa protein was markedly attenuated in the absence of Ca2+ . The phospholipase C (PLC) inhibitor, U73122, greatly inhibited PTTH-stimulated phosphorylation of this protein, indicating the involvement of Ca2+ and PLC. A mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor (U0126), a phosphoinositide 3-kinase (PI3K) inhibitor (LY294002) and a chemical activator of adenosine 5'-monophosphate-activated protein kinase (AMPK) (5-aminoimidazole-4-carboxamide-1-ß-d-ribofuranoside) did not affect PTTH-stimulated phosphorylation of the 37-kDa protein, implying that ERK and PI3K/AMPK are not the upstream signalling pathways for PKC-dependent protein phosphorylation. The mitochondrial oxidative phosphorylation inhibitors (the uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone and diphenylene iodonium) inhibited PTTH-stimulated phosphorylation of the 37-kDa protein, indicating its redox regulation. Treatment with PKC inhibitors (either calphostin C, chelerythrine C or rottlerin) reduced PTTH-stimulated phosphorylation of the 37-kDa protein. PTTH-stimulated ecdysteroidogenesis was also inhibited by treatment with rottlerin, thus further confirming participation of PKC-dependent phosphorylation in PTTH signalling. From these results, we demonstrated that redox-regulated PTTH-stimulated PKC signalling is involved in ecdysteroid secretion in Bombyx PGs.

[Progress in clinical diagnosis and treatment of multiple primary lung cancer].

With the application of high-resolution chest imaging system and lung cancer screening program, patients with multiple primary lung cancer (MPLC) are becoming a growing population in clinical practice. However, the diagnostic criteria of MPLC and its differentiation from intrapulmonary metastasis of lung cancer (IM) are still controversial, especially in cases with similar histology. On the basis of reviewing the existing literature, this paper discusses the changes of the diagnostic criteria of MPLC and the differential diagnosis methods of imaging, histology and molecular genetics of MPLC and IM, and briefly introduces the application of multidisciplinary diagnosis, algorithm, predictive model and artificial intelligence in the differential diagnosis of MPLC. In addition, we also discuss the latest progress in the treatment of MPLC. Radical surgery is the main method for the treatment of MPLC. Stereotactic body radiation therapy (SBRT) is safe and feasible for inoperable MPLC patients, and targeted therapy and immunotherapy can also be used in MPLC after appropriate patient selection.

[Imaging features of posterior polymorphous corneal dystrophy observed by in vivo confocal microscopy].

Objective: To identify and analyze imaging features of posterior polymorphous corneal dystrophy (PPCD) by in vivo confocal microscopy (IVCM). Methods: This retrospective case series enrolled 27 eyes of 18 patients (including 10 males and 8 females) who were diagnosed with PPCD at the Department of Ophthalmology in Peking University Third Hospital between January 2013 and December 2019. The mean age was (23.61±14.81) years. There were 9 monocular and 9 binocular cases. All patients were examined by slit-lamp biomicroscopy and IVCM. The visual acuity, the mean endothelial cell density, and the images of IVCM were analyzed in all cases. Results: The mean best-corrected visual acuity was 0.76±0.33, and the mean endothelial cell density was (1 723.6±698.3) cells/mm2. The IVCM images of type 1 PPCD (vesicular lesions) showed hyperreflective, placoid or homocentric lesions at the level of the Descemet's membrane, hyporeflective, oval or round lesions at the level of the Descemet's membrane, and hyporeflective, crater-like lesions at the level of the endothelial cell layer. The IVCM images of type 2 PPCD (band lesions) displayed hyperreflective, band lesions and a fibrous strand structure at the level of the Descemet's membrane, hyporeflective, vesicular lesions at the level of the Descemet's membrane, and hyporeflective, trough-and ridge-like lesions at the level of the endothelial cell layer. The IVCM images of type 3 PPCD (geographic placoid opacities) showed loss of the hexagonal features of endothelial cells and epithelial-like cell transformation. Conclusions: PPCD primarily affects the endothelium and Descemet's membrane. IVCM could highlight the special characteristics of PPCD including hyperreflective lesions at the level of the Descemet's membrane, hyporeflective lesions at the level of the endothelial cell layer, and epithelial-like cell transformation of endothelial cells. IVCM is an invaluable tool for clinical diagnosis and dynamic monitoring of PPCD.

Involvement of RSK phosphorylation in PTTH-stimulated ecdysone secretion in prothoracic glands of the silkworm, Bombyx mori.

It is well known that phosphorylation of extracellular signal-regulated kinase (ERK) is involved in prothoracicotropic hormone (PTTH)-stimulated ecdysteroidogenesis in insect prothoracic glands (PGs). In the present study, we further investigated the downstream signalling pathways. Our results showed that PTTH stimulated p90 ribosomal S6 kinase (RSK) phosphorylation at Thr573 in Bombyx mori PGs both in vitro and in vivo. The in vitro PTTH stimulation was stage- and dose-dependent. The absence of Ca2+ reduced PTTH-stimulated RSK phosphorylation. Stimulation of RSK phosphorylation was also observed after treatment with either A23187 or thapsigargin. A phospholipase C (PLC) inhibitor, U73122, blocked PTTH-stimulated RSK phosphorylation. These results indicate the involvement of Ca2+ and PLC. Treatment with diphenylene iodonium (DPI), a mitochondrial oxidative phosphorylation inhibitor, blocked PTTH-regulated RSK phosphorylation, indicating its redox regulation. A mitogen-activated protein kinase (MAPK)/ERK kinase (MEK) inhibitor, U0126, but not a phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002, decreased PTTH-stimulated RSK phosphorylation, indicating that ERK is an upstream signalling. A protein kinase C (PKC) inhibitor, chelerythrine C, inhibited PTTH-stimulated RSK phosphorylation, and a PKC activator, phorbol 12-myristate acetate (PMA) stimulated RSK phosphorylation, indicating the involvement of PKC. BI-D1870, a specific RSK inhibitor, partly prevented PTTH-stimulated RSK phosphorylation and significantly inhibited PTTH-stimulated ecdysteroid secretion, indicating that PTTH-stimulated RSK phosphorylation is involved in ecdysteroidogenesis. Taken together, these data indicate that PTTH activates RSK phosphorylation which plays important roles in PTTH-stimulated ecdysteroidogenesis.

Brain-specific monoallelic expression of bovine UBE3A is associated with genomic position.

Genomic imprinting is a rare epigenetic process in mammalian cells that leads to monoallelic expression of a gene with a parent-specific pattern. The UBE3A (ubiquitin protein ligase E3A) gene is imprinted with maternal allelic expression in the brain but biallelically expressed in all other tissues in humans. The silencing of the paternal UBE3A allele is thought to be caused by the paternally expressed antisense RNA transcript of UBE3A-ATS. The aberrant imprinted expression of the UBE3A is associated with several neurodevelopmental syndromes and psychological disorders. Cattle are a valuable model species in determining the genetic etiology of sporadic human disorder, and maternal expression of UEB3A has been revealed by next-generation sequencing study in the bovine conceptus. In this study, we investigated the allelic expression of UBE3A and UBE3A-ATS in adult bovine somatic tissues. To confirm the splicing pattern of bovine UBE3A, five 5' alternative transcripts (MT210534-MT210538) were first obtained from bovine brain tissue by RT-PCR. Based on 10 SNP genotypes, we found that the brain-specific monoallelic expression of bovine UBE3A did not occur along the entire locus, and there was a shift from biallelic expression to monoallelic expression in exon 14 of the UBE3A gene. However, the brain-specific monoallelic expression of bovine UBE3A-ATS occurred in the entire gene. These observations demonstrated that the monoallelic expression did not occur along the bovine UBE3A entire locus and was associated with the genomic position.

[Etiology of severe community-acquired pneumonia in immunocompromised patients].

Objective: To analyze the etiology of severe community-acquired pneumonia (SCAP) in immunocompromised patients, and to investigate the relationship between underlying diseases and infectious microorganisms. Methods: A retrospective analysis was performed on SCAP in immunocompromised patients admitted to the Fourth Department of Respiratory and Critical Medicine (MICU) of China-Japan Friendship Hospital from January 1, 2017 to December 31, 2019. A total of 119 SCAP patients were finally enrolled, including 65 males (54.6%), with an average age of (59.3±14.5) years. The average of Sequential Organ Failure Assessment (SOFA) score was 6.7±3.6 and the acute physiology and chronic health evaluation (APACHE) Ⅱ score was 19.4±6.8. Sixty (50%) of these patients were finally improved and discharged. Long-term glucocorticoid treatment was the main risk factor for immunocompromise. The difference of pathogenic microorganisms between patients with and without structural lung diseases, and the influence of different pathogenic microorganisms on hospital mortality were calculated, respectively. P<0.05 was considered to be statistically significant. Results: In this study, 99 (83.2%) patients were identified to have positive etiological results, and the incidence of concurrent infection was 54.5%. The top three pathogens were Pneumocystis Jiroveci (55.6%), Cytomegalovirus (47.5%) and Aspergillus (23.2%). Staphylococcus aureus was the most common bacterium, followed by Pseudomonas aeruginosa and Klebsiella pneumoniae. The risk of Pneumocystis Jiroveci infection was significantly higher in patients without underlying lung diseases as compared to those with underlying lung diseases (64.3% vs. 44.2%, P = 0.046). The in-hospital mortality was not different among patients infected with different pathogens(all P>0.05), but was higher in those with mixed infections(56.7% vs. 33.9%, P=0.013). Conclusions: Pneumocystis Jiroveci and Cytomegalovirus were the most common pathogens in immunocompromised patients with severe community-acquired pneumonia, and the incidence of Pneumocystis Jiroveci was significantly higher in patients without underlying lung diseases.

[Hepatitis B virus antigen peptide presentation by Epstein-Barr virus-transformed peripheral blood B cells].

Objective: To establish an Epstein-Barr virus-transformed peripheral blood B cell line (BCL), and explore its phenotypic characteristics, the ability to secrete antibodies and cytokines, and the ability to present hepatitis B virus (HBV) antigen peptide. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from patients with HBV infection. Epstein-Barr virus supernatant was incubated to construct BCL. The expression of CD19, CD138, CD38, CD27 and the production levels of IFN - γ, IL-10, IL-6 were detected by flow cytometry. BCL loaded with HBV antigen peptide was incubated with in vitro-expanded autologous T cells. Intracellular staining was used to detect the level of interferon-gamma produced by T cells. Results: Compared with untransformed peripheral blood B cells, BCL had high expression levels of CD138, CD38 and CD27, and the difference was statistically significant (P < 0.05), while the level of IL-6 production was decreased, and the difference was statistically significant (P < 0.01). BCL loaded with HBV antigen peptide had significantly enhanced the production of interferon-gamma by in vitro-expanded autologous T cells, and the difference was statistically significant (P < 0.01). Conclusion: BCL highly expresses CD138, CD38 and CD27, but its ability to produce IL-6 decreases. BCL can improve the immune response efficiency of HBV-specific T cells to HBV antigen peptide, and serve as a new tool for hepatitis B immune research.

A ring system detected around the Centaur (10199) Chariklo.

Hitherto, rings have been found exclusively around the four giant planets in the Solar System. Rings are natural laboratories in which to study dynamical processes analogous to those that take place during the formation of planetary systems and galaxies. Their presence also tells us about the origin and evolution of the body they encircle. Here we report observations of a multichord stellar occultation that revealed the presence of a ring system around (10199) Chariklo, which is a Centaur--that is, one of a class of small objects orbiting primarily between Jupiter and Neptune--with an equivalent radius of 124 ± 9 kilometres (ref. 2). There are two dense rings, with respective widths of about 7 and 3 kilometres, optical depths of 0.4 and 0.06, and orbital radii of 391 and 405 kilometres. The present orientation of the ring is consistent with an edge-on geometry in 2008, which provides a simple explanation for the dimming of the Chariklo system between 1997 and 2008, and for the gradual disappearance of ice and other absorption features in its spectrum over the same period. This implies that the rings are partly composed of water ice. They may be the remnants of a debris disk, possibly confined by embedded, kilometre-sized satellites.

[Strengthening the quality control of coronary artery bypass grafting].

The quality control of coronary artery bypass grafting (CABG) is an important prerequisite to the graft patency and the long-term outcomes. The evaluation of target vessel is the basis, the choice of surgical types is the means, the high-quality acquisition of graft harvesting is the guarantee, and the anastomotic method and quality is the core. As the most commonly used quality control tool, intraoperative transit time flow measurement can effectively detect the coronary graft failure caused by anastomotic stenosis and guide to repair of the graft. However, some studies showed that the positive predictive value is low, and the evidence is insufficient for the relationship with the long-term patency rate of grafts. Intraoperative instantaneous flow measurement combined with high-resolution epicardial ultrasound can improve the quality, safety and effectiveness of CABG, which should be an important recommendation for CABG quality control. Once the shape of the grafts and anastomotic ports is abnormal and the blood flow is not satisfied, it needs to adjust or re-anastomose immediately. The quality control of CABG requires comprehensive judgment and individualized measures to ensure the safety and long-term outcome of patients.

Integrative transcriptomic and genomic analysis of odorant binding proteins and chemosensory proteins in aphids.

Odorant binding proteins (OBPs) and chemosensory proteins (CSPs) play essential roles in insect chemosensory recognition. Here, we identified nine OBPs and nine CSPs from the Myzus persicae transcriptome and genome. Genomic structure analysis showed that the number and length of the introns are much higher, and this appears to be a unique feature of aphid OBP genes. Three M. persicae OBP genes (OBP3/7/8) as well as CSP1/4/6, CSP2/9 and CSP5/8 are tandem arrayed in the genome. Phylogenetic analyses of five different aphid species suggest that aphid OBPs and CSPs are conserved in single copy across all aphids (with occasional losses), indicating that each OBP and CSP class evolved from a single gene in the common ancestor of aphids without subsequent duplication. Motif pattern analysis revealed that aphid OBP and CSP motifs are highly conserved, and this could suggest the conserved functions of aphid OBPs and CSPs. Three OBPs (MperOBP6/7/10) are expressed antennae specifically, and five OBPs (MperOBP2/4/5/8/9) are expressed antennae enriched, consistent with their putative olfactory roles. M. persicae CSPs showed much broader expression profiles in nonsensory organs than OBPs. None of the nine MperCSPs were found to be antennae specific, but five of them (MperCSP1/2/4/5/6) showed higher expression levels in the legs than in other tissues. MperCSP10 mainly expressed in the antennae and legs. The broad and diverse expression patterns of M. persicae CSPs suggest their multifunctions in olfactory perception, development and other processes.

Enterococcus faecalis induces apoptosis and pyroptosis of human osteoblastic MG63 cells via the NLRP3 inflammasome.

AIM: To investigate the ability of E. faecalis to cause apoptosis and pyroptosis of human osteoblastic MG63 cells and whether the inflammasome is involved in this process. METHODOLOGY: MG63 cells were infected with E. faecalis at a multiplicity of infection (MOI) of 10, 100, 500 and 1000 for 6 and 12 h. The cell proliferation was determined with the Cell Counting Kit-8. Apoptosis and pyroptosis after E. faecalis infection was evaluated by flow cytometry and a lactate dehydrogenase (LDH) cytotoxicity assay kit. Then, MG63 cells transfected with specific small interfering RNAs (siRNAs) targeting the NLR family pyrin domain-containing 3 (NLRP3) gene were infected with E. faecalis and subjected to the LDH release and apoptotic cell assays. One-way anova test and Student-Newman-Keuls test were used to evaluate the differences amongst groups in each experiment. An independent sample t-test was performed to analyse the differences between the 12- and 6-h time-points. P < 0.05 was regarded as significant. RESULTS: E. faecalis induced apoptosis and inflammatory cell death (pyroptosis) of MG63 cells in a MOI dose-dependent manner. The NLRP3 inflammasome and caspase-1 were activated in E. faecalis-infected MG63 cells. However, the percentages of induced apoptotic and pyroptic cell death decreased significantly when the NLRP3 inflammasome was downregulated using siRNAs (P < 0.05). CONCLUSIONS: E. faecalis promoted apoptosis and pyroptosis of MG63 cells via the NLRP3 inflammasome. This indicates that E. faecalis infection may result in the delayed reconstruction of periapical lesions, and NLRP3 is the potential target of new intracanal therapeutic agents.

[Using next generation sequencing technology to analyze gene mutations in patients with acute myeloid leukemia and the impact on prognosis].

Objective: To analyze the distribution of gene mutations in newly diagnosed acute myeloid leukemia (AML) patients, based on next generation sequencing technology (NGS) and to evaluate their value in AML risk stratification. Methods: The study analyzed 453 newly diagnosed AML(excluded acute promyelocytic leukemia, APL) patients from seven hospitals in Shanghai, from January 1st 2014 to December 31th 2017. RNA and DNA were extracted from pretreatment bone marrow mononuclear cells and targeted sequencing of AML genes were performed. The data of different groups was compared. Results: A total of 453 newly diagnosed AML patients were enrolled in the study, including 247 males and 206 females with a median age of 49.5 (range,11-85) years. A total of 540 mutations/fusion genes were detected in 289 patients, 29.1% (132/259) of whom with two or more mutations/fusion genes. In all patients, NPM1 was the most common mutation(12.8%), followed by ETO and TET2 mutation (11.92% and 11.04%, respectively) . And WT1 over-expression accounted for 10.6%. Patients over the age of 50 were with a higher frequency of mutations associated with epigenetic modification, 11.93% for ASXL1, 13.99% for DMNT3A, 6.58% for IDH1/IDH2, and 13.17% for TET2. The frequency of DMNT3A mutations was three times higher than that of patients under 50 years of age (P=0.017). In this study, a relatively low proportion of genetic mutations was observed in low-risk karyotype group. In the medium-risk karyotype group, the relatively high mutation frequencies were observed in NPM1, TET2, FLT3-ITD, DNMT3A, ASXL1, and CEBPA genes. In the poor-risk karyotype group, the mutation frequencies of ASXL1, TET2, DNMT3A and PHF6 genes were more than 10%, especially ASXL1 and PHF6 mutation frequencies were significantly higher than other molecular risk stratification groups (P<0.05). Of the 254 patients (56%) with normal karyotype AML (NK-AML), 56 patients were detected to have gene mutations about epigenetic modification. The median OS of this group was worse than that of patients without related mutations, while the median LFS had no significant difference. In patients with NK-AML older than 50 years, the OS and LFS of patients with epigenetic modification related gene mutations was 12 months and 10 months, versus 18 months and 12 months of patients without mutations. Conclusions: The gene mutations frequencies in AML patients with different age and molecular risk stratification groups are different. Epigenetics gene mutation frequencies, such as DNMT3A, ASXL1, IDH1/IDH2 and TET2,are higher in patients older than 50 years. A shorter OS can be observed in older patients(>50 years) with epigenetics gene mutation.