Vegetation-fire feedbacks increase subtropical wildfire risk in scrubland and reduce it in forests.

Climate dictates wildfire activity around the world. But East and Southeast Asia are an apparent exception as fire-activity variation there is unrelated to climatic variables. In subtropical China, fire activity decreased by 80% between 2003 and 2020 amid increased fire risks globally. Here, we assessed the fire regime, vegetation structure, fuel flammability and their interactions across subtropical Hubei, China. We show that tree basal area (TBA) and fuel flammability explained 60% of fire-frequency variance. Fire frequency and fuel flammability, in turn, explained 90% of TBA variance. These results reveal a novel system of scrubland-forest stabilized by vegetation-fire feedbacks. Frequent fires promote the persistence of derelict scrubland through positive vegetation-fire feedbacks; in forest, vegetation-fire feedbacks are negative and suppress fire. Thus, we attribute the decrease in wildfire activity to reforestation programs that concurrently increase forest coverage and foster negative vegetation-fire feedbacks that suppress wildfire.

The association between mammographic density and breast cancer molecular subtypes: a systematic review and meta-analysis.

AIM: To conduct a systematic review and meta-analysis to evaluate the whether high mammographic density (MD) is differentially associated with all subtypes of breast cancer. MATERIALS AND METHODS: The PubMed, Cochrane Library, and Embase databases were searched systematically in October 2022 to include all studies that investigated the association between MD and breast cancer subtype. Aggregate data of 17,193 breast cancer cases from 23 studies were selected, including five cohort/case-control and 18 case-only studies. The relative risk (RR) of MD were combined using random/fixed effects models for case-control studies, and for case-only studies, relative risk ratios (RRRs) were a combination of luminal A, luminal B, and HER2-positive versus triple-negative tumours. RESULTS: Women in the highest density category in case-control/cohort studies had a 2.24-fold (95% confidence interval [CI] 1.53, 3.28), 1.81-fold (95% CI 1.15, 2.85), 1.44-fold (95% CI 1.14, 1.81), and 1.59-fold (95% CI 0.89, 2.85) higher risk of triple-negative, HER-2 (human epidermal growth factor receptor 2) positive, luminal A, and luminal B breast cancer compared to women in the lowest density category. RRRs for breast tumours being luminal A, luminal B, and HER-2 positive versus triple-negative in case-only studies were 1.62 (95% CI 1.14, 2.31), 1.81 (95% CI 1.22, 2.71) and 2.58 (95% CI 1.63, 4.08), respectively, for BIRADS 4 versus BIRADS 1. CONCLUSION: The evidence indicates MD is a potent risk factor for the majority of breast cancer subtypes to different degrees. Increased MD is more strongly linked to HER-2-positive cancers compared to other breast cancer subtypes. The application of MD as a subtype-specific risk marker may facilitate the creation of personalised risk prediction models and screening procedures.

[Diagnostic and prognostic values of flow cytometry in diffuse large B-cell lymphoma with bone marrow involvement].

Objective: To analyze the diagnostic and prognostic values of flow cytometry (FC) in diffuse large B cell lymphoma (DLBCL) with bone marrow involvement (BMI). Methods: The clinical data of 412 patients with newly diagnosed DLBCL, including 243 males and 169 females, aged 64 (28-92) years old, in the Department of Hematology at Peking University Third Hospital from December 2012 to June 2022 were retrospectively analyzed. All patients underwent bone marrow biopsy (BMB) and bone marrow FC. The patients with BMI by FC were further detected by fluorescence in situ hybridization (FISH) for gene analysis. The positive rates and consistency of BMI detected by BMB and FC were evaluated. According to the results of BMB and FC examinations, all patients were divided into four groups: the BMB+FC+group (115 cases), the BMB-FC+group (50 cases), the BMB+FC-group (8 cases, the results did not include in statistical analysis because of small sample size), and the BMB-FC-group (239 cases). The clinical features, treatment response rates, 5-year survival rates, and immunophenotype characteristics by FC in different groups were analyzed. Results: Among the 412 patients with DLBCL, the positivity rates of BMB and FC for BMI detection were 29.9% (123/412) and 40.0% (165/412), respectively. Good consistency between BMB and FC was found (Kappa=0.841, P=0.001). The numbers of extranodal involvement≥2, splenomegaly, huge mass, higher Ki-67 score, higher international prognostic index (IPI) score, thrombocytopenia, and elevated lactate dehydrogenase level were more prevalent in the BMB+FC+group than those in the BMB-FC+group and the BMB-FC-group (all P<0.05). The treatment response rate in BMB+FC+group was 63.5% (73/115), which was lower than those in BMB-FC+group (88.0%, 44/50, P=0.048) and BMB-FC-group (90.0%, 215/239, P=0.032), respectively. The 5-year overall survival rates in three groups were (53.6±9.7) %, (72.5±8.6) %, and (75.2±7.6) %, respectively, with a statistically significant difference (P=0.037). According to the FISH results of bone marrow, 102 cases were diagnosed as not otherwise specified (NOS), 48 cases were diagnosed as double hit lymphoma (DHL), and 15 cases were diagnosed as triple hit lymphoma (THL). Compared with NOS subtypes, the tumor cells in DHL or THL subtypes had higher proportion of increased side scatter (SSC), higher positive rates of CD10 expression, CD38 strong expression and CD56 expression, and lower proportion of surface immunoglobulin light chain restriction (all P<0.05). Conclusions: FC is well consistent with BMB in diagnosing DLBCL with BMI. Combined with FISH detection, FC can contribute to the auxiliary diagnosis and risk stratification for DHL and THL, and provide reference for the prognostic evaluation in DLBCL with BMI.

[Primary cardiac angiosarcoma: a clinicopathological and molecular genetic analysis of thirteen cases].

Objective: To investigate the clinicopathological and molecular features of primary cardiac angiosarcoma (PCAS), and to analyze the correlation between KDR mutation and the clinicopathological features of PCAS. Methods: Thirteen cases of PCAS were collected at Beijing Anzhen Hospital, Capital Medical University from January 2007 to December 2021. The clinicopathological features, diagnosis, differential diagnosis and outcome were retrospectively analyzed. KDR mutation was detected by next-generation sequencing (NGS) and then the expression of KDR (VEGFR2) was determined by immunohistochemistry (IHC), with review of relevant literatures. Results: There were eight males and five females with a mean age of 45 years. The primary tumor was in the right atrium in 10 cases, left atrium in two cases and right ventricle in one case. The histomorphology was mainly poorly differentiated angiosarcoma (11 cases), with highly pleomorphic spindle or round cells in solid sheets, brisk mitotic activity and extensive necrosis. Vascular lumen formation was observed in two cases of high to moderate differentiation, and biphenotypic differentiation was seen in five cases. IHC staining showed CD34, CD31, Fli1, ERG and vimentin were diffusely positive, pan-cytokeratin was positive, Ki-67 index ranged from 3% to 90%, which was positively correlated with the differentiation degree and grade of the PCASs (P<0.05). At the end of follow-up period, one patient was alive, two patients were lost to follow-up, and the remaining 10 patients had an average survival time of 4.6 months. Finally, NGS sequencing was performed on seven samples after screening, and the results showed that KDR and NF1 mutations were both present in three cases. VEGFR2 expression had no significant correlation with the differentiation degree and grade of PCAS (P>0.05), and it was not related to KDR mutation. Conclusions: PCASs mainly occur in the right atrium, and are mainly poorly differentiated. Ki-67 index is helpful to assess the degree and grade of tumor differentiation. The occurrence and development of PCAS may be related to the pathway involved in KDR mutation, but KDR mutation has no clear correlation with clinicopathological characteristics of PCAS, and immunohistochemical staining can not replace gene detection to determine whether the tumor had KDR mutation.

[Rapid determination of acetaminophen in plasma by LC-MS/MS].

Objective: To establish a method for the rapid determination of acetaminophen (APAP) in human plasma by LC-MS/MS. Methods: The plasma samples were extracted by methanol and acetonitrile (1: 1) and purified directly. C(18) column was used for sample separation. The mobile phase were methanol (5 mmol/L ammonium acetate) and water (5 mmol/L ammonium acetate). Samples were analyzed by LC MS/MS with the electrospray ionization multi reaction monitoring (MRM) mode. Results: The calibration curves of APAP was linear in the concentration range of 0~10 mg/L, the correlation coefficient (r) was greater than 0.999 0. The relative standard deviation within and between batches was less than 10%. The recovery rate were 96.81%~101.7%. The detection limit of the method was 0.1 µg/L and the lower limit of quantification was 0.3 µg/L. Conclusion: This method has strong specificity, high sensitivity and reliable determination results. It is suitable for the rapid analysis of clinical plasma samples.

C1q/TNF-related protein-9 suppresses inflammation in synovial cells from patients with osteoarthritis.

OBJECTIVE: Synovial inflammation contributes to cartilage degeneration and osteoarthritis (OA) development. Targeting the inflammation process may provide a promising strategy for OA treatment. It has been demonstrated that C1q/tumour necrosis factor-related protein-9 (CTRP9) has immunosuppression capabilities. Thus, we conducted this study to investigate the role of CTRP9 in OA and its therapeutic potential. METHOD: The expression level of CTRP9 was quantified in peripheral blood mononuclear cells (PBMCs), serum, and synovial cells (SCs) isolated from OA patients by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. The relationship between the expression level of CTRP9 and the disease activity of OA was determined. The inflammation-suppressing effects of CTRP9 were assessed in vitro. RESULTS: The expression level of CTRP9 was increased in the PBMCs and serum of OA compared to healthy controls. The serum level of CTRP9 was found to be positively correlated with erythrocyte sedimentation rate, C-reactive protein, and visual analogue scale score. In addition, CTRP9 protein suppressed the expression of pro-inflammatory cytokines, including tumour necrosis factor-α, interleukin-6, and interleukin-1ß, in PBMCs and SCs in vitro. CTRP9 was increased in OA patients and positively correlated with the disease activity. The recombinant CTRP9 had inflammation-suppressing activities in vitro. CONCLUSION: CTRP9 may have therapeutic potential for treating OA. Osteoarthritis (OA) is characterized as cartilage destruction resulting from synovial inflammation (1-6). According to the clinical symptoms and levels of inflammation, OA has been divided into primary generalized osteoarthritis (PGOA) and erosive inflammatory osteoarthritis (EIOA) (7). The only available treatment for OA is joint replacement. Thus, it is necessary to develop novel and effective therapeutic strategies to treat OA. Because synovial inflammation contributes to OA development, targeting the inflammation process may provide a promising strategy for OA treatment. Previous investigations showed that pro-inflammatory factors promoted OA development (8-10), while anti-inflammatory factors suppressed it (11-14). Thus, we conducted the present study to investigate the role of C1q/tumour necrosis factor-related protein-9 (CTRP9), an anti-inflammatory factor (15), in OA, and its therapeutic potential.

[Clinicopathological characteristics and molecular alterations of primary cardiac leiomyosarcoma: report of five cases].

Objective: To investigate the clinical, pathologic and radiologic features and molecular alterations in patients with primary cardiac leiomyosarcoma (PCLMS). Methods: Five cases of PCLMS were collected in Beijing Anzhen Hospital from January 2016 to December 2020. The clinical, pathologic and radiologic data, and molecular alterations were analyzed, and the patients were followed up. Results: All five patients were female, and had no history of leiomyosarcoma in other parts of the body. The age of patients ranged from 37 to 62 years (median 47 years). The main clinical symptoms were chest pain and dyspnea, one also presented with palpitation and lower limb weakness and one with dizziness. Two tumors were located in the left atrium, two in the right atrium, and one in the right ventricle, and they maximal diameter ranged from 2.5 to 14.0 cm (mean 6.2 cm). The neoplasms presented as medium-echo masses with a broad base in the echocardiography, and as a low-density, solid mass when detected by contrast-enhanced CT. Histologically, two tumors were well-differentiated and three were moderately and poorly differentiated, and two included extensive, loose myxoid stroma. Immunohistochemical staining showed that PCLMS was positive for SMA, desmin, MDM2, and epidermal growth factor receptor. Fluorescence in situ hybridization showed ALK gene rearrangement in two cases, and COL1A1-PDGFB fusion in three cases. All cases received surgical excision and two cases received chemotherapy. Three patients died within 0-11 months (mean survival of 7.7 months) and two patients were alive. Conclusions: PCLMS is a malignant tumor with a high recurrence rate and poor prognosis. These cases may provide useful information to improve the diagnosis and management of PCLMS.

[Fast determination of bongkrekic acid in plasma by high performance liquid chromatography-tandem mass spectrometry].

Objective: To establish a method for rapid determination of bongkrekic acid (BA) in plasma by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Methods: In November 2020, plasma samples were extracted by methanol and acetonitrile (1∶1) and purified directly. The samples were separated by C18 column. Gradient elution was carried out with 5 mmol/L ammonium acetate water acetonitrile solution as mobile phase. Under the optimized instrument conditions, the electrospray ionization multiple reaction monitoring (MRM) mode was used, and the external standard method was used for quantitative analysis. Results: The linear relationship of BA in plasma was good in the concentration range of 2-100 µg/L, the correlation coefficient was 0.9998, the average recovery was 83.7%-112.0%, the relative standard deviation within and between batches was less than 10%, the detection limit of the method was 0.7 µg/L and the lower limit of quantification was 2.0 µg/L. Conclusion: The method is simple, rapid, accurate and sensitive, and can meet the requirements for the determination of BA in blood samples of poisoning patients.

The effect of D-(+)-glucosamine, N-acetyl-D-glucosamine and tetraethylene glycol on the stability of oxytocin in aqueous solution.

The aim of the present study was to identify the effect of D-(+)-glucosamine, N-acetyl-D-glucosamine, tetraethyleneglycol, and the mixture of these additives on the stability of oxytocin in phosphate and acetate buffer solutions, at pH 4.5. Our findings demonstrate that tetraethyleneglycol has a destabilizing effect on oxytocin in both phosphate buffer and acetate buffer. D-(+)-Glucosamine hydrochloride had small to negligible effect at low concentrations, yielding a slight improvement lower concentrations of the additive in the presence of the buffers used, but at higher concentrations it increased the rate of degradation. N-Acetyl-D-glucosamine showed a possibly slight improvement to the stability of oxytocin. It is hypothesized that the different effect of N-acetyl-D-glucosamine compared to D-(+)-glucosamine is a consequence of the free amine group in D-(+)-glucosamine promoting a faster degradation, while the amino group is acetylated in N-acetyl-D-glucosamine and therefore no longer reactive in the same way. While it remains unclear why tetraethyleneglycol has a destabilizing effect on oxytocin, the D-(+)-glucosamine results aid in deepening our understanding of the degradation mechanism of oxytocin.

[Application of deep learning neural network in pathological image classification of non-inflammatory aortic membrane degeneration].

Objective: To investigate the value of deep learning in classifying non-inflammatory aortic membrane degeneration. Methods: Eighty-nine cases of non-inflammatory aortic media degeneration diagnosed from January to June 2018 were collected at Beijing Anzhen Hospital, Capital Medical University, China and scanned into digital sections. 1 627 hematoxylin and eosin stained photomicrographs were extracted. Combined with the ResNet18-based deep convolution neural network model, 4-category classification of pathological images were performed to diagnose the non-inflammatory aortic lesion. Results: The prediction model of artificial intelligence assisted diagnosis had the best accuracy, sensitivity and precision in identifying lesions with smooth muscle cell nuclei loss, which were 99.39%, 98.36% and 98.36%, respectively. The classification accuracy of elastic fiber fragmentation and/or loss lesions was 98.08%, while that of intralamellar mucoid extracellular matrix accumulation lesions was 96.93%. The overall accuracy of the classification model was 96.32%, and the area under the curve was 0.982. Conclusions: The accuracy of deep learning neural network model in the 4-category classification of non-inflammatory aortic lesionsis confirmed based on digital photomicrographs. This method can effectively improve the diagnostic efficiency of pathologists.

[Absence of arterial duct in fetus: an autopsy analysis].

Objective: To analyze the absence of congenital arterial duct in fetus and to improve the diagnostic accuracy. Methods: Four hundred cases of congenital heart disease diagnosed by echocardiography during pregnancy were examined the fetal cardiovascular malformation and visceral malformation, and the absence of arterial duct was analyzed. Results: There were 24(6%)cases of absence of arterial duct, including 19 cases of left aortic arch and five cases of right aortic arch. There were 21 cases with main pulmonary arteries and 3 cases without main pulmonary arteries and branches. There were 15 cases of pulmonary artery stenosis with absence of arterial duct and the major cardiovascular malformations included six cases of single ventricle, six cases of atrial septal defect, four cases of single atrium, four cases of right atrium isomerism, four cases of double outlet right ventricle, four cases of anomalous pulmonary venous drainage, three cases of tetralogy of Fallot, and three cases of persistent left superior vena cava. There were seven cases of pulmonary atresia with absence of arterial duct and with systemic-pulmonary collateral circulation. There was one case of tetralogy of Fallot with absent pulmonary valve and absent arterial duct and the pulmonary artery was dilated. There was one case of aortopulmonary septal defect with absent arterial duct, with normal pulmonary artery. There were also seven cases of asplenia, seven cases of pulmonary abnormality and seven cases of visceral inversion. Conclusions: The absence of arterial duct is often associated with congenital heart disease. Pulmonary atresia is often associated with systemic-pulmonary collateral circulation. The visceral malformations are related to the accompanying congenital cardiovascular malformations.

[A comparative study between retro-auricular single-site endoscopic thyroidectomy and transoral endoscopic thyroidectomy vestibular approach: a single-center retrospective analysis].

Objectives: To compare the efficiacy of retro-auricular single-site endoscopic thyroidectomy (RASSET) and that of transoral endoscopic thyroidectomy vestibular approach (TOETVA). Methods: In Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, 10 patients underwent RASSET from June 2021 to August 2021, and 21 patients underwent TOETVA from January 2016 to August 2021. All the 21 patients' clinical data was analyzed retrospectively. There were 2 males and 8 females in the RASSET group, aging (48.2±13.9) years (range: 28 to 67 years). There were 5 males and 16 females in the TOETVA group, aging (31.3±8.2) years (range: 21 to 49 years). All patients underwent thyroid lobectomy. A 3 cm in length incision was cut on single auricula posterior sulci to creat the approach in the RASSET group. Then a Trocar made with of a glove was inserted. Retaining the omohyoid, the sternocleidomastoid muscle and anterior cervical muscle were pulled apart, exposing a single lobe of the thyroid gland and lymphatic tissue of zone Ⅵ, for en-bloc resection. The clinical data of the two groups were collected and analyzed by t test, Mann-Whitney U test, Fisher exact test or χ2 test. Clinical data and postoperative efficacy indexes such as operation time, postoperative C reactive protein level, and postoperative complications were recorded. Results: Compared with the TOETVA group, the operation time was longer in the RASSET group ((256.8±77.0) minutes vs. (201.2±54.9) minutes, t=2.31, P=0.028), and increase of postoperative C reaction protein (24 hours postoperative vs. preoperative) was lower in the RASSET group (8.58(13.24) mg/L vs. 46.24(48.88) mg/L, Z=-4.311, P<0.01). But there was no significant difference between the RASSET group and TOETVA group in the number of lymph nodes dissection (2(5) vs. 2(3), Z=-0.326, P=0.759). Besides, there were no complications in the RASSET group. Conclusion: Retro-auricular single-site endoscopic thyroid loectomy is easy to achieve the en-bloc resection of tumors with a well-concealed scar and less traumatic dissection.

Serum Prealbumin Improves the Sensitivity of Pneumonia Severity Index in Predicting 30-day Mortality of CAP Patients.

BACKGROUND: Serum prealbumin (PAB) is an effective tool to evaluate patients with malnutrition. In recent years, studies have shown that PAB is statistically reduced during the course of disease infection. The pneumonia severity index (PSI) scoring system is one of the most widely used scoring tools to evaluate the condition and prognosis of community acquired pneumonia (CAP) patients. However, few studies have reported on PSI combined with blood indicators to predict the prognosis of pneumonia. The aim of this study was to investigate the prognostic value of PAB combined with PSI in patients with CAP. METHODS: We retrospectively analyzed the data of 400 patients who met the inclusion criteria. Death and survival were selected as prognostic indicators of pneumonia. On the first day after admission, venous blood samples were taken to test PAB and PSI scores. Subject operating characteristic curve (ROC) was used to evaluate PSI, PAB, and PSI combined with PAB to predict 30-day mortality of CAP patients. RESULTS: The 30-day mortality rate of CAP patients was 10.5% (42/400). PAB and PSI score were independent risk factors for 30-day mortality in CAP patients. The sensitivity, specificity, positive predictive value, and negative predictive value of PAB predicting the death of CAP patients were 86.3%, 79%, 50.74%, and 95.83%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of PSI predicting the death of CAP patients were 74.80%, 63%, 33.71%, and 90.99%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of the combined index predicting the death of CAP patients were 95.20%, 77.80%, 51.70% and 98.41%, respectively. CONCLUSIONS: Serum prealbumin is a relatively simple acquired index and an independent risk factor for death in CAP patients. Serum prealbumin improves the sensitivity of pneumonia severity index in predicting 30-day mortality of CAP patients.

[Analysis of clinical characteristics, treatment and survival of elderly patients with large diffuse B-cell lymphoma].

Objective: To analyze the clinical feature,treatment and survival outcome of elderly patients older than 80 years with large diffuse B-cell lymphoma. Methods: A total of 46 patients aged over 80 years with large diffuse B-cell lymphoma who were treated in Third Hospital of Peking University during the period from 2002 to 2018 were retrospectively analyzed, and the clinical features, laboratory data, survival and prognostic factors were included in Kaplan-Meier and prognostic analysis. Results: Patients older than 80 years old accounted for 15.7% (46/293) in all elderly patients, and the median age was 83 years old. There were 78.3% (36/46)patients who belonged to stage Ⅲ or Ⅳ, 63%(29/46) who had more than two extranodal organ involvement, and the higher proliferation index(Ki-67≥80%) was present in 53.7%(22/41) patients. Immunohistochemistry showed that 37% patients in 27 cases were double-expressed DLBCL. With a median follow-up of 25 months, the overall response rate (ORR) for the whole group was 63.0%, the complete response (CR) rate was 36.4%, the 2, 3-year progression-free survival (PFS) rate was 49.9% and 41.7%, the 2, 3-year overall survival (OS) rate was 54.6% and 43.6% respectively. The ORR for patients who received anthracycline-based therapies and non-anthracycline-based therapies were 81.8% and 55.0%, and the 3-year OS rate were 50.0% and 39.0%, respectively, but the difference was not statistically significant (P>0.05). 45.5% patients had hematologic toxicity of Grade Ⅲ or above, and 56.8% patients experienced infections during the treatment. Among the patients who died, the treatment-related mortality rate in group with high score of Charlson comorbidity index(CCI) was higher (43.8% vs 16.7%, P=0.03) . The National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) score, nodal involvement area ≥3, 6 cycles of chemotherapy, CCI score, initial treatment outcome and refractory-relapsed were predictive of overall survival. Multivariate analysis indicated the CCI score (HR=6.463, P=0.008) and initial treatment outcome (HR=0.086, P=0.001) were independent prognostic risk factors. Conclusions: The clinical and pathological features of patients older than 80 years were highly aggressive with poor chemotherapy tolerance and high adverse reaction rate. Anthracycline-based therapies may be less important in the treatment of DLBCL patients aged over 80 years. Patients with high CCI score have higher treatment-related mortality and CCI can help identify elderly patients who are suitable for larger chemotherapy dose.

CRISPR/Cas9-mediated disruption of the immediate early-0 and 2 as a therapeutic approach to Bombyx mori nucleopolyhedrovirus in transgenic silkworm.

The CRISPR/Cas9 system is a powerful tool for the treatment of infectious diseases. In our previous study, we knocked out the Bombyx mori nucleopolyhedrovirus (BmNPV) key genes and BmNPV-dependent host factor to generate transgenic antiviral strains. To further expand the range of target genes for BmNPV and more effectively prevent and control pathogenic infections, we performed gene editing and antiviral analysis by constructing a target-directed baculovirus early transcriptional activator immediate early-0 (ie-0) and 2 (ie-2) transgenic silkworm line. We hybridized it with Cas9 transgenic line to produce a double-positive transgenic Cas9(+)/sgIE0-sgIE2(+) line that could activate the CRISPR gene editing system. We first demonstrated that the system is capable of efficiently editing target genes and resulting in fragment deletions in the BmNPV genome. Survival rate of the transgenic Cas9(+)/sgIE0-sgIE2(+) line reached 65% after inoculation with 1 × 106 occlusion bodies/larva. Molecular analysis showed that BmNPV DNA replication and viral gene expression level in the transgenic Cas9(+)/sgIE0-sgIE2(+) line were significantly inhibited compared with the control Cas9(-)/sgIE0-sgIE2(-) line. These results indicated that IE-0 and IE-2, as baculovirus early transcriptional activators, can be used as target sites for gene therapy and that multigene editing could expand the range of target sites for research to create silkworm resistance breeds.

Interactome analysis reveals ZNF804A, a schizophrenia risk gene, as a novel component of protein translational machinery critical for embryonic neurodevelopment.

Recent genome-wide association studies identified over 100 genetic loci that significantly associate with schizophrenia (SZ). A top candidate gene, ZNF804A, was robustly replicated in different populations. However, its neural functions are largely unknown. Here we show in mouse that ZFP804A, the homolog of ZNF804A, is required for normal progenitor proliferation and neuronal migration. Using a yeast two-hybrid genome-wide screen, we identified novel interacting proteins of ZNF804A. Rather than transcriptional factors, genes involved in mRNA translation are highly represented in our interactome result. ZNF804A co-fractionates with translational machinery and modulates the translational efficiency as well as the mTOR pathway. The ribosomal protein RPSA interacts with ZNF804A and rescues the migration and translational defects caused by ZNF804A knockdown. RNA immunoprecipitation-RNAseq (RIP-Seq) identified transcripts bound to ZFP804A. Consistently, ZFP804A associates with many short transcripts involved in translational and mitochondrial regulation. Moreover, among the transcripts associated with ZFP804A, a SZ risk gene, neurogranin (NRGN), is one of ZFP804A targets. Interestingly, downregulation of ZFP804A decreases NRGN expression and overexpression of NRGN can ameliorate ZFP804A-mediated migration defect. To verify the downstream targets of ZNF804A, a Duolink in situ interaction assay confirmed genes from our RIP-Seq data as the ZNF804A targets. Thus, our work uncovered a novel mechanistic link of a SZ risk gene to neurodevelopment and translational control. The interactome-driven approach here is an effective way for translating genome-wide association findings into novel biological insights of human diseases.

Elevated Adenosine Dehydrogenase (ADH) and Positive Tuberculin Test Firstly Misdiagnosed as Tuberculous Pleural Effusion Finally Proved as Pleural Mesothelial Sarcoma by Thoracoscopic Biopsy Pathology: a Case Report and Literature Review.

BACKGROUND: In China, tuberculous pleural effusion is the most common cause for pleural effusion. Elevated ADH and positive tuberculin test usually are characteristic of tuberculous pleural effusion. We reported a 71-year-old male patient with elevated ADH and positive tuberculin test firstly misdiagnosed as tuberculous pleural effusion finally proven as pleural mesothelial sarcoma by thoracoscopic pathology. METHODS: Appropriate laboratory tests and thoracentesis were carried out. Thoracoscopy and pathological biopsy were performed to differentiate tuberculous pleural effusion. RESULTS: Chest CT showed right pleural effusion. ADH in pleural effusion was over 45 U/L and PPD test was positive. No abnormal cells were found in pleural effusion pathology. Pathology of thoracoscopic biopsy proved pleural mesothelioma. CONCLUSIONS: Elevated ADH and positive tuberculin test are not a specific index for tuberculosis and thoracoscopic biopsy pathology is crucial for differential diagnosis.

Hemoptysis and High-Density Shadow of Both Lungs Combined with Elevated Serum G-Lipopolysaccharide Misdiagnosed as Bronchiectasis with Gram-Negative Bacterium Infection Ultimately Confirmed as Mycobacterium Iranicum Infection by CT-guided Percutaneous Lung Biopsy and Next Generation Sequencing (NGS): a Case Report and Literature Review.

BACKGROUND: G-lipopolysaccharide, a component of the cell wall of Gram-negative bacteria, is called lipopolysaccharide. The detection of G-lipopolysaccharide can be used for the early diagnosis of infectious diseases, but some-times G-lipopolysaccharide provides limited help. We report a case of a patient with hemoptysis and high-density shadow of both lungs combined with elevated serum G-lipopolysaccharide which mimicked bronchiectasis with Gram-negative bacterium infection. It was ultimately confirmed as Mycobacterium iranicum infection by CT-guided percutaneous lung biopsy and next generation sequencing. METHODS: The chest computed tomography (CT) scan, CT-guided percutaneous lung biopsy, and NGS were performed for diagnosis and blood tests explored for the latent etiology. RESULTS: The chest CT scan showed a high-density shadow of both lungs, atelectasis of right middle lobe, multiple enlarged lymph nodes in mediastinum and right hilum. Pathology of CT-guided percutaneous lung biopsy indicated fibrous tissue proliferation and granulation tissue formation and some alveolar epithelial cells slightly proliferated with focal carbon powder deposition in alveolar sacs and spaces. The lung tissue NGS confirmed Mycobacterium iranicum infection. CONCLUSIONS: Elevated serum G-lipopolysaccharide is not a specific index for infectious diseases. CT-guided percutaneous lung biopsy and lung tissue NGS has high specificity in pathogen detection of infectious diseases.

Positive Serum Beta-D-glucan by G Test and Aspergillus Fumigatus Sputum Culture Mimic Invasive Pulmonary Aspergillosis in a Pulmonary Nocardia Patient: a Case Report and Literature Review.

BACKGROUND: Invasive pulmonary aspergillosis and nocardia overlap in clinical and radiological presentations, so differentiating between nocardia and invasive pulmonary aspergillosis is confusing. Though sputum culture could distinguish between nocardia and aspergillus fumigatus, but for the ultimate diagnosis, sputum culture provided limited help. Here we report a case of a patient with positive G test and aspergillus fumigatus sputum culture mimic invasive pulmonary aspergillosis ultimately diagnosed as nocardia through bronchoalveolar lavage culture combined metagenomic next-generation sequencing (NGS). METHODS: Bronchoalveolar lavage culture combined metagenomic NGS for infectious diseases were performed for diagnosis. RESULTS: Bronchoalveolar lavage culture combined metagenomic next-generation sequencing showed Nocardia Gelsenkirchen. CONCLUSIONS: Positive G test and sputum culture were not specific, while bronchoalveolar lavage culture and NGS gave more information for a differential diagnosis between nocardia and aspergillus fumigatus.

[Diagnostic test for detection of cervical lymph node metastasis from oral squamous cell carcinoma via infrared thermal imaging].

OBJECTIVE: To evaluate the diagnostic performance of a non-invasive, non-radiating, economical and convenient infrared thermal imaging in the detection of oral squamous cell carcinoma (OSCC) cervical lymph node metastasis, and evaluate its applicability via parallel test and series test. METHODS: This study was a prospective clinical study which passed the ethical review by the Biomedical Ethics Committee, Hospital of Stomatology, Peking University, and had been submitted for clinical trial registration. Totally 74 OSCC patients who were to undergo a neck dissection were included in this study. The inclusion criteria were patients who: (1) were pathologically diagnosed as malignant tumors and planned to undergo surgical treatment including neck dissection; (2) agreed to participate in this study. The exclusion criteria were those who: (1) had undergone surgeries at head and neck previously; (2) with a history of systemic tumor adjuvant therapies such as radiotherapy or chemotherapy etc; (3) were unwilling or unable to cooperate. Basal information as well as clinical examination results were collected, such as physical examination and contradictive enhanced CT. Besides, infrared thermal imaging was done ahead of surgery. Analysis of the diagnostic power of infrared thermal imaging followed the principles of diagnostic test. The positive signs of infrared thermal imaging were: (1) asymmetric thermographic pattern including vascular pattern in ROI; (2) thickening image of unilateral facial artery/vein, submental artery/vein or external carotid artery; (3) surface temperature of ROI raised over 1 °C compared with the opposite side; (4) changes of neck profile with abnormal temperature pattern. The gold standard of this diagnostic test was pathology diagnosis of cervical lymph nodes. RESULTS: The sensitivity of infrared thermal imaging was 75.0%, while the specificity was 69.0%, accuracy was 71.6%, positive predictive value was 64.9% and negative predictive value was 78.4%. The sensitivity of parallel test which stood for the combination of infrared thermal imaging and conventional clinical examinations was 87.9% while the specificity of series test was 97.6%. CONCLUSION: Infrared thermal imaging is a promising non-invasive, non-radiating and economical tool in the detection of cervical lymph node metastasis from OSCC when combined with conventional pre-operative examination.