Weakened black carbon trans-boundary transport to the Tibetan Plateau during the COVID-19 pandemic.

The lockdowns implemented during the coronavirus disease 2019 (COVID-19) pandemic provide a unique opportunity to investigate the impact of emission sources and meteorological conditions on the trans-boundary transportation of black carbon (BC) aerosols to the Tibetan Plateau (TP). In this study, we conducted an integrative analysis, including in-situ observational data, reanalysis datasets, and numerical simulations, and found a significant reduction in the trans-boundary transport of BC to the TP during the 2020 pre-monsoon season as a result of the lockdowns and restrictive measures. Specifically, we observed a decrease of 0.0211 µgm-3 in surface BC concentration over the TP compared to the 2016 pre-monsoon period. Of this reduction, approximately 6.04 % can be attributed to the decrease in emissions during the COVID-19 pandemic, surpassing the 4.47 % decrease caused by changes in meteorological conditions. Additionally, the emission reductions have weakened the trans-boundary transport of South Asia BC to the TP by 0.0179 µgm-2s-1; indicating that the recurring spring atmospheric pollution from South Asia to the TP will be alleviated through the reduction of anthropogenic emissions. Moreover, it is important to note that BC deposition on glaciers contributes significantly to glacier melting due to its enrichment, posing a threat to the water sustainability of the TP. Therefore, urgent measures are needed to reduce emissions from adjacent regions to preserve the TP as the "Asian Water Tower."

Loss of chromosome 9p21 is associated with a poor prognosis in adenosquamous carcinoma of the pancreas.

Adenosquamous carcinoma of the pancreas (ASCP) is a rare histological subtype of pancreatic cancer with a poor prognosis and a high metastasis rate. However, little is known about its genomic landscape and prognostic biomarkers. A total of 48 ASCP specimens and 98 pancreatic ductal adenocarcinoma (PDAC) tumour specimens were sequenced to explore the genomic landscape and prognostic biomarkers. The homozygous deletion of the 9p21.3 region (including CDKN2A, CDKN2B, and MTAP) (9p21 loss) occurred in both ASCP and PDAC, and a higher frequency of 9p21 loss was observed in ASCP (12.5% vs 2.0%, P = 0.022). Notably, 9p21 loss was significantly associated with poor disease-free survival (DFS) in ASCP patients (mDFS (Median DFS) = 4.17 vs 7.33 months, HR (Hazard Ratio) = 3.70, P = 0.009). The most common gene alterations in patients with ASCP were KRAS (96%), TP53 (81%), CDKN2A (42%), SMAD4 (21%), CDKN2B (13%), and FAT3 (13%). The mutation rates of ACVR2A (6.25% vs 0%), FANCA (6.25% vs 0%), RBM10 (6.25% vs 0%), and SPTA1 (8.33% vs 1.02%) were significantly higher in ASCP than in PDAC. In conclusion, we have comprehensively described the genomic landscape of the largest cohort of ASCP patients to date and highlight that 9p21 loss may be a promising prognostic biomarker for ASCP, which provides a molecular basis for prognosis prediction and new therapeutic strategies for ASCP.

Acute Glycemic Variability and Early Outcomes After Cardiac Surgery: A Meta-Analysis.

The influence of acute glycemic variability (GV) on early outcomes of patients after cardiac surgery remains not fully determined. We performed a systematic review and meta-analysis to evaluate the association between acute GV and in-hospital outcomes of patients after cardiac surgery. Relevant observational studies were obtained by search of electronic databases including Medline, Embase, Cochrane Library, and Web of Science. A randomized-effects model was selected to pool the data by incorporating the influence of potential heterogeneity. Nine cohort studies involving 16 411 patients after cardiac surgery were included in this meta-analysis. Pooled results showed that a high acute GV was associated with an increased risk of major adverse events (MAE) during hospitalization for patients after cardiac surgery [odds ratio [OR]: 1.29, 95% CI: 1.15 to 1.45, p<0.001, I22=38%]. Sensitivity analysis limited to studies of on-pump surgery and GV evaluated by coefficient of variation of blood glucose showed similar results. Subgroup analysis suggested that a high acute GV was related to an increased incidence of MAE in patients after coronary artery bypass graft, but not for those after isolated valvular surgery (p=0.04), and the association was weakened after adjustment of glycosylated hemoglobin (p=0.01). Moreover, a high acute GV was also related to an increased risk of in-hospital mortality (OR: 1.55, 95% CI: 1.15 to 2.09, p=0.004; I22=0%). A high acute GV may be associated with poor in-hospital outcomes in patients after cardiac surgery.

Next generation sequencing predicting clinical effect of immunotherapy on adult rhabdomyosarcoma patient: A case report.

RATIONALE: Rhabdomyosarcoma (RMS) is a rare sarcoma that rarely occurs in adults and accounts for only 1% of all adult tumors. The standard treatment for RMS is surgical resection, radiotherapy, and chemotherapy. PATIENT CONCERNS: Adult patients often present with an aggressive course and poor prognosis. DIAGNOSES: The patient was diagnosed with RMS in September 2019 and was confirmed by hematoxylin-eosin staining and immunohistochemistry after surgical resection. INTERVENTIONS: The patient received surgical resection in September 2019. He was admitted to another hospital after the first recurrence in November 2019. After the second routine surgical resection, the patient underwent chemotherapy, radiotherapy, and anlotinib maintenance treatment. He relapsed again in October 2020 and was admitted to our hospital. Next-generation sequencing was performed on the punctured tissue of the patient's lung metastatic lesion, and high tumor mutational burden (TMB-H), high microsatellite instability (MSI-H), and positive programmed death-ligand 1 (PD-L1) were observed. The patient then received toripalimab and anlotinib combined therapy and was evaluated for a partial response after 2 months. OUTCOMES: This benefit has persisted for more than 17 months. LESSONS: This is the longest progression-free survival for PD-1 inhibitors in RMS, and there is a trend of continued extension of progression-free survival in this patient. This case supports the hypothesis that positive PD-L1, TMB-H, and MSI-H could be beneficial biomarkers for immunotherapy in adult RMS.

Differences in DNA damage repair gene mutations between left- and right-sided colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide. Studies have shown that the DNA damage response (DDR) mutation is strongly associated with microsatellite instability (MSI) status and is an indication for patients with CRCs receiving immune checkpoint inhibitor (ICI) treatment. However, DDR mutation in microsatellite stable (MSS) CRC remains unclear. METHODS: In this study, Fisher's exact test, Student'st-test, Wilcoxon rank-sum test and Cox proportional hazards regression model were performed, and a p value of < 0.05 was considered statistically significant. RESULTS: The most common gene alterations were APC (77%), TP53 (73%), KRAS (48%), and PIK3CA (25%). The mutationfrequency of APC and TP53 in left-sided CRC was significantly higher than that for right-sided CRC, while the mutation frequency of PIK3CA, ACVR2A, FAT4, and RNF43 in right-sided CRC was significantly higher than that for left-sided CRC. DDR mutations occurred in100% of MSI CRCs and in 83.77% of MSS CRCs, with the most frequently mutated DDR genes being ARID1A (7.5%), ATM (5.7%,) and BRCA2 (2.6%). When right- and left-sided CRCs were compared, no significant difference was observed for DDR genes and pathways. A survival analysis indicated that the DDR mutation was not associated with overall survival (OS) in MSS CRCs, while left-sided patients with homologous recombination repair (HRR) pathway mutations had a significantly prolonged OS compared with right-sided CRCs. CONCLUSIONS: Here, we found that stage and grade were statistically significant independent prognostic factors in the left-sided CRC and the right-sided CRC, recommending treatment for these patients stratified by stage. For the future, utilizing DDR gene defects for expanding treatment options and improving prognosis is an issue worth exploring.

Responses of Arctic sea ice to stratospheric ozone depletion.

The Arctic has experienced several extreme springtime stratospheric ozone depletion events over the past four decades, particularly in 1997, 2011 and 2020. However, the impact of this stratospheric ozone depletion on the climate system remains poorly understood. Here we show that the stratospheric ozone depletion causes significant reductions in the sea ice concentration (SIC) and the sea ice thickness (SIT) over the Kara Sea, Laptev Sea and East Siberian Sea from spring to summer. This is partially caused by enhanced ice transport from Barents-Kara Sea and East Siberian Sea to the Fram Strait, which is induced by a strengthened and longer lived polar vortex associated with stratospheric ozone depletion. Additionally, cloud longwave radiation and surface albedo feedbacks enhance the melting of Arctic sea ice, particularly along the coast of the Eurasian continent. This study highlights the need for realistic representation of stratosphere-troposphere interactions in order to accurately predict Arctic sea ice loss.

Colorectal leiomyosarcoma with BRCA2 mutation benefit from treatment with olaparib: a case report.

Background: Colorectal leiomyosarcoma (LMS) is a rare colorectal malignancy accounting for approximately 1% of all colorectal malignancies with a poor prognosis and limited treatment options. Targeted therapies have been applied for breast cancer 2 (BRCA2) alterations, but their role remains to be explored in colorectal LMS. This case could provide clinical proof for the application of olaparib for LMS patients. Case Description: Here, we present a case of colorectal LMS with BRCA2 alterations who was treated with olaparib and achieved progression-free survival (PFS) for 1 year. In August 2016, a 46-year-old female patient was admitted to hospital due to a mass in the left lower abdomen and was diagnosed with LMS of the sigmoid colon. After surgical resection, chemotherapy with ifosfamide or ifosfamide combined with pirarubicin was given and achieved stable disease (SD) until the disease progressed 1.5 years later. Afterwards, a multi-target tyrosine kinase inhibitor, anlotinib, was taken. Before the observation of lung and liver metastasis, the patient's disease was stable for 1 year. BRCA2 mutation and rearrangement was revealed by next-generation sequencing (NGS), and the targeted therapy, olaparib, was given. Efficacy evaluation showed SD for 1 year, and no obvious toxic and side effects were observed. Conclusions: Our case suggested that NGS should be considered for further treatment of patients with colorectal LMS, and poly (ADP-ribose) polymerase (PARP) inhibitors could be a feasible therapy for LMS patients with BRCA2 alterations.

Molecular Landscape and Prognostic Biomarker Analysis of Advanced Pancreatic Cancer and Predictors of Treatment Efficacy of AG Chemotherapy.

Purpose: Although mutational analysis of pancreatic cancer has provided valuable clinical information, it has not significantly changed treatment prospects. The purpose of this study is to further investigate molecular alterations in locally advanced pancreatic cancer and identify predictors of the efficacy of nab-paclitaxel plus gemcitabine (AG) chemotherapy. Experimental design: Tumor samples from 118 pancreatic cancer patients who received AG chemotherapy as first-line treatment were sequenced and genomic profile was generated. Molecular alterations and the involved signaling pathways were analyzed. Genes with a significant difference in mutation frequency between primary and metastatic tumors were identified, and prognostic-related mutant genes were screened using SPSS version 22.0. Results: The most common altered genes in the patients were KRAS (94.9%), TP53 (81.4%), CDKN2A (36.4%), and SMAD4 (22.9%). The mutational frequencies of CDKN2B (14.8% vs. 0%, p = 0.001), FAT3 (7.4% vs. 0%, p = 0.041), MTAP (13% vs. 1.6%, p = 0.023), and SMAD4 (31.4% vs. 15.6%, p = 0.049) in metastatic tumors were significantly higher than that in primary tumors. TP35 and KRAS mutations were significantly correlated with objective response rate, while EPHA7, RNF43, and HMGA2 mutations were significantly correlated with disease control rate. Additionally, patients with TGFR2B, FGF23, EPHA7, SMARCA4, CARD11, ADGRA2, CCNE1, and ACVR2A alterations had a worse overall survival. Further, EPHA7, CARD11, NOTCH1, GATA6, ACVR2A, and HMGA2 mutations indicated undesirable progression-free survival. Conclusions: CDKN2B, FAT3, MTAP, and SMAD4 may be biomarkers that distinguish primary tumors from metastases. EPHA7 mutation may serve as a prognostic biomarker to predict the treatment efficacy of AG chemotherapy in locally advanced pancreatic cancer.

Case Report: Two Cases of Soft-Tissue Sarcomas: High TMB as a Potential Predictive Biomarker for Anlotinib Combined With Toripalimab Therapy.

Soft-tissue sarcomas (STS), with over 100 different histologic subtypes, are rare tumors that account for 1% of all adult malignancies. Immune checkpoint inhibitors (ICIs) display certain benefits in some subtypes, especially in undifferentiated pleomorphic sarcoma (UPS), alveolar soft part sarcoma (ASPS), and leiomyosarcoma (LMS). However, efficacy is difficult to predict. High tumor mutational burden (TMB-H) and programmed death-ligand 1 (PD-L1) expression are the strongest features associated with the efficacy of immunotherapy, although they are rarely found in STS patients. Until now, whether or not PD-L1 expression and TMB are related to the efficacy of immunotherapy has not been determined. In this study, we report data obtained from two STS patients, one ASPS and one UPS with a high TMB, that benefited from anlotinib combined with toripalimab following resistance to anlotinib monotherapy. A 26 year-old female patient was diagnosed with ASPS. PD-L1 was negative. Next generation sequencing (NSG) revealed ASPSCR1-TFE3 fusion and TMB-H. Following eight months of anlotinib monotherapy, the patient's disease progressed but continued to benefit from subsequent use of anlotinib combined with toripalimab for 19 months. Another 63 year-old male patient was diagnosed with UPS. PD-L1 was positive and NGS revealed TMB-H. Following 19 months of anlotinib monotherapy, the patient's disease progressed but continued to benefit from subsequent use of anlotinib combined with toripalimab. DFS is 23 months to follow-up time. The results presented are the first to report the relationship between TMB and the efficacy of immunotherapy in STS. Based on our results, we hypothesis that anlotinib combined with toripalimab is effective for the treatment of some advanced ASPS or UPS. TMB may be a potential predictive biomarker for ICI treatment and deserves additional study.

A novel fusion between CDC42BPB and ALK in a patient with quadruple wild-type gastrointestinal stromal tumor.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most common type of mesenchymal tumor in gastrointestinal tract, with striking features of morphology and immunohistochemistry. But GISTs in pregnancy could seldom be found. Pathogenic activating mutations of the proto-oncogene KIT and PDGFRA are detected in majority GISTs, and adjuvant imatinib therapy targeting KIT and PDGFRA mutations is recommended for patients with high-risk GIST. However, some rare subgroups with distinct molecular features remain uncovered and more therapeutic targets need to be revealed. METHODS: The DNA/RNA samples were detected using the NGS-based YuanSu450 gene panel. After identifying the CDC42BPB-ALK fusion by NGS, this novel fusion was further confirmed by Sanger sequencing. Subsequently, FISH analysis was performed using the Vysis ALK Break Apart FISH Probe kit to testify the ALK status. ALK protein expression was confirmed by IHC (D5F3 and 5A4). RESULTS: Herein, we reported the first case of quadruple wild-type (WT) GIST with ALK-CDC42BPB fusion and ALK (D5F3) overexpression. In this study, we described a 33-year-old pregnant patient in lactation who had a massive space occupying lesion (with the maximum diameter of 22 cm) in the stomach and was eventually diagnosed as quadruple WT GIST (KITWT /PDGFRAWT /SDHWT /RAS-PWT ). CONCLUSION: We unexpectedly found that this GIST patient showed ALK (D5F3) overexpression and harbored a novel fusion CDC42BPB exon 24-ALK in exon 20.

Olaparib effectively treats local recurrence of extrahepatic cholangiocarcinoma in a patient harboring a BRCA2-inactivating mutation: a case report.

Cholangiocarcinoma (CCA) is a malignant tumor with poor prognosis and high recurrence rate. There is no standard treatment for advanced CCA beyond first-line chemotherapy, which provides only limited benefits. In this study, we report a case of a postoperative recurrence ECC patient harboring a breast cancer 2 (BRCA2)-inactivating rearrangement mutation that had an obvious reaction to olaparib therapy. The patient was a 68-year-old man with postoperative recurrence of extrahepatic CCA (ECC) who declined systemic chemotherapy. In August 2015, abdominal computed tomography (CT) of the patient revealed intrahepatic bile duct dilatation, obstruction at the hepatic hilar region proximal to the common hepatic duct, and splenomegaly, and radical surgical resection was performed. Postoperative histopathology diagnosis was ECC without metastases. In February 2017, abdominal CT revealed local recurrence, and the patient refused chemotherapy. BRCA2 rearrangement were detected by next-generation sequencing. Oral administration of olaparib was initiated. The patient achieved stable disease 1 month later, progression-free survival for >10 months without any significant adverse reactions, and an overall survival (OS) of 27 months. This is the first report demonstrating the clinical benefits of olaparib in a BRCA2 rearrangement-harboring patient with ECC. This observation would help determine the best treatment option for advanced ECC patients.

Response to crizotinib in a patient with MET-amplified hepatocellular carcinoma.

AIMS: Molecular profiling of hepatocellular carcinoma (HCC) has helped identify actionable genomic alterations that could guide therapeutic decision-making and clinical trial enrollment. However, in clinical practice, next-generation sequencing (NGS) is not extensively used in routine clinical care to identify patients with HCC who are likely to benefit from genome-directed targeted therapies. METHODS: Here, we describe the case of a 66-year-old man with advanced HCC. After rapid progression on transarterial chemoembolization, the tissue sample obtained from biopsy was subjected to NGS to verify whether precision therapy was an option. RESULTS: Our analysis revealed high MET amplification. The patient received crizotinib (250 mg, bid) and showed a remarkable response. CONCLUSIONS: Our case report suggests NGS could help identify patients with high MET amplification in HCC who were likely to benefit from MET inhibitors; moreover, this requires further investigation in clinical trials.

How Buffers Resist Electrochemical Reaction-Induced pH Shift under a Rotating Disk Electrode Configuration.

In mild acidic or alkaline solutions with limited buffer capacity, the pH at the electrode/electrolyte interface (pHs) may change significantly when the supply of H+ (or OH-) is slower than its consumption or production by the electrode reaction. Buffer pairs are usually applied to resist the change of pHs during the electrochemical reaction. In this work, by taking H2X ⇄ 2H+ + X + 2e- under a rotating disk electrode configuration as a model reaction, numerical simulations are carried out to figure out how pHs changes with the reaction rate in solutions of different bulk pHs (pHb in the range from 0 to 14) and in the presence of buffer pairs with different pKa values and concentrations. The quantitative relation of pHs, pHb, pKa, and concentration of buffer pairs as well as of the reaction current density is established. Diagrams of pHs and ΔpH (ΔpH = pHs - pHb) as a function of pHb and the reaction current density as well as of the jmax-pHb plots are provided, where jmax is defined as the maximum allowable current density within the acceptable tolerance of deviation of pHs from that of pHb (e.g., ΔpH < 0.2). The j-pHs diagrams allow one to estimate the pHs and ΔpH without direct measurement. The jmax-pHb plots may serve as a guideline for choosing buffer pairs with appropriate pKa and concentration to mitigate the pHs shift induced by electrode reactions.

Case Report: Effectiveness of Targeted Treatment in a Patient With Pancreatic Cancer Harboring PALB2 Germline Mutation and KRAS Somatic Mutation.

Pancreatic cancer is one of the most leading causes of cancer death worldwide. The rapid development of next-generation sequencing (NGS) and precision medicine promote us to seek potential targets for the treatment of pancreatic cancer. Here, we report a female pancreatic cancer patient who underwent radical surgical excision after neoadjuvant chemotherapy. After the surgery, the patient underwent gemcitabine + S-1 therapy, capecitabine + albumin paclitaxel therapy and irinotecan therapy successively, however, MRI review revealed tumor progression. The surgical tissue sample was subjected to next-generation sequencing (NGS), and PALB2 germline mutation and KRAS somatic mutation were identified. The patient then received olaparib (a PARP inhibitor) + irinotecan and the disease stabilized for one year. Due to the increased CA19-9, treatment of the patient with a combination of trametinib (a MEK inhibitor) and hydroxychloroquine resulted in stable disease (SD) with a significant decrease of CA19-9. This case demonstrated that the NGS may be a reliable method for finding potential therapeutic targets for pancreatic cancer.

Case report: EGFR-mutant lung adenocarcinoma with the TP53 and RB1 mutations showed resistance to TKI therapy.

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are a standard treatment for patients with advanced non-small-cell lung cancer (NSCLC) harboring classic EGFR mutations. However, resistance to TKIs remains a major clinical challenge. The transformation from adenocarcinoma to small-cell lung cancer (SCLC) is a rare resistance mechanism to EGFR-TKIs. In this article, we report on 2 lung adenocarcinoma patients with EGFR mutations who developed EGFR-TKI resistance. In case one, the patient was initially diagnosed as lung adenocarcinoma with EGFR L858R, RB1 R445*, and TP53 Y205C mutations. EGFR-TKI failed to bring satisfactory curative effect with the emergence of EGFR T790M mutation and MET amplification and finally passed away. In case two, the patient was diagnosed with lung cancer harboring EGFR L747 and TP53 R342* mutations, and EGFR-TKIs brought a progression-free survival for nine months. However, EGFR-TKI resistance was acquired, and adenocarcinoma transformed into a complex of neuroendocrine carcinoma, SCLC, and lung adenocarcinoma, with the emergence of the EGFR L747, TP53 R342*, and RB1 mutations. Follow-up treatments failed to prevent tumor progression, and the patient died These 2 cases expand our understanding of EGFR-TKI resistance, SCLC transformation, and highlight the importance of histopathology and molecular characteristics for therapeutic strategies for transformed SCLC patients.

Platelet-to-lymphocyte ratio is associated with prognosis in patients with coronavirus disease-19.

Since December 2019, novel coronavirus infected pneumonia emerged in Wuhan city and rapidly spread throughout China. In severe novel coronavirus pneumonia cases, the number of platelets, their dynamic changes during the treatment, platelet-to-lymphocyte ratio (PLR) were a concern. We sought to describe the platelet feature of these cases. Single-center case series of the 30 hospitalized patients with confirmed coronavirus disease (COVID)-19 in Huizhou municipal central hospital from January 2020 to February 2020 were retrospectively analyzed. Demographic, clinical, blood routine results, other laboratory results, and treatment data were collected and analyzed. Outcomes of severe patients and nonsevere patients were compared. Univariate analysis showed that: age, platelet peaks, and PLR at peak platelet were the influencing factors in severe patients, multivariate analysis showed that the PLR value at peak platelet during treatment was an independent influencing factor in severe patients. The average hospitalization day of patients with platelet peaks during treatment was longer than those without platelet peaks (P < .05). The average age of patients with platelet peaks during treatment was older than those without platelet peaks (P < .05). The patients with significantly elevated platelets during treatment had longer average hospitalization days. And the higher PLR of patients during treatment had longer average hospitalization days. Single-center case series of the 30 hospitalized patients with confirmed COVID-19 in Huizhou Municipal Central Hospital, presumed that the number of platelets and their dynamic changes during the treatment may have a suggestion on the severity and prognosis of the disease. The patient with markedly elevated platelets and longer average hospitalization days may be related to the cytokine storm. The PLR of patients means the degree of cytokine storm, which might provide a new indicator in the monitoring in patients with COVID-19.

Spinal Cord Syphilitic Gumma Presenting with Brown-Séquard Syndrome: A Case Report and Literature Review.

BACKGROUND: Spinal neurosyphilis manifesting as a solitary syphilitic gumma is exceedingly rare. There are non-specific imaging findings and challenges in the diagnosis of spinal syphilitic gumma, which could be easily misdiagnosed as tumor lesions and require surgical resection or biopsy. CLINICAL PRESENTATION: We report the case of a 45-year-old female patient who was diagnosed with Spinal syphilitic gumma. Our case is the first reported case of spinal cord syphilitic gumma with intradural-extramedullary and intramedullary involvement. CONCLUSION: Spinal syphilitic gumma exhibits diverse clinical manifestations, lacks specific imaging features, accompanied by the patient's history deliberately concealed. Since clinicians do not have sufficient knowledge about such rare cases, misdiagnosis and missed diagnosis will be likely. When there is clinical suspicion for spinal syphilitic gumma, clinicians should pay close attention to relevant medical history, carry out a comprehensive physical examination and specific serological tests and cerebrospinal fluid (CSF) analysis. In summary, in cases with stable neurologic conditions, a trial administration of intravenous penicillin with follow-up imaging may be the optimal treatment option, and in cases with rapid progression or acute exacerbation, a surgical resection together with systemic antibiotic treatment for syphilis after surgery may be the best treatment strategy.