Bronchoalveolar lavage fluid metagenomic next-generation sequencing assay for identifying pathogens in lung cancer patients

Background:For patients with lung cancer,timely identification of new lung lesions as infectious or non-infectious,and accurate identification of pathogens is very important in improving OS of patients.As a new auxiliary examination,metagenomic next-generation sequencing(mNGS)is believed to be more accurate in diagnosing infectious diseases in patients without underlying diseases,compared with conventional microbial tests(CMTs).We designed this study tofind out whether mNGS has better performance in distinguishing infectious and non-infectious diseases in lung cancer patients using bronchoalveolar lavagefluid(BALF).Materials and Methods:This study was a real-world retrospective review based on electronic medical records of lung cancer patients with bronchoalveolar lavage(BAL)and BALF commercial mNGS testing as part of clinical care from 1 April 2019 through 30 April 2022 at The First Affiliated Hospital of Sun Yat-sen University.164 patients were included in this study.Patients were categorized into the pulmonary non-infectious disease(PNID)group(n=64)and the pulmonary infectious disease(PID)group(n=100)groups based onfinal diagnoses.Results:BALF mNGS increased the sensitivity rate by 60%compared to CMTs(81%vs.21%,p<0.05),whereas there was no significant difference in specificity(75%vs.98.4%,p>0.1).Among the patients with PID,bacteria were the most common cause of infection.Fungal infections occurred in 32%of patients,and Pneumocystis Yersini was most common.Patients with Tyrosine kinase inhibitors(TKIs)therapy possess longer overall survival(OS)than other anti-cancer agents,the difference between TKIs and immuno-checkpoint inhibitors(ICIs)was insignificant(median OS TKIs vs.ICIs vs.Anti-angiogenic vs.Chemo vs.Radiotherapy=76 vs.84 vs.61 vs.58 vs.60).Conclusions:our study indicates that BALF mNGS can add value by improving overall sensitivity in lung cancer patients with potential pulmonary infection,and was outstanding in identifying Pneumocystis infection.It could be able to help physicians adjust the follow-up treatment to avoid the abuse of antibiotics.

Spontaneous gastrojejunal fistula is a complication of gastric ulcer

Spontaneous gastrojejunal fistula formation is an extremely rare complication of gastric ulcer disease. We report a 77-year old woman who presented with diffuse abdominal pain, weight loss, malaise, nausea, and occasional dark stools. Laboratory tests showed extreme hyposideremic anemia with inflammatory syndrome. In addition, biochemical parameters of malnourishmen were presented. Upper endoscopy revealed the paten esophagus along the full length without any pathologica changes. Large and deep ulceration with perforation in the small intestine was detected in the posterior gastric wall. The small intestine loop was reached by endoscope through spontaneously developed gastrojejunal fistula Polytopic biopsies of described ulcerative change were carried out. Histopathologically reepithelialized ulcerous zone was seen in the gastric mucosa. Also gastrojejunal fistula was visualized after wide opening o hepatogastric and gastrocolic ligament. Jejunal loop 25 cm from ligament of Treitz was attached to mesocolon and posterior gastric wall because of ulcer penetration Postoperative course was uneventful. Per oral intake started on the 4th postoperative day, and the patient was discharged on the 8th postoperative day. In summary this case indicates that persistent symptoms of peptic ulcer disease associated with nutritional disturbances may be caused by gastrojejunal fistula.

Antitumor effect of RNA interference on non-small- cell lung cancer in vivo

客观的肺癌症在世界上作为癌症死亡的一个领先的原因出现了。当前的治疗是无效的，这样新的途径被需要改进治疗学的比率。RNA 干扰(RNAi ) 在 vitro，在为 non-small-cell 的治疗开发新方法，肺癌症(NSCLC ) 需要进一步在 vivo 被测试其潜力在基因 silencing 显示出诺言。在这研究，化学上综合了指向表皮的生长因素受体(EGFR ) 的双 stranded RNA (dsRNA ) 是进 NSCLC 房间线 SPC-A1 房间的 transfected 并且证实肿瘤麻烦了裸体老鼠建模调查 dsRNA 是否能在 vivo 在 NSCLC 房间导致基因 silencing 的 athymic。方法 SPC-A1 是 transfected， EGFR 顺序特定的 dsRNA 与 Lipofectamine 2000 提出了。SPC-A1 房间(在 200 μL 的 10 7/mL) 是的 1 ×进老鼠的左胁腹区域的注射 s.c 麻烦了裸体老鼠建模的 athymic 建立肿瘤。由测量直径和肿瘤的重量计算肿瘤生长抑制率。Immunohistochemistry 和西方的污点被用来在 EGFR 蛋白质的生产监视减小。实时 RT-PCR 被用来检测 EGFR mRNA 水平的 silencing。EGFR 显著地定序特定的 dsRNA (dsRNA-EGFR ) ，这显示了的结果在 vivo 禁止了肿瘤生长。肿瘤生长抑制率是 75.03% 。dsRNA-EGFR 明确地与 EGFR 蛋白质生产的 53.6% 下面规定和 EGFR mRNA 的 32.3% silencing 定序 silenced EGFR 水平。结论 DsRNA-EGFR 显示出轰动效果在在 EGFR mRNA 的规定下面在 vivo 的肿瘤生长的水平和蛋白质生产，和抑制。

Plasma and platelet serotonin levels in patients with liver cirrhosis

AIM: To analyze the relationship between plasma and platelet serotonin levels and the degree of liver insufficiency. METHODS: The prospective study included 30 patients with liver cirrhosis and 30 healthy controls. The degree of liver failure was assessed according to the Child-Pugh classification. Platelet and platelet poor plasma serotonin levels were determined. RESULTS: The mean plasma serotonin level was higher in liver cirrhosis patients than in healthy subjects (215.0 ± 26.1 vs 63.1 ± 18.1 nmol/L; P < 0.0001). The mean platelet serotonin content was not significantly different in patients with liver cirrhosis compared with healthy individuals (4.8 ± 0.6; 4.2 ± 0.3 nmol/platelet; P > 0.05). Plasma serotonin levels were significantly higher in Child- Pugh grade A/B than in grade C patients (246.8 ± 35.0 vs 132.3 ± 30.7 nmol/L; P < 0.05). However, platelet serotonin content was not significantly different between Child-Pugh grade C and grade A/B (4.6 ± 0.7 vs 5.2 ± 0.8 nmol/platelet; P > 0.05). CONCLUSION: Plasma serotonin levels are significantly higher in patients with cirrhosis than in the controls and represent the degree of liver insufficiency. In addition, platelet poor plasma serotonin estimation is a better marker for liver insufficiency than platelet serotonin content.

Effect of intramuscular injection of hepatocyte growth factor plasmid DNA with electroporation on bleomycin-induced lung fibrosis in rats

Background So far, there is no efficient treatment for pulmonary fibrosis. The objective of this study was to determine whether intramuscular injection of the hepatocyte growth factor （HGF） pfasmid DNA by in vivo electroporation could prevent bleomycin-induced pulmonary fibrosis in rats, and to investigate the possible mechanisms. Methods Twenty male Wistar rats were randomly divided into four groups： control group （group C）, model group （group M）, early intervention group （group Ⅰ ） and late intervention group （groupⅡ）. Groups M, Ⅰ and Ⅱ were intratracheally infused with bleomycin, then injected the plasmid pcDNA3.1-hHGF to group Ⅰ on day 7, 14 and 21. Group Ⅱ received the same treatment like Group Ⅰ on day 14 and 21. All the rats were killed on day 28 after bleomycin injection. We detected Homo HGF expression in the rats with ELISA method and estimated the pathological fibrosis score of lung tissue using hematoxylin eosin （HE） and Massion staining. The mRNA expression of transforming growth factor-β1 （TGF-β1）, cycloxygenase-2 （COX-2）, and rat HGF in rat pulmonary parenchyma were evaluated by RT-PCR. Immunohistochemistry and Western blotting were performed to determine the protein expression of transforming TGF-β1 and COX-2 in lung parenchyma. Results The plasmid pcDNA3.1-hHGF could express hHGF in NIH3T3 cells and the hHGF protein is secreted into the culture medium. The expression of hHGF protein could be monitored in quadriceps muscle, plasma and lung in Groups Ⅰ and Ⅱ. Pulmonary fibrosis levels of Groups Ⅰ and Ⅱ were obviously lower than that of group M （P〈0.05）. Expression of TGF-β1 protein and mRNA in lung tissue was markedly decreased in Groups Ⅰ and Ⅱ compared with Group M （P〈0.05）. The level of expression of HGF and COX-2 mRNA was higher in Groups Ⅰ and Ⅱ than in Group M （P〈0.05）. Conclusions Injection of the plasmid pcDNA3.1-hHGF into skeletal muscle with electroporation has a potential role in the treatment of bleomycin-induced lung fibrosis. Exogenous HGF may inhibit the expression of TGF-β1 and regulate the crosstalk between AECs and mesenchymal fibroblasts.

Treating COVID-19 with Chloroquine

A novel coronavirus disease 2019(COVID-19)emerged around December 2019 in Wuhan,China and has spread rapidly worldwide(Lu et al.,2020).Until March 27,2020,the Chinese health authorities had reported 82082 confirmed COVID-19 cases in China with 3298 deaths and 381443 confirmed cases with 20787 deaths outside China.The World Health Organization(WHO)named the virus SARS-CoV-2,which belongs to a distinct clade from the human severe acute respiratory syndrome CoV(SARS-CoV)and Middle East respiratory syndrome CoV(MERSCoV)(Zhu et al.,2020).

Lung ultrasound:a valuable tool for assessing COVID-19 patients with different severity

To the Editor:Lung ultrasound(LUS)may be a promising technique to assess lung injury from coronavirus disease 2019(COVID-19).However,the LUS characteristics and their assessment value have not been well described.We aimed to explore the LUS characteristics and their assessment value in COVID-19 patients with different levels of disease severity.