Impact of Pulmonary microbiota on lung cancer treatment-related pneumonia.

Background: The use of immunotherapy is progressively expanding for the treatment of lung cancer, either alone or in combination with radiotherapy. However, treatment-related adverse events, especially pneumonia, significantly limit the drug's effectiveness in treating lung cancer. The occurrence of lung cancer, immunotherapy, and pulmonary radiotherapy can all contribute to the imbalance in the pulmonary microbiota, rendering the lungs more susceptible to inflammatory reactions. Methods: Mouse models of lung transplantation tumor were treated with either PD-1 monoclonal antibody or radiotherapy alone, or in combination. The differences in lung inflammation among the different treatment groups were regularly observed by micro-CT. Further, bronchoalveolar lavage fluid was extracted for macrogenomic and cytokine detection. The transcriptional genome of tumor-filled lung tissue was also sequenced. Results: When treated with a combination of PD-1 and radiotherapy, the CT scans showed more severe pulmonary inflammation. However, with the addition of continuously administered antibiotics, no exacerbation of pneumonia signs was observed. Moreover, the differential gene expression and cytokine profiles in the combination treatment group differed from those in the PD-1 monotherapy group and the radiotherapy monotherapy group. This discrepancy does not seem to be a straightforward superimposition of radiation-induced pneumonia and immune-related pneumonia. Further exploration of changes in pulmonary microbiota revealed specific bacterial interactions with DEGs and cytokines. Conclusions: The underlying causes of this susceptibility are intricate and may be associated with the complexity of pulmonary microbiota imbalance, along with fluctuations in the abundance of specific microbiota species.

Quantitative cellular pathology of the amygdala in temporal lobe epilepsy and correlation with magnetic resonance imaging volumetry, tissue microstructure, and sudden unexpected death in epilepsy risk factors.

OBJECTIVE: Amygdala enlargement can occur in temporal lobe epilepsy, and increased amygdala volume is also reported in sudden unexpected death in epilepsy (SUDEP). Apnea can be induced by amygdala stimulation, and postconvulsive central apnea (PCCA) and generalized seizures are both known SUDEP risk factors. Neurite orientation dispersion and density imaging (NODDI) has recently provided additional information on altered amygdala microstructure in SUDEP. In a series of 24 surgical temporal lobe epilepsy cases, our aim was to quantify amygdala cellular pathology parameters that could predict enlargement, NODDI changes, and ictal respiratory dysfunction. METHODS: Using whole slide scanning automated quantitative image analysis methods, parallel evaluation of myelin, axons, dendrites, oligodendroglia, microglia, astroglia, neurons, serotonergic networks, mTOR-pathway activation (pS6) and phosphorylated tau (pTau; AT8, AT100, PHF) in amygdala, periamygdala cortex, and white matter regions of interest were compared with preoperative magnetic resonance imaging data on amygdala size, and in 13 cases with NODDI and evidence of ictal-associated apnea. RESULTS: We observed significantly higher glial labeling (Iba1, glial fibrillary acidic protein, Olig2) in amygdala regions compared to cortex and a strong positive correlation between Olig2 and Iba1 in the amygdala. Larger amygdala volumes correlated with lower microtubule-associated protein (MAP2), whereas higher NODDI orientation dispersion index correlated with lower Olig2 cell densities. In the three cases with recorded PCCA, higher MAP2 and pS6-235 expression was noted than in those without. pTau did not correlate with SUDEP risk factors, including seizure frequency. SIGNIFICANCE: Histological quantitation of amygdala microstructure can shed light on enlargement and diffusion imaging alterations in epilepsy to explore possible mechanisms of amygdala dysfunction, including mTOR pathway activation, that in turn may increase the risk for SUDEP.

Application of ultrasound-guided medical thoracoscopy in patients with small amounts or without pleural effusion.

BACKGROUND: Pleural disease is a common clinical condition, and some patients present with a small amount of pleural effusion or no pleural effusion. It is difficult to diagnose such patients in clinical practice. Medical thoracoscopy is the gold standard for the diagnosis of pleural effusion with unknown origin, and guidelines recommend that pneumothorax should be induced in such patients before medical thoracoscopy examination. However, the process of inducing pneumothorax is tedious and has many complications. Our study was conducted to clarify the value of thoracic ultrasound combined with medical thoracoscopy in patients with small amounts or without pleural effusion to simplify the process of medical thoracoscopy examination. METHODS: In this retrospective study, we included patients who were assigned to complete medical thoracoscopy. Successful completion of medical thoracoscopy in patients was regarded as letting the endoscope get into the pleural cavity and completion of the biopsy. Finally, we analyzed the value of preoperative ultrasound in patients without or with small amounts of pleural effusion. RESULTS: Seventy-two patients were finally included in the study. Among them, 68 patients who underwent ultrasound positioning of the access site successfully completed the examination and four patients failed the examination. Fifty-one cases showed no fluid sonolucent area at the access site, of which 48 cases had pleural sliding signs at the access site, and 47 patients successfully completed the examination; 3 cases without pleural sliding signs at the access site failed to complete thoracoscopy. In 21 cases, the fluid sonolucent area was selected as the access site, and all of them successfully completed thoracoscopy. CONCLUSION: Medical thoracoscopy is one of the methods to confirm the diagnosis in patients with pleural disease with small amounts or without pleural effusion. The application of thoracic ultrasound before medical thoracoscopy can be used for the selection of the access site. It is possible to replace pneumothorax induction before medical thoracoscopy.

Casticin inhibits migration and invasion of hepatocellular carcinoma MHCC97H cells through miR-148a-3p/Wnt1 signaling pathway / 中国药理学通报

Aim To investigate the effect of casticin (CAS) on the migration and invasion of MHCC97H cells and preliminarily explore the molecular mechanism. Methods CCK-8 kit was used to detect the effect of different concentrations of CAS on the viability of MHCC97H cells; cell migration and invasion assays were carried out in groups to assess the migration and invasion ability of MHCC97H cells; reverse transcription fluorescence quantitative PCR (RT-qPCR) was performed to detect the miR-148a-3p and Wnt1 mRNA expression in MHCC97H cells after CAS treatment; migration-invasion related proteins (MMP2, MMP9) and Wnt1 protein expression were detected by Western blot; Dual-Luciferase reporter gene was used to detect the binding of miR-148a-3p to Wnt1 3′-UTR. Results CAS significantly inhibited the viability of MHCC97H cells. The IC

Potent SARS-CoV-2 neutralizing antibodies selected from a human antibody library constructed decades ago

Combinatorial antibody libraries not only effectively reduce antibody discovery to a numbers game, but enable documentation of the history of antibody responses in an individual. The SARS-CoV-2 pandemic has prompted a wider application of this technology to meet the public health challenge of pandemic threats in the modern era. Herein, we used a combinatorial human antibody library constructed 20 years before the COVID-19 pandemic to discover three highly potent antibodies that selectively bind SARS-CoV-2 spike protein and neutralize authentic SARS-CoV-2 virus. Compared to neutralizing antibodies from COVID-19 patients with generally low somatic hypermutation (SHM), these antibodies contain over 13-22 SHMs, many of which are involved in specific interactions in crystal structures with SARS-CoV-2 spike RBD. The identification of these somatically mutated antibodies in a pre-pandemic library raises intriguing questions about the origin and evolution of human immune responses to SARS-CoV-2.

Comparison between Ye Tianshi and Xue Shengbai in treatment of diarrfea with damp-heat / 中国中药杂志

Ye Tianshi and Xue Shengbai are two febrile disease specialists in same time, and for the treatment of dampness and heat, they have different medication ideas. With the help of traditional Chinese medicine(TCM), author has studied two specialists' consilias of dampness and heat, through the statistics and analysis of their medicine during the treatment of dampness and heat, summarizes the similarities and differences of Ye and Xue's medicine application's assoations and models. Ye Tianshi and Xue Shengbai were both thought that the reason of dampness and heat was damp heat pathogenic factors, for this reason, the spleen and stomach conduction disordered, They both treated from the middle-jiao of Yangming and Taiyin, focused on warm-natured medicine, cold-natured medicine, used less cool-natured and heat-natured medicine, and more bitter, pungent, sweet medicine; Ye Tianshi usually use Scutellariae Radix, Paeoniae Radix Alba, Coptidis Rhizoma, Polyporus, Poria, Alismatis Rhizoma; Xue Shengbai commonly use Poria, Citri Reticulatae Pericarpium, Magnoliae officinalis Cortex, Patchouli, Glycyrrhizae Radix et Rhizoma, Angelicae Sinensis Radix, Paeoniae Radix Alba, Lablab Semen Album, Puerariae Lobatae Radix, Mume Fructus, Tsaoko Fructus, Amomi Fructus, Coptidis Rhizoma and Phellodendri Chinensis Cortex. The differences between the two masters in medicine application provide a reference for the clinical treatment of dampness and heat.

Comparison between Ye Tianshi and Xue Shengbai in treatment of distention with damp-heat / 中国中药杂志

Ye Tianshi and Xue Shengbai were both epidemic febrile diseases specialists in same time of Qing dynasty. The Traditional Chinese Medicine Inheritance Support System was used to compare and analyze the therapeutic characteristics of these two specialists in treating damp-heat type fullness or distension in stomach. Distension is commonly caused by qi stagnation accompanied with damp-heat from internal and external factors. In treatment, separation of damp and heat and removing dampness and heat from sanjiao separately were their common therapeutic principles. Both Ye Tianshi and Xue Shengbai paid much greater attention to eliminating dampness, and the herbs with bitter and pungent flavor, warm in property were usually chosen to regulate qi flow and reduce dampness. Invigorating spleen, nourishing stomach and dispersing lung were the frequently used treatment to balance the organs'harmony. The difference between specialist Ye and specialist Xue was the preference of herbs. Hou Pu (Magnoliae Officinalis Cortex), Xing Ren (Armeniacae Semen Amarum), Chen Pi (Citri Reticulatae Pericarpium), and Hua Shi (Talcum) were often used in both administrations. Besides, Ye Tianshi preferred to use Ban Xia (Pinelliae Rhizoma), Huang Qin (Scutellariae Radix), Huang Lian (Coptidis Rhizoma), Fuling, et al. Xue Shengbai on the other hand enjoyed using Fu Lingpi(Poriae Cutis), Cao Guo (Tsaoko Fructus), and Guang Huoxiang (Pogostemonis Herba), et al. In herbs compatibility, both of the two specialists were fond of using Chen Pi-Hou Pu, Hou Pu-Xing Ren. Moreover, Ye Tianshi often used Ban Xia- Xing Ren, Ban Xia-Huang Qin, and Hua Shi-Xing Ren to achieve the expected outcome of the treatment. While, Chen Pi, Fu Lingpi, and Hou Pu were the common combination with each other in Xue's cases. The similarities and differences of their administration should have the guidance in current clinical Chinese medicine practice for damp-heat type fullness or distension in stomach.

Tissue distribution and excretion of 5-fluorouracil from indomethacin 5-fluorouracil-1-ylmethylester in rats / 药学学报

To study the tissue distribution and excretion of indomethacin 5-fluorouracil-1-ylmethyl ester (IFM) metabolite 5-fluorouracil in rats, an accurate and specific high performance liquid chromatography method for quantifying IFM in rat plasma and tissues was developed. Biological samples were prepared by liquid-liquid extraction and separated on a Diamonsil C18 column (250 mm x 4.6 mm ID, 5 microm). The mobile phase for tissue samples, plasma samples and feces samples were composed of methanol-water-36% acetic acid (3:96.9:0.1, v/v) and the mobile phase for urine samples was a mixture of methanol-water-36% acetic acid (10:89.9:0.1, v/v). The eluate was monitored by UV absorbance at 260 nm. After a single ig dose of 100 mg x kg(-1) IFM in rats, 5-Fu was mainly distributed in stomach, small intestine, and liver. The concentrations of 5-fluorouracil in other tissues and plasma were low. The excretion of 5-Fu in urine and feces amounted to 0.0065% and 0.063% of the dose, respectively. The method is shown to be accurate and specific, and suitable for preclinical pharmacokinetic studies of IFM.

Hypogastric artery autograft treating hemorrhage with infection of external iliac artery secondary to renal transplantation / 中华创伤杂志(英文版)

Massive hemorrhage from infected anastomosed site between the graft artery and the external iliac artery is one of the most serious complications of renal transplantation. Clinically, it is a rare but fatal occasion. We reported here one case of hemorrhage with infection in the iliac artery anastomosed site treated successfully with hypogastric artery autograft interposition in March 2003.