The efficacy of hydrogen/oxygen therapy favored the recovery of omicron SARS-CoV-2 variant infection: results of a multicenter, randomized, controlled trial.

Clinical studies had found that hydrogen/oxygen mixed inhalation was beneficial to ameliorate the respiratory symptoms in the adjuvant treatment of patients with COVID-19. We aimed to explore the efficacy of hydrogen/oxygen therapy in favoring the recovery of Omicron SARS-CoV-2 variant infection. There were 64 patients who randomly assigned to receive hydrogen/oxygen inhalation (32 patients) and oxygen inhalation (32 patients). The average shedding duration of Omicron in hydrogen/oxygen group was shorter than oxygen group. The trend of cumulative negative conversion rate of Omicron increased gradually after the third day. The IL-6 levels in hydrogen/oxygen group decreased by 22.8% compared with the baseline. After hydrogen/oxygen mixed gas inhalation, the lymphocyte count increased to 61.1% of the baseline on the 3rd day in the hydrogen/oxygen group. More patients in the hydrogen/oxygen group had resolution of pulmonary lesions. Our study showed the beneficial trends of molecular hydrogen in treating patients with COVID-19, which may offer a prospective solution to adjuvant therapy for COVID-19 Patients.

A diagnostic test of three-dimensional magnetic resonance elastography imaging for preoperative prediction of microvascular invasion in patients with T1 stage clear cell renal carcinoma.

Background: Detection of microvascular invasion (MVI) of kidney tumors is important for selecting the optimal therapeutic strategy. Currently, the prediction of MVI lacks an accurate imaging biomarker. This study evaluated the performance of three-dimensional (3D) magnetic resonance elastography (MRE) imaging in predicting microvascular invasion (MVI) of T1 stage clear cell renal carcinoma (ccRCC). Methods: In this prospective study, we conducted pre-surgical imaging with a clinical 3.0 T magnetic resonance imaging (MRI) system. Firstly, 83 consecutive patients were enrolled in this study. A 3D MRE stiffness map was generated and transferred to a post-processing workstation. Contrast-enhanced computed tomography (CT) was conducted to calculate the tumor enhancement ratio. The presence of MVI was evaluated by histopathological analysis and graded according to the risk stratification based upon the number and distribution. The mean stiffness and CT tumor enhancement ratio was calculated for tumors with or without MVI. The diagnostic performance [sensitivity, specificity, positive predictive value, negative predictive value, area under the curve (AUC)] and independent predicting factors for MVI were investigated. Results: Finally, A total of 80 patients (aged 46.7±13.2 years) were enrolled, including 22 cases of tumors with MVI. The mean MRE stiffness of kidney parenchyma and kidney tumors was 4.8±0.2 and 4.5±0.7 kPa, respectively. There was significant difference in the mean MRE stiffness between tumors with MVI (5.4±0.6 kPa) and tumors without MVI (4.1±0.3 kPa) (P<0.05). The sensitivity, specificity, positive predictive value, negative predictive value, and the AUC for mean stiffness in the prediction of MVI were 100%, 75%, 63%, 96%, and 0.87 [95% confidence interval (CI): 0.72, 0.94], respectively. The corresponding values for the CT tumor enhancement ratio were 90%, 80%, 63%, 96%, and 0.88 (95% CI: 0.71, 0.93), respectively. The odds ratio (OR) value for MRE tumor stiffness and CT kidney tumor enhancement ratio in the prediction of MVI was 2.9 (95% CI: 1.8, 3.7) and 1.2 (95% CI: 1.0, 1.7), respectively (P>0.05). Conclusions: 3D MRE imaging has promising diagnostic performance for predicting MVI in T1 stage ccRCC, which may improve the reliability of surgical strategy selection with T1 stage ccRCC.

Stem cell therapy for chronic obstructive pulmonary disease.

ABSTRACT: Chronic obstructive pulmonary disease (COPD), characterized by persistent and not fully reversible airflow restrictions, is currently one of the most widespread chronic lung diseases in the world. The most common symptoms of COPD are cough, expectoration, and exertional dyspnea. Although various strategies have been developed during the last few decades, current medical treatment for COPD only focuses on the relief of symptoms, and the reversal of lung function deterioration and improvement in patient's quality of life are very limited. Consequently, development of novel effective therapeutic strategies for COPD is urgently needed. Stem cells were known to differentiate into a variety of cell types and used to regenerate lung parenchyma and airway structures. Stem cell therapy is a promising therapeutic strategy that has the potential to restore the lung function and improve the quality of life in patients with COPD. This review summarizes the current state of knowledge regarding the clinical research on the treatment of COPD with mesenchymal stem cells (MSCs) and aims to update the understanding of the role of MSCs in COPD treatment, which may be helpful for developing effective therapeutic strategies in clinical settings.

Arterial Spin Labeling MRI for Predicting Microvascular Invasion of T1 Staging Renal Clear Cell Carcinoma Preoperatively.

BACKGROUND: Microvascular invasion (MVI) is a valuable factor for T1 staging renal clear cell carcinoma (ccRCC) operation strategy decision, which is confirmed histopathologically post-operation. This study aimed to prospectively evaluate the performance of arterial spin labeling (ASL) MRI for predicting MVI of T1 staging ccRCC preoperatively. METHODS: 16 volunteers and 39 consecutive patients were enrolled. MRI examinations consisted of ASL (three post label delays separately) of the kidney, followed by T1 and T2-weighted imaging. Two sessions of ASL were used to evaluate the reproducibility on volunteers. Renal blood flow of renal cortex, medulla, the entire and solid part of the tumor were measured on ASL images. Conventional imaging features were extracted. MVI and WHO/ISUP classification were evaluated histopathologically. A paired t-test was used to compare the renal cortex and medulla between ASL 1 and ASL 2. The reproducibility was assessed using the intraclass correlation. Differences in mean perfusion between the entire and the solid parts of tumors with or without MVI were assessed separately using Student's t test. The diagnostic performance was assessed. Logistic regression analysis was used to indicate the independent prediction index for MVI. RESULTS: The two sessions of ASL showed no significant difference between the mean cortex values of RBF. The cortical RBF measurements demonstrated good agreement. 12 ccRCCs presented with MVI histopathologically. Mean perfusion of the solid part of tumors with MVI were 536.4 ± 154.8 ml/min/100 g (PLD1), 2912.5 ± 939.3 ml/min/100 g (PLD2), 3280.3 ± 901.2 ml/min/100 g (PLD3). Mean perfusion of the solid part of tumors without MVI were 453.5 ± 87.2 ml/min/100 g (PLD1), 1043.6 ± 695.8 ml/min/100 g (PLD2), 1577.6 ± 1085.8 ml/min/100 g (PLD3). These two groups have significant difference at all the PLDs (p < 0.05). The RBF of PLD1 of the solid part of tumor perfusion showed well diagnostic performance for predicting MVI: sensitivity 75%, specificity 100%, positive predictive value 66.7%, and negative predictive value 95.7%. The maximum diameter of the tumor, ill-defined margin, and the solid part of tumor perfusion were the independent prediction index for MVI. CONCLUSION: ASL MR imaging has good reproducibility for renal cortex, and good diagnostic performance for predicting MVI for ccRCC.

Independent Risk Factors of Early Recurrence After Curative Resection for Perihilar Cholangiocarcinoma: Adjuvant Chemotherapy May Be Beneficial in Early Recurrence Subgroup.

PURPOSE: In current clinical practice, early recurrence (ER) is not commonly discussed in perihilar cholangiocarcinoma (pCCA), and its risk factors for this disease have not been well clarified. We carried out this study to analyze the risk factors contributing to ER and explored the prognostic factors after curative resection for pCCA. PATIENTS AND METHODS: A total of 335 consecutive pCCA patients were retrospectively analyzed. Risk factors contributing to ER were evaluated using univariate and multivariate logistic regression analyses. Prognostic factors of the ER group were determined by univariate and multivariate Cox regression models. The overall survival (OS) rate was calculated using the Kaplan-Meier method. The Log rank test was used for OS comparison. RESULTS: Of the 335 cases, 258 patients (77.0%) developed tumor recurrence, 136 patients (40.6%) developed ER, and 122 patients (36.4%) developed late recurrence (LR) postoperatively. The median OS of the ER and LR groups was 15 months and 36 months, respectively (P<0.001). The multivariate analysis revealed that poor pathological differentiation (P=0.006; moderate vs well, odds ratio [OR]=2.162, 95% confidence interval [CI] 0.753-6.208, P=0.152; poor vs well, OR=4.839, 95% CI 1.544-15.170, P=0.007), perineural invasion (OR=4.797, 95% CI 1.586-14.510, P=0.005), and high levels of preoperative carbohydrate antigen 19-9 (CA19-9) (OR=2.205, 95% CI 1.208-4.026, P=0.010) were independent risk factors of developing ER after resection. Adjuvant chemotherapy (HR=0.383, 95% CI 0.154-0.953, P=0.039) remained as the independent protective factor of OS in patients with ER. CONCLUSION: It is recommended that patients with poorly differentiated tumors, presence of perineural invasion, and high levels of preoperative CA19-9 receive closer follow-up and adjuvant chemotherapy following surgery.

Costunolide alleviates HKSA-induced acute lung injury via inhibition of macrophage activation.

Staphylococcus aureus (S. aureus) infection leads to a severe inflammatory response and causes acute lung injury (ALI), eventually threatening human life. Therefore, it is of importance to find an agent to inhibit inflammation and reduce ALI. Here, we found that costunolide, a sesquiterpene lactone, displays anti-inflammatory effects and ameliorates heat-killed S. aureus (HKSA)-induced pneumonia. Costunolide treatment attenuated HKSA-induced murine ALI in which pulmonary neutrophil infiltration was inhibited, lung edema was decreased, and the production of pro-inflammatory cytokines was significantly reduced. In addition, costunolide dose-dependently inhibited the generation of IL-6, TNF-α, IL-1ß, and keratinocyte-derived cytokine (KC), as well as the expression of iNOS, in HKSA-induced macrophages. Furthermore, costunolide attenuated the phosphorylation of p38 MAPK and cAMP response element-binding protein (CREB). Collectively, our findings suggested that costunolide is a promising agent for alleviating bacterial-induced ALI via the inhibition of the MAPK signaling pathways.

A network meta-analysis on the beneficial effect of medical expulsive therapy after extracorporeal shock wave lithotripsy.

We applied a newly introduced method, network meta-analysis, to re-evaluate the expulsion effect of drugs including tamsulosin, doxazosin, nifedipine, terazosin and rowatinex after extracorporeal shock wave lithotripsy (ESWL) as described in the literature. A systematic search was performed in Medline, Embase and Cochrane Library for articles published before March 2016. Twenty-six studies with 2775 patients were included. The primary outcome was the number of patients with successful stone expulsion. The data were subdivided into three groups according to duration of follow-up. A standard network model was established in each subgroup. In 15-day follow-up results, SUCRA outcome showed the ranking of effects was: doxazosin > tamsulosin > rowatinex > nifedipine > terazosin (88.6, 77.4, 58.6, 32.2 and 30.4, respectively). In 45-day follow-up results, SUCRA ranking was: tamsulosin > nifedipine > rowatinex (69.4, 67.2 and 62.6, respectively). In 90-day follow-up results, SUCRA ranking was: doxazosin > rowatinex > tamsulosin (84.1, 68.1 and 49.1, respectively). In conclusion, doxazosin and tamsulosin have potential to be the first choice for pharmacological therapy to promote the expulsion of urinary stone fragments after ESWL, with this doxazosin can improve the SFR in the long term, while tamsulosin may result more in accelerating the process of expulsion.

Different Tract Sizes of Miniaturized Percutaneous Nephrolithotomy Versus Retrograde Intrarenal Surgery: A Systematic Review and Meta-Analysis.

PURPOSE: Miniaturized percutaneous nephrolithotomy (MPCNL), including minipercutaneous nephrolithotomy (PCNL), ultramini-PCNL, and micro-PCNL, have been developed recently. The aim of this meta-analysis was to compare the safety and efficacy of different tract sizes of MPCNL with retrograde intrarenal surgery (RIRS) in the management of kidney stones. MATERIALS AND METHODS: We searched PubMed, Embase, and Web of Science to identify case-control trials and randomized controlled trials, which evaluated MPCNL vs RIRS before February 2017. Two reviewers independently evaluated the methodologic quality of the included studies, and the disagreements were solved by discussion. Meta-analysis was performed with Review Manager version 5.3 software. RESULTS: Fourteen publications involving 1279 patients were included. Mini-PCNL provided a significantly higher stone-free rate (SFR; odds ratio [OR] OR 1.66; p = 0.005), especially for lower pole renal stones (OR 2.65; p = 0.003), but brought longer hospital stay (weighted mean difference [WMD] 1.23; p = 0.0001) and larger hemoglobin drop (WMD 0.77; p < 0.00001). There were no statistically significant differences between mini-PCNL and RIRS in the complications (OR 0.77; p = 0.23) and operative time (WMD: -6.52; p = 0.42). For ultramini-PCNL and micro-PCNL, the safety and efficacy were similar to RIRS. CONCLUSIONS: Mini-PCNL offers a significantly higher SFR than RIRS, for lower pole renal stones, the advantage of mini-PCNL is more obvious. However, RIRS is associated with shorter hospital stay and less hemoglobin drop. For ultramini-PCNL and micro-PCNL, tract size is smaller than mini-PCNL, and the SFR is similar to RIRS. In terms of the evidence at present, we recommend mini-PCNL for patients focusing more on the high SFR.

[Electrophysiological study on rat conduit pulmonary artery smooth muscle cells under normoxia and acute hypoxia].

The present study was designed to investigate the electrophysiological characteristics of rat conduit pulmonary artery smooth muscle cells (PASMCs) and the response to acute hypoxia. PASMCs of the 1st to 2nd order branches in the conduit pulmonary arteries were obtained by enzymatic isolation. The PASMCs were divided into acute hypoxia preconditioned group and normoxia group. Hypoxia solutions were achieved by bubbling with 5% CO2 plus 95% N2 for at least 30 min before cell perfusion. Potassium currents were compared between these two groups using whole-cell patch clamp technique. The total outward current of PASMCs was measured under normoxia condition when iBTX [specific blocking agent of large conductance Ca-activated K(+) (BK(Ca)) channel] and 4-AP [specific blocking agent of delayed rectifier K(+) (K(DR)) channel] were added consequently into bath solution. PASMCs were classified into three types according to their size, shape and electrophysiological characteristics. Type I cells are the smallest with spindle shape, smooth surface and discrete perinuclear bulge. Type II cells show the biggest size with banana-like appearance. Type III cells have the similar size with type I, and present intermediary shape between type I and type II. iBTX had little effect on the total outward current in type I cells, while 4-AP almost completely blocked it. Most of the total outward current in type II cells was inhibited by iBTX, and the remaining was sensitive to 4-AP. In type III cells, the total outward current was sensitive to both iBTX and 4-AP. Acute hypoxia reduced the current in all three types of cells: (1614.8+/-62.5) pA to (892.4+/-33.6) pA for type I cells (P<0.01); (438.3+/-42.8) pA to (277.5+/-44.7) pA for type II cells (P<0.01); (1 042.0+/-37.2) pA to (613.6+/-23.8) pA for type III (P<0.01), and raised the resting membrane potentials (E(m)) in all these three types of cells: (-41.6+/-1.6) mV to (-18.6+/-1.5) mV (P<0.01), (-42.3+/-3.8) mV to (-30.6+/-3.0) mV (P<0.01), (-43.3+/-1.6) mV to (-28.4+/-1.4) mV (P<0.01), for type I, II, III cells, respectively. These results suggest that acute hypoxia suppresses the potassium current and improves the E(m) in PASMCs. These effects may be involved in the modulation of constriction/relaxation of conduit artery under acute hypoxia. Different distribution of K(DR) and BK(Ca) channels in these three types of PASMCs might account for their different constriction/relaxation response to acute hypoxia.

[Construction and identification of cDNA library from peripheral blood lymphocytes of Tibetans in Qinghai-Tibet plateau].

AIM: To construct the full length cDNA library of the peripheral blood lymphocytes in Tibetans and to identify the quality of the library. METHODS: The lymphocytes were separated from healthy Tibetan fresh blood, and total RNA was extracted. The full length cDNA library was constructed by SMART (switching mechanism at 5' end of RNA transcript) technique. The unamplified library was titered, and the percentage of recombinant clones were determined. The library was amplified, and the size of the inserts was identified by PCR. RESULTS: The titer of the constructed cDNA library was 1.8x10(9) pfu/L with the percentage of recombinant clones above 98%, and that of the amplified library was 8x10(12) pfu/L. The insert's size ranged from 0.75 to 2.0 kb with the average length of 1.35 kb. CONCLUSION: The constructed cDNA library of peripheral blood lymphocytes of Tibetans has excellent quality, and it lays a solid founclation for further screening and cloning hypoxia-related genes of Tibetans living at high altitudes.

A mitochondrial genome sequence of the Tibetan antelope (Pantholops hodgsonii).

To investigate genetic mechanisms of high altitude adaptations of native mammals on the Tibetan Plateau, we compared mitochondrial sequences of the endangered Pantholops hodgsonii with its lowland distant relatives Ovis aries and Capra hircus, as well as other mammals. The complete mitochondrial genome of P. hodgsonii (16,498 bp) revealed a similar gene order as of other mammals. Because of tandem duplications, the control region of P. hodgsonii mitochondrial genome is shorter than those of O. aries and C. hircus, but longer than those of Bos species. Phylogenetic analysis based on alignments of the entire cytochrome b genes suggested that P. hodgsonii is more closely related to O. aries and C. hircus, rather than to species of the Antilopinae subfamily. The estimated divergence time between P. hodgsonii and O. aries is about 2.25 million years ago. Further analysis on natural selection indicated that the COXI (cytochrome c oxidase subunit I) gene was under positive selection in P. hodgsonii and Bos grunniens. Considering the same climates and environments shared by these two mammalian species, we proposed that the mitochondrial COXI gene is probably relevant for these native mammals to adapt the high altitude environment unique to the Tibetan Plateau.