Background Regulatory interactions between microRNAs (miRNAs) and messenger RNAs (mRNAs) are involved in the progression of pulmonary fibrosis, which can either promote or inhibit the development of this disease. Objective To explore the miRNA-mRNA regulatory network during the progression of silica (SiO₂)-induced pulmonary fibrosis in mice using integrated mRNA-seq and miRNA-seq analysis. Methods A mouse model of pulmonary fibrosis was established by dynamic SiO₂ dust exposure. The experimental design included a blank control group and four SiO₂-exposed groups (7, 14, 28, and 56 d, n=10 per group). Successful model induction was confirmed by histopathological analysis (HE and Masson staining), hydroxyproline (HYP) quantification, and expression of key fibrosis-related cytokines [fibroblast growth factor (FGF), interleukin-6 (IL-6), transforming growth factor-β (TGF-β), and tumor necrosis factor-α (TNF-α)]. Lung tissues from mice in each group were subjected to sequencing, and Mfuzz was used for time-series gene clustering to identify dynamic progression patterns. DESeq2 was utilized to identify differentially expressed genes (DEGs) and differentially expressed miRNAs. Enrichment analysis of DEGs was performed to identify critical signaling pathways and biological processes underlying pulmonary fibrosis progression. Expression of four selected miRNAs was subsequently validated by real-time quantitative polymerase chain reaction (RT-qPCR). The target mRNAs of key miRNAs were comprehensively predicted by integrating miRBase, starBase, and miRTarBase to construct the regulatory networks and investigate potential functions. Results SiO₂ exposure led to time-dependent aggravation of pulmonary fibrosis in mice, evidenced by increased fibrous deposition, elevated HYP levels (P < 0.01), and up-regulation of four kinds of pro-fibrotic cytokines (P < 0.01) compared with the NT group. Mfuzz clustering revealed the stage-specific characteristics. Compared to controls, 231, 662, 448, and 1020 DEGs were identified after SiO₂ exposure at 7, 14, 28, and 56 d, respectively, primarily enriched in immune responses and chemokine signaling. During critical fibrotic phases—7 d (acute inflammation and initiation) and 28 d (chronic inflammation and establishment)—18 differentially expressed miRNAs were identified; notably mmu-miR-135b-5p was significantly dysregulated at both time points. The expression trends of the four key miRNAs (mmu-miR-135b-5p, mmu-miR-708-5p, mmu-miR-21a-3p, and mmu-miR-205-5p) were consistent with the sequencing results. Furthermore, bioinformatics databases were used to predict the target mRNAs of key miRNAs. The constructed network highlighted critical miRNA-mRNA pairs—including mmu-miR-135b-5p and Meis1, mmu-miR-708-5p and Mmp25, mmu-miR-21a-3p and Cacna1d, mmu-miR-205-5p and Ereg which were closely associated with inflammatory response, extracellular matrix deposition, and fibroblast activation. Conclusion The progression of pulmonary fibrosis is accompanied by dynamic changes in miRNA-mRNA regulatory networks. The identified miRNA-target axes (e.g., miR-135b-5p and Meis1, mmu-miR-708-5p and Mmp25, mmu-miR-21a-3p and Cacna1d, and mmu-miR-205-5p and Ereg—) may play important roles in fibrogenesis and provide potential therapeutic targets for pulmonary fibrosis.

Background Regulatory interactions between microRNAs (miRNAs) and messenger RNAs (mRNAs) are involved in the progression of pulmonary fibrosis, which can either promote or inhibit the development of this disease. Objective To explore the miRNA-mRNA regulatory network during the progression of silica (SiO₂)-induced pulmonary fibrosis in mice using integrated mRNA-seq and miRNA-seq analysis. Methods A mouse model of pulmonary fibrosis was established by dynamic SiO₂ dust exposure. The experimental design included a blank control group and four SiO₂-exposed groups (7, 14, 28, and 56 d, n=10 per group). Successful model induction was confirmed by histopathological analysis (HE and Masson staining), hydroxyproline (HYP) quantification, and expression of key fibrosis-related cytokines [fibroblast growth factor (FGF), interleukin-6 (IL-6), transforming growth factor-β (TGF-β), and tumor necrosis factor-α (TNF-α)]. Lung tissues from mice in each group were subjected to sequencing, and Mfuzz was used for time-series gene clustering to identify dynamic progression patterns. DESeq2 was utilized to identify differentially expressed genes (DEGs) and differentially expressed miRNAs. Enrichment analysis of DEGs was performed to identify critical signaling pathways and biological processes underlying pulmonary fibrosis progression. Expression of four selected miRNAs was subsequently validated by real-time quantitative polymerase chain reaction (RT-qPCR). The target mRNAs of key miRNAs were comprehensively predicted by integrating miRBase, starBase, and miRTarBase to construct the regulatory networks and investigate potential functions. Results SiO₂ exposure led to time-dependent aggravation of pulmonary fibrosis in mice, evidenced by increased fibrous deposition, elevated HYP levels (P < 0.01), and up-regulation of four kinds of pro-fibrotic cytokines (P < 0.01) compared with the NT group. Mfuzz clustering revealed the stage-specific characteristics. Compared to controls, 231, 662, 448, and 1020 DEGs were identified after SiO₂ exposure at 7, 14, 28, and 56 d, respectively, primarily enriched in immune responses and chemokine signaling. During critical fibrotic phases—7 d (acute inflammation and initiation) and 28 d (chronic inflammation and establishment)—18 differentially expressed miRNAs were identified; notably mmu-miR-135b-5p was significantly dysregulated at both time points. The expression trends of the four key miRNAs (mmu-miR-135b-5p, mmu-miR-708-5p, mmu-miR-21a-3p, and mmu-miR-205-5p) were consistent with the sequencing results. Furthermore, bioinformatics databases were used to predict the target mRNAs of key miRNAs. The constructed network highlighted critical miRNA-mRNA pairs—including mmu-miR-135b-5p and Meis1, mmu-miR-708-5p and Mmp25, mmu-miR-21a-3p and Cacna1d, mmu-miR-205-5p and Ereg which were closely associated with inflammatory response, extracellular matrix deposition, and fibroblast activation. Conclusion The progression of pulmonary fibrosis is accompanied by dynamic changes in miRNA-mRNA regulatory networks. The identified miRNA-target axes (e.g., miR-135b-5p and Meis1, mmu-miR-708-5p and Mmp25, mmu-miR-21a-3p and Cacna1d, and mmu-miR-205-5p and Ereg—) may play important roles in fibrogenesis and provide potential therapeutic targets for pulmonary fibrosis.

Objective:To evaluate the recovery of daytime and nighttime urinary continence in patients with robotic-assisted radical cystectomy and ileal orthotopic neobladder from 1 to 60 months after surgery, and systematically analyze the influencing factors of daytime and nighttime urinary continence recovery.Methods:The convenient sampling method was used to select clinical data of 60 patients who underwent robotic-assisted radical cystectomy and ileal orthotopic neobladder by a single operator from December 2014 to January 2020 and they were followed up for daytime and nighttime use of urine pads and prognosis. A total of 44 patients were eligible for follow-up data. Satisfactory recovery of daytime and nighttime urinary continence was defined as the use of less than or equal to 1 pad, and complete recovery of daytime and nighttime urinary continence was defined as no urine leakage. The daytime and nighttime urinary continence recovery in patients with robotic-assisted radical cystectomy and ileal orthotopic neobladder was assessed at 1, 3, 6, 12, 24, 36, and 60 months. Cox regression was used to analyze the influencing factors of postoperative urinary continence recovery.Results:Cox regression multivariate analysis showed that preservation of neurovascular bundles was associated with satisfactory recovery of daytime urinary continence, satisfactory recovery of nighttime urinary continence and complete recovery of daytime urinary continence ( P<0.05) . Clevien grading of complications within 90 d could affect the satisfaction of daytime urinary control recovery. Preoperative hydronephrosis was an independent factor affecting the satisfaction of nighttime urinary continence recovery. Conclusions:Preserving neurovascular bundles is an influencing factor in promoting postoperative urinary continence recovery in patients with robotic-assisted radical cystectomy and ileal orthotopic neobladder. In addition, postoperative complications and preoperative hydronephrosis are independent factors affecting the satisfaction of daytime and nighttime urinary continence recovery, respectively, but it need to be further confirmed by multicenter prospective studies.

Objective:To examine the clinical application effects of two-complex and one-plane technique for the renal artery dissected location in transperitoneal laparoscopic radical nephrectomy(LRN).Methods:Clinical data of patients diagnosed as renal tumor between January 2016 and December 2019 that treated with transperitoneal LRN and the two-complex and one-plane technique was performed to locate and dissect the renal arteries were analyzed retrospectively. A total of 206 qualified patients were enrolled, included 71 cases from Kaifeng Central Hospital and 135 cases from the First Affiliated Hospital of Zhengzhou University. There were 126 males and 80 females with median age of 54 years (range: 35 to 82 years). Renal tumor lived at left kidney in 102 cases and at the right in 104 cases, with a maximum tumor diameter of (6.8±2.5)cm (range: 3.0 to 12.7 cm). During the procession of transperitoneal LRN, The genital veins was followed to locate renal veins, soon the renal vein complex and renal lower pole complex and psoas major muscle plane that named as “two-complex and one-plane”anatomical markers were applied to the dissected location of renal arteries. The established application of two-complex and one-plane technique for renal artery location, and the anatomical features along with its locational time of renal artery, as well as vascular-related complications were recorded and analysed. The χ 2 test or t test was used to compare the results of different lateral operations. Results:The surgical procedures were successful in all 206 patients. The operation time was (54.4±13.6) minutes (range:22 to 116 minutes), no injury to liver, spleen or intestine. Two-complex and one-plane technique was used to complete renal arteries location of 206 patients that accompanied with one or more arterial branch in the procession of transperitoneal LRN. Single renal artery branch was found in 163 cases, two or more renal artery branches were found in 43 cases, and 60 branches of accessory renal artery that in addition to the main trunks were detected in 14 cases (13.7%, 14/102) on left-side and 29 cases (27.9%, 29/104) on the right(χ2=6.251, P=0.012).The main branch of renal artery that directly been located inferior or posterior to renal vein in 165 cases, and the other 41 cases that born with higher-position of main branch been located through an upper“window-opening”of renal veins complex. Of the 60 accessory renal artery, 46 branch (76.6%, 46/60) been located inferior or posterior to renal veins, and the other 14 branch with higher-position (23.3%, 14/60) been located by a"window-opening"technique. The renal artery dissected location time was (21.2±9.4) minutes (range:11 to 43 minutes) in left-side and (17.5±9.3) minutes (range:9 to 32 minutes) in the right ( t=2.840, P=0.005).The intraoprative bleeding was (51.8±25.2) ml (range:20 to 400 ml). There were 4 cases of vascular injury occured and treated with laporoscopy, only one need blood transfusion. Conclusions:The anatomical markers of renal vein complex and renal lower pole complex and psoas major muscle plane that can apply to locate various anatomical position types of renal artery in transperitoneal LRN effectively. The exactly application of two-complex and one-plane technique that could shorten the operational time of renal artery location and reduce the complications of vascular injury.

Objective:To examine the clinical application effects of two-complex and one-plane technique for the renal artery dissected location in transperitoneal laparoscopic radical nephrectomy(LRN).Methods:Clinical data of patients diagnosed as renal tumor between January 2016 and December 2019 that treated with transperitoneal LRN and the two-complex and one-plane technique was performed to locate and dissect the renal arteries were analyzed retrospectively. A total of 206 qualified patients were enrolled, included 71 cases from Kaifeng Central Hospital and 135 cases from the First Affiliated Hospital of Zhengzhou University. There were 126 males and 80 females with median age of 54 years (range: 35 to 82 years). Renal tumor lived at left kidney in 102 cases and at the right in 104 cases, with a maximum tumor diameter of (6.8±2.5)cm (range: 3.0 to 12.7 cm). During the procession of transperitoneal LRN, The genital veins was followed to locate renal veins, soon the renal vein complex and renal lower pole complex and psoas major muscle plane that named as “two-complex and one-plane”anatomical markers were applied to the dissected location of renal arteries. The established application of two-complex and one-plane technique for renal artery location, and the anatomical features along with its locational time of renal artery, as well as vascular-related complications were recorded and analysed. The χ 2 test or t test was used to compare the results of different lateral operations. Results:The surgical procedures were successful in all 206 patients. The operation time was (54.4±13.6) minutes (range:22 to 116 minutes), no injury to liver, spleen or intestine. Two-complex and one-plane technique was used to complete renal arteries location of 206 patients that accompanied with one or more arterial branch in the procession of transperitoneal LRN. Single renal artery branch was found in 163 cases, two or more renal artery branches were found in 43 cases, and 60 branches of accessory renal artery that in addition to the main trunks were detected in 14 cases (13.7%, 14/102) on left-side and 29 cases (27.9%, 29/104) on the right(χ2=6.251, P=0.012).The main branch of renal artery that directly been located inferior or posterior to renal vein in 165 cases, and the other 41 cases that born with higher-position of main branch been located through an upper“window-opening”of renal veins complex. Of the 60 accessory renal artery, 46 branch (76.6%, 46/60) been located inferior or posterior to renal veins, and the other 14 branch with higher-position (23.3%, 14/60) been located by a"window-opening"technique. The renal artery dissected location time was (21.2±9.4) minutes (range:11 to 43 minutes) in left-side and (17.5±9.3) minutes (range:9 to 32 minutes) in the right ( t=2.840, P=0.005).The intraoprative bleeding was (51.8±25.2) ml (range:20 to 400 ml). There were 4 cases of vascular injury occured and treated with laporoscopy, only one need blood transfusion. Conclusions:The anatomical markers of renal vein complex and renal lower pole complex and psoas major muscle plane that can apply to locate various anatomical position types of renal artery in transperitoneal LRN effectively. The exactly application of two-complex and one-plane technique that could shorten the operational time of renal artery location and reduce the complications of vascular injury.

The discovery of antibiotics is a big revolution in human history, and its clinical application has saved countless lives. However, with the widespread and abuse of antibiotics, many pathogens have developed resistance, and even "Super Bacteria" resistance to multiple drugs have evolved. In the arms race between humans and pathogens, humans are about to face a situation where no medicine is available. Research on microbial antibiotic resistance genes, resistance mechanisms, and the spread of resistance has attracted the attention of many scientific researchers, and various antibiotic resistance gene databases and analysis tools have emerged. In this review, we collect the current databases that focus on antibiotics resistance genes, and discuss these databases in terms of database types, data characteristics, antibiotics resistance gene prediction models and the types of analyzable sequences. In addition, a few gene databases of anti-metal ions and anti-biocides are also involved. It is believed that this summary will provide a reference for how to select and use antibiotic resistance gene databases.
Anti-Bacterial Agents/pharmacology* ; Bacterial Infections ; Drug Resistance, Bacterial/genetics* ; Drug Resistance, Microbial/genetics* ; Humans ; Metals

Pheochromocytoma/paraganglioma(PPGL) was a kind of neuroendocrine tumor that derived from chromaffin tissue, which seems to be an important etiology of secondary hypertension. With the development of molecular detection technology, at least 17 kinds of pathogenic genes of PPGL has been discovered, which is related to 35%-40% PPGL, and about 40% malignant PPGL is associated with SDHB gene mutation. In this study, we reported a case with a novel splicing mutation of SDHB gene induced paraganglioma.

Objective To discuss the operating skills of transperitoneal laparoscopic radical nephrectomy(LRN).Methods From Dec 2008 to Dec 2010,105 patients with renal tumors were treated by transperitoneal LRN.Fifty-one tumors were located in left kidney,and 54 in the right kidney.The mean diameter of renal tumor was(5.8 ± 2.4)cm.There were 48 cases of T1N0M0,51 of T2N0M0,6 of T3aN0M0.During the process of transperitoneal LRN,vena genitalis was constantly used as an operative mark for seeking and ligating the renal artery and vein.The specimens were cut completely and removed through Pfannensteil incision.Results All the 105 cases were performed by transperitoneal LRN with vena genitalis marking method successfully.Twenty-eight cases of homolateral adrenal gland were resected and 16 cases of regional lymph node were cleaned.There was no serious injury of liver,spleen or bowels.The operating time ranged 44-78 min with an average of 55 min,and the blood loss was 35-600 ml with the mean of 85 ml.The post-operative length of stay was 4-11 d with an average of 6 d.Major complications included 3 cases of vessel injury,1 case with an injury of diaphragmatic muscle and 2 cases with a lymphous leakage.Post-operative staging included 44 cases of T1 N0 M0,1 of T1 N1 M0,47 of T2 N0 M0,1 of T2 N1 M0,7of T3aN0M0,1 of T3aN1 M0,2 of T4N0M0,and 2 cases with benign lesion.The patients were followed up for 9-33 months with an average of 18 months.One case had an incisional hernia,1 had a local tumor recurrence and 1 died of pulmonary metastasis.Conclusions Transperitoneal LRN with vena genitalis marking method could be safe for the treatment of renal tumors.The vena genitalis may act as a mark for the accurate location and quick ligation for the renal pedicle without serious injuries,and such patients could recover fastly with fewer complications.Pfannensteil incision has a good quality of little trauma and could meet with the need of aesthetics.

Objective:To investigate the effect and safety of the hi-channel in one-stage of minimally invasive pereutaneous nephrolithotomy (mPCNL) in management of complicated renal calculi, compared with single chan-nel in two-stage of mPCNL. Methods: 57 patients underwent mPCNL in treatment of complicated renal calculi were retrospectively reviewed. 31 eases in group A underwent bi-channel in one-stage of mPCNL;26 eases in group B underwent single channel in two-stage of mPCNL. Results= The mean bleeding in the group A was 146. 4 m1(75-262.5 ml), compared with the group B 154.3 ml(75-300 ml), there was no statistically difference between the two groups (P>0.05). The mean operation time in the group A was 88. 4 rain(65-136 min), compared with the group B 123.1 min(70-180 min), there was statistically difference between them(P<0.05). Compared of the clearance rate of stone in the group A 83.9 % (26/31) and B 57.8% (15/26), there was statistically difference be-tween them (P<0.05). Conclusions:According the treatment of complicated renal calculi, the bi-ehannel in one-stage of mPCNL has shorter operation time, higher clearanee rate of stone, compared with single channel in two-stage of mPCNL. The patients need less expenses and shorter time staying in hospital. It is an ideal method.