RBM22 regulates RNA polymerase II 5' pausing, elongation rate, and termination by coordinating 7SK-P-TEFb complex and SPT5.

BACKGROUND: Splicing factors are vital for the regulation of RNA splicing, but some have also been implicated in regulating transcription. The underlying molecular mechanisms of their involvement in transcriptional processes remain poorly understood. RESULTS: Here, we describe a direct role of splicing factor RBM22 in coordinating multiple steps of RNA Polymerase II (RNAPII) transcription in human cells. The RBM22 protein widely occupies the RNAPII-transcribed gene locus in the nucleus. Loss of RBM22 promotes RNAPII pause release, reduces elongation velocity, and provokes transcriptional readthrough genome-wide, coupled with production of transcripts containing sequences from downstream of the gene. RBM22 preferentially binds to the hyperphosphorylated, transcriptionally engaged RNAPII and coordinates its dynamics by regulating the homeostasis of the 7SK-P-TEFb complex and the association between RNAPII and SPT5 at the chromatin level. CONCLUSIONS: Our results uncover the multifaceted role of RBM22 in orchestrating the transcriptional program of RNAPII and provide evidence implicating a splicing factor in both RNAPII elongation kinetics and termination control.

Application opportunity of Doppler ultrasound combined with CT angiography in diabetic lower extremity arterial disease and the analysis of the risk factors.

Objective: This study examined the potential of combining Doppler ultrasound (DUS) and CT angiography (CTA) for early detection and intervention of lower extremity arterial disease (LEAD) in diabetes.Concurrently, risk factors influencing LEAD progression were analyzed. Methods: 106 Type-2 diabetes patients with LEAD, having undergone DUS and CTA, were divided into four stages according to Fontaine stage. Results of DUS and CTA were compared across stages and potential risk factors were analyzed. Results: Positive detection rates of LEAD differed between DUS and CTA for Fontaine stages I and II (P < 0.05), with no significant difference for stages III and IV (P > 0.05). CTA identified subgroups with mild to moderate stenosis and severe stenosis or occlusion, with positive rates on DUS of 17.95% and 89.9% respectively. Hypertension was found as an independent risk factor affecting LEAD progression. Conclusion: CTA should be performed early for LEAD in diabetes patients at Fontaine stages I and II, regardless of DUS results. For diabetes patients with LEAD, stringent blood pressure control is crucial to delay disease progression.

Efficacy and safety of alectinib in ALK-positive non-small cell lung cancer and blood markers for prognosis and efficacy: a retrospective cohort study.

Background: Alectinib is a second generation of ALK-tyrosine kinase inhibitors (ALK-TKIs), which has attracted much attention in the treatment of ALK-positive non-small cell lung cancer (NSCLC). At present, there are few reports on the efficacy and safety of alectinib in Chinese population. Moreover, biomarkers reflecting prognosis and efficacy are exceedingly needed. This study assessed the efficacy of alectinib in patients with ALK-positive NSCLC and analyzed the prognostic factors. Methods: Patients with ALK-positive NSCLC who were confirmed by histopathology or cytology at the Affiliated Cancer Hospital of Nanjing Medical University between October 2018 and October 2021 were enrolled. All patients were treated with alectinib. The clinical characteristics and circulating tumor biomarkers before and after treatment were collected. Kaplan-Meier test was used to calculate the progression-free survival (PFS). Univariate and multivariate Cox regression analyses were used to explore the influencing factors on PFS. Incidence of adverse events was observed. Results: Twenty patients progressed after first-line treatment (n=59) with alectinib, and 21 patients progressed following second-line treatment (n=36) with alectinib. The median PFS of first-line treatment patients was not achieved, and the median PFS of patients undergoing second-line treatment was 15.0 months [95% confidence interval (CI): 0.00-32.23]. The most common adverse reactions were liver dysfunction (37.50%), anemia (37.50%), and constipation (20.83%). The incidence of grade III and above adverse reactions was 6.25%. Univariate analysis showed that neutrophil-to-lymphocyte ratio [NLR; hazard ratio (HR) =0.424, P=0.005] carcinoembryonic antigen (CEA; HR =0.482, P=0.029), lactate dehydrogenase (LDH; HR =0.327, P<0.001), carbohydrate antigen (CA)199 (HR =0.313, P=0.002), and circulating cell free DNA (cfDNA; HR =0.229, P=0.008) concentration levels were associated with PFS, and multivariate analysis showed that NLR (HR =3.058, P=0.034) was independent prognostic factor. After three months of treatment, CEA, CA199, NLR, and LDH, could further predict the prognosis of alectinib treatment. Conclusions: The efficacy and safety of alectinib as a first-line or second-line treatment for ALK-positive NSCLC in keeping with published prospective studies. CEA, CA199, NLR, and LDH within the normal range after three months of treatment were associated with good prognosis. Detection of serum tumor markers can indicate therapeutic success in patients treated with alectinib.

Incineration experiment of medical waste of novel coronavirus pneumonia (COVID-19) in a mobile animal carcass incinerator.

Incineration experiment of medical waste was carried out in a mobile animal carcass incinerator. Simulated medical waste (69% cotton, 1.5% wood product, 4.5% mask and 25% moisture) was used as raw material. The temperature trend of first and second combustion chamber, the operating conditions and the emission characteristics of gaseous pollutants were studied. The results indicated that the temperature of first combustion chamber can be maintained at 550-650 °C without external heating, while in the final stage a burner was used to realize the burnout of material. The temperature of the second combustion chamber was always lower than that of the first combustion after the burner stopped working. The concentration of CO emission in flue gas was high due to the low disposal efficiency of the mobile incinerator, while NOX and SO2 emission concentrations were far below the standard limit value (GB 18484-2001).

Influence on gaseous pollutants emissions and fly ash characteristics from co-combustion of municipal solid waste and coal by a drop tube furnace.

Co-combustion experiments of municipal solid waste and coal were carried out in a drop tube furnace at high temperature 1300 °C. The effect of different simulated municipal solid waste (SMSW) added proportion (0, 7.5, 15, 20 and 25 wt%) in the blend fuels on the characteristics of gaseous pollutants emissions, e.g. CO, HCl, SO2, NOx, and heavy metals, and fly ash were studied. The results indicated that CO and CH4 emission concentrations were at a low level under all conditions. With the increasing proportion of SMSW, the combustion efficiency decreased slightly, the HCl emission increased obviously at 25% conditions while at lower proportion conditions the change was not significant; the NOx emission concentration showed a tendency to rise first and then decrease, while the SO2 showed an exactly opposite trend; besides, Fe, Cl and S content in the fly ash increased obviously. Under all experimental conditions, only a small amount of heavy metals were emitted in the flue gas while most of the heavy metals were retained in the fly ash. The leaching results showed that Ni leaching concentration was beyond the national standard which means the fly ash needs further treatment before they can be disposed of by landfill, while the HCl, NOx and SO2 emissions can easily reach the national emission standard under the desulfurization and denitrification system operating conditions in real power plants. These findings are helpful for the further development of co-combustion with renewable energy in coal-fired incinerators, yet more investigation on heavy metal emission in fly ash is still required to be further conducted in the future.

Laparoscopy-assisted total gastrectomy with trans-orally inserted anvil (OrVil™): a single institution experience.

AIM: To investigate the feasibility of laparoscopy-assisted total gastrectomy (LATG) using trans-orally inserted anvil (OrVil™) in terms of operative characteristics and short term outcomes. RESULTS: Characteristics of 27 patients with gastric cancer who underwent LATG from October 2009 to October 2012 in the Foshan Affiliated Hospital of South Medical University were retrospectively reviewed. Among these patients, six were reconstructed by mini-laparotomy and 21 by OrVil™. The clinicopathological characteristics, total operation time, total blood loss, abdominal incision and complications of anastomosis including stenosis and leakage, were compared between the groups undergoing LATG with OrVil™ and the group undergoing mini-laparotomy. RESULTS: The operations were successfully performed on all the patients without intraoperative complications or conversion to open surgery. Two (10%) patients received palliative procedure under laparoscope who were prepared for LATG preoperatively. One case had hepatic metastatic carcinoma and 1 case had tumor recurrence near the anastomosis 8 mo after surgery. The mean follow-up duration was 10 mo (range, 2-24 mo). Operation time was significantly reduced by the use of OrVil™ (198.42 ± 30.28 min vs 240.83 ± 8.23 min). The postoperative course with regard to occurrence of stenosis and leakage was not different between the two groups. There were no significant differences in estimated blood loss. The upper abdominal incision was smaller in OrVil™ group than in mini-laparotomy group (4.31 ± 0.45 cm vs 6.43 ± 0.38 cm). CONCLUSION: LATG using OrVil™ is a technically feasible surgical procedure with sufficient lymph node dissection, less operation time and acceptable morbidity.