RNA-based gene therapy has been widely used for various diseases, and extensive studies have proved that suitable delivery routes greatly help the development of RNA therapeutics. Identifying a safe and effective delivery system is key to realizing RNA therapeutics' clinical translation. Inhalation is a non-invasive pulmonary delivery modality that can enhance the retention of therapeutic agents in the lungs with negligible toxicity, thereby improving patient compliance. Inhaled RNA therapeutics are increasingly becoming an area of focus for researchers; however, only several clinical trials have explored inhaled delivery of RNA for pulmonary diseases. This review presents an overview of recent advances in inhaled delivery systems for RNA therapeutics, including viral and nonviral systems, highlighting state of the art regarding inhalation in the messenger RNA (mRNA) field. We also summarize the applications of mRNA inhalants in infectious and other lung diseases. Simultaneously, the research progresses on small interfering RNAs (siRNAs), antisense oligonucleotides (ASOs), and different types of RNA are also discussed to provide new strategies for developing RNA inhalation therapy. Finally, we clarify the challenges inhaled RNA-based therapeutics face before their widespread adoption and provide insights to help advance this exciting field to the bedside.

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Objective To study the safety,efficacy and advantages of enhanced recovery after surgery (ERAS) combined with clinical pathway management in laparoscopic common bile duct exploration and lithotomy (Laparoscopic common bile duct exploration,LCBDE).Methods 78 patients who underwent LCBDE in the Department of Hepatobiliary and Pancreatic Surgery in the First Hospital of Fuyang District in Hangzhou were selected as the non-ERAS group (the control group).76 patients who underwent LCBDE treated with fast track surgery and ERAS clinical pathway management were selected as the ERAS group.The data between the two groups which included the postoperative insulin resistance index,changes in C-reactive protein,duration of postoperative analgesic use and analgesia,timing of first passage of postoperative flatus,postoperative abdominal tube removal,postoperative bile leakage,recurrence of biliary stones,intestinal ileus and other complications.Results All the two groups were discharged home successfully.On preoperative 7 day,the differences on the postoperative insulin resistance index and the levels of C reactive protein were significantly different (P＜0.05).The time to first get out of bed after operation,the postoperative analgesic use,the time to first passage of flatus,the time to postoperative abdominal drainage tube removal,and the time to clamping of the T tube after operation were significantly different (all P＜0.05).The postoperative complications of pulmonary infection,abdominal infection and the incidence of prolonged intestinal ileus were significantly different (all P＜0.05).Conclusions ERAS combined with clinical pathway management reduced postoperative stress reaction and complication rate.The treatment accelerated recovery and shortened hospital stay for patients who underwent LCBDE,which led to good social and economic benefits.

Objective To systematically assess the clinical efficacy and safety of acupuncture treatment for vertigo with excess syndrome. Methods Chinese and English literature about acupuncture treatment of vertigo with excess syndrome published in recent years was comprehensively searched. The quality of the retrieved literature meeting the inclusion criteria of randomized controlled trial was assessed and its data was collected. A Meta analysis of the included studies was carried out.Results Finally, 10 articles with randomized controlled trials containing a total of 688 patients were included in the analysis. The included literature was assessed at lower quality using Cochrane evaluation member manual 5.1. A Meta analysis showed that the efficacy rate of acupuncture treatment for vertigo with excess syndrome was higher than that of Western drugs alone [M-H OR 4.84, 95%CI (2.39, 9.81),P<0.0001]. Combined acupuncture and Chinese herbal medicine was superior to Chinese herbal medicine alone [M-H OR 3.82, 95%CI (2.06, 7.10),P<0.0001]. Vertigo symptom and function scoring showed day 3 of treatment [MD 4.66, 95%CI (2.97, 6.35)], day 7 of treatment [MD 0.95, 95%CI (0.03, 1.86)] and day 14 of treatment [MD 0.89, 95%CI (0.71, 2.49)]. There were statistically significant differences in the vertigo symptom and function scores between the two groups of patients at day 3 and 7 of treatment. There were no statistically significant differences in the scores between the two groups of patients at day 14 of treatment. Conclusions Acupuncture or combined acupuncture and Chinese herbal medicine are effective and highly safe in treating vertigo with excess syndrome, but high-quality, multi-center and large-sample RCT studies still need to be conducted for validation and support.

Objective To investigate the postoperative analgesic effect of dezocine and sufentanil in patients with col-orectal cancer. Methods Sixty-eight cases with colon cancer, rectal cancer undergoing radical operation in our hospital from January 2011 to June 2013, were randomLy divided into control group and observation group, 34 patients in each group, the patients in control group were given sufentanil analgesia after surgery, and patients in the observation group were given dezocine and sufentanil for analgesia. The VAS and Ramsay sedation score in 2h, 6h, 12h, 24h, 48h and the incidence ratio of adverse reaction during analgesia were compared in two groups. Results There was no statistical significance in the difference of the two groups of sex ratio, age distribution, body weight, ASA classification (P>0.05);there was no significnt difference in VAS scores between the two groups at different time points (P>0.05);There were statistically significant in differences of Ramsay scores among different time points of two groups (P<0.05);There were statistically significant in differences of the incidence ratio of adverse reaction of two groups during analgesia (drowsiness, nausea and vomiting, urinary retention) (P<0.05). Conclusion Analgesic effect of using dezocine and sufentanil with less adverse reaction, good safety is obvious better than sufentanil only in the patients with colorectal cancer after operation, and is worth the clinical promotion.

Objective To evaluate the efficacy and adverse effect of brachial plexus block with morphine and ropivacaine for postoperative analgesia in children. Methods Forty-five children undergone upper extremity surgery were randomly divided into three groups (n = 15) , ie, Croup A (brachial plexus block with ropivacaine), Croup B (brachial plexus block with ropivacaine and subcutaneous injection of morphine) and Croup C (brachial plexus block with morphine and ropivacaine). The analgesic effect and the analgesia maintenance time were recorded by FLACC method at 1, 2, 4, 6, 8, 12, 24 hours after operation. The adverse reactions were observed 48 hours after operation. Results There was no statistical difference between Croup A and Croup B in the analgesia maintenance time and the number of cases without analgesic therapy at each time point (P > 0. 05). Compared with Croup A or Croup B, the analgesia maintenance time in Croup C were significantly extended and the number of cases without analgesic therapy at 4, 6, 8, 12, 24 hours after operation were significantly increased (P < 0.05). The adverse effect was fairly light in three groups. Conclusion Brachial plexus block with morphine and ropivacaine may extend analgesia maintenance time effectively and safely in children undergone upper extremity surgery.