Perineal nerve block versus periprostatic block for patients undergoing transperineal prostate biopsy (APROPOS): a prospective, multicentre, randomised controlled study.

Background: We aimed to investigate perineal nerve block versus periprostatic block in pain control for men undergoing a transperineal prostate biopsy. Methods: In this prospective, randomised, blinded and parallel-group trial, men in six Chinese hospitals with suspected prostate cancer were randomly assigned (1:1) at the point of local anaesthesia to receive a perineal nerve block or periprostatic block and followed by a transperineal prostate biopsy. Centres used their usual biopsy procedure. Operators who performed anaesthesia were trained in both techniques before the trial and were masked to the randomised allocation until the time of anaesthesia and were not involved in the subsequent biopsy procedure and any assessment or analysis. Other investigators and the patients were masked until trial completion. The primary outcome was the level of the worst pain experienced during the prostate biopsy procedure. Secondary outcomes included pain (post-biopsy at 1, 6 and 24 h), changes in blood pressure, heart rate and breathing rate during the biopsy procedure, external manifestations of pain during biopsy, anaesthesia satisfaction, the detection rate of PCa and clinically significant PCa. This trial is registered on ClinicalTrials.gov, NCT04501055. Findings: Between August 13, 2020, and July 20, 2022, 192 men were randomly assigned to perineal nerve block or periprostatic block, 96 per study group. Perineal nerve block was superior for the relief of pain during the biopsy procedure (mean 2.80 for perineal nerve block and 3.98 for periprostatic block; adjusted difference in means -1.17, P < 0.001). Although the perineal nerve block had a lower mean pain score at 1 h post-biopsy compared with the periprostatic block (0.23 vs 0.43, P = 0.042), they were equivalent at 6 h (0.16 vs 0.25, P = 0.389) and 24 h (0.10 vs 0.26, P = 0.184) respectively. For the change in vital signs during biopsy procedure, perineal nerve block was significantly superior to periprostatic block in terms of maximum value of systolic blood pressure, maximum value of mean arterial pressure and maximum value of heart rate. There are no statistical differences in average value of systolic blood pressure, average value of mean, average value of heart rate, diastolic blood pressure and breathing rate. Perineal nerve block was also superior to periprostatic block in external manifestations of pain (1.88 vs 3.00, P < 0.001) and anaesthesia satisfaction (8.93 vs 11.90, P < 0.001). Equivalence was shown for the detection rate of PCa (31.25% for perineal nerve block and 29.17% for periprostatic block, P = 0.753) or csPCa (23.96% for perineal nerve block and 20.83% for periprostatic block, P = 0.604). 33 (34.8%) of 96 patients in the perineal nerve block group and 40 (41.67%) of 96 patients in the periprostatic block group had at least one complication. Interpretation: Perineal nerve block was superior to periprostatic block in pain control for men undergoing a transperineal prostate biopsy. Funding: Grant 2019YFC0119100 from the National Key Research and Development Program of China.

The chromosome-scale genome of Phoebe bournei reveals contrasting fates of terpene synthase (TPS)-a and TPS-b subfamilies.

Terpenoids, including aromatic volatile monoterpenoids and sesquiterpenoids, function in defense against pathogens and herbivores. Phoebe trees are remarkable for their scented wood and decay resistance. Unlike other Lauraceae species investigated to date, Phoebe species predominantly accumulate sesquiterpenoids instead of monoterpenoids. Limited genomic data restrict the elucidation of terpenoid variation and functions. Here, we present a chromosome-scale genome assembly of a Lauraceae tree, Phoebe bournei, and identify 72 full-length terpene synthase (TPS) genes. Genome-level comparison shows pervasive lineage-specific duplication and contraction of TPS subfamilies, which have contributed to the extreme terpenoid variation within Lauraceae species. Although the TPS-a and TPS-b subfamilies were both expanded via tandem duplication in P. bournei, more TPS-a copies were retained and constitutively expressed, whereas more TPS-b copies were lost. The TPS-a genes on chromosome 8 functionally diverged to synthesize eight highly accumulated sesquiterpenes in P. bournei. The essential oil of P. bournei and its main component, ß-caryophyllene, exhibited antifungal activities against the three most widespread canker pathogens of trees. The TPS-a and TPS-b subfamilies have experienced contrasting fates over the evolution of P. bournei. The abundant sesquiterpenoids produced by TPS-a proteins contribute to the excellent pathogen resistance of P. bournei trees. Overall, this study sheds light on the evolution and adaptation of terpenoids in Lauraceae and provides valuable resources for boosting plant immunity against pathogens in various trees and crops.

Effect of Compound Propofol Nanoemulsion on Immune Function in Patients with Pancreatic Cancer.

Pancreatic cancer is a common malignant tumor of the digestive system, and its incidence is increasing worldwide. The treatment of pancreatic cancer is mainly surgery, but the development of traditional surgery, chemoradiotherapy has entered the plateau stage, and immunotherapy has received more and more attention. Different anesthesia methods, anaesthetic drugs and their preparations have different effects on the perioperative immune function of patients with pancreatic cancer, and even affect the long-term prognosis of patients. Suppression of immune function caused by surgery and anesthesia may promote tumor recurrence and metastasis, thereby affecting the longterm prognosis of patients. The use of propofol intravenous anesthesia during surgery can reduce pro-inflammatory factors and increase anti-inflammatory factors, thereby effectively improving the immune function of perioperative tumor patients. At the same time, using nanoemulsion as a carrier in a drug delivery system can improve the solubility and loading capacity of poorly soluble drugs, and increase the absorption rate and bioavailability of fat-soluble drugs in the body. Therefore, in this study, a combination of propofol nano-injection and remifentanil injection liquid combined with propofol nanoemulsion preparation and propofol injection alone was used in the operation of pancreatic cancer patients. By comparing the two groups of patients Basic indicators during and after surgery, hemorheology levels, lymphocyte subsets, and proinflammatory cytokines, to study the use of the compound propofol nanoemulsion preparation in patients with pancreatic cancer during surgery Effects of immune function. The results showed that compound propofol nanoemulsion can improve the immune function of patients with pancreatic cancer during surgery, reduce the level of inflammatory factors, and has a good prognosis and high safety.

Development and validation of a prognostic model for kidney renal clear cell carcinoma based on RNA binding protein expression.

Dysregulated expression of RNA-binding proteins (RBPs) is strongly associated with the development and progression of multiple tumors. However, little is known about the role of RBPs in kidney renal clear cell carcinoma (KIRC). In this study, we examined RBP expression profiles using The Cancer Genome Atlas database and identified 133 RBPs that were differentially expressed in KIRC and non-tumor tissues. We then systematically analyzed the potential biological functions of these RBPs and established PPIs. Based on Lasso regression and Cox survival analyses, we constructed a risk model that could independently and accurately predict prognosis based on seven RBPs (NOL12, PABPC1L, RNASE2, RPL22L1, RBM47, OASL, and YBX3). Survival times were shorter in patients with high risk scores for cohorts stratified by different characteristics. Gene set enrichment analysis was also performed to further understand functional differences between high- and low-risk groups. Finally, we developed a clinical nomogram with a concordance index of 0.792 for estimating 3- and 5-year survival probabilities. Our results demonstrate that this risk model could potentially improve individualized diagnostic and therapeutic strategies.

A novel Bifidobacterium infantis-mediated TK/GCV suicide gene therapy system exhibits antitumor activity in a rat model of bladder cancer.

Bladder cancer is the ninth most common malignancy in the world. Successful clinical management remains a challenge. In order To search for novel targeted and efficacious treatment, we sought to investigate anti-tumor activity of BI-TK suicide gene therapy system in a rat model of bladder tumors. We first constructed and tested an anaerobic Bifidobacterium infantis-mediated thymidine kinase (BI-TK) suicide gene therapy system. To test the in vivo efficacy of this system, we established a rat model of bladder tumors, which was induced by N-methyl-nitrosourea perfusion. Bifidobacterium infantis containing the HSV-TK (i.e., BI-TK) were constructed by transformation of recombinant plasmid pGEX - TK. The engineered BI-TK was injected into tumor-bearing rats via tail vein, followed by intraperitoneal injection of ganciclovir (GCV). Using the rat model of bladder tumors, we found that bladder tumor burdens were significantly lower in the rats treated with BI-TK/GCV group than that treated with normal saline control group (p <0.05). While various degrees of apoptosis of the tumor cells were detected in all groups using in situ TUNEL assay, apoptosis was mostly notable in the BI-TK/GCV treatment group. Immunohistochemical staining further demonstrated that the BI-TK/GCV treatment group had the highest level of caspase3 protein expression than that of the empty plasmid group and normal saline group (p < 0.05). Thus, our results demonstrate that the Bifidobacterium infantis-mediated TK/GCV suicide gene therapy system can effectively inhibit rat bladder tumor growth, possibly through increasing caspase 3 expression and inducing apoptosis.