Advances in Minimally Invasive Treatment of Benign Prostatic Hyperplasia

Benign prostatic hyperplasia (BPH) is a chronic condition that is more common in older men. BPH most commonly causes symptoms associated with LUTS and bladder outlet obstruction. Lower urinary tract symptoms (LUTS) in men with BPH are a major cause of reduced quality of life in older men. If bladder outlet obstruction persists for a longer period of time, the contractility and voiding capacity of the detrusor muscle will gradually be affected by the obstructive factors, eventually leading to a loss of compensatory phase, characterised by a reduced electrical stimulation response, replacement of bladder muscle tissue by connective tissue, and a possible increase in voiding pressure, but a decrease in contractility of the detrusor muscle. As BOO progresses, it eventually leads to permanent contractile dysfunction of the detrusor muscle. Therefore, early initiation of surgical treatment in patients who are not well controlled by medication can reduce the complications associated with prostate enlargement. With the rise of minimally invasive treatment and the complications of open surgery, minimally invasive treatment of BPH has attracted increasing attention. Various emerging minimally invasive surgical modalities are being developed in clinical practice, and more and more minimally invasive techniques and concepts are focusing on safety, improving quality of life and reducing long-term complications to meet the different needs of different patients. Transurethral resection of the prostate (TURP) is currently the “gold standard” of minimally invasive surgical treatment, but with concerns about post-operative complications, the search for safer and more effective minimally invasive surgical options has become even more important. In recent years, with the increasing clinical application of new minimally invasive techniques such as various lasers, interventional treatments and implantable devices, there are more options for minimally invasive treatment of BPH. This article provides a brief review of research advances in the minimally invasive treatment of benign prostatic hyperplasia, with a view to informing clinical decisions.

Contrast-enhanced fluorescence microscope by LED integrated excitation cubes

Fluorescence microscopy is a powerful tool for scientists to observe the microscopic world,and the fluorescence excitation light source is one of the most critical components.To compensate for the short operation lifetime,integrated light sources,and low excitation efficiency of conventional light sources such as mercury,halogen,and xenon lamps,we designed an LED-integrated excitation cube(LEC)with a decentralized structure and high optical power density.Using a Fresnel lens,the light from the light-emitting diode(LED)was effectively focused within a 15 mm mounting distance to achieve high-efficiency illumination.LEC can be easily designed in the shape of fluorescence filter cubes for installation in commercial fluorescence microscopes.LECs’optical efficiency is 1–2 orders of magnitude higher than that of mercury lamps;therefore,high-quality fluorescence imaging with spectral coverage from UV to red can be achieved.By replacing conventional fluorescence filter cubes,LEC can be easily installed on any commercial fluorescence microscope.A built-in LEC driver can identify the types of LEDs in different spectral bands to adopt the optimal operating current and frequency of pulses.Moreover,high-contrast images can be achieved in pulse mode by time-gated imaging of long-lifetime luminescence.

Etoposide,dexamethasone,and pegaspargase with sandwiched radiotherapy in early-stage natural killer/T-cell lymphoma:A randomized phase III study

Methotrexate,etoposide,dexamethasone,and pegaspargase(MESA)with sandwiched radiotherapy is known to be effective for early-stage extranodal natural killer/T-cell lymphoma,nasal type(NKTCL).We explored the efficacy and safety of reduced-intensity,non-intravenous etoposide,dexamethasone,and pegaspargase(ESA)with sandwiched radiotherapy.This multicenter,randomized,phase III trial enrolled patients aged between 14 and 70 years with newly diagnosed early-stage nasal NKTCL from 27 centers in China.Patients were randomly assigned(1:1)to receive ESA(pegaspargase 2,500 IU/m^(2)intramuscularly on day 1,etoposide 200 mg orally,and dexamethasone 40 mg orally on days 2–4)or MESA(methotrexate 1 g/m^(2)intravenously on day 1,etoposide 200 mg orally,and dexamethasone 40 mg orally on days 2–4,and pegaspargase 2,500 IU/m^(2)intramuscularly on day 5)regimen(four cycles),combined with sandwiched radiotherapy.

Human 8-cell embryos enable efficient induction of disease-preventive mutations without off-target effect by cytosine base editor

Approximately 140 million people worldwide are homozygous carriers of APOE4(ε4),a strong genetic risk factor for late onset familial and sporadic Alzheimer’s disease(AD),91%of whom will develop AD at earlier age than heterozygous carriers and noncarriers.Susceptibility to AD could be reduced by targeted editing of APOE4,but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies.Here,we first screened eight cytosine base editor variants at four injection stages(from 1-to 8-cell stage),and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate(up to 100%)with the lowest bystander effects.In particular,80%of AD-susceptibleε4 allele copies were converted to the AD-neutralε3 allele in humanε4-carrying embryos.Stringent control measures combined with targeted deep sequencing,whole genome sequencing,and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells.Furthermore,base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage.Finally,we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia.Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos,a potential approach for reducing human susceptibility to AD or other genetic diseases.

Challenges in the control of COVID-19 outbreaks caused by the delta variant during periods of low humidity:an observational study in Sydney,Australia

Background: Since the appearance of severe acute respiratory coronavirus 2 (SARS-CoV-2) and the coronavirus disease 2019 (COVID-19) pandemic, a growing body of evidence has suggested that weather factors, particularly temperature and humidity, influence transmission. This relationship might differ for the recently emerged B.1.617.2 (delta) variant of SARS-CoV-2. Here we use data from an outbreak in Sydney, Australia that commenced in winter and time-series analysis to investigate the association between reported cases and temperature and relative humidity.Methods: Between 16 June and 10 September 2021, the peak of the outbreak, there were 31,662 locally-acquired cases reported in five local health districts of Sydney, Australia. The associations between daily 9:00 am and 3:00 pm temperature (°C), relative humidity (%) and their difference, and a time series of reported daily cases were assessed using univariable and multivariable generalized additive models and a 14-day exponential moving average. Akaike information criterion (AIC) and the likelihood ratio statistic were used to compare different models and determine the best fitting model. A sensitivity analysis was performed by modifying the exponential moving average.Results: During the 87-day time-series, relative humidity ranged widely (< 30-98%) and temperatures were mild (approximately 11-17℃). The best-fitting (AIC: 1,119.64) generalized additive model included 14-day exponential moving averages of 9:00 am temperature (P < 0.001) and 9:00 am relative humidity (P < 0.001), and the interaction between these two weather variables (P < 0.001). Humidity was negatively associated with cases no matter whether temperature was high or low. The effect of lower relative humidity on increased cases was more pronounced below relative humidity of about 70%;below this threshold, not only were the effects of humidity pronounced but also the relationship between temperature and cases of the delta variant becomes apparent.Conclusions: We suggest that the control of COVID-19 outbreaks, specifically those due to the delta variant, is particularly challenging during periods of the year with lower relative humidity and warmer temperatures. In addition to vaccination, stronger implementation of other interventions such as mask-wearing and social distancing might need to be considered during these higher risk periods.

Optimization of COVID-19 prevention and control measures during the Beijing 2022 Winter Olympics:a model-based study

Background:The continuous mutation of severe acute respiratory syndrome coronavirus 2 has made the coronavirus disease 2019(COVID-19)pandemic complicated to predict and posed a severe challenge to the Beijing 2022Winter Olympics and Winter Paralympics held in February and March 2022.Methods:During the preparations for the Beijing 2022 Winter Olympics,we established a dynamic model with pulsedetection and isolation efect to evaluate the efect of epidemic prevention and control measures such as entry policies,contact reduction,nucleic acid testing,tracking,isolation,and health monitoring in a closed-loop managementenvironment,by simulating the transmission dynamics in assumed scenarios.We also compared the importance ofeach parameter in the combination of intervention measures through sensitivity analysis.Results:At the assumed baseline levels,the peak of the epidemic reached on the 57th day.During the simulationperiod(100 days),13,382 people infected COVID-19.The mean and peak values of hospitalized cases were 2650and 6746,respectively.The simulation and sensitivity analysis showed that:(1)the most important measures to stopCOVID-19 transmission during the event were daily nucleic acid testing,reducing contact among people,and dailyhealth monitoring,with cumulative infections at 0.04%,0.14%,and 14.92%of baseline levels,respectively(2)strictlyimplementing the entry policy and reducing the number of cases entering the closed-loop system could delay thepeak of the epidemic by 9 days and provide time for medical resources to be mobilized;(3)the risk of environmentaltransmission was low.Conclusions:Comprehensive measures under certain scenarios such as reducing contact,nucleic acid testing,health monitoring,and timely tracking and isolation could efectively prevent virus transmission.Our research resultsprovided an important reference for formulating prevention and control measures during the Winter Olympics,andno epidemic spread in the closed-loop during the games indirectly proved the rationality of our research results.