Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.

Objective To evaluate the effect of water exchange method versus conventional methods including air insufflation and carbon dioxide insufflation method for the quality of colonoscopy.Methods We searched related randomized controlled trials published up to October 2022 from PubMed,Web of Science,the Cochrane Library,SinoMed databases,CNKI,Wanfang data.Two reviewers independently searched the literatures based on standards to extract the data and evaluate the quality.Meta-analysis was conducted by RevMan 5.4.1.Results 23 studies involving 10654 patients were included.Although cecal intubation time was prolonged in water exchange(MD=1.81,95％CI:1.28～2.35,P=0.000),but water exchange had higher adenoma detection rate(ADR)(O(R)=1.40,95％CI:1.26～1.55,P=0.000),cecal intubation rate(O(R)=1.62,95％CI:1.24～2.10,P=0.000)and scores of bowel preparation quality(MD=0.61,95％CI:0.42～0.79,P=0.000)compared with conventional colonoscopy.In addition,WE had significantly lower pain sores(MD=-1.07,95％CI:-1.39～-0.76,P=0.000),number of abdominal compression(O(R)=0.42,95％CI:0.29～0.60,P=0.000)and number of position change(O(R)=0.59,95％CI:0.42～0.82,P=0.002)than conventional colonoscopy.Conclusion Although water exchange colonoscopy prolongs cecal intubation time,but it can significantly increase ADR,cecal intubation rate and scores of bowel preparation quality.Beyond that,water exchange reduces patient pain,the proportion of abdominal compression and position change.Water exchange is a better choice for high-quality colonoscopy.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

The main protease (M^pro) of SARS-CoV-2 is an attractive target in anti-COVID-19 therapy for its high conservation and major role in the virus life cycle. The covalent M^pro inhibitor nirmatrelvir (in combination with ritonavir, a pharmacokinetic enhancer) and the non-covalent inhibitor ensitrelvir have shown efficacy in clinical trials and have been approved for therapeutic use. Effective antiviral drugs are needed to fight the pandemic, while non-covalent M^pro inhibitors could be promising alternatives due to their high selectivity and favorable druggability. Numerous non-covalent M^pro inhibitors with desirable properties have been developed based on available crystal structures of M^pro. In this article, we describe medicinal chemistry strategies applied for the discovery and optimization of non-covalent M^pro inhibitors, followed by a general overview and critical analysis of the available information. Prospective viewpoints and insights into current strategies for the development of non-covalent M^pro inhibitors are also discussed.

Objective To investigate the relationship between serum micro RNA(miRNAs)-873 and micro RNA-138-5p expression and tumor immune microenvironment(TIME)and prognosis in patients with non-small cell lung cancer(NSCLC).Methods A total of 108 NSCLC patients(NSCLC group)and 65 healthy volunteers(control group)who were admitted to Ba'nan Hospital Affiliated to Chongqing Medical University from February 2019 to February 2021 were selected.Real-time quantitative fluorescence polymeric chain reaction(qRT-PCR)was used to detect the expression of miR-873 and miR-138-5p in serum,and multiple immunofluorescence staining was used to detect tumor immune microenvironment indicators.Regular follow-up was conducted after discharge.Pearson analyzed the correlation between the expression of miR-873 and miR-138-5p in serum and the TIME index,and Kaplan-Meier and COX proportional risk regression analyzed the relationship between miR-873 and miR-138-5p and the prognosis of NSCLC patients.Results Comparison with control group,the expressions of miR-873(1.02±0.23 vs 3.15±0.82)and miR-138-5p(1.21±0.26 vs 3.54±0.92)in serum of NSCLC group were decreased,and the differences were statistically significant(t=-25.426,-24.769,all P＜0.05).The expressions of serum miR-873 and miR-138-5p of patients with low-to-moderate differentiation in TNM stages Ⅲ to Ⅳ were lower than those with highly differentiated patients in TNM stages Ⅰ to Ⅱ(t=9.615,10.253;6.889,3.361,all P＜0.05).The expressions of miR-873 and miR-138-5p in serum were negatively correlated with the values of PD-1,PD-L1,CD4 and CD8 H(r=-0.418～-0.673,all P＜0.05).The OS survival rate of NSCLC patients with low expression of miR-873 and miR-138-5p was lower than that of those with high expression of miR-873 and miR-138-5p(Log-Rankχ2=4.724,5.607,P＜0.05).TNM stage Ⅲ～Ⅳ was a risk factor for poor prognosis in patients with NSCLC(P＜0.05),and miR-873 and miR-138-5p were protective factors(P＜0.05).Conclusion The expressions of miR-873 and miR-138-5p in serum of NSCLC patients are down-regulated,which is related to TIME and low survival rate.

As a common protease with high similarity among coronavirus species, the main protease (M^pro) of SARS-CoV-2 is responsible for the catalytic hydrolysis of viral precursor proteins into functional proteins, which is essential for coronavirus replication and is one of the ideal targets for the development of broad-spectrum antiviral drugs. This paper reviews the main protease inhibitors of SARS-CoV-2, including their molecular structures, potencies and drug-like profiles, binding modes and structure-activity relationships, etc.

Indolylarylsulfones (IASs) are classical HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) with a unique scaffold and possess potent antiviral activity. To address the high cytotoxicity and improve safety profiles of IASs, we introduced various sulfonamide groups linked by alkyl diamine chain to explore the entrance channel of non-nucleoside inhibitors binding pocket. 48 compounds were designed and synthesized to evaluate their anti-HIV-1 activities and reverse transcriptase inhibition activities. Especially, compound R₁₀L₄ was endowed with significant inhibitory activity towards wild-type HIV-1 (EC_50(WT) = 0.007 μmol/L, SI = 30,930) as well as a panel of single-mutant strains exemplified by L100I (EC₅₀ = 0.017 μmol/L, SI = 13,055), E138K (EC₅₀ = 0.017 μmol/L, SI = 13,123) and Y181C (EC₅₀ = 0.045 μmol/L, SI = 4753) which were superior to Nevirapine and Etravirine. Notably, R₁₀L₄ was characterized with significantly reduced cytotoxicity (CC₅₀ = 216.51 μmol/L) and showed no remarkable in vivo toxic effects (acute and subacute toxicity). Moreover, the computer-based docking study was also employed to characterize the binding mode between R₁₀L₄ and HIV-1 RT. Additionally, R₁₀L₄ presented an acceptable pharmacokinetic profile. Collectively, these results deliver precious insights for next optimization and indicate that the sulfonamide IAS derivatives are promising NNRTIs for further development.

Objective To explore the effect of Xiangpi Shengji Ointment on wound healing and apoptosis-related Fas/Fas L pathway in model rats after anal fistula operation.Methods Thirty-six SD rats were used to construct the anal fistula model by using steel wire hanging line and indwelling for 30 days.After successful modeling,27 rats with anal fistula were randomly selected for"fistulectomy"to construct a postoperative wound model.After operation,the wound model rats were randomly divided into three groups,9 rats in each group,which were Xiangpi Shengji Ointment Group,Vaseline Group and Model Group,and the remaining 9 rats with anal fistula were sham operation group.The rats in the Xiangpi Shengji Ointment group were externally applied with Xiangpi Shengji Ointment gauze,while those in the Vaseline group were externally applied with Vaseline gauze.The rats in the model group were only disinfected and rinsed.No special treatment was given to the rats in the sham operation group.The wound healing was observed on the 3rd,5th,7th and 10th day after medication intervention,and the wound healing rate was calculated.After 10 days of continuous intervention,wound tissues were taken from each group,and the histopathological changes,the number of apoptosis,the expressions of Fas,Fas L,caspase-8 and cyto-c in wound tissues were observed by HE staining,TUNEL staining and immunohistochemistry respectively,and the mRNA expressions of Fas,Fas L and cyto-c in wound tissues were detected by RT-PCR.Results Compared with the model group,Xiangpi Shengji ointment group and Vaseline group significantly promoted wound healing at 7 and 10 days after intervention(P<0.01),and the wound healing rate of Xiangpi Shengji ointment group was significantly higher than that of Vaseline group(P<0.01).After 10 days of drug intervention,compared with sham operation group,the apoptosis rate of Xiangpi Shengji ointment group,Vaseline group and model group increased significantly(P<0.01),and the relative expressions of Fas,Fas L and cyto-c mRNA and the expression levels of Fas,Fas L,caspase-8 and cyto-c protein in wound tissue increased significantly(P<0.05,P<0.01).Compared with the model group,the apoptosis rate,the relative expression of Fas,Fas L and cyto-c mRNA and the expression level of Fas,Fas L,caspase-8 and cyto-c protein in Xiangpi Shengji ointment and Vaseline groups decreased significantly(P<0.05,P<0.01).Compared with Vaseline group,the apoptosis rate of Xiangpi Shengji ointment group decreased significantly(P<0.01),and the relative expression of Fas,Fas L and cyto-c mRNA and the expression level of Fas,Fas L,caspase-8 and cyto-c protein decreased significantly(P<0.05,P<0.01).Conclusion Xiangpi Shengji Ointment can inhibit the activation of Fas/Fas L pathway,reduce the apoptosis of wound tissue cells and promote wound healing after anal fistula operation.

Background:Complete colonoscopy is key to the diagnosis and treatment of colorectal disease,its role in reducing the morbidity and mortality of colorectal cancer is well known.Nonetheless,there are numerous factors,not just from the endoscopist's perspective but also from the patient's,that can potentially increase the difficulty of completing a colonoscopy.Aims:To identify patient-related factors that influenced the difficulty of a colonoscopy.Methods:Through two rounds of expert consultation,the factors that might affect the difficulty of colonoscopy were selected.A total of 1621 consecutive painless colonoscopies from Jan.2021 to Jan.2022 at the endoscopy center of The Affiliated Wuxi People's Hospital of Nanjing Medical University were evaluated in a retrospective manner.Factors including demographic data,cecal insertion time,adenoma detection rate and so on were recorded.These factors were analyzed to determine their association with difficulty by using Logistic regression model.Results:A total of 29 patient-related factors affecting the difficulty of colonoscopy were selected.Through retrospective analysis,the mean age of 1621 cases was(47.45±13.27)years,of which 45.8%were male and the mean body mass index was(23.32±3.11)kg/m2.Logistic regression analysis revealed that age≥60 years(OR=2.890,95%CI:1.957-4.269,P<0.001),female gender(OR=0.324,95%CI:0.217-0.484,P<0.001),history of gynecological surgery(OR=14.895,95%CI:9.741-22.776,P<0.001),constipation for 20-30 years(OR= 1.412,95%CI:0.925-2.156,P=0.010)were independent risk factors for difficult colonoscopy.Conclusions:This retrospective study identified several patient-related factors that influence the technical difficulty of colonoscopy.These findings had implications for practice and teaching of colonoscopy.

COVID-19 epidemic continues to spread around the world till these days, and it is urgent to develop more safe and effective new drugs. Due to the limited P3 biosafety laboratories for directly screening inhibitors of virulent viruses with high infectivity, it is necessary to develop rapid and efficient screening methods for viral proteases and other related targets. The main protease (M^pro), which plays a key role in the replication cycle of SARS-CoV-2, is highly conserved and has no homologous proteases in humans, making it an ideal target for drug development. From two different levels, namely, molecular level and cellular level, this paper summarizes the reported screening methods of SARS-CoV-2 M^pro inhibitors through a variety of representative examples, expecting to provide references for further development of SARS-CoV-2 M^pro inhibitors.