In March 2020, the outflow of age limited videos from ICU in Spain inspired us to rethink whether there is age discrimination in the allocation of scarce medical resources. This paper frist reflected on the problem of age discrimination caused by this phenomenon from four moral intuitions: the sacred view of life, the quality of life and values, public health ethics and Chinese culture, and then examined whether it is illegal from the legal level, finally pointed out the negative impact on the society, and put forward that taking age as the standard for the allocation of scarce medical resources is not suitable for China’s national conditions.

Objective:To evaluate the effect of the remimazolam-flumazenil regimen on the emergence of patients undergoing endoscopic retrograde cholangiopancreatography (ERCP).Methods:Eighty-four American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ patients, regardless of gender, aged 18-78 yr, with body mass index of 18-30 kg/m 2, undergoing elective ERCP under general anesthesia, were allocated into 2 groups ( n=42 each) using a random number table method: remimazolam-flumazenil group (RF group) and propofol group (P group). Anesthesia was induced as follows: Remimazolam 0.2 mg/kg and remifentanil 2 μg/kg were intravenously injected in RF group, and propofol 1.5 mg/kg and remifentanil 2 μg/kg were intravenously injected in P group. Anesthesia was maintained as follows: Remimazolam was intravenously infused at a rate of 0.5-2.0 mg·kg -1·h -1 and remifentanil at a rate of 0.1-0.2 μg·kg -1·min -1 in RF group, and propofol was intravenously infused at a rate of 2-8 mg·kg -1·h -1 and remifentanil at a rate of 0.1-0.2 μg·kg -1·min -1 in P group, maintaining a bispectral index value of 40-60. At the end of procedure, RF group received an intravenous injection of flumazenil at 0.2 mg, while P group received an equal volume of normal saline. The emergence time, laryngeal mask removal time, duration of post-anesthesia care unit stay, development of adverse events during the emergence period, patients′ satisfaction scores, endoscopists′ satisfaction scores, and 15-item Quality of Recovery scale scores at 24 h after operation were recorded. Results:Compared to P group, the emergence time, laryngeal mask removal time and duration of post-anesthesia care unit stay were significantly shortened, and the incidence of euphoria was decreased in RF group ( P<0.05). There were no statistically significant differences between the two groups in the incidence of agitation, dizziness, nausea/vomiting, and re-sedation, patients′ satisfaction scores, endoscopists′ satisfaction scores, and 15-item Quality of Recovery scale scores at 24 h after operation ( P>0.05). Conclusions:Compared to propofol, the remimazolam-flumazenil regimen can shorten the emergence time and improve the quality of recovery when used for ERCP procedures.

ObjectiveTo determine the characteristics， viral load and immunological status of HIV-infected persons and their spouses who became HIV-positive， and the reasons for HIV seroconversion in 55 HIV discordant couples in Dehong Dai and Jingpo Autonomous Prefecture （Dehong Prefecture）， Yunan Province. MethodsData on the 55 couples meeting the criteria of having a previously positive spouse were retrieved from the AIDS Integrated Prevention and Control Data Information System of the China Disease Control and Prevention Information System during 2015-2021. General socio-demographic information， age at diagnosis， exposure history， CD4⁺T lymphocyte count， and antiviral treatment were collected. Descriptive analysis and chi-square test were used to compare the distribution of pre-HIV-positive spouses and their HIV seroconverted spouses. ResultsA total of 55 spouses from HIV discordant couples had HIV seroconversion. Of them， 72.7% （40/55） of pre-HIV-positive spouses were husbands. The most recent CD4⁺T lymphocyte count in the pre-HIV-positive spouses was （328.31±246.27） cells·μL^-1 at the time of diagnosis of their seroconverted spouses， of which 36.3% （20/55） had a CD4⁺T lymphocyte count of less than 200 cells·μL^-1. Furthermore， of those pre-HIV-positive spouses with low CD4⁺T lymphocyte count， 45.0% （9/20） had an undetectable viral load， 15.0% （3/20） <400 copies·mL^-1， and 25.0%（5/20） ≥400 copies·mL^-1. Additionally， 16.4% （9/55） of the pre-HIV-positive spouses did not have a viral load test. The main reasons for HIV seroconversion among HIV-negative spouses in the discordant couples were poor condom use， poor compliance with antiviral therapy， and treatment discontinuation. ConclusionThe follow-up management of HIV discordant couples should be strengthened in Dehong Prefecture， especially the monitoring of viral load levels and immunological status of pre-HIV-positive spouses， to improve their compliance with antiviral therapy and reduce treatment discontinuation， which would effectively prevent and control HIV transmission between spouses.

Objective:To evaluate the effect of remimazolam on hemodynamics when used for anesthesia induction in patients undergoing coronary artery bypass grafting (CABG).Methods:Sixty patients of either sex, aged 18-64 yr, of American Society of Anesthesiologists Physical Status classification Ⅱ-Ⅲ, with ejection fraction>35%, cardiac index (CI) >2.0 L·min -1·m -2 and body mass index <28 kg/m 2, undergoing CABG under general anesthesia, were divided into 2 groups ( n=30 each)using a random number table method: remazolam group (group R) and midazolam group (group M). Group R received intravenous remimazolam 0.08 mg/kg, and group M received intravenous midazolam 0.05 mg/kg, and both groups used sufentanil, etomidate, and rocuronium bromide for anesthesia induction to maintain the BIS value at 40-65. Before anesthesia induction, at 1-2 min after intravenous injection of remimazolam/midazolam-sufantanil-etomidate, immediately before tracheal incubation, at 30 s-15 min after tracheal intubation, and immediately before skin incision, blood pressure, heart rate, mean arterial pressure, CI, stroke volume index, systemic vascular resistance index, and left heart systolic index were measured, and vasoactive drugs were used to maintain the stability of vital signs and to record the cardiovascular events. Results:Compared with group M, the incidence of hypotension and usage rate of vasoactive drugs were significantly decreased, and the incidence of decrease in CI and stroke volume index by more than 20% and changes in left heart systolic index were decreased in group R( P<0.05). Conclusions:Remimazolam can reduce the disturbance of hemodynamics to a certain extent when used for anesthesia induction as compared with midazolam in patients undergoing CABG.

ObjectiveTo determine the characteristics and influencing factors of hepatitis C virus （HCV） co-infection among HIV concordant couples in Dehong Prefecture. MethodsUsing the data of newly reported HIV concordant couples in Dehong Prefecture from 2016 to 2019， we collected the demographic characteristics， exposure history， and HCV infection to determine the characteristics of HCV co-infection among HIV concordant couples. ResultsAmong the 160 HIV concordant couples included in the study， 46 （28.8%） males and 14 （8.8%） females were co-infected with HCV. The prevalence of HIV-HCV co-infection was higher among the male spouses who were diagnosed less than 40， Jingpo ethnic， Burmese， illiteracy， farmers， and intravenous drug users. In contrast， the prevalence of HIV-HCV co-infection was higher among the female spouses who were diagnosed less than 40， Jingpo ethnic， and Burmese. Logistic regression analysis among male spouses showed that the Jingpo ethnic and intravenous drug users had higher risk of HCV co-infection. ConclusionHIV concordant couples in Dehong Prefecture have high prevalence of HIV-HCV co-infection. Effective intervention strategies should be developed based on ethnic-specific factors and exposure characteristics among male and female spouses of HIV concordant couples.

In March 2020, the outflow of age limited videos from ICU in Spain inspired us to rethink whether there is age discrimination in the allocation of scarce medical resources. This paper frist reflected on the problem of age discrimination caused by this phenomenon from four moral intuitions: the sacred view of life, the quality of life and values, public health ethics and Chinese culture, and then examined whether it is illegal from the legal level, finally pointed out the negative impact on the society, and put forward that taking age as the standard for the allocation of scarce medical resources is not suitable for China’s national conditions.

Objective:To investigate the molecular mechanism of VRC01 resistance in HIV-1 subtype B′ strains isolated from a patient (DRVI01) with broadly neutralizing antibody (bNAb).Methods:Sequences of the HIV-1 subtype B′ strains isolated from patient DRVI01 were compared with those of HIV-1 subtype B′ strains that were isolated at the same time but sensitive to VRC01 antibody. Key amino acids that might affect the neutralization of VRC01 were selected according to literature reports. Effects of the selected amino acids on VRC01 neutralization were verified by site-directed mutation and sequence exchange of membrane proteins from different patients.Results:Single-point mutations of E279D and R282K in LoopD region and N460A and N463Q in V5 region reversed the viral sensitivity to VRC01 neutralization. Combined mutations in two or three above-mentioned sites significantly increased the viral sensitivity to VRC01 antibody compared with single-point mutations. Contrary to literature reports, the glycosylation site mutation of N276 had no influence on the viral sensitivity to VRC01.Conclusions:HIV-1 subtype B′ strains isolated from patient DRV01 with bNAb carried the mutations of D279 and K282 in LoopD region and N460 and N463 in V5 region, resulting in resistance to VRC01 antibody.

Objective:To understand the infection status of HCV and Treponema pallidum (TP) in HIV/AIDS cases in Yunnan province,and identify the risk factors. Methods:Between January 1 and June 30 in 2020,a cross-sectional survey was conducted in Yunnan. Two enzyme-linked immunosorbent assay (ELISA) kits were used to detect anti-HCV, the positive results of both two kits indicated HCV infection. ELISA and syphilis toluidine red untreated serum test were applied to identify TP infection. Both Excel 2016 and SPSS 22.0 software were used for statistical analysis, and logistic regression model was conducted to identify the relevant factors of HCV and TP infection.Results:A total of 5 922 HIV/AIDS cases were included in this study, the infection rates of HCV and TP were 6.5% (383/5 922) and 5.8% (344/5 922) respectively. The co-infection rate of HCV and TP was 0.4% (22/5 922). The risk for HCV infection in HIV/AIDS cases was higher in younger age groups compared with age group ≥50 years (15-19:a OR=3.53;20-29:a OR=3.02;30-39:a OR=2.91;40-49:a OR=3.61), in males than in females (a OR=2.31), in the married and unmarried than in the divorced or widowed (married:a OR=1.61;unmarried:a OR=1.63), in other ethnic groups than in Han ethnic group (a OR=1.70), in people with lower education level than in people with education level of college and above (primary school degree and below:a OR=4.69;middle school:a OR=3.96), in people living in the central and western Yunnan than in people living in eastern Yunnan (central Yunnan:a OR=2.46; western Yunnan:a OR=7.08), in injection drug users than in MSM (a OR=131.08). The risk of TP infection in HIV/AIDS cases was higher in people with education level of college and primary school than in middle school degree (primary school and below:a OR=1.73;college and above:a OR=1.77), in people with other occupations than in farmers (a OR=1.39), in people living in eastern Yunnan than in people living in western Yunnan (a OR=1.75); in MSM than in people with heterosex (a OR=9.75). Conclusions:A certain proportion of HIV/AIDS cases reported between January and June in 2020 in Yunnan were co-infected with HCV and TP, many factors were associated with the co-infection. It is suggested to strengthen HCV and TP tests in HIV/AIDS cases and conduct active treatment of the co-infection.

Many human genetic diseases, including Hutchinson-Gilford progeria syndrome (HGPS), are caused by single point mutations. HGPS is a rare disorder that causes premature aging and is usually caused by a de novo point mutation in the LMNA gene. Base editors (BEs) composed of a cytidine deaminase fused to CRISPR/Cas9 nickase are highly efficient at inducing C to T base conversions in a programmable manner and can be used to generate animal disease models with single amino-acid substitutions. Here, we generated the first HGPS monkey model by delivering a BE mRNA and guide RNA (gRNA) targeting the LMNA gene via microinjection into monkey zygotes. Five out of six newborn monkeys carried the mutation specifically at the target site. HGPS monkeys expressed the toxic form of lamin A, progerin, and recapitulated the typical HGPS phenotypes including growth retardation, bone alterations, and vascular abnormalities. Thus, this monkey model genetically and clinically mimics HGPS in humans, demonstrating that the BE system can efficiently and accurately generate patient-specific disease models in non-human primates.
Animals ; Disease Models, Animal ; Female ; Gene Editing ; Humans ; Lamin Type A/metabolism* ; Macaca fascicularis ; Progeria/pathology*

Objective:To analyze the characteristics of HIV-1 molecular network in men who have sex with men (MSM) from 2016 to 2018 in Kunming, Yunnan province, explore the risk factors associated with HIV-1 transmission network and provide evidence for the effective implementation of intervention.Methods:A total of 540 samples of newly reported HIV-1 positive MSM were consecutively collected in Kunming from 2016 to 2018, the pol gene fragments were amplified by nested polymerase chain reaction (PCR). HIV-1 molecular networks were constructed according to the bootstrap value of the maximum likelihood evolutionary tree over 95% and the genetic distance less than 3%. The factors associated with the subjects entering network and network growth were further analyzed. Results:Among 459 successfully sequenced samples, seven genotypes were found, in which CRF07_BC (49.2%, 226/459) and CRF01_AE (40.3%, 185/459 ) were predominant. Other genotypes included URFs (4.8%, 22/459), CRF08_BC (3.1%, 14/459), CRF55_01B (1.7%, 8/459), B (0.7%, 3/459) and CRF68_01B (0.2%, 1/459). A total of 163 sequences entered the network, with an entry rate of 35.5%(163/459), forming 56 clusters with the number of individuals in the cluster was between 2 and 13. The analysis of the factors associated with entering network showed that the MSM who married and had multiple homosexual partners were more likely to be found in HIV-1 molecular networks. Multivariate logistic regression analysis showed that the number of sexual partners was the factor for the growth of HIV-1 molecular network. According to the criteria for the emergence of three or more newly reported cases in every year, six transmission clusters were judged as active transmission clusters, in which MSM who were not Kunming natives, had sexually transmitted diseases (STD), were divorced and students were the key targets of intervention.Conclusions:HIV-1 genotypes in MSM in Kunming were becoming complex, the risk factors associated with transmission networks in MSM in Kunming included being married and having multiple partners, the intervention targets in active transmission clusters included MSM who were not Kunming natives, had STD, were divorced and students. This study provided the basis for applying HIV-1 molecular networks to real-time intervention in this population.