Objective: To explore the intra-host genetic evolution of HIV-1 pol gene via follow-up for treatment-naïve HIV infections, and estimate the infection time with Bayesian coalescent theory, so as to support the evaluation of HIV epidemic. Methods: Five cases were recruited and followed up. The pol gene fragments were amplified for the characteristics of transmitted drug resistance ( TDR ) by RT-PCR. Bayesian coalescent theory was utilized to construct maximum clade credibility ( MCC ) tree for genetic evolution and calculate the time to the most recent common ancestor ( tMRCA ). Results: The five cases were all male, and aged from 27 to 50 years old.Five to nine sampling times were obtained from each case, and the pol gene sequences from each case formed a unique subcluster (posterior probability: 100% ), with different evolution characteristics, in the MCC tree. The three cases in primary HIV-1 infection were estimated to be infected one to five months before the first positive reaction of HIV screening, whereas the two HIV-1 diagnosed cases at first screening were extrapolated to get infected fourteen months and seven months before diagnosis, respectively. One case with acute HIV-1 infection carried TDR mutation ( M46I ) , expressing fast disease progress and quasispecies variation. Conclusions The general infection time can be estimated by analyzing the characteristics of intra-host genetic evolution of HIV-1 pol gene with Bayesian coalescent theory, and this method can help to estimate the HIV epidemic.

ObjectiveTo observe the effects of Xibining （XBN） and adipose stem cell exosome （ADSC-Exos） in the cases of separate or joint application on cartilage degeneration and mitochondrial autophagy and explore its mechanism of action to improve knee osteoarthritis （KOA）. MethodSD rats were divided into a sham operation group （sham group）， a model group， an ADSC-Exos group （Exos group）， an XBN group， and an ADSC-Exos+XBN group （Exos+XBN group）. KOA model was established by using anterior cruciate ligament transection （ACLT）. The pain sensitivity status of rats was evaluated， and the degeneration degree of the knee joint and cartilage tissue was detected by Micro-CT and pathological staining. The expression of p62 and LC3B was observed by immunofluorescence， and the serum levels of TNF-α， IL-1β， IL-6， and IL-15 in rats were detected by ELISA. The Western blot was used to detect the protein expression levels of MMP-3， MMP-13， ADAMTS5， ColⅡ， TIMP， ACAN， PINK1， Parkin， p62， and LC3A/B. ResultCompared with the sham group， rats in the model group showed decreased cold-stimulated foot-shrinkage thresholds and mechanical pain sensitivity thresholds， varying degrees of abrasion and loss of cartilage tissue， degeneration of cartilage tissue， elevated serum IL-1β， IL-6， IL-15， and TNF-α levels （P<0.01）， and increased protein expression of MMP-3， MMP-13， and ADAMTS5 in cartilage tissue. In addition， the protein expression of ColⅡ， TIMP1， and ACAN was decreased （P<0.01）. Compared with the model group， rats in each treatment group showed higher cold-stimulated foot-shrinkage thresholds and mechanical pain sensitivity thresholds， reduced cartilage tissue degeneration， lower serum levels of IL-1β， IL-6， IL-15， and TNF-α （P<0.05，P<0.01）， decreased protein expression of MMP-3， MMP-13， and ADAMTS5， and higher protein expression of Cold， TIMP1， and ACAN in cartilage tissue （P<0.05，P<0.01）. Moreover， the changes were the most obvious in the Exos+XBN group. ConclusionBoth ADSCs-Exos and XBN can increase the level of mitochondrial autophagy in chondrocytes and delay cartilage tissue degeneration by promoting the expression of the PINK1/Parkin signaling pathway， and the combination of the two can enhance the therapeutic effect.