Longitudinal analysis of immune reconstitution and metabolic changes in women living with HIV: A real-world observational study / 中华医学杂志(英文版)

BACKGROUND@#Women comprise more than half of people living with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) worldwide and incomplete immune recovery and metabolic abnormalities affect them deeply. Studies of HIV antiretroviral therapy (ART) have a low female representation in China. We aimed to investigate immune reconstitution and metabolic changes of female HIV-positive cohort in China longitudinally.@*METHODS@#HIV-positive women who initiated ART from January 2005 to June 2021 and were followed up regularly at least once a year were included in this study. Immunological indicators (cluster of differentiation 4 [CD4] counts and CD8 counts), viral load (VL), and metabolic indicators were collected at follow-up. All data were collected from the China Disease Prevention and Control Information System (CDPCIS). VL was tested half a year, 1 year after receiving ART, and every other year subsequently according to local policy. CD4/CD8 ratio normalization was considered as the primary outcome and defined as a value ≥1. Incidence rate and probability of CD4/CD8 ratio normalization were estimated through per 100 person-years follow-up (PYFU) and Kaplan-Meier curve, respectively. Multivariate Cox regression was used to identify independent risk factors associated with CD4/CD8 ratio normalization. We further studied the rate of dyslipidemia, hyperuricemia, diabetes, liver injury, and renal injury after ART initiation with the chi-squared tests or Fisher's exact probability tests, and a generalized estimating equation model was used to analyze factors of dyslipidemia and hyperuricemia.@*RESULTS@#A total of 494 female patients with HIV/AIDS started ART within 16 years from January 2005 to June 2021, out of which 301 women were enrolled with a median duration of ART for 4.1 years (interquartile range, 2.3-7.0 years). The overall incidence rate of CD4/CD8 ratio normalization was 8.9 (95% confidence interval [CI], 7.4-10.6) per 100 PYFU, and probabilities of CD4/CD8 normalization after initiating ART at 1 year, 2 years, 5 years, and 10 years follow-up were 11.7%, 23.2%, 44.0%, and 59.0%, respectively. Independent risk factors associated with CD4/CD8 normalization were baseline CD4 cell counts <200 cells/μL, CD8 counts >1000 cells/μL, and more than 6 months from the start of combined ART (cART) to first virological suppression. Longitudinally, the rate of hypercholesterolemia (total cholesterol [TC]) and high triglyceride (TG) showed an increasing trend, while the rate of low high-density lipoprotein cholesterol (HDL) showed a decreasing trend. The rate of hyperuricemia presented a downtrend at follow-up. Although liver and renal injury and diabetes persisted during ART, the rate was not statistically significant. Older age and protease inhibitors were independent risk factors for increase of TC and TG, and ART duration was an independent factor for elevation of TC and recovery of HDL-C.@*CONCLUSIONS@#This study showed that women were more likely to normalize CD4/CD8 ratio in comparison with findings reported in the literature even though immune reconstruction was incomplete.

Risk of tuberculosis in patients with rheumatoid arthritis treated with biological and targeted drugs: meta-analysis of randomized clinical trials / 中华医学杂志(英文版)

BACKGROUND@#Concerns exist regarding the potential development of tuberculosis in patients with rheumatoid arthritis (RA) treated with biological and targeted drugs. We assessed systematically whether biological therapy increased the risk of tuberculosis in patients with RA by meta-analysis of randomized controlled trials (RCTs).@*METHODS@#A systematic literature search was conducted in PubMed, Embase, the Cochrane Library, and China Biology Medicine disc for RCTs evaluating biological therapy in patients with RA from inception through August 2021. Traditional meta-analysis and network meta-analysis were performed to compare the risk of tuberculosis for each biologics class in patients with RA. Peto odds ratio (Peto OR) and its 95% confidence interval (CI) were calculated as the primary effect measure.@*RESULTS@#In total, 39 studies with 20,354 patients were included in this meta-analysis, and 82 patients developed tuberculosis. The risk of tuberculosis was increased in patients treated with biologics compared with non-biologics (Peto OR: 3.86, 95% CI: 2.36-6.32, P < 0.001). Also, tumor necrosis factor-α (TNF-α) inhibitors had a higher probability of developing tuberculosis than placebo (Peto OR: 3.98, 95% CI: 2.30-6.88, P < 0.001). However, network meta-analysis demonstrated that there was no significant difference in the risk of tuberculosis for each biologics class in patients with RA. Noticeably, tuberculosis was significantly more common in patients treated with a high dose compared with patients receiving a low dose of tofacitinib (Peto OR: 7.39, 95% CI: 2.00-27.31, P = 0.003).@*CONCLUSION@#This meta-analysis demonstrates the evidence of an elevated risk of tuberculosis in patients with RA treated with TNF-α inhibitors, and a dose-dependent elevated risk of tuberculosis in patients treated with tofacitinib.

C-reactive protein is associated with impaired working capacity in Chinese patients with ankylosing spondylitis in paid employment: the real-world evidence from Smart-phone SpondyloArthritis Management System / 中华内科杂志

To investigate the relationship between serum C-reactive protein (CRP) levels and work impairment in patients with ankylosing spondylitis (AS) based on real-world evidence. Outpatients with confirmed AS at Chinese PLA General Hospital were recruited consecutively by Smart-phone SpondyloArthritis Management System (SpAMS) from April 2016 to April 2018. The relationship between CRP and work productivity and activity impairment questionnaire (WPAI) were evaluated. Five hundred and fifty-one outpatients with AS in paid employment were recruited. The presenteeism, overall work impairment, and activity impairment rates increased by 1.4% (1.1%, 1.8%), 1.1% (0.5%, 1.6%), and 1.7% (1.3%, 2.1%), respectively, for every 10 mg/L increase in the CRP level (all P value<0.01). However, the CRP level was not associated with absenteeism after adjusting for covariates [0.5%(-0.4%, 1.0%), P>0.05]. There is a significant association between increased serum CRP levels at baseline and the previous 7-day work impairment in patients with AS. Higher CRP levels contribute to worse presenteeism, overall work impairment, and activity impairment rates, which suggests the necessity of monitoring CRP on treatment, and also indicates that anti-inflammatory therapy may be effective for improving work productivity.

GPA: A Microbial Genetic Polymorphisms Assignments Tool in Metagenomic Analysis by Bayesian Estimation / 基因组蛋白质组与生物信息学报·英文版

Identifying antimicrobial resistant (AMR) bacteria in metagenomics samples is essential for public health and food safety. Next-generation sequencing (NGS) technology has provided a powerful tool in identifying the genetic variation and constructing the correlations between genotype and phenotype in humans and other species. However, for complex bacterial samples, there lacks a powerful bioinformatic tool to identify genetic polymorphisms or copy number variations (CNVs) for given genes. Here we provide a Bayesian framework for genotype estimation for mixtures of multiple bacteria, named as Genetic Polymorphisms Assignments (GPA). Simulation results showed that GPA has reduced the false discovery rate (FDR) and mean absolute error (MAE) in CNV and single nucleotide variant (SNV) identification. This framework was validated by whole-genome sequencing and Pool-seq data from Klebsiella pneumoniae with multiple bacteria mixture models, and showed the high accuracy in the allele fraction detections of CNVs and SNVs in AMR genes between two populations. The quantitative study on the changes of AMR genes fraction between two samples showed a good consistency with the AMR pattern observed in the individual strains. Also, the framework together with the genome annotation and population comparison tools has been integrated into an application, which could provide a complete solution for AMR gene identification and quantification in unculturable clinical samples. The GPA package is available at https://github.com/IID-DTH/GPA-package.

Rapid identification of geographical origins and determination of polysaccharides contents in Ganoderma lucidum based on near infrared spectroscopy and chemometrics / 中国中药杂志

Near infrared spectroscopy combined with chemometrics methods was used to distinguish Ganoderma lucidum samples collected from different origins, and a prediction model was established for rapid determine polysaccharides contents in these samples. The classification accuracy for training dataset was 96.87%, while for independent dataset was 93.33%; as for the prediction model, 5-fold cross-validation was used to optimize the parameters, and different signal processing methods were also optimized to improve the prediction ability of the model. The best square of correlation coefficients for training dataset was 0.965 4, and 0.851 6 for validation dataset; while the root-mean-square deviation values for training dataset and validation dataset were 0.018 5 and 0.023 6, respectively. These results showed that combining near infrared spectroscopy with suitable chemometrics approaches could accuracy distinguish different origins of G. lucidum samples; the established prediction model could precious predict polysaccharides contents, the proposed method can help determine the activity compounds and quality evaluation of G. lucidum.

Therapeutic effect of arterial thrombolysis for acute cerebral infarction：analysis of related factors / 介入放射学杂志

Objective To investigate the relationship between the residual forward blood flow and the therapeutic outcome in patients with acute cerebral infarction after arterial thrombolysis treatment. Methods During the period from January 2009 to December 2013 at authors’ hospital, a total of 40 patients with acute anterior circle cerebral infarction were treated with arterial thrombolysis. The clinical data were retrospectively analyzed. The patients were divided into group A (n=23) when residual forward blood flow and/or collateral circulation were presented, and group B (n=17) if no residual forward blood flow and/or collateral circulation were detected. The NIHSS scores and hemorrhagic transformation state were determined 14 days after the thrombolysis treatment, and the results were compared between the two groups. Results In group A, 21 cases (91.3%) showed complete or partial re- canalization of the infracted vessels, and asymptomatic hemorrhagic transformation was seen in one case. The pre-treatment NIHSS score was 12.69 ± 3.88 and the post-treatment NIHSS score was 6.05 ± 3.25. In group B, complete or partial re-canalization of the infracted vessels was seen in 15 cases (88.2%), asymptomatic hemorrhagic transformation was found in one case and symptomatic hemorrhagic transformation occurred in one case, who died of massive cerebral hemorrhage seven hours after the thrombolysis treatment. The pre-treatment NIHSS score was 13.51 ± 4.19 and the post-treatment NIHSS score was 8.68 ± 5.16. The differences between the two groups were statistically significant (P < 0.05). The obvious effect rate in group A and group B was 68.1% and 43.8% respectively, and the effective rate in group A and group B was 86.3% and 56.3% respectively, indicating that the clinical outcome of group A was much better than that of group B. Conclusion The therapeutic effect of arterial thrombolysis for acute cerebral infarction patients is not only closely related to the time window but also to the residual forward blood flow. The more the residual forward blood flow there is, the better the therapeutic result with less risk of hemorrhagic transformation will be.

Effects of the Three Gorges project and change of water level on local mouse density / 中国地方病学杂志

Objective To study the impacts of the Three Gorges dam and change of water level on the survival of the local rodents, and to provide scientific basis to control the outbreak of rodent-borne diseases.Methods Four villages located around the Three Gorges dam were selected in the study. The mouse populations by using Elton night trapping method was monitored. Metallic spring traps were set for two consecutive nights. The mouse density and identified the mouse species was calculated. The mouse species indoor and outdoor, as well as the mouse density indoor and outdoor were compared. The impacts of water level in the dam and cleaning work on local mouse density were also analyzed. Results A total of 678 mice were caught in this study, 517 were caught indoor and 161 outdoor. Indoor dominant species was flavipectus; accounting for 36.49%(189/517), while outdoor was apodemus, reaching 56.88% (91/161). For mouse species, there was a significant difference between indoor and outdoor(x2 = 678.00, P ＜ 0.01 ). The average mouse density was 8.44%(678/8036) in trap nights. Indoor mouse density reached 14.44%(517/3581 ), which was significantly higher than that of outdoor(3.61%, 161/4455 ).For mouse density, there was a significant difference between indoor and outdoor(x2 = 301.04, P ＜ 0.01 ). When the water level was up to 156 m, mouse density reached 10%(513/5132), which was higher than that of before (5.68%, 165/2904). There was a significant difference in mouse density before and after reserving water (x2 = 44.68, P ＜ 0.01 ). With the change of water level, upstream mouse density formed a high platform from May 2007 to May 2008, followed by 12.25%(80/653), 13.16%(90/684), 12.95%(90/695), and decreased to 8.38%(28/334) after cleaning of the dam. Conclusions The Three Gorges dam and change of water level actually alter the survival environment of the local mouse, and affect local mouse density and mouse species. These may lead to local outbreak or epidemic of rodent-borne diseases.

Proteomic identification and comparison of differentiation-related proteins in gastric carcinoma cell lines / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the differentiation-related proteins in human gastric carcinoma cell lines by comparative proteomics.</p><p><b>METHODS</b>The holoproteins of human gastric carcinoma cell lines MKN28, SGC7901 and BGC823 were measured by two-dimensional gel electrophoresis and matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Some proteins identified by proteomics were tested by Western blot in the cell strains and tissues of gastric carcinoma.</p><p><b>RESULTS</b>14 differential protein spots were found in the 3 gastric carcinoma cell lines, among them 8 spots were identified by MALDI-TOF-MS. These proteins were probably thioredoxin peroxidase, glyceraldehyde-3-phosphate dehydrogenase (GAPD), beta-tubulin polypeptide, hypothetical protein, zinc finger protein (ZNF) 139, protein-tyrosine kinase, calreticulin precursor, and tropomyosin, proteins related with biological behavior of gastric carcinoma cells such as signal transduction, cellular homeostasis, glycolysis, antioxidation action, multidrug resistance(MDR), etc. The expressions of those proteins in gastric cancer cells and tissues identified by Western blot were consistent with the results obtained by proteomics.</p><p><b>CONCLUSION</b>Differential proteins are found in 3 human gastric carcinoma cell lines, mainly, proteins related with cell signaling, maintenance of homeostasis, glycolysis, metabolism of anti-cancer drug and anti-oxidative injury, etc.</p>

Effects of warming-reinforcing acupuncture combined with rehabilitation training on the early motor function of hemiparalysis patients caused by ischemic brain stroke: a randomized and controlled study / 中国针灸

<p><b>OBJECTIVE</b>To verify the improvement function of warming-reinforcing acupuncture combined with rehabilitation training on the early motor function of hemiparalysis patients caused by ischemic brain stroke.</p><p><b>METHODS</b>Eighty cases were randomly divided into a warming-reinforcing acupuncture combined with rehabilitation training group (group A) and a rehabilitation training group (group B), 40 cases in each group. Both groups were treated with internal routine treatment. The Motor Relearning Program rehabilitation was used in group B, while warming-reinforcing acupuncture combined with Motor Relearning Program rehabilitation were used in group A. Jianyu (LI 15), Quchi (LI 11), Hegu (LI 4), Yanglingquan (GB 34), Yinlingquan (SP 9), Zusanli (ST 36), Sanyinjiao (SP 6) were selected, and warming-reinforcing method was used in these points, they were treated for 3 weeks. The neurological functional deficits scores of hemiparalysis patients, Fugl-Meyer Score, Motor Function Assessment Score (MAS), Barthel Index and Mini-mental State Examination (MMSE) were used to evaluate the condition of hemiparalysis patients before and after treatment.</p><p><b>RESULTS</b>The effective rate of group A (87.5%, 35/40) superior to that of group B (67.5%, 27/40) (P < 0.05). The neurological functional deficit scores, Fugl-Meyer score, MAS and Barthel Index of both groups were improved after treatment (P < 0.01, P < 0.05), and the improved degree of group A was better than that of group B (P < 0.01, P < 0.05).</p><p><b>CONCLUSION</b>There is obvious improvement function of warming-reinforcing acupuncture combined with rehabilitation training on the early motor function of hemiparalysis patients caused by ischemic brain stroke, and the function is better than that of simple rehabilitation training.</p>

Effect of ulinastatin on intestinal mucosal barrier function of rats with obstructive jaundice / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of ulinastatin on intestinal mucosal barrier function of rats with obstructive jaundice.</p><p><b>METHODS</b>Seventy-two male SD rats were randomly divided into sham operation, obstructive jaundice, and ulinastatin treatment groups (groups A, B, and C, respectively). In groups B and C, the common bile duct was ligated to induce obstructive jaundice. The rats in group C were given intraperitoneal injection of ulinastatin at the daily dose of 40,000 IU/kg after the operation, while those in groups A and group B received equal amount of normal saline. At 3, 5, 7 and 10 days after the operation, the liver function and plasma endotoxin level were evaluated and measured, and bacterial culture of the mesenteric lymph nodes, liver and spleen was performed. The terminal ileum mucosa was observed under light microscope, and the intestinal villi and mucosal thinckness was examined with image analysis system.</p><p><b>RESULTS</b>The indices relative to the liver function and plasma endotoxin level were higher at different time points of observation in group B than in group A (P<0.01), and were lower in group C than in group B (P<0.01). Plasma endotoxin level was similar between groups A and C 3 days after the operation (P>0.05). The rate of bacterial translocation was higher in group B than in group A and C (P<0.01, P<0.05), but comparable between groups A and C (P>0.05). Intestinal mucosal injury was observed in group B 3 days after operation, and aggravated with the passage of time. The injury was milder in group C. The intestinal villus length and mucosal thickness were greater in groups A and C than in group B (P<0.01 or P<0.05), but comparable between the former two groups 3 days after operation (P>0.05).</p><p><b>CONCLUSION</b>In early stage of obstructive jaundice, the intestinal mucosal barrier may sustain injuries which aggravate with time; ulinastatin has significant effect in protecting the mucosal barrier function especially against early pathological changes.</p>

Investigation on the vectors of Borrella burgdorferi and on the identification of the isolates along China-Russia border in Eastern Heilongjiang province, China / 中华流行病学杂志

<p><b>OBJECTIVE</b>To explore the fact that the east border of Heilongjiang had been a lyme disease natural focus,we investigated the species and distribution of ticks and isolated bacteria from ticks and identified genomic species of Borrelia burdorferi sensu lato. This study provided evidence for prevention and control of lyme disease.</p><p><b>METHODS</b>Ticks were caught by flagging method and Direct immunofluorescence method was used to detect the rate of bacteria borne by the tick. BSK UI culture medium was used to isolate the agent and Specific McAbs were used to identify the bacteria. SDS-PAGE protein profile and PCR-RFLP method were also used to identify the species of Spirochetes.</p><p><b>RESULTS</b>Ticks, collected from China-Russia border of east Heilongiiang province were classified including Ixodes persulcatus Schulze, Dermacentor sivarum Olener, Haemaphysalis concinna Kock,and Haemaphysalis japonica Kock. We found that the distributon of ticks was different under different circumstances and the predominant species were also different in different ports. The rate of bacteria borne by Iodes persulaatus Schulze was 31.4% ,by Dermacentor sivarum Olener and Haemaphysalis concinna Kock were 2.2% and 3.8%, respectively. However,it was negative for Haenaphysalis japonica Kock. Spirochetes isolated from Ixodes persulcatus Schulze were collected from Dongning and Tongjiang while Genomic species of Spirochetes, isolated from ticks of the border belonged to B. garinii.</p><p><b>CONCLUSION</b>All the results showed that the east border of Heilongjiang province was the natural focus of lyme disease.</p>

Relationship between B virus hepatitis genotypes and therapeutic efficacy in early treatment for chronic hepatitis B by using lamivudine / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between hepatitis B virus (HBV) genotype and therapeutic efficacy during the early phase of lamivudine treatment.</p><p><b>METHODS</b>Totally 595 patients with chronic hepatitis B were treated with lamivudine 100 mg/day for 12 months. HBV genotypes, contents of HBV DNA, HBeAg/anti-HBe and YMDD mutation after lamivudine treatment for 12 months were determined. The data were analyzed with SPSS software.</p><p><b>RESULTS</b>In 595 patients, 8 (1.4%) were genotype A; 53 (8.9%) genotype B; 360 (60.5%) genotype C; 112 (18.8%) were coinfection of genotype B and C; 14 (2.4%) of A and C; 15 (2.5%) A and B; 6 (1.0%) of A, B, and C, and remaining 27 (4.5%) were unspecified. Patients were treated with lamivudine 100 mg/day for 12 months. Genotype B with HBV DNA levels turned to be negative (HBV DNA < 0.1 ng/L) was 87.2%, genotype C was 89.51%, coinfection of genotype B and C was 93.04% (P > 0.05). HBeAg seroconversion of genotype B was 11.65%, of genotype C was 20.64%, and of coinfection of genotype B and C was 18.57% (P > 0.05). All 69 strains of YMDD mutation were detected after lamivudine treatment for 12 months, in which genotype B was in 16.98%, genotype C in 15.38%, and coinfection of genotype B and C was in 13.86% (P > 0.05).</p><p><b>CONCLUSION</b>There was no difference in HBV genotypes and the rate of development of YMDD mutations, HBeAg seroconversion, descending of HBV DNA level in Chinese patients with chronic hepatitis B.</p>

Drug distribution in gastric cancer and adjacent tissues by preoperative intraperitoneal chemotherapy with Co-fluorouracil liposome / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To examine the distribution of fluorouracil in gastric cancer (CA), lymph node (LN), normal gastric mucosa (NG), peritoneum (PE), greater omentum (GO) and lesser omentum (LO) by preoperative intraperitoneal chemotherapy with Co-fluorouracil liposome (Co 5-Fu), and offer an experimental basis for clinic practice.</p><p><b>METHODS</b>Ninety-six gastric cancer patients were divided into four groups: Co 5-Fu i.v. injection group (Co 5-Fu i.v.), Co 5-Fu intraperitoneal perfusion group (Co 5-Fu i.p.), 5-Fu i.v. injection group (5-Fu i.v.) and intraperitoneal perfusion group (5-Fu i.p.) given on day-2, day-1 and 60 minutes before operation. Fluorouracil concentration in all tissues collected during operation were examined by high performance liquid chromatography (HPLC).</p><p><b>RESULTS</b>The fluorouracil concentration in the tissues in Co 5-Fu i.p. group was significantly higher than that in Co 5-Fu i.v. or 5-Fu i.p. group (P < 0.05 or P < 0.01), and that in 5-Fu i.p. group was greatly higher than that at 5-Fu i.v. group (P < 0.01). In Co 5-Fu i.p. group, the concentration of drug in LN, CA, PE, NG, GO and LO decreased gradually with the former 3 tissues significantly higher than the latter 3 tissues (P < 0.01), and adjacent lymph node was the highest. In Co 5-Fu i.v. group, the ranking was LN, CA, NG, PE, GO and LO with the former 3 tissues significantly higher than the latter 3 tissues (P < 0.01) and showing tumor tissues higher than the other tissues (P < 0.01). In 5-Fu i.p. group, the ranking was PE, LN, CA, NG, GO and LO with the former 2 tissues significantly higher than the latter tissues (P < 0.01).</p><p><b>CONCLUSION</b>Co 5-Fu possesses drug targeting, slow release and long effect in gastric cancer tissues and adjacent lymph nodes. Preoperative chemotherapy with Co 5-Fu i.p. is more advantageous than 5-Fu given i.v. or 5-Fu i.p.</p>

Effects of ketamine on the expression of N-methyl-D-aspartate receptor-1 in a rat model of focal cerebral ischemia / 中华麻醉学杂志

Objective To investigate the effects of ketamine on the expression of NMDA receptor-1(NRⅠ)in a rat model of focal cerebral ischemia and the possible mechanism of the neuroprotection.Methods Forty healthy male SD rats weighing 250-290g were randomly divided into 2 group(n=20 each):groupⅠketamine and groupⅡpentobarbital.The aminals were anesthetized with intraperitoneal ketamine 60 mg?kg~(-1) in groupⅠor pentobarbital 40 mg?kg~(-1) in groupⅡ.Focal cerebral ischemia was produced by permanent middle cerebral artery occludion(MCAO).The animals were killed at 24 h and 72 h of MCAO and their brains removed for determination of infarct size,the number of living neurons in the penumbra and the expression of NRⅠprotein(immuno- histochemistry).Results The infarct size was significantly smaller;the number of living neurons in penumbra significantly larger and NRⅠexpression significantly down-regulated in ketamine group than in pentobarbital group.Conclusion Ketamine can protect the brain against ischemia through downregulation of NMDA receptor-1.

A STUDY ON THE EXPRESSION OF PAI-2 DURING THE DIFFERENTIATION OF KERATINOCYTE IN THE HUMAN EMBRYONIC EPIDERMS / 解剖学报

Objective To study the regulating roles of PAI 2 in the differentiation mechanism of the human epidermis. Methods Human skins were take from the early, middle and late human embryos respectively and observed with immunocytochemistry and in situ hybridization techniques. The cell culture and dot blot were also used in the observation of the materials from late embryo. Results 1 PAI 2 exhibits a very high experssion in the development of embryonic period, with the highest level in the middle embryonic phase while the transcripts of PAI 2 still keep a rather high level in the late human embryonic stage. 2 PAI 2 is mainly localized in the superficial, more differentiatied layers of the epidermis.3 PAI 2 is localizated in peripheral cytoplasm of the vitro or vivo keratinocyte.Conclusion PAI 2 is involved in the regulation of the keratinocyte differentiation. [