The liver has diverse functions such as metabolism， detoxification， and immune defense， and the maintenance of hepatic microenvironment homeostasis is crucial for overall bodily health. The hepatic microenvironment consists of the components such as parenchymal cells， non-parenchymal cells， and non-cellular components. Chronic inflammatory responses induced by various etiological factors may promote the formation and progression of liver fibrosis. During the dynamic progression of liver fibrosis， from the early to advanced stages， various components within the hepatic microenvironment undergo a series of changes， which can promote the malignant progression of liver fibrosis. An in-depth exploration of the mechanisms underlying such changes in each component of the liver fibrosis microenvironment is of great significance for understanding the pathogenesis of liver fibrosis and discovering potential treatment strategies.

Acute-on-chronic liver failure （ACLF） is a complex clinical syndrome， and early identification and accurate prognostic evaluation are of great importance for patient treatment and management. In recent years， with in-depth research on the pathogenesis of ACLF， multiple prognostic biomarkers have been proposed and used in clinical practice. This article systematically reviews the research advances in prognostic biomarkers for ACLF from the aspects of clinical predictive models， immunological biomarkers， metabolic biomarkers， genetic and epigenetic biomarkers， microbiome-related biomarkers， and emerging technologies such as artificial intelligence and multi-omics， and it also discusses the value and application prospects of these biomarkers in the prognostic evaluation of ACLF and proposes future research directions， in order to provide a scientific and comprehensive reference for clinicians， guide individualized treatment and management of ACLF patients， and finally improve the clinical outcomes of patients.

ObjectiveTo explore the effects of Bushen Tiaojing Formula （补肾调经方） on the quality of early embryos in repeated controlled ovarian stimulation （COS） and its possible mechanism. MethodsA total of 150 ICR female mice were divided into a normal group， a model group， an inhibitor group， a low-dose and a high-dose Bushen Tiaojing Formula group. Mice in the normal group， inhibitor group and model group were gavaged with distilled water 0.25 ml a day， and mice in the low- and high-dose groups were given 25.6 and 51.2 g/（kg·d） of Bushen Tiaojing Formula， respectively. All groups were gavaged once a day for 13 days as a cycle. Mice in the normal group were injected intraperitoneally with 0.1 ml normal saline on the 11th day of gavage， while mice in the other four groups were used to establish COS models. The inhibitor group was injected with the endoplasmic reticulum stress inhibitor 4-phenylbutyric acid 0.2 ml one hour before modelling. All groups were injected by gavage and intraperitoneal injection for 3 consecutive cycles， with an interval of 4 days between cycles. Immediately after the third intraperitoneal injection， mice were grouped with male mice of the same strain in a ratio of 2∶1， and at 8AM of the second day， the mice were examined， and those with spermatozoa or spermatozoa in the vaginal smears were recorded as pregnant. The mice were executed in the afternoon of the 4th day of pregnancy， and the blastocysts were obtained under an inverted microscope. The morphology of the blastocysts was observed， and the total number of blastocysts and the number of high-quality blastocysts were recorded to calculate the rate of high-quality blastocysts； the apoptosis of blastocyst cells was detected by the Tunel method， and the apoptosis rate was calculated； the endoplasmic reticulum molecular chaperone protein glucose-regulated protein 78 （GRP78）， C/EBP homologous protein （CHOP）， B-lymphoblastoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cystathionin 3 （Caspase-3） and cystathionin 12 （Caspase-12） protein levels and their mRNA expression were detected by immunofluorescent assay and RT-qPCR assay， respectively. ResultsIn the normal group， blastocysts had regular morphology， good morphological development and low fragmentation rate； in the model group， blastocysts were poorly developed， cell morphology was irregular， fragmentation rate was high， and there was some stagnation； in the inhibitor group and high-dose， low-dose Bushen Tiaojing Formula groups， cell morphology could be seen to be better developed， with regular morphology and less fragmentation rate. Compared with the normal group， the rate of high-quality blastocysts in the model group reduced， the rate of apoptosis of blastocyst cells increased， the levels of GRP78， CHOP， Caspase-12， Caspase-3， Bax protein and its mRNA expression in blastocysts increased， while the level of Bcl-2 protein and its mRNA reduced （P＜0.01）. Compared with the model group， the rate of high-quality blastocysts increased， the rate of apoptosis of blastocysts decreased， the levels of GRP78， CHOP， Caspase-12， Caspase-3， Bax protein and their mRNA expression decreased， and the levels of Bcl-2 protein and its mRNA expression increased in the blastocysts in the inhibitor group and the high-dose and low-dose Bushen Tiaojing Formula groups （P＜0.01）. Compared with the inhibitor group， GRP78， CHOP， Caspase-12， Bax protein levels and their mRNA expressions increased in the high-dose Bushen Tiaojing Formula group， and Caspase-12， Caspase-3， Bax protein levels and their mRNA expressions increased in the low-dose formula group （P＜0.05 or P＜0.01）. ConclusionBushen Tiaojing Formula can inhibit the apoptosis of blastocyst cells caused by repeated controlled ovarian stimulation by improving endoplasmic reticulum stress， which plays a role in improving the quality of early embryos.

Voriconazole is a broad spectrum triazole antifungal agent, widely used in the prevention and treatment of invasive fungal diseases.Long-term use of voriconazole can induce periostitis and cutaneous squamous cell carcinoma, accounting for serious adverse effects on patients, which has been reported in increasing clinical cases.This review is to characterize the epidemiological and clinical manifestations of periostitis and squamous cell carcinoma induced by voriconazole, and to analyze the mechanisms of triggering periostitis and squamous cell carcinoma, so as to promote the rational use of voriconazole in clinics.

OBJECTIVE:To observe clinical efficacy and safety of salmeterol fluticasone combined with tiotropium bromide in the treatment of COPD via different inhalation devices.METHODS:Eighty COPD patients were selected from our hospital during Jan.2014 to Jan.2015,and then divided into trial group and control group according to random number table,with 40 cases in each group.Both groups were given Salmeterol fluticasone inhalant 500 μg,bid+Tiotropium bromide inhalant 18 μg,qd.Control group was given medicine via inhalation device coming with medicine,while trial group was given medicine via gas compression type ultrasonic spray inhalator.Both groups were treated for 1 year.Blood concentration of medicine 0.5 h after medication,mMRC score and COPD acsessment test (CAT) score 3,6,9 months after treatment,the times of acute exacerbation during treatment,FEV1％ before and af ter treatment were all observed in 2 groups.The occurrence of ADR was recorded.RESULTS:Four cases withdrew from trial group and 1 case from control group.After medication,there was no statistical significance in blood concentration of fluticasone,salmeterol and tiotropium bromide between 2 groups (P＞0.05).0.5 h after medication,mMRC score of trial group was slightly lower than that of control group,without statistical significance (P＞0.05);CAT score of it was significantly lower than that of control group,with statistical significance (P＜0.05).The times of acute exacerbation in trial group during treatment was significantly less than control group,with statistical significance (P＜0.05).The decrease of FEV1％ in trial group was slightly lower than control group,without statistical significance (P＞0.05).The incidence of ADR in trial group was significantly lower than control group,with statistical significance (P＜0.05).CONCLUSIONS:For COPD patients,salmeterol fluticasone combined with tiotropium bromide via gas compression type ultrasonic spray inhalator is better than inhalation device coming with medicine in clinical efficacy and safety.

Objective To explore the characteristics of blood oxygen level dependent (BOLD) magnetic resonance imaging (MRI) in healthy native kidneys. To investigate the relationship between BOLD-MRI and common physiological in-dexes. Methods GE 3.0T MRI scanner and Torsopa phased-array coil were employed to acquire renal coronal T1WI and BOLD image. Ninety patients who were ruled out chronic kidney diseases underwent BOLD-MRI with T2*-spoiled gradient recalled echo (T2*SPGR) sequence. BOLD images were analyzed on R2*map software. Cortical and medullary R2*values were analyzed in bilateral kidneys and in different gender. Different regional R2*values in cortex and medulla were also ana-lyzed. Physiological indices including age, body height and weight, body mass index (BMI), body surface area (BSA), estimat-ed glomerular filtration rate (eGFR) were recorded. Correlation between R2*value and physiological indices were analyzed. Results Bilateral renal cortical R2*values [left (16.56±1.40) Hz and right (16.66±1.28)Hz, respectively] were less than val-ues in medulla [left (28.82±3.71)Hz and right (28.36±3.72)Hz, respectively]. Female and male cortical R2*values [female (16.55±1.30Hz) and male (16.66±1.38)Hz, respectively] were also less than corresponding values in medulla [female (28.46± 3.64) Hz and male (28.70±3.78) Hz, respectively]. In bilateral renal medullary region, R2*values in low pole (27.29±3.05) Hz was less than values in middle (29.32±3.47) Hz and upper pole (29.16±4.21)Hz (F=15.184, P<0.001). Age was positive-ly correlated with R2* values in medulla (r =0.284, P =0.002). However, eGFR was negatively correlated with medullary R2*value (r=-0.232, P=0.007). Conclusion R2*values reflected the levels of renal partial pressure of oxygen and as-sessed the degree of renal ischemia. BOLD MRI could offer a simple, convenient and noninvasive method for to evaluate renal oxygen metabolism in cortex and medulla.

This paper explored the multi-angle, comprehensive and systematic clinical prac-tice teaching system for international students. Six teaching methods were integrated: bedside teach-ing, standardized patients teaching, electronic patients clinic teaching, Chinese students one-to-one help foreign students, a variety of English clinic small presentation and many after-school social activi-ties. The multi-angle, comprehensive and systematic clinical practice teaching system was evidently a better choice than traditional teaching system for international students.

Objective To profile the omp1 genotypes of Chlamydia trachomatis (Ct) in patients with nongonococcal urethritis (cervicitis) in Guangzhou region. Methods Swab samples were obtained from the urethra of males and cervix of females in clinical settings of venereology and gynecology as well as at outreach sites for the prevention and control of sexually transmitted diseases (STDs). DNA was extracted from the swabs and nested PCR was performed to amplify the variable domain (VD) 1 - 3 of omp1 gene of Ct followed by gene sequencing. The genotypes of Ct were determined based on the amino acid mutation in VD 1 - 2 of omp1 gene. Results Totally, 1208 swabs were collected. Of them, 132 were Ct positive, and 130 positive samples underwent genotyping. Ten ompl genotypes were determined in total, including serotype E (38, 29.23%), D (25, 19.23%), J(24, 18.46%), F(21, 16.15%), G(7, 5.38%), H(5, 3.85%), K(5, 3.85%), B(2, 1.54%), Ja (2, 1.54%), I (1, 0.77%). E, D, J and F were the dominant type of Ct in this region, and amounted to 83% of all the Ct isolates. Mutations were observed within VD 1 and 2 of omp1 gene in serotype D, B and K.Serotypes were undetermined for Ct in 2 patients with mixed infection. Conclusions In Guangzhou region, E,D, F and J are the predominant genotypes of Ct, and amount to 83% of all the Ct isolates. Ct serotype B is also observed in the urethra of males and cervix of females in this region.

In order to confirm the alteration and significance of cigarette smoke exposure on SP-A in rats, 20 Wistar rats were assigned randomly to two groups: an N group (n=10), and an S group (n=10). The ultra-structural change was observed by electron microscopy. The number of cells positive for SPA was by immunohistochemically measured. The mRNA expression in the lung tissues was determined by reverse transcription polymerase chain reaction (RT-PCR). The number of cells positive for SPA of the S group (0.52 +/- 0.05) was lower than that of the N group (0.72+/-0.06) (P<0.05). The levels of mRNA of SPA in the lung tissues of the S group (0.3522+/-0.0512) was significantly lower than that of the N group (0.4432+/-0.05628) (P<0.05). It is concluded that cigarette smoke alone decreased the level of SP-A and that might have an important effect on surfactant metabolism and the host defense functions of surfactant in the peripheral airways, which might play a crucial role in the development of chronic obstructive lung disease.
Gene Expression Regulation ; Immunohistochemistry/methods ; Lung/metabolism ; Microscopy, Electron ; Pulmonary Surfactant-Associated Protein A/*biosynthesis ; RNA, Messenger/metabolism ; Rats, Wistar ; Reverse Transcriptase Polymerase Chain Reaction ; Smoking/*adverse effects ; Tobacco Smoke Pollution/*adverse effects

In order to confirm the alteration and significance of cigarette smoke exposure on SP-A in rats, 20 Wistar rats were assigned randomly to two groups: an N group (n=10), and an S group (n=10). The ultra-structural change was observed by electron microscopy. The number of cells positive for SPA was by immunohistochemically measured. The mRNA expression in the lung tissues was deter-mined by reverse transcription polymerase chain reaction (RT-PCR). The number of cells positive for SPA of the S group (0.52±0.05) was lower than that of the N group (0.72±0.06) (P<0.05). The lev-els of mRNA of SPA in the lung tissues of the S group (0.3522±0.0512) was significantly lower than that of the N group (0.4432±0.05628) (P<0.05). It is concluded that cigarette smoke alone decreased the level of SP-A and that might have an important effect on surfactant metabolism and the host deense functions of surfactant in the peripheral airways, which might play a crucial role in the devel-opment of chronic obstructive lung disease.