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.

Threatened abortion is a common disease of obstetrics and gynecology and one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in TCM obstetrics and gynecology， Western medicine obstetrics and gynecology， and pharmacology to deeply discuss the advantages of TCM and integrated Chinese and Western medicine treatment as well as the medication plans for threatened abortion. After discussion， the experts concluded that chromosome， endocrine， and immune abnormalities were the key factors for the occurrence of threatened abortion， and the Qi and blood disorders in thoroughfare and conception vessels were the core pathogenesis. In the treatment of threatened abortion， TCM has advantages in preventing miscarriages， alleviating clinical symptoms and TCM syndromes， relieving anxiety， regulating reproductive endocrine and immune abnormalities， personalized and diversified treatment， enhancing efficiency and reducing toxicity， and preventing the disease before occurrence. The difficulty in diagnosis and treatment of threatened abortion with traditional Chinese and Western medicine lies in identifying the predictors of abortion caused by maternal factors and the treatment of thrombophilia. Recurrent abortion is the breakthrough point of treatment with integrated traditional Chinese and Western medicine. It is urgent to carry out high-quality evidence-based medicine research in the future to improve the modern diagnosis and treatment of threatened abortion with TCM.

Objective:To investigate the effect of different concentrations and infection durations of varicella-zoster virus (VZV) on nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3) inflammasome-related proteins in mouse brain astrocytes.Methods:Mouse brain astrocytes were infected with different dilutions (10 0 [undiluted original concentration] - 10 -7) of cell-free VZV suspension, and the cytopathic effect was observed under a microscope in each group to determine the concentration and infection duration of VZV for subsequent experiments. Some mouse brain astrocytes were infected with cell-free VZV suspension at dilutions of 10 0, 10 -2, 10 -4, and 10 -6, and samples were collected on day 5; some other mouse brain astrocytes were infected with cell-free VZV suspension at the median tissue culture infective dose (TCID 50) of 1.0 × 10 5/ml, and the samples were collected on days 3, 5, 7, and 9, separately; normally cultured mouse brain astrocytes served as control groups in the above experiments. Western blot analysis was performed to determine the protein expression of VZV glycoprotein E (gE), NLRP3, caspase-1, and interleukin-1β (IL-1β) in mouse brain astrocytes in each group. One-way analysis of variance was used for comparisons of data with a normal distribution, and least significant difference- t test was used for multiple comparisons. Results:On day 3 after infection with VZV at the dilution of 10 0, the number of cells decreased, some cells became irregular, lost their original shapes, and showed granular cytoplasm and an unclear nucleus structure, while some cells fused and formed multinucleated giant cells; on day 5, ≥ 50% of cells showed the aforementioned changes and some intercellular spaces were dilated giving a network-like appearance in the 10 0-dilution group; on day 9, the 10 0- - 10 -6- dilution groups all showed dilated intercellular spaces arranged in networks and cytopathic effect in ≥ 50% of cells; on day 10, some cells in the control group exhibited cytoplasmic vacuolation, exfoliation and flotation. Based on these results, the following experiments were conducted with VZV at a concentration gradient ranging from 10 0 to 10 -6 dilutions, and the observations were performed from day 3 to day 9. Western blot analysis showed increased protein expression of VZV gE, NLRP3, caspase-1, and IL-1β in the VZV infection groups compared with the control group, and there were significant differences among different VZV concentration groups ( F = 21.45, 43.82, 21.85, 29.53, respectively, all P < 0.05) and different infection duration groups ( F = 224.10, 78.79, 186.50, 85.08, respectively, all P < 0.05). With the increasing dilution ratios, the expression of inflammasome-related proteins (NLRP3, caspase-1, and IL-1β) decreased, with the highest expression observed in the 10 0-dilution group and the lowest in the 10 -6-dilution group (all P < 0.05). On days 3, 5, and 7 after VZV infection, the expression of NLRP3 inflammasome-related proteins increased over time, with the highest expression observed on day 7 and the lowest on day 3 (all P < 0.05), while their expression decreased on day 9. Conclusion:The expression of NLRP3 inflammasome-related proteins was up-regulated in mouse brain astrocytes after VZV infection, and their expression levels increased along with the increase in the VZV concentration and infection duration in a certain range.

Objective To investigate the effect of dietary intake on the childbirth outcomes of primipara women with full-term labor analgesia. Methods A total of 400 primipara women with full-term labor analgesia were randomly divided into observation group and control group. The observation group received intake management and individualized dietary guidance, while the control group ate and drank according to their own wishes. The childbirth quality, the incidence of vomiting, the use of oxytocin due to uterine atony, the rate of intrapartum fever, the rate of perineal incision, the rate of cesarean section, the rate of vaginal assisted delivery, and the rate of postpartum hemorrhage were compared between the two groups. The duration of the first stage of labor, the duration of the second stage of labor, the duration of labor analgesia, and the amount of postpartum hemorrhage within 2 hours were also compared. Neonatal Apgar score, random blood glucose, umbilical artery blood pH value, umbilical artery blood lactic acid (Lac) value, the incidence of neonatal asphyxia, the incidence of neonatal fever, and the incidence of neonatal hypoglycemia were compared between the two groups. Results The observation group had lower incidences of vomiting, oxytocin use rate due to uterine atony, intrapartum fever rate, perineal incision rate, transferring cesarean section rate, and vaginal assisted delivery compared to the control group(P < 0.05). The observation group had lower rates of postpartum hemorrhage, shorter duration of the first and second stages of labor, shorter duration of labor analgesia, and less postpartum hemorrhage within 2 hours compared to the control group, and the incidences of neonatal hyperglycemia and hypoglycemia in the observation group were lower than those in the control group (P < 0.05). There were no statistically significant differences in umbilical artery blood pH value, Lac value, neonatal Apgar score, random blood glucose, neonatal asphyxia rate, and neonatal fever rate between the two groups (P>0.05). Conclusion Intake management and individualized dietary guidance during labor can reduce the incidence of uterine atony, shorten the duration of labor, decrease the incidence of dystocia, reduce postpartum hemorrhage within 2 hours and decrease the incidence of neonatal glucose abnormality.

Objective:To identify the risk factors for intrapartum fever during labor analgesia and establish the prediction model.Methods:The medical records from pregnant women with intrapartum fever during labor analgesia were retrospectively analyzed. According to whether the highest body temperature ≥38 ℃, the parturients were divided into intrapartum fever group and non-fever group. The general data from patients, duration of hospital stay before labor, induced labor, prenatal hemoglobin concentration, body msaa index (BMI) during pregnancy, artificial rupture of membranes in the incubation period, frequency of vaginal examination and etc. were collected. The risk factors of which P values were less than 0.05 would enter the logistic regression analysis to stratify intrapartum fever-related risk factors, and the weighted score regression prediction model was established. Hosmer-Lemshow Test was used to assess the fit of the model, and the receiver operating characteristic curve was drawn to evaluate the model. The nomogram was drawn for visually presenting the regression model. The clinical calibration curve, decision curve analysis and clinical impact curve were drawn to assess the created prediction model. Results:There were 99 parturients developed fever during labor analgesia, with an incidence of 34.7%. The results of logistic regression analysis showed that duration of hospital stay before labor, prenatal hemoglobin concentrations, BMI during pregnancy, induced labor, artificial rupture of membranes in the incubation period and frequency of vaginal examination were the independent risk factors for intrapartum fever during labor analgesia. The area under the receiver operating characteristic curve was 0.943, 95% confidence interval was 0.916-0.969, the sensitivity was 86.9%, the specificity was 88.6%, and the Youden index was 0.755. The prediction model of the line chart was assessed by Hosmer-Lemshow, P=0.898. Conclusions:Duration of hospital stay before labor, hemoglobin concentrations, BMI during pregnancy, induced labor, artificial rupture of membranes in the incubation period and frequency of vaginal examination are independent risk factors for intrapartum fever during labor analgesia in parturients, and the risk prediction model developed can effectively predict the occurrence of intrapartum fever during labor analgesia.

BACKGROUND: The clinical features of enthesitis in patients with psoriatic arthritis (PsA) have been reported in some Western countries, but data in China are very limited. This study aimed to describe the characteristics of enthesitis in Chinese patients with PsA and compared them with those in other cohorts. METHODS: Patients with PsA enrolled in the Chinese Registry of Psoriatic Arthritis (CREPAR) (December 2018 to June 2021) were included. Data including demographics, clinical characteristics, disease activity measures, and treatment were collected at enrollment. Enthesitis was assessed by the Spondyloarthritis Research Consortium of Canada (SPARCC), Maastricht ankylosing spondylitis enthesitis score (MASES), and Leeds enthesitis index (LEI) indices. A multivariable logistic model was used to identify factors related to enthesitis. We also compared our results with those of other cohorts. RESULTS: In total, 1074 PsA patients were included, 308 (28.7%) of whom had enthesitis. The average number of enthesitis was 3.3 ± 2.8 (range: 1.0-18.0). More than half of the patients (165, 53.6%) had one or two tender entheseal sites. Patients with enthesitis had an earlier age of onset for both psoriasis and arthritis, reported a higher proportion of PsA duration over 5 years, and had a higher percentage of axial involvement and greater disease activity. Multivariable logistic regression showed that axial involvement (odds ratio [OR] 2.21, 95% confidence interval [CI], 1.59-3.08; P <0.001), psoriasis area and severity index (PASI) (OR: 1.03, 95% CI: 1.01-1.04; P = 0.002), and disease activity score 28-C reactive protein (DAS28-CRP) (OR: 1.25, 95% CI: 1.01-1.55; P = 0.037) were associated with enthesitis. Compared with the results of other studies, Chinese patients with enthesitis had a younger age, lower body mass index (BMI), a higher rate of positive human leukocyte antigen (HLA)-B27, more frequent dactylitis, and a higher proportion of conventional synthetic disease-modifying antirheumatic drugs' (csDMARDs) use. CONCLUSIONS Enthesitis is a common condition among Chinese patients with PsA. It is important to evaluate entheses in both peripheral and axial sites.
Humans ; Arthritis, Psoriatic/drug therapy* ; East Asian People ; Enthesopathy/complications* ; Registries ; Severity of Illness Index ; Spondylarthritis/epidemiology*

Objective:To investigate effects of the autophagy inducer rapamycin and autophagy inhibitor 3-methyladenine on viral structures and biosynthesis of functional proteins in dorsal root ganglia in a guinea pig model of varicella-zoster virus (VZV) infection, and to explore their possible mechanisms.Methods:VZV was cultured and proliferated in human embryonic lung fibroblasts (HELFs) , and peripheral blood mononuclear cells (PBMCs) were isolated from guinea pigs. VZV-HELFs and PBMCs were co-cultured for 18-20 hours, and VZV-PBMCs were collected by centrifugation. Thirty-two guinea pigs were randomly and equally divided into 4 groups (8 mice in each group) : blank control group was injected with autologous PBMCs via the medial canthal venous plexus; autophagy inhibition group, autophagy induction group, and VZV infection group were intraperitoneally injected with 3 mg/kg 3-methyladenine solution, 0.5 mg/kg rapamycin solution, and the same volume of 0.9% NaCl solution respectively, followed 2 hours later by injections with 50 μl of VZV-PBMCs via the medial canthal venous plexus. Fourteen days later, the guinea pigs in each group were sacrificed, and dorsal root ganglion tissues were collected. The transmission electron microscope was used to observe the morphology of virus particles, as well as the morphology and number of autophagic vesicles, Western blot analysis was performed to determine the expression of VZV nucleocapsid protein (NCP) , immediate-early protein 62 (IE62) , and autophagy-related proteins Beclin-1 and p62, and immunohistochemical study to determine the expression of anti-VZV antibodies in VZV-infected dorsal root ganglia. Statistical analysis was carried out by using two-independent-sample t test, one-way analysis of variance, least significant difference- t test or Kruskal-Wallis H test. Results:Nucleocapsid-containing virions and scattered autophagosomes were seen in the dorsal root ganglia in the VZV infection group under the transmission electron microscope. The number of autophagic vesicles significantly differed among the blank control group, VZV infection group, autophagy induction group and autophagy inhibition group ( M[ Q1, Q3]: 0, 5[4, 6], 7[5, 9], 0, respectively; H = 135.60, P < 0.01) , and was significantly higher in the VZV infection group than in the blank control group and autophagy inhibition group (both P < 0.05) , as well as in the autophagy induction group than in the autophagy inhibition group ( P<0.05) , but there was no significant difference between the VZV infection group and autophagy induction group ( P>0.05) . Western blot analysis showed that the expression level of IE62 protein was significantly higher in the VZV infection group (1.49 ± 0.06) than in the blank control group (0.50 ± 0.09, t = 9.17, P < 0.05) ; the expression of anti-VZV antibodies was significantly lower in the autophagy inhibition group than in the autophagy induction group and VZV infection group ( t = 9.24, 7.78, respectively, both P < 0.01) , while there was no significant difference between the autophagy induction group and VZV infection group ( P > 0.05) . Conclusion:Autophagy occurred in the dorsal root ganglia of guinea pigs after VZV infection; the inhibition of autophagy could affect the structure of VZV and decrease the expression of VZV functional proteins in the dorsal root ganglia of guinea pigs.

Objective:To investigate the correlation of interferon (IFN) -γ rs2430561 single nucleotide polymorphisms (SNPs) and serum IFN-γ levels with susceptibility to herpes zoster.Methods:Blood samples were collected from 74 patients with herpes zoster and 40 healthy controls in General Hospital of Southern Theatre Command and the Fifth People Hospital of Hainan Province from November 2019 to November 2020. PCR and Sagner resequencing were conducted to detect the IFN-γ rs2430561 SNPs in the subjects, fluorescence-based quantitative PCR was performed to determine the copy number of varicella-herpes zoster virus (VZV) DNA in the serum of the patients with herpes zoster, and enzyme-linked immunosorbent assay was conducted to detect the serum IFN-γ level. Measurement data were compared by using t test or non-parametric test, and enumeration data by using chi-square test or Fisher′s exact test. Results:As rs2430561 genotyping showed, there were 4 patients with AA genotype, 37 with TT genotype and 33 with TA genotype in the herpes zoster group, as well as 13 subjects with TA genotype and 27 with TT genotype in the healthy control group, and the frequency of A allele of rs2430561 was significantly higher in the herpes zoster group (27.70%) than in the control group (16.25%, P=0.036) . The serum IFN-γ level ( M[ P25, P75]) was significantly lower in the herpes zoster group (33.45[0.80, 95.01]pg/ml) than in the control group (67.83[2.74, 318.35]pg/ml, U=1 822, P=0.028) . The VZV DNA copy number (expressed as a logarithm to the base of 10) per milliliter was 3.23 ± 0.71 in the serum of the patients with herpes zoster, and the serum IFN-γ level was negatively correlated with the VZV DNA copy number ( r=-0.302, P=0.009) . Conclusion:The carriage of rs2430561 A allele may affect the expression of IFN-γ, leading to higher susceptibility to herpes zoster.

Objective: To observe changes in expression of autophagy proteins in peripheral CD4⁺ T lymphocytes and the epidermis of skin lesions, as well as generation of autophagy vesicles in epidermal cells in skin lesions of patients with herpes zoster, and to explore the relationship between varicella-herpes zoster virus (VZV) infection and autophagy. Methods: Totally, 35 patients with herpes zoster were enrolled from Department of Dermatology, General Hospital of Southern Theater Command of PLA between December 2017 and December 2018, including 20 males and 15 females. Their age ranged from 18 to 79 (59.23 ± 9.27) years, pain duration was 5.14 ± 2.28 days, and lesion duration (from the onset of the lesion to the clinic visit) was 3.45 ± 1.77 days. Flow cytometry was performed to determine the expression of autophagy proteins including microtubule-associated protein 1 light chain 3B (LC3B) , Beclin-1 and p62 in peripheral blood CD4⁺ T lymphocytes of these patients. Thirty healthy adults served as control group. Lesional skin tissues were obtained from 12 patients with herpes zoster, and perilesional normal skin tissues of the same patient served as the control. Immunohistochemical study was conducted to determine the expression of autophagy proteins LC3B, Beclin-1 and p62 in epidermal tissues, and transmission electron microscopy to observe the generation of autophagy vesicles in epidermal cells. Two independent-sample t-test was carried out for intergroup comparison. Results: The expression rates of autophagy proteins LC3B and Beclin-1 in peripheral CD4⁺ T lymphocytes were significantly higher in the herpes zoster group (61.23% ± 7.61%, 35.84% ± 4.22%, respectively) than in the control group (36.56% ± 4.27%, 15.34% ± 1.89%, respectively; t = 15.75, 24.56 respectively, both P < 0.01) , while the expression rate of p62 (5.75% ± 0.67%) was significantly lower in the herpes zoster group than in the control group (10.03% ± 1.15%, t = 18.65, P < 0.01) . Among the 12 patients with herpes zoster, the expression levels of LC3B and Beclin-1 in the epidermis were significantly higher in the skin lesions than in the perilesional normal skin tissues (t = 2.86, 4.58, P < 0.05) , but the expression level of p62 was significantly lower in the skin lesions than in the perilesional normal skin tissues (t = 2.43, P < 0.05) . Transmission electron microscopy showed formation of autophagy vesicles containing virus particles in epidermal cells in the skin lesions of 12 patients with herpes zoster, and vesicle counts were significantly higher in the skin lesions than in perilesional normal skin tissues (t = 9.67, P < 0.01) . Conclusion The autophagy level was elevated in peripheral CD4⁺ T lymphocytes and epidermis of skin lesions of patients with herpes zoster.

Objective:To evaluate the effect of imatinib on growth impairment in children with chronic myeloid leukemia (CML-CP) in the chronic phase.Methods:From July 2018 to July 2019, questionnaires were distributed to CML children aged <18 years at the time of diagnosis who were receiving imatinib for at least 3 months or to their parents in China. The height-for-age standard deviation score (HtSDS) and the difference of standard deviation integral (△HtSDS) were used to explore the change in height with imatinib therapy.Results:The data of 238 respondents were included; 138 (58.0% ) respondents were men. The median age at the first diagnosis of CML was 11.0 years (range, 1.4-17.9 years) , and 93 (39.0% ) respondents were at the prepuberty stage. At the time of completing the questionnaires, the median age was 15.0 years (range, 2.0-34.0 years) . The median duration of imatinib therapy was 28 months (range, 3-213 months) . Among all the respondents, the mean HtSDS when completing the questionnaires (-0.063±1.361) was significantly lower than that at the time of starting imatinib treatment (0.391±1.244) ( P<0.001) . Total 71.0% respondents showed growth impairment that was more common in those starting imatinib therapy at prepubertal age than in those starting at pubertal age. Multivariate analysis showed that younger at the start of imatinib therapy ( P<0.001) and longer duration of imatinib therapy ( P<0.001) were significantly associated with severe growth impairment on imatinib therapy. Conclusions:Imatinib induced growth impairment in children with CML-CP. Younger the age of initiation and longer the duration of imatinib therapy, more obvious the effect of imatinib on growth impairment.