Clinicopathological and prognostic significance of PD-L1 and TIM-3 expression in medullary thyroid carcinoma: a retrospective immunohistochemistry study.

PURPOSE: Expression of the programmed death-ligand 1 (PD-L1) and T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) in medullary thyroid carcinoma (MTC) has been controversial and rarely reported. METHODS: Surgical specimens of 190 MTC patients who had initial curative-intent surgery were collected. Immunohistochemistry of PD-L1 and TIM-3 was performed using 22C3 pharmDx (Dako, Carpinteria, CA) and anti-TIM-3 (1:500, ab241332, Abcam). Stained slides were scored using a combined positive score (CPS) with a cutoff of ≥ 1. We established correlations between PD-L1 expression, TIM-3 expression, clinicopathological, and survival data. RESULTS: 13 cases (13/190, 6.84%) were positive for PD-L1 expression, and 42 cases (42/154, 27.27%) for TIM-3 expression. PD-L1 expression was correlated to TIM-3 expression (P = 0.002), but was not related to overall survival (OS) or progression-free survival (PFS). TIM-3 expression was correlated to perineural invasion (P = 0.040). Multivariate Cox analysis showed that lymphovascular invasion (LVI) was independently associated with OS. And tumor size, LVI, and lymph node metastases were significantly associated with PFS. Furthermore, the multivariate logistic analysis showed multifocal status, LVI, pathological T stage and lymph node metastasis were independent risk factors for biochemical recurrence/persistent disease. CONCLUSIONS: We demonstrated that PD-L1 and TIM-3 expression were not frequent in MTC and were not associated with survival prognosis. Our results should be considered when clinical trials of PD-L1 or TIM-3 blockades are implemented.

Dung treated by high-temperature composting is an optimal bedding material for suckling calves according to analyses of microbial composition, growth performance, health status, and behavior.

Bedding materials are important for suckling buffalo calves. Treated dung has been used as a bedding material for dairy cows but the lack of an appropriate safety assessment limits its application. In this study, we evaluated the feasibility of treated dung (TD) as a bedding material for suckling calves by comparing TD with rice husk (RH) and rice straw (RS) bedding materials. The TD was prepared through high-temperature composting by Bacillus subtilis. Thirty-three newborn suckling buffalo calves (Bubalus bubalis, 40.06 ± 5.79 kg) were randomly divided into 3 bedding material groups (TD, RH, and RS) and bedded with 1 of the 3 bedding materials for 60 d. We compared cost, moisture content, bacterial counts, and microbial composition of the 3 bedding materials, and investigated growth performance, health status, behavior, rumen fermentation, and blood parameters of bedded calves. The results showed that TD contained the fewest gram-negative bacteria and coliforms on d 1 and 30 and the lowest relative abundance of Staphylococcus throughout the experiment. The RH and TD bedding materials had the lowest cost. Calves in the TD and RS groups showed a higher dry matter intake, and final body weight and average daily gain in the TD and RS groups tended to be higher than in the RH group. Calves in the TD and RS groups had a lower disease incidence (diarrhea and fever), fewer antibiotic treatments, and lower fecal score than calves in the RH group. Higher contents of IgG, IgA, and IgM were observed in calves of the TD and RS groups than in calves of the RH group on d 10, indicating higher immune ability in TD and RS groups. Furthermore, TD bedding increased the butyric acid content in the calf's rumen, whereas RS bedding increased the acetate content, which might be attributed to the longer time and higher frequency of eating bedding material in the RS group. Considering all of the above indicators, we concluded that TD is the optimal bedding material for calves based on economics, bacterial count, microbial diversity, growth performance, and health status. Our findings provide a valuable reference for bedding material choice and calf farming.

[Surgical management strategies of thulium laser enucleation of the prostate in different prostate volumes].

As the good functions of cutting, vaporization and hemostasis, the thulium laser has high safety and effectiveness in the enucleation of prostate. The surgery strategy of thulium laser also changes when enucleating different volumes of the prostate. In this paper, the prostate volume is divided into three types: small volume (<40 ml), moderate volume (40-80 ml), and large volume(>80 ml). The surgical strategies of thulium laser enucleation of the prostate in three different prostate volumes are discussed respectively. The operative techniques of thulium laser and preventive measures for complications are emphasized to cope with complex situations and provide reference for clinicians.

[Analysis on the vaccination coverage of 13-valent pneumococcal conjugate vaccine in China from 2017 to 2021].

Objective: To explore the vaccination coverage of the 13-valent pneumococcal conjugate vaccine (PCV13) in China from 2017 to 2021. Methods: Using the reported number of PCV13 administrated doses from 2017 to 2021 and the population data from 31 provinces in China, which were collected by the Immunization Program Information System and summarized data at different levels (prefecture, provincial, and national). Collecting batch release data of PCV13 during the same period through the official website of the National Institutes for Food and Drug Control. The average coverage level of PCV13 was calculated by comparing the number of PCV13 vaccinations reported annually to the number of births in that year, and the spatial auto-correlation analysis was conducted in 2021 at the prefecture level. The coverage of PCV13 vaccination was estimated by the total vaccine doses administered each year divided by the number of newborn in the year, as of the administrated dose number per 100 people. Results: From March 2017 to December 2020, the total batch release of PCV13 was 20.06 million, with a total of 71.54, 384.75, 475.45, and 10.8886 million doses each year. During the same period, PCV13 reported doses were 20.2369 million and the vaccination doses from 2017 to 2021 were 4.08, 170.46, 407.52, 599.77, and 8.4185 million doses, respectively. From 2017 to 2021, the ratio of PCV13 doses administrated per 100 infants in each year was 0.25, 10.26, 23.81, 38.16, and 69.90 doses per 100 people, respectively. The range of the ratio in each province increased from 3.85 doses in 2017 to 264.41 doses per 100 people in 2021. The spatial auto-correlation analysis results showed that based on prefecture-level cities, there was spatial clustering in a certain area of PCV13 coverage from 2017 to 2021, and the spatial correlation in 2021 was the highest. The hotspot analysis showed that the hotspot areas with high coverage levels of PCV13 were concentrated in Jiangsu, Zhejiang, Shanghai, Fujian and their surrounding areas. The cold spots with low vaccine coverage were concentrated in Yunnan, Qinghai, Tibet, and their surrounding areas. Conclusion: The average coverage level of PCV13 is low in China with significant regional differences.

Deep Underground Laboratory Measurement of

The ^{13}C(α,n)^{16}O reaction is the main neutron source for the slow-neutron-capture process in asymptotic giant branch stars and for the intermediate process. Direct measurements at astrophysical energies in above-ground laboratories are hindered by the extremely small cross sections and vast cosmic-ray-induced background. We performed the first consistent direct measurement in the range of E_{c.m.}=0.24 to 1.9 MeV using the accelerators at the China Jinping Underground Laboratory and Sichuan University. Our measurement covers almost the entire intermediate process Gamow window in which the large uncertainty of the previous experiments has been reduced from 60% down to 15%, eliminates the large systematic uncertainty in the extrapolation arising from the inconsistency of existing datasets, and provides a more reliable reaction rate for the studies of the slow-neutron-capture and intermediate processes along with the first direct determination of the alpha strength for the near-threshold state.

[Interpretation of defeating meningitis by 2030: a global road map].

Meningitis is a life-threatening disease. In order to reduce its threat to public health, the World Health Assembly indorsed a resolution in 2020 for urgent global action to prevent and control meningitis. Defeating Meningitis by 2030: a Global Roadmap was officially launched by the World Health Organization in 2021. We interpreted some key information of the roadmap from the aspects of coverage, objectives and pillar strategies, providing ideas for further strengthening the prevention and control of bacterial meningitis in China.

Increased expression of CXCL2 in ACPA-positive rheumatoid arthritis and its role in osteoclastogenesis.

Anti-citrullinated protein/peptide antibodies (ACPA) play important roles in the pathogenesis of rheumatoid arthritis (RA). ACPA-positive (ACPA+ ) and ACPA-negative (ACPA- ) RA were suggested to be different disease subsets, with distinct differences in genetic variation and clinical outcomes. The aims of the present study were to compare gene expression profiles in ACPA+ and ACPA- RA, and to identify novel candidate gene signatures that might serve as therapeutic targets. Comprehensive transcriptome analysis of peripheral blood mononuclear cells (PBMCs) from ACPA+ and ACPA- RA patients and healthy controls was performed via RNA sequencing. A validation cohort was used to further investigate differentially expressed genes via polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Spearman's correlation test was used to evaluate the correlation of differentially expressed genes and the clinical and laboratory data of the patients. The role of differentially expressed genes in osteoclastogenesis was further investigated. Expression of C-X-C motif chemokine ligand 2 (CXCL2) was significantly increased in ACPA+ RA than in ACPA- RA, which was validated in PBMCs and serum. CXCL2 promoted the migration of CD14+ monocytes and increased osteoclastogenesis in RA patients. RAW264.7 macrophages were used to investigate specific mechanisms, and the results suggested that CXCL2 stimulated osteoclastogenesis via extracellular receptor kinase (ERK) mitogen-activated protein kinase (MAPK) and nuclear factor kappa B pathways. In conclusion, CXCL2 was highly expressed in ACPA+ RA than in ACPA- RA. CXCL2 promoted osteoclastogenesis and was related to bone erosion in RA, which suggests that the blockade of CXCL2 might be a novel strategy for the treatment of RA.

Climate and air pollution exposure are associated with thyroid function parameters: a retrospective cross-sectional study.

OBJECTIVES: There are still controversies about the impact of climatic and environmental factors on thyroid function parameters in healthy populations. We investigated the relationships between climate, air pollution exposure, and thyroid function fluctuations. METHODS: We retrospectively reviewed 327,913 individuals attending routine health checks from December 2013 to December 2018. We analyzed the associations between thyroid function and climatic factors using Spearman's correlation analysis. We explored the relationships between thyroid function and air pollution exposure using multiple linear regression analysis, after adjusting for age, sex, season, and outdoor temperature. We also performed subgroup analyses by age and sex and sensitivity analyses of different anti-thyroid peroxidase antibody status. RESULTS: Thyroid-stimulating hormone (TSH) and free triiodothyronine (FT3) were negatively associated with outdoor temperature (r = - 0.66, P < 0.001; r = - 0.55, P < 0.001), while free thyroxine (FT4) and FT4/FT3 were positively associated with temperature (r = 0.35, P < 0.001; r = 0.79, P < 0.001). An increase of 10 µg/m3 in fine particulate matter ≤ 2.5 µm (PM2.5) was associated with a decrease of 0.12 pmol/L in FT4 and an increase of 0.07 pmol/L in FT3 (both P < 0.01). FT4/FT3 was significantly negatively associated with PM2.5 (coefficient: - 0.06, P < 0.01). These results remained robust in hierarchical analyses and sensitivity analyses. CONCLUSIONS: Thyroid function parameters are associated with climate and air pollution exposure. These factors may influence variations in thyroid function. Our results also highlight the importance of public health interventions to reduce air pollution.

[Clinical features and risk factors of metabolic syndrome in adult hypopituitary patients].

Objective: To investigate the clinical features and risk factors of metabolic syndrome (MS) in adult hypopituitary patients (HP). Methods: Patients diagnosed with HP in the outpatient or inpatient department of the endocrinology department in West China Hospital from January,2012 to December,2019 were selected as the experimental group (HP group), and patients with normal pituitary function treated for saddle lesions were selected as the control group. HP patients with or without MS were divided into MS group and non-MS group HP patients were divided into four groups according to the level of growth hormone by the quartile method (GH>0.35 µg/L、0.13 µg/L0.35 µg/L、0.13 µg/L

[Considerations on vaccines and immunization against COVID-19 for epidemic control in China].

The Delta variant of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a new global wave of the Coronavirus Disease 2019 (COVID-19) pandemic. COVID-19 vaccines currently available in China show high effectiveness against severe illness and death. However, transmission of the virus is not fully stopped by vaccination alone, therefore, integrated vaccination and non-pharmacological interventions is necessary to prevent and control the epidemic in the near future. Further expanded vaccine coverage of primary doses as well as booster shots in China's domestic population are needed to reduce severe illness and death. In order to provide evidence necessary for adjusting and optimizing immunization strategies and pandemic control measures, it is essential to conduct research on vaccine effectiveness against emerging variants, persistence of vaccine-induced protection, surveillance of adverse event following immunization with large-scale vaccine use, and modelling studies on strategic combinations of vaccination and non-pharmacological interventions.

[Clinical characteristics and prognosis of young (<35 years) patients with acute ST-segment elevation myocardial infarction].

Objective: To analyze the risk factors and clinical characteristics as well as long-term prognosis of young patients (aged 18-35 years) with acute ST-segment elevation myocardial infarction (STEMI). Methods: In this retrospective study, from January 2007 to December 2017, STEMI patients who were hospitalized in Beijing Anzhen Hospital, Capital Medical University and younger than 45 years old were collected. Patients were divided to the 18-35 years old group and 36-44 years old group. The basic information of patients, clinical laboratory results, surgical information and discharge diagnosis of enrolled patients were extracted from the electronic medical record system. Subgroup analysis on STEMI patients aged 18 to 35 years was performed to compare the clinical features and outcome of patients with normal coronary angiography or stenotic coronary angiography. Results: 496 patients (20.3%) were between 18 and 35 years old, 480 cases (96.8%) were men, and 371 cases (74.8%) were smokers. The proportion of hypertension and diabetes was lower, but percent of obese (122 cases (43.3%)), level of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), uric acid and homocysteine ​​(Hcy) were significantly higher in patients aged 18 to 35 years compared with STEMI patients aged 36 to 44 years (all P<0.05). In the 18-35 years old group, there were 53 patients (10.7%) with normal coronary angiography and 443 patients (89.3%) with stenosis. The age, proportion of hypertension and diabetes, TC, LDL-C, and triglyceride (TG) levels were lower in the normal coronary angiography group than those in the coronary artery stenosis group (all P<0.05). The main coronary artery lesions were single vessel lesions (263 cases (59.4%)), and the main culprit vessels were left anterior descending artery lesions (238 cases (53.7%)). The follow-up time was 7.0 (4.0, 10.0) years, cardiovascular events were reported in 62 patients (18.9%), of which 14 patients (3.2%) died. The survival rate of patients without cardiovascular events in normal coronary angiography group was higher than that in stenosis group (P=0.029). Multivariate Cox regression analysis showed that diabetes (HR=2.713, 95%CI 1.479-4.976, P=0.001) and dyslipidemia (HR=2.819, 95%CI 1.564-5.079, P=0.001) were independent risk factors for recurrence of cardiovascular events in adult STEMI patients aged 18 to 35 years. Conclusions: STEMI patients aged 18 to 35 years were featured by male sex, obese and smokers. The proportion of hypertension and diabetes was low, while the levels of LDL-C, uric acid and Hcy were high in these patients. Coronary artery stenosis was common, and the stenosis was more likely to occur in the left anterior descending branch. Patients with normal coronary angiography had a better prognosis than those with stenosis. Diabetes and hyperlipidemia increased the risk of recurrent cardiovascular events.

[Safety and efficacy of transcatheter tricuspid valve replacement with LuX-Valve in patients with severe tricuspid regurgitation].

Objectives: To evaluate the safety and efficacy of LuX-Valve on the treatment of severe tricuspid regurgitation (TR). Methods: This is a prospective observational study. From September 2018 to March 2019, 12 patients with severe TR, who were not suitable for surgery, received LuX-Valve implantation in Changhai Hospital. LuX-Valve was implanted under general anesthesia and the guidance of transesophageal echocardiography and X-ray fluoroscopy. Access to the tricuspid valve was achieved via a minimally invasive thoracotomy and transatrial approach. Main endpoints were surgery success and device success. Surgery success was defined as successful implanting the device and withdrawing the delivery system, positioning the valve correctly and stably without severe or life-threatening adverse events. Device success was defined as satisfied valve function (TR severity reduction ≥ 2 grades, tricuspid gradient ≤ 6 mmHg (1 mmHg=0.133 kPa)), absence of malposition, valve failure and reintervention, major adverse events including device related mortality, embolization, conduction system disturbances and new onset shunt across ventricular septum at day 30 post implantation. Results: A total of 12 patients with severe to torrential TR were included in this study. The age was (68.5±6.9) years and 7 were female. All patients had typical right heart failure symptoms. Procedural success was achieved in all cases, there was no intraprocedural mortality or transfer to open surgery. TR significantly improved after LuX-Valve implantation (none/trivial in 8 patients, mild in 3 patients and moderate in 1 patient). The average device time was (9.2±4.2) minutes. Intensive care unit duration was 3.0 (2.0, 4.8) days. One patient died at postoperative day 18 due to non-surgery and device reasons. Transthoracic echocardiography at 30 days after operation showed that TR was significantly reduced (none/trivial in 8 patients, mild in 2 patients and moderate in 1 patient) and device success was achieved in 11 cases. All survived patients experienced a significant improvement in life quality with significantly improvement in New York Heart Association (NYHA) classification (Ⅰ and Ⅱ: 6/11 post operation vs. 0/11 before operation, P=0.012) and there were no device related complications in this patient cohort. Conclusions: LuX-Valve implantation is feasible, safe and effective for the treatment of patients with severe TR.

[Application of Correspondence Analysis in the Analysis of Accidental Death of Chinese Residents].

ABSTRACT: Objective To study the preference relation between residence, sex, age and causes of accidental death of Chinese residents. Methods In this study, 72 residence-sex-age groups and 8 causes of accidental death were qualitatively and quantitatively analyzed by correspondence analysis using the official statistical yearbook issued from 2014 to 2018, and the preference values were calculated. Results Among the 576 pairs of correspondences between the residence-sex-age groups and causes of accidental death, 352 pairs （61.11%） showed a preference relation （preference value>0）. In terms of residence and sex, accidental death preference among Chinese residents was higher in rural areas than in urban areas, and males were higher than females. In terms of the causes of accidental death, the overall risk of accidental mechanical asphyxia and motor vehicle accidents was the highest among all age groups of Chinese residents. In terms of age, with the increase of age, the preference value of accidental death of Chinese residents showed a trend of first increasing and then decreasing. The comparative analysis results of the preference values of various causes of accidental death in different age groups showed that motor vehicle traffic accidents, accidental poisoning, death by crush and electric shock were more likely to occur in the working age group between 20 and 59 years old, accidental fall and fire were more likely to occur in the elderly group over 80 years old, and drowning and accidental mechanical asphyxia were more likely to occur in the minor group between 1 and 19 years old. Conclusion There are different preference relations between residence-sex-age groups and causes of accidental death in China. Therefore, effective control strategies and measures should be formulated for Chinese residents with preference for accidental death.

Effects of sophorolipids on fungal and oomycete pathogens in relation to pH solubility.

AIMS: The objective of this study was to determine the effects of sophorolipids on several fungal and oomycete plant pathogens and the relationship between sophorolipids at different pH and antimicrobial activities. METHODS AND RESULTS: Sophorolipids had different solubility at different pH with a dramatic increase in solubility when pH was 6 or higher. Inhibition of mycelial growth of Phytophthora infestans by sophorolipids was affected by pH values, showing that when the pH value was higher, the inhibition rate was lower. Sophorolipids inhibited spore germination and mycelial growth of several fungal and oomycete pathogens in vitro including Fusarium sp., F. oxysporum, F. concentricum, Pythium ultimum, Pyricularia oryzae, Rhizoctorzia solani, Alternaria kikuchiana, Gaeumannomyces graminis var. tritici and P. infestans and caused morphological changes in hyphae by microscope observation. Sophorolipids reduced ß-1,3-glucanase activity in mycelia of P. infestans. In greenhouse studies, foliar application of sophorolipids at 3 mg ml-1 reduced severity of late blight of potato caused by P. infestans significantly. CONCLUSION: Sophorolipids influenced spore germination and hyphal tip growth of several plant pathogens and pH solubility of sophorolipids had an effect on their efficacy. Application of sophorolipids reduced late blight disease on potato under greenhouse conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: The findings indicated that sophorolipids have the potential to be developed as a convenient and easy-to-use formulation for managing plant diseases.

[Closed percutaneous reduction and minimally invasive treatment of spastic hammery deformity].

Objective: To investigate the efficacy of percutaneous extensor tendon reconstruction in treating spastic hammery deformity. Methods: From February 2009 to July 2018, the clinicaldata of 36 patients with fresh sputum hammer fingers treated in Jinan People's Hospital were analyzed retrospectively. The tendon was percutaneously sutured with PDS Ⅱmonofilament suture and the distal end of the tendon was fixed to the base of the distal phalanx through the bone hole. Removal of the K-wire 6 weeks after the operation, the brace was used to fix the affected finger in the dorsal extension. For 8-10 weeks, only the brace was worn at night and the flexion and extension of the affected finger was gradually strengthened.The extension and flexion function of the interphalangeal joint of the finger was compared pre and post the operation with t test. Results: A total of 36 patients were enrolled but only 33 patientswere followed up for 6 to 15 months. The hammer-shaped deformity was corrected and there was no pain when moving fingers after the operation.The straightening angle of the interphalangeal joint of the finger improved from 46.2°±6.3° before surgery to 7.5°±0.6° after (t=35.12, P<0.05). The passive straightening angle decreased from 3.2°±0.3° before surgery to 0.9°±0.2° after (t=37.11, P<0.05). According to the Crawford functional assessment: excellent in 19 fingers, good in 10 fingers, can be in 4 fingers. The excellent rate was 87.9%. There was no knot exposure, skin necrosis and other complications. Conclusions: Percutaneous resection of the extensor tendon is fixed in the basal phalanx. It is a simple and feasible minimally invasive surgery for hammer-shaped deformity. It can obviously correct the hammer-shaped deformity and has fewer complications.

[Early containment strategies and core measures for prevention and control of novel coronavirus pneumonia in China].

In December 2019, novel coronavirus pneumonia epidemic occurred in Wuhan, Hubei Province, and spread rapidly across the country. In the early stages of the epidemic, China adopted the containment strategy and implemented a series of core measures around this strategic point, including social mobilization, strengthening case isolation and close contacts tracking management, blocking epidemic areas and traffic control to reduce personnel movements and increase social distance, environmental measures and personal protection, with a view to controlling the epidemic as soon as possible in limited areas such as Wuhan. This article summarizes the background, key points and core measures in the country and provinces. It sent prospects for future prevention and control strategies.

Forensic Significance of Skin Injury and Fracture Caused by Child Abuse.

ABSTRACT: In recent years, cases of child abuse that result in injuries and death have occurred from time to time in China, and there may be more undetected child abuse cases. However, many pediatricians and forensic doctors lack professional knowledge and formal training in detecting child abuse, which leads to the missed diagnosis, misdiagnosis and misidentification of many cases of child abuse. This paper reviews a large number of relevant domestic and foreign literatures, combined with practical work experience and China's national conditions, preliminarily summarizes the main points of clinical diagnosis and forensic identification of child abuse cases, in order to provide some help for early detection, accurate identification of child abuse cases and timely and effective treatment and protection for abused children.

PAI-1 and Maspin gene evolution analysis in plateau zokor (Myospalax baileyi).

Hypoxia is one of the most obvious environmental characteristics of the Qinghai-Tibet Plateau. Increasing tissue microvessel density is an important mechanism for plateau animals to adapt to the hypoxic environment.

[Clinical characteristics of hepatic flare and efficacy of antiviral therapy in pregnant women with chronic hepatitis B virus infection].

Objective: To analyze the clinical characteristics of hepatic flare and evaluate efficacy of antiviral treatment in pregnant women with chronic HBV infection. Methods: A single-center, open-label, prospective study was conducted, and pregnant women with chronic HBV infection were enrolled. Liver function, HBV serum markers and HBV DNA of pregnant women with chronic HBV infection were reviewed during every 4 to 12 weeks of gestation period. The proportion and clinical characteristics of hepatitis flare during pregnancy were observed. Logistic regression analysis was used to predict hepatic flare in pregnant women with chronic HBV infection. Antiviral therapy with telbivudine (LdT) or tenofovir dipivoxil (TDF) was used to treat hepatic flare during pregnancy. Sequential entecavir (ETV) or TDF was applied after the delivery. Treatment course and drug withdrawal in pregnant women with hepatic flare was the same as those of the general patients with chronic hepatitis B. Liver function, HBV serum markers and HBV DNA were measured in pregnant women with hepatic flare at different time points (4, 12, 24 and 52 weeks). A t-test was used to compare the hepatic flare in pregnant women with and without hepatitis group. HBsAg and HBeAg were used to quantify the receiver operating characteristic (ROC) curve of pregnant women with hepatic flare during pregnancy. Area under the ROC curve was used to calculate the optimal cut-off value corresponding to the maximum sensitivity and specificity of the ROC curve. Results: Of the 220 pregnant women with chronic HBV infection, 55 (25%) had hepatitis flare during pregnancy and received antiviral treatment. Among the 55 women with hepatic flare during gestation, 47 (85.46%) had hepatic flare in the mid-second trimester (12-24 weeks); average peak value of alanine aminotransferase (ALT) was 220.62 U/L, and the average peak value of ALT in 32 cases (58.18%) of pregnant women with hepatic flare was between 2-5 × ULN. HBsAg and HBeAg quantification were significantly lower in pregnant women with hepatic flare during pregnancy than with non-hepatitis (t = -3.745, P < 0.001; t = -2.186, P = 0.030). Multivariate logistic regression analysis showed that pregnant women with HBeAg < 3.065 log10 s/co were 7.576 times more likely to have hepatic flare during pregnancy (95% confidence interval: 3.779-15.190). ALT normalization, undetectable HBV DNA levels, HBeAg loss and HBeAg seroconversion in 55 pregnant women with hepatic flare at 52-week treatment was 100% (55/55), 74.55% (41/55), 47.27% (26/55) and 41.82% (23/55), respectively. HBsAg quantification at 52 weeks was significantly lower than baseline HBsAg quantification (3.32 + 0.37) log(10) IU/ml and (3.95 + 0.40) log(10) IU/ml; t = 8.465, P < 0.001). Conclusion: Hepatic flare often occurs in the second trimester of pregnancy in pregnant women with chronic HBV infection and baseline HBeAg quantification is an independent predictor of hepatic flare. HBeAg seroconversion rate increased at 52 weeks after antiviral therapy.

[AKR1B10 inhibitor enhances the inhibitory effect of sorafenib on liver cancer xenograft].

Objective: To investigate the inhibitory effect of AKR1B10 inhibitor combined with sorafenib on hepatocellular carcinoma (HCC) xenograft growth. Methods: HepG2 xenograft model was established in nude mice. The mice were then randomly divided into four groups: control group, epalrestat monotherapy group, sorafenib monotherapy group and combination treatment group. Tumor volume, tumor weight, T/C ratio and the change in body weight of nude mice in each group were compared to evaluate the curative effect. Immunohistochemistry staining was used to detect the expression of Ki-67 in tumor tissues to evaluate the proliferation status of tumor cells. One-way analysis of variance was used to compare the differences between the groups. Student's t-test was used to test means of two groups and chi-square test was used for multiple samples. Results: The differences of the grafted tumor volume before and after treatment between the control group, epalrestat group, sorafenib group and combined therapy group was 238.940 ± 39.813, 124.991 ± 84.670, -26.111 ± 11.518, and -54.072 ± 17.673(mm(3)), respectively, (F = 37.048, P < 0.001). The tumor mass were 0.273 ± 0.140, 0.158 ± 0.078, 0.079 ± 0.054, 0.045 ± 0.024 (g), (F = 16.594, P < 0.001); T/C ratio were 100%, 57.9%, 28.9%, 16.5%, and Ki-67 positive rate were 23.295 ± 6.218, 13.503 ± 3.392, 7.325 ± 2.257, 4.664 ± 1.189 (%), (χ(2) = 822.203, P < 0.001) . The tumor volume (t = -3.579, P = 0.002) and Ki-67 positive rate (t = -10.003, P < 0.001) in epalrestat monotherapy group were significantly lower than control group. The tumor volume (t = 2.056, P = 0.025), tumor mass (t = 2.101, P = 0.043), and Ki-67 positive rate (t = -2.850, P = 0.005) in combination treatment group were significantly lower than sorafenib monotherapy group. Compared with the control group, the body weight of nude mice in the treatment group decreased to a certain extent, but there was no statistically significant difference between epalrestat monotherapy group and control group (t = -1.599, P = 0.262), and combined therapy and sorafenib monotherapy group (t = -0.051, P = 0.96). Conclusion: AKR1B10 inhibitor enhanced the inhibitory effect of sorafenib on hepatocellular carcinoma xenograft.