Chemotherapy remains a primary treatment option for hepatocellular carcinoma (HCC), yet its clinical benefits are often unsatisfactory. Utilizing arsenic trioxide (ATO) as a model, this study elucidates the role of autophagy inhibition in modulating the cellular response to chemotherapy, shifting cell death from apoptosis to pyroptosis via the caspase-3-GSDME pathway, thereby augmenting the anti-tumor efficacy. Building upon these findings, an ATO nanomedicine delivery system capable of autophagy inhibition to promote pyroptosis for enhanced tumor treatment was developed. Folic acid-modified albumin served as the stabilizer for nano self-assemblies formed through ion pairing between Mn²⁺ and ATO, encapsulating DNAzyme (Dz) targeting Beclin 1, a key autophagy regulator. Characterization studies confirmed efficient encapsulation of ATO and Dz within nanoparticles, designed to disintegrate in the intracellular microenvironment, releasing the all-active components, i.e., ATO, Mn²⁺, and Dz. Mn²⁺ acted as a metal cofactor to activate Dz for Beclin 1 mRNA cleavage, inhibiting autophagy and augmenting ATO-induced cell pyroptosis. Elevated cell pyroptosis levels not only enhance ATO's direct tumor cell killing capacity but also trigger anti-tumor immune responses, synergistically enhancing efficacy. Upon intravenous injection, the nanomedicine accumulated in tumor tissue and targeted liver cancer cells. Compared to free ATO, the nanomedicine exhibited significantly improved in vivo anti-tumor effects, achieving a 100% 45-day survival rate in mice with favorable biosafety profiles. This study offers novel insights into tumor chemotherapy sensitization and presents a promising strategy for ATO nanoformulation development.

African swine fever(ASF)is a highly contagious and pathogenic disease affecting both domestic and wild pigs,which is caused by African swine fever virus(ASFV).In European epidem-ics,low-virulence strains of ASFV,which do not have hemadsorbing properties,have been identi-fied.Following the identification of highly virulent genotype Ⅱ ASFV strains in China in 2018,subsequently,low-virulence strains of genotype Ⅱ and genotype Ⅰ emerged.Recombination be-tween genotypes Ⅰ and Ⅱ has also led to the occurrence of high-virulence strains.This indicates a complex and diverse genetic evolution of ASFV during the epidemiological transmission,which po-ses significant challenges for vaccine development and disease surveillance.Here,we provide an o-verview of the novel epidemiological characteristics of ASFV,with a focus on genetic variations and pathogenic differences during the outbreaks of ASF.We also explore how ASFV genetic varia-tions impact immune escape and pathogenicity of the virus,and the challenges they pose for vac-cine development,disease diagnosis,and surveillance.The aim of this review is to enhance our un-derstanding of the genetic evolution and mutation mechanisms of ASFV,providing a theoretical basis for the development of vaccines and research on diagnostic technologies.

Although immune checkpoint inhibitors(ICIs)are widely used in cancer therapy,showing great advantages and development potential,it is accompanied by a series of immune-related adverse reactions,of which myositis is a potentially fatal adverse event,which has attracted great attention.Herein,we reported a case of advanced esophageal cancer with myositis after treatment with camrelizumab,which was characterized by myasthenia gravis(MG)with myasthenic crisis,and recovered after active rescue by multidisciplinary cooperation.

Objective:To investigate the longitudinal trajectory and influencing factors of cancer-related fatigue (CRF) in breast cancer patients during chemotherapy.Methods:From March 2019 to January 2020, breast cancer patients in Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine and Peking Union Medical College Hospital were selected as the research objects to conduct follow-up investigation. The survey tools included general information questionnaire, Cancer-related Fatigue Assessment Scale, International Physical Activity Questionnaire, and the Pittsburgh Sleep Quality Index Scale.Results:A total of 91 patients were included in the study. The incidence of severe CRF at each time point before chemotherapy, 3 weeks after chemotherapy and 6 weeks after chemotherapy were 1.1% (1/91), 8.8% (5/57) and 2.1% (1/48), respectively. The results of the generalized estimation equation showed that the trajectory of the total score CRF firstly increased and then decreased, reaching a peak at 3 weeks after chemotherapy (35.45±13.07), and mild CRF change showed statistical difference ( P<0.05). In addition, BMI and sleep and daytime dysfunction were the influencing factors of the total score of CRF. Disease stage, sleep disturbance and daytime dysfunction were the influencing factors of CRF with different severity. Conclusions:CRF is a prominent problem in breast cancer patients during chemotherapy. Attention should be paid to high-risk individuals with abnormal BMI and daytime function by medical staff.

Objective:To study the epidemic status of drinking tea type endemic fluorosis in Qinghai Province.Methods:In 2019, in counties (cities, districts, referred to as counties) that had the habit of drinking brick tea in 8 cities (prefectures) of Qinghai Province, epidemiological investigation of drinking tea type endemic fluorosis was carried out in villages. Ten households were randomly selected from each village, to investigate the demographic data of each household and the drinking situation of brick tea, residents' drinking water and brick tea samples were collected to determine the fluorine content, and calculate the daily per capita tea fluorine intake. At the same time, skeletal fluorosis was examined in all adults over 25 years old, and dental fluorosis was examined in all children aged 8 to 12 years old in survey sites. The content of fluorine in tea and water was detected by ion selective electrode method; the diagnosis of skeletal fluorosis was based on "Diagnostic Criteria for Endemic Skeletal Fluorosis" (WS 192-2008), the diagnosis of dental fluorosis was based on "Diagnosis of Dental Fluorosis" (WS/T 208-2011).Results:The mean (range) of fluorine of the 3 602 water samples was 0.31 (0.20 - 1.00) mg/L. The geometric mean (range) of fluorine of the 31 067 brick tea samples was 646 (40 - 2 295) mg/kg, the fluorine content of the brick tea ≤300 mg/kg accounted for 7.80% (2 422/31 067) of the total samples. The proportion of drinking Fu brick-tea was 89.97% (27 952/31 067); and the daily per capita tea fluorine intake was 1.93 mg, the daily per capita tea fluorine intake in Guoluo, Yushu and Hainan prefectures were higher than the health standard (3.50 mg). The detection rate of skeletal fluorosis in adults was 0.16% (2 357/1 484 907), Yushu Prefecture was the highest [29.23% (592/2 025)], followed by Guoluo Prefecture, which was 8.21% (771/9 393). The detection rate of dental fluorosis in children was 4.79% (8 076/168 623), Yushu Prefecture was the highest [32.61% (1 562/4 790)].Conclusion:Drinking tea type endemic fluorosis is prevalent in Qinghai Province, with obvious regional characteristics, covering a large population. The disease is relatively popular in Yushu Prefecture and Guoluo Prefecture.

Objective To investigate the efficacy and safety of domestic bortezomibˉbased chemotherapy for patients with multiple myeloma (MM). Methods The clinical data of 60 MM patients treated with domestic bortezomibˉbased chemotherapy regimen (the observation group) in the First Affiliated Hospital of Zhengzhou University from April 2018 to October 2018 were retrospectively analyzed, which were compared with 112 MM patients treated with original treatment regimen (the control group) at the same hospital from November 2010 to November 2014. According to the disease stage, the patients were divided into newly diagnosed MM (NDMM) group and relapsed refractory MM (RRMM) group, and efficacy and adverse reactions of domestic bortezomib were evaluated. Results The total response rate (ORR) of the observation group was 71.7% (43/60), severe complete response (sCR) + complete response (CR) rate was 16.7% (10/60), very good partial response (VGPR) rate was 18.3% (11/60), and partial response (PR) rate was 36.7% (22/60). The ORR of NDMM group (45 cases) and RRMM group (15 cases) was 82.2% (37/45) and 40.0% (6/15), respectively, and the difference was statistically significant (χ2＝ 9.877, P < 0.05). There was no significant difference between ISS stage Ⅰ+Ⅱ and stage Ⅲ [ORR: 75.7% (28/37) vs. 65.2% (15/23), respectively; χ2＝0.764, P >0.05]. ORR and CR rates in the NDMM group and RRMM group of the observation group and the control group were not statistically different (all P>0.05). In the treatment of bortezomibˉbased chemotherapy, the common adverse reaction was peripheral neuropathy, mostly belonging to grade 1-2. Other side effects included hematocytopenia, gastrointestinal events and herpes zoster, which could be alleviated or restored to normality after supportive treatments. One patient died of pulmonary infection, respiratory failure and septic shock during the intermittent period of chemotherapy. Conclusion ORR of domestic bortezomibˉbased chemotherapy in treatment of the patients with MM is high, and the incidence of adverse reactions shows no significant increase compared with original drugs.

Objective: To analyze the comparability of different detection systems and methods for tumor markers (TM) by reviewing the results of TM external quality assessment (EQA) in Shandong province during 2015 and 2017. Methods: The results of TM EQA from the Shandong Provincial Clinical Laboratory Center during 2015 and 2017 were collected, and grouped by the detection system or method. After outliers were removed by the CLInet EQA software, the mean and coefficient of variation (CV) in each group were calculated with median as the target value. The difference of TM results in different detection systems were compared by the Kruskal-Wallis H test. Results: Taking alpha-fetoprotein (AFP) as an example, the average CV of different detection methods of TM EQA during 2015 and 2017 ranged from small to large in order of microparticle enzyme immunoassay, electrochemiluminescence, acridine ester chemiluminescence and chemiluminescence. The trends of CV of the other tumor markers were similar to AFP. The average CV of individual marker in electrochemiluminescence group was lower than that in microparticle enzyme immunoassay group. The intra-group CVs of imported detection systems such as Roche, Beckman etc. were relatively ideal, and the average CVs of most tumor markers were less than 10%. However, the intra-group CVs of domestic detection systems such as Shenzhen Snibe, Zhengzhou Autobio etc. were not ideal, and the average CVs of most tumor markers were more than 10%. The target values of different detection systems varied with different items and batches, and there were great variation in carbohydrate antigen (CA) series. Conclusion The results of TM detected by the same automatic detection system are comparable. However, the results of TM detected by most different detection systems and methods are not comparable.

Objective: To investigate the clinical characteristics and prognostic factors in elderly patients with acute myeloid leukemia(AML). Methods: Clinical data of 232 patients with acute myelocytic leukemia(AML, except for acute promyelocytic leukemia) admitted in our hospital from January 2012 to December 2015 were retrospectively analyzed.Factors affecting complete remission(CR) were analyzed by using χ² test, and Kaplan-Meier survival analysis was conducted.Univariate and multivariate analysis of prognostic factors were performed by using Log-Rank test and Cox regression model respectively. Results: Of 232 patients, 195 patients received induction chemotherapy, among whom 8 patients died in early phase, efficacy could not be evaluated in 25 cases, with 162 patients for final statistical study.The CR rate was 37.0%(60/162) after the first therapy course, and overall CR rate was 54.9%(89/162). Thirty-seven patients received palliative treatment, among whom 6 patients died in early phase and none achieved CR.Therefore, the 162 patients receiving an induction chemotherapy, whose efficacy can be evaluated, could be clinically analyzed.They were in 60-69 years old(χ²=4.102, P=0.043), with ECOG score≤2(χ²=9.917, P=0.002), NPM1⁺ FLT3-ITD^-(χ²=6.423, P=0.038), favorable karyotypes(χ²=6.033, P=0.049), and related to a higher CR rate.The median overall survival(OS) was 205 days in the 232 patients.Univariate analysis results demonstrated that age(χ²=8.700, P=0.003), white blood cell(WBC) count≥100×10⁹/L(χ²=4.249, P=0.039), karyotypes(χ²=4.807, P=0.028), palliative treatment(χ²=191.221, P=0.000) were influencing factors for the prognosis.Multivariable analysis showed that age(HR=0.464, 95%CI: 0.245-0.877, P=0.018), karyotypes(HR=3.618, 95%CI: 1.491-6.728, P=0.003) and whether or not to receive induction chemotherapy(HR=0.076, 95%CI: 0.030-0.194, P=0.000) were independent influencing factors for OS in elderly patients with AML. Conclusions The prognosis of elderly patients with AML is affected by multiple factors.Age, karyotypes and whether or not to receive induction chemotherapy are independent influencing factors for OS in elderly patients with AML.

OBJECTIVE: To carry out genetic diagnosis for a pregnant woman and her fetus. METHODS: Chromosome G-banding and microarray analysis were used to analyze the woman featuring dysmorphism and recognition defect and her fetus featuring developmental retardation. RESULTS: The karyotype of the woman was normal, but chromosome microarray analysis showed that she has carried a 1423 kb deletion at 7q11.23 region. Her fetus has carried a 1530 kb deletion at the same region. Both individuals were diagnosed as Williams-Beuren syndrome. CONCLUSION Familiarity with its clinical features and proper selection of genetic testing methods are crucial for the diagnosis of Williams-Beuren syndrome.
Child ; Chromosome Banding ; Chromosomes, Human, Pair 7 ; Female ; Genetic Testing ; Humans ; Karyotyping ; Pregnancy ; Prenatal Diagnosis ; Williams Syndrome ; diagnosis

Objective To evaluate the effect of dexmedetomidine on receptor-interacting protein 1 (RIP1) signaling pathway during brain injury after cardiac arrest and resuscitation in pigs.Methods Twenty-one healthy domestic male white pigs,weighing 33-41 kg,were divided into 3 groups (n =7 each) using a random number table method:sham operation group (group S),cardiac arrest-resuscitation group (group CA-R) and dexmedetomidine group (group D).Ventricular fibrillation was electrically induced and untreated for 8 min followed by 5 min of cardiopulmonary resuscitation to establish the model of brain injury after cardiac arrest and resuscitation in anesthetized domestic white pigs.Dexmedetomidine was infused via the femoral vein in a loading dose of 0.5 μg/kg at 5 min after successful resuscitation,followed by an infusion of 0.5 μg · kg-1 · h-1 for 6 h in group D.The equal volume of normal saline was given instead in S and CA-R groups.The concentrations of neuron-specific endase (NSE) and S-100β protein in serum were measured at 1,3,6 and 24 h after resuscitation (T1-4).Neurologic deficit score (NDS) was evaluated at T4.The animals were sacrificed at T4,brains were removed and cerebral cortex tissues were obtained for determination of the expression of RIP1,RIP3 and mixed lineage kinase domain-like protein (MLKL) by Western blot.Results Compared with group S,the serum concentrations of NSE and S-100β protein were significantly increased at T1-4,the NDS was increased at T4,and the expression of RIP1,R1P3 and MLKL in cerebral cortex tissues was up-regulated in CA-R and D groups (P＜0.05).Compared with group CA-R,the serum concentrations of NSE and S-100β protein were significantly decreased at T3,4,the NDS was decreased at T4,and the expression of RIP1,RIP3 and MLKL in cerebral cortex tissues was down-regulated in group D (P＜0.05).Conclusion The mechanism by which dexmedetomidine reduces brain injury after cardiac arrest and resuscitation may be related to inhibiting the activation of RIP 1 signaling pathway in pigs.