ObjectiveTo investigate the features of serum HBV RNA in different stages of the natural history of chronic hepatitis B virus （HBV） infection without antiviral treatment， as well as its correlation with serum HBV DNA and HBsAg. MethodsA total of 306 treatment-naïve patients with chronic HBV infection who attended Department of Infections Diseases and Hepatoloty， the Second Hospital of Shandong University from January 2023 to June 2024 were divided into six groups based on the different stages of natural history， i.e.， HBeAg-positive chronic HBV infection group with 29 patients， HBeAg-positive chronic hepatitis B （CHB） group with 107 patients， HBeAg-negative chronic HBV infection group with 18 patients， HBeAg-negative CHB group with 60 patients， HBeAg-positive indeterminate-phase chronic HBV infection group with 7 patients， and HBeAg-negative indeterminate-phase chronic HBV infection group with 85 patients. Real-time isothermal RNA amplification was used to measure serum high-sensitivity HBV RNA. The Kruskal-Wallis H test was used for comparison between multiple groups of continuous data， while the Mann-Whitney U test was used for comparison between two groups. The Spearman method was used to investigate the correlation of HBV RNA with HBV DNA and HBsAg. ResultsThe HBeAg-positive chronic HBV infection group showed the highest level of serum HBV RNA ［7.5 （7.4‍ ‍—‍ ‍7.9） log₁₀ copies/mL］， followed by the HBeAg-positive CHB group ［7.4 （6.4‍ ‍—‍ ‍7.9） log₁₀ copies/mL］， the HBeAg-negative CHB group ［4.5 （3.0‍ ‍—‍ ‍5.7） log₁₀ copies/mL］， and the HBeAg-negative chronic HBV infection group ［1.0 （1.0‍ ‍—‍ ‍2.0） log₁₀ copies/mL］； the HBeAg-positive indeterminate-phase chronic HBV infection group had a serum HBV RNA level of 3.9 （3.7‍ ‍—‍ ‍5.7） log₁₀ copies/mL， and the HBeAg-negative indeterminate-phase chronic HBV infection group had a serum HBV RNA level of 2.0 （1.0‍ ‍—‍ ‍3.0） log₁₀ copies/mL； there was a significant difference in serum HBV RNA level between the six groups （H=830.770， P<0.001）. There was a significant difference in HBV RNA level between the HBeAg-positive chronic HBV infection group and all the other groups except the HBeAg-positive CHB group （all P<0.001）. In the 306 patients with HBV infection， HBV RNA was strongly correlated with HBV DNA （r=0.92， P<0.001） and was moderately correlated with HBsAg （r=0.67， P<0.001）. The correlation between serum HBV RNA and HBsAg in HBeAg-positive patients （r=0.61， P<0.001） was stronger than that in HBeAg-negative patients （r=0.31， P<0.001）. For the patients with HBeAg-positive chronic HBV infection， the male patients with ALT>30 U/L and the female patients with ALT>19 U/L had a significantly lower serum HBV RNA level than the male patients with ALT≤30 U/L and the female patients with ALT≤19 U/L （P<0.001）， and there was no significant difference in serum HBV RNA level between the latter group of patients and the HBeAg-positive CHB group （P>0.05）. ConclusionIn patients with chronic HBV infection who do not receive antiviral therapy， there is a difference in serum HBV RNA level in different stages of natural history， and serum HBV RNA level has the strongest correlation with HBV DNA and a relatively weak correlation with HBsAg. In patients with HBeAg-positive chronic HBV infection， serum HBV RNA level in male patients with ALT>30 U/L and female patients with ALT>19 U/L are in the transition stage between HBeAg-positive chronic HBV infection and HBeAg-positive CHB.

OBJECTIVE To provide reference for the rational use of antiemetic drugs in tumor chemotherapy patients. METHODS The data of tumor patients who were given antiemetic drugs were collected from 9 departments of our hospital with hospital information system from Oct. 1st to Nov. 30th in 2022， such as oncology department， radiotherapy department， gynecology department， and gastroenterology department. The application of chemotherapy drugs and the use of antiemetic drugs were analyzed statistically， and the irrational use of antiemetic drugs was analyzed. RESULTS A total of 520 patients were included， involving 248 （47.69%） using chemotherapy drugs with a moderate emetogenic risk level and 135 （25.96%） with a high emetogenic risk level. A total of 461 cases （73.06%） of 5-hydroxytryptamine 3-receptor antagonists were used， including palonosetron in 333 cases， ondansetron in 106 cases， tropisetron in 15 cases and granisetron in 7 cases， and only 148 cases of patients were prioritized for the use of nationally procured medicines and national essential medicines （32.10%）. Neurokinin-1 receptor antagonists were used in 170 cases （26.94%）， including fosaprepitant in 112 cases and aprepitant in 58 cases. The use of antiemetic drugs was unreasonable in 162 patients （31.15%）； among the types of irrational drugs， the antiemetic regimen was unreasonable in the largest number of cases （22.40%）， followed by the irrational pharmacoeconomics （19.13%）. CONCLUSIONS The emetogenic risk levels of chemotherapy drugs used for tumor patients in our hospital are primarily moderate to high， and there is irrational use of antiemetic regimen and pharmacoeconomics. Clinicians， nurses， pharmacists and hospital departments should collaborate as multiple teams to strengthen full supervision of the standardization of antiemetic drugs， reasonably select antiemetic drugs based on emetogenicity rating， and improve the compliance of doctors with the guidelines to ensure the safety， effectiveness， and cost-effective of patient medication.

ObjectiveTo investigate the role of proinflammatory cytokines tumor necrosis factor alpha （TNFα） and interleukin-1β （IL-1β） in rostral ventromedial medulla （RVM） in chronic postsurgical pain （CPSP） induced by skin/muscle incision and retraction （SMIR）. MethodsSD rats were randomly divided into 5 groups： ① Sham group； ② SMIR group； ③ SMIR+TNFα/IL-1β neutralizing antibody group； ④ SMIR+TNFα/IL-1β group and ⑤ SMIR+vehicle group. 50% paw mechanical withdrawal threshold （MWT） was measured by the up-down method， immunofluroscence was used to detect the TNFα and IL-1β expression and ELISA for the 5-Hydroxytryptamine （5-HT） level. ResultsSMIR elicited persistent nociceptive sensitization， upregulated TNFα and IL-1β expression in RVM neurons and astrocytes. Microinjection of TNFα or IL-1β neutralizing antibody into RVM inhibited the development of nociceptive sensitization and decreased the level of 5-HT in both RVM and spinal dorsal horn. While microinjection of recombinant TNFα or IL-1β into RVM enhanced the development of nociceptive sensitization and increased the level of 5-HT in both RVM and spinal dorsal horn. ConclusionUp-regulation of proinflammatory cytokines in RVM may contribute to SMIR induced CPSP by promoting 5-HT release.

Objective:To explore the genetic etiology and clinical phenotype of a child with Triadin knockout syndrome (TKOS), and to review the relevant literature of TKOS patients due to variants of TRDN gene. Methods:A child who was admitted to the Children′s Hospital of Xi′an Jiaotong University on March 19, 2023 due to sudden cardiac arrest 3 days earlier was selected as the study subject. Peripheral blood samples (2 to 3 mL) were collected from the child and her parents for the extraction of genomic DNA and whole exome sequencing (WES). Pathogenic variants were searched from databases such as the Genome Aggregation Database (gnomAD) and Online Mendelian Inheritance in Man (OMIM), and were assessed based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Sanger sequencing was carried out for family validation of the pathogenic variants. Using keywords such as " arrhythmias" " TRDN" and " Triadin" both in Chinese and English, relevant literature on TKOS patients due to variants of the TRDN gene was retrieved from the CNKI, Wanfang Data Knowledge Service Platform, and PubMed databases, and the time of literature retrieval was set from January 1, 2012 to December 1, 2023. This study has been approved by the Ethics Committee of the Affiliated Children′s Hospital of Xi′an Jiaotong University (No. 20230097), and informed consent was obtained from the parents of the child. Results:The child had experienced syncope and cardiac arrest after exercise. Electrocardiographic examination revealed QTc interval prolongation, T-wave inversion in precordial leads V1-V3, polymorphic ventricular premature beat (VPB), and ventricular tachycardia (VT) along with increased heart rate. WES and Sanger sequencing revealed that the child has harbored a homozygous c.463del(p.E155Kfs*20) variant of the TRDN gene, for which both of the parents were heterozygous. Based on the guidelines from the ACMG, the variant was classified as pathogenic (PVS1+ PM2+ PM3). The child was ultimately diagnosed with TKOS. In total 12 publications on TOKS cases caused by TRDN gene variants were retrieved, which involved 30 patients and 28 carriers of single heterozygous variant of the TRDN gene. Among the 30 TKOS patients, 20 had carried homozygous variants of the TRDN gene, and 10 had carried compound heterozygous variants, and all had exhibited significant clinical phenotype of arrhythmia, with most cases had experienced malignant arrhythmia induced by exercise and/or excitement during infancy or early childhood, leading to recurrent syncope and cardiac arrest. Of note, none of the 28 carriers of single heterozygous variant had abnormal clinical phenotype. Conclusion:The homozygous c.463del(p.E155Kfs20) variant of the TRDN gene probably underlay the pathogenesis of cardiac arrest in this child. Above discovery has enriched the mutational spectrum of the TRDN gene.This mutation may represent a genetic cause for cardiac arrest in children with TKOS.

This article retrospectively analyzes the clinical data of a patient with Addison′s disease complicated by torsades de pointes treated in Children′s Hospital Affiliated to Xi′an Jiaotong University in July 2021.The patient, female, aged 12 years, was hospitalized multiple times due to recurrent seizures, syncope, and coma, and had been successively diagnosed with fulminant myocarditis, supraventricular tachycardia, etc.She was later transferred to Children′s Hospital Affiliated to Xi′an Jiaotong University, where during hospitalization, electrocardiogram (ECG) monitoring revealed torsades de pointes associated with the attacks.The ECG between attacks showed a prolonged Q-T interval, with the longest Q-Tc of 564 ms.Echocardiography suggested a slight enlargement of the left ventricle and reduced left ventricular ejection fraction.After a comprehensive examination, she was diagnosed with Addison′s disease.Treatment with intravenous Hydrocortisone for 3 days, followed by oral Hydrocortisone tablets, was administered sequentially.After treatment, symptoms such as syncope did not recur, and the Q-T interval gradually returned to normal.After continued treatment for 1 year, echocardiography revealed no abnormality.This report aims to enhance pediatricians′ understanding and research on the relationship between pediatric endocrine diseases and arrhythmias.

Objective:To reveal the effect of β-sitosterol on cerebral ischemia-reperfusion injury (CIRI) in rats and whether its mechanism is related to endoplasmic reticulum stress (ERS).Methods:Fifty-three CIRI rats (CIRI models established by modified Longa method) were randomly divided into model group ( n=14), β-sitosterol low-dose group ( n=13), β-sitosterol medium-dose group ( n=13) and β-sitosterol high-dose group ( n=13); 12 rats underwent the same operation without blocking the middle cerebral artery were selected as sham-operated group. Rats in the sham-operated group and model group were given intragastric administration of 1 mL 5 g/L sodium carboxymethyl cellulose daily. Rats in the β-sitosterol low-dose group, β-sitosterol medium-dose group and β-sitosterol high-dose group were given intragastric administration of 1 mL β-sitosterol at 10, 20 and 40 mg/kg/d (dissolved in 5 g/L sodium carboxymethyl cellulose), respectively, for 14 consecutive d. Neurological function was evaluated according to Zea Longa 5 method. Rats were sacrificed and brain tissues were collected. Volume of cerebral infarction was measured by 2,3,5-triphenyl tetrazolium chloride (TTC) staining. Brain injury and neuronal apoptosis were evaluated by HE staining, Nissl staining and TUNEL. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) contents were detected by water-soluble tetrazolium 1 (WST-1) method, colorimetric method or thiobarbituric acid (TBA) method, respectively. The mRNA and protein expression levels of protein kinase R-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme-1 (IRE-1), activated transcription factor-6 (ATF-6), glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP) and Caspase-12 in the brain tissues were detected by qRT-PCR or Western blotting. Results:Compared with the sham-operated group, the model group had significantly increased neurological function score, cerebral infarction volume and TUNEL positive rate, decreased SOD and GSH-Px content, increased MDA content, and increased mRNA and protein expressions of PERK, IRE-1, ATF-6, GRP78, CHOP and Caspase-12 ( P<0.05). Compared with the model group, the β-sitosterol low-dose group, β-sitosterol medium-dose group and β-sitosterol high-dose group had significantly decreased neurological function score, cerebral infarction volume, and TUNEL positive rate, increased SOD and GSH-Px content, and decreased MDA content ( P<0.05); the β-sitosterol low-dose group, β-sitosterol medium-dose group and β-sitosterol high-dose group had significantly decreased mRNA and protein PERK expressions (mRNA: 2.17±0.17, 1.79±0.07 and 1.33±0.07; protein: 5.11±0.52, 2.91±0.26 and 1.98±0.17), IRE-1 expressions (mRNA: 1.75±0.18, 1.65±0.08 and 1.32±0.08; protein: 5.00±0.31, 4.05±0.27 and 1.98±0.14), ATF-6 expressions (mRNA: 2.24±0.12, 1.77±0.14 and 1.37±0.13; protein: 4.93±0.45, 4.04±0.30 and 3.10±0.20), GRP78 expressions (mRNA: 2.67±0.16, 2.11±0.16 and 1.69±0.11; protein: 5.02±0.38, 2.97±0.26 and 2.05±0.22), CHOP expressions (mRNA: 2.01±0.16, 1.70±0.19 and 1.40±0.10; protein: 4.92±0.39, 4.02±0.27 and 3.08±0.22) and Caspase-12 expressions (mRNA: 1.85±0.09, 1.61±0.09 and 1.30±0.09; protein: 3.03±0.20, 2.19±0.11 and 1.82±0.11) compared with the model group (mRNA: 2.99±0.28, 2.27±0.12, 2.57±0.21, 3.46±0.20, 2.50±0.23 and 2.35±0.16; protein: 6.98±0.48, 6.03±0.58, 5.98±0.63, 7.10±0.45, 6.00±0.53 and 5.02±0.43, P<0.05). Conclusion:β-sitosterol attenuates CIRI in rats, whose mechanism may be related to inhibition of ERS signal pathway.

Objective:To explore the predictive value of 18F-FDG PET/CT metabolic parameters combined with inflammatory markers for the medium-term efficacy of chemotherapy in patients with primary gastrointestinal diffuse large B cell lymphoma (PGI-DLBCL). Methods:From April 2011 to May 2020, 67 patients (37 males, 30 females, age: 28-85 years) with PGI-DLBCL examined by 18F-FDG PET/CT before chemotherapy in Changhai Hospital, Navy Medical University were retrospectively analyzed. All patients were treated with cyclophosphamide+ doxorubicin+ vincristine+ prednisone (CHOP) or rituximab+ CHOP (R-CHOP) regimens, and the medium-term efficacy was evaluated after 2-4 cycles of chemotherapy. The effect outcome was divided into complete remission (CR) group and non-CR (NCR) group based on the Lugano lymphoma response evaluation criteria. Mann-Whitney U test was used to compare the differences of SUV max, peak of SUV (SUV peak), metabolic tumor volume (MTV), total lesion glycolysis (TLG), platelet/lymphocyte ratio (PLR) and neutrophil/lymphocyte ratio (NLR) between two groups. The independent risk factors of NCR were analyzed by multivariate logistic regression and the binary logistic regression model was established according to the results. The model was tested with external validation data ( n=15). Results:Of 67 PGI-DLBCL patients, 28(41.8%) were CR and 39(58.2%) were NCR. SUV peak, MTV, TLG, PLR and NLR in NCR group (17.3(12.3, 28.1), 73.8(42.9, 141.7) cm 3, 887.5(300.9, 2 075.3) g, 203.9(155.7, 297.1), 3.9(3.0, 4.9)) were significantly higher than those in CR group (9.5(6.2, 15.2), 11.3(4.7, 23.2) cm 3, 85.2(35.5, 214.6) g, 149.3(102.8, 173.1), 2.2(1.8, 4.6); z values: from -6.41 to -2.33, all P<0.05). The logistic regression model was as follows: P=1/(1+ e - x), x=0.100×MTV+ 0.024×PLR-8.064. The prediction accuracy for NCR risk was 86.57%(58/67), with the accuracy of 13/15 tested by external validation data. Conclusion:MTV combined with PLR has a good predictive value for medium-term efficacy of CHOP/R-CHOP chemotherapy in patients with PGI-DLBCL.

Objective To study the value of regulated upon activation,normal T-cell expressed and secreted (RANTES) and macrophage migration inhibitory factor (MIF) in the prediction of cognitive dysfunction associated with Parkinson disease (PD). Methods A total of 62 PD patients who received treatment in our hospital from January 2020 to January 2022 were recruited. All patients were treated with levodopa for 5 months. The levels of RANTES,MIF,interleukin-6 (IL-6),and tumor necrosis factor (TNF)-α were measured by enzyme-linked immunosorbent assay. Results Among the 62 PD patients,21 (33.87%) developed cognitive dysfunction after 5 months of levodopa treatment. The levels of RANTES,MIF,IL-6,and TNF-α were significantly lower in patients with cognitive dysfunction than in those without cognitive dysfunction (P<0.05). A multiple regression model was established with the basic data of patients as covariates and the presence or absence of cognitive dysfunction as the dependent variable. Adjustment was made for family history of PD,clinical subtype,comorbidity of hypertension,smoking history,course of disease,sex,and age. The results showed that serum RANTES,MIF,IL-6,and TNF-α levels were independent risk factors for cognitive dysfunction in PD patients (P<0.05). The receiver operating characteristic(ROC) curve showed an area under the ROC curve(AUC) of 0.798 for serum RANTES level to predict cognitive dysfunction in PD patients,with specificity,sensitivity,and Youden index of 0.743,0.705,and 0.448,respectively. The AUC was 0.802 for serum MIF level in the prediction of cognitive dysfunction in PD patients,with specificity,sensitivity,and Youden index of 0.552,0.973,and 0.525,respectively. The combination of serum RANTES and MIF had an AUC of 0.958 in predicting cognitive dysfunction in PD patients. Conclusion High levels of serum RANTES and MIF are risk factors for cognitive dysfunction in PD patients. In clinical practice,serum RANTES and MIF levels can be determined to predict the risk of cognitive dysfunction for early intervention and treatment.