Correlation Analysis and Comparison of Adult CE-Chirp ABR Response Threshold and Pure Tone Hearing Threshold / 法医学杂志

Objective To study the application of CE-Chirp in the evaluation of hearing impairment in forensic medicine by testing the auditory brainstem response(ABR)in adults using CE-Chirp to ana-lyze the relationship between the V-wave response threshold of CE-Chirp ABR test and the pure tone hearing threshold.Methods Subjects(aged 20-77 with a total of 100 ears)who underwent CE-Chirp ABR test in Changzhou De'an Hospital from January 2018 to June 2019 were selected to obtain the V-wave response threshold,and pure tone air conduction hearing threshold tests were conducted at 0.5,1.0,2.0 and 4.0 kHz,respectively,to obtain pure tone listening threshold.The differences and statistical differences between the average pure tone hearing threshold and V-wave response threshold were compared in different hearing levels and different age groups.The correlation,differences and statistical differences between the two tests at each frequency were analyzed for all subjects.The lin-ear regression equation for estimating pure tone hearing threshold for all subjects CE-Chirp ABR V-wave response threshold was established,and the feasibility of the equation was tested.Results There was no statistical significance in the CE-Chirp ABR response threshold and pure tone hearing threshold dif-ference between different hearing level groups and different age groups(P>0.05).There was a good correlation between adult CE-Chirp ABR V-wave response threshold and pure tone hearing threshold with statistical significance(P<0.05),and linear regression analysis showed a significant linear correla-tion between the two(P<0.05).Conclusion The use of CE-Chirp ABR V-wave response threshold can be used to evaluate subjects'pure tone hearing threshold under certain conditions,and can be used as an audiological test method for forensic hearing impairment assessment.

Efficacy,metabolic characteristics,safety and immunogenicity of AK-HER2 compared with reference trastuzumab in patients with metastatic HER2-positive breast cancer:a multicenter,randomized,double-blind phase Ⅲ equivalence trial / 中国癌症杂志

Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

Predictive value of esophageal deviation index for clinical outcomes of patients with left-sided congenital diaphragmatic hernia / 中华围产医学杂志

Objective:To evaluate the predictive value of postnatal esophageal deviation index for clinical outcomes of fetuses with left-sided congenital diaphragmatic hernia (L-CDH).Methods:This retrospective study analyzed the clinical data of 103 neonates with prenatally diagnosed L-CDH who were admitted to Guangzhou Women and Children's Medical Center from January 2016 to February 2023. These patients were divided into the survival group ( n=82) and the death group ( n=21) according to the outcomes, and the extracorporeal membrane oxygenation (ECMO) group ( n=25) and the non-ECMO group ( n=78) according to whether ECMO support was required. Thoracoabdominal X-ray screening was performed on all neonates within 24 h after admission and the esophageal deviation index and cardiac deviation index were calculated. Independent sample t-test or Fisher's exact probability test were used to analyze the differences in general condition and postnatal imaging features between different groups. Receiver operating characteristic (ROC) curve was used to evaluate the value of postnatal imaging features in predicting the prognosis of L-CDH. Results:The esophageal deviation index and the cardiac deviation index of neonates in the survival group were lower than those in the death group [(10.5±5.3)% vs. (18.0±4.5)%, t=－5.47; (37.7±7.1)% vs. (42.8±8.2)%, t=－2.62; both P<0.05], while that were both higher in the ECMO group compared with the non-ECMO group [(18.0±4.3)% vs. (10.1±5.2)%, t=6.34; (42.4±7.9)% vs. (37.6±7.1)%, t=2.63; both P<0.05]. ROC curve showed that the area under the curve (AUC) for predicting the need for ECMO support was 0.879 (95% CI: 0.805-0.953) for esophageal deviation index and 0.712 (95% CI: 0.570-0.854) for cardiac deviation index, with the optimal cut-off values of 11.7% and 41.7%, respectively. The AUC for predicting the survival rate in patients with L-CDH by esophageal deviation index and cardiac deviation index were 0.854 (95% CI: 0.761-0.947) and 0.735 (95% CI: 0.582-0.887), respectively, with the corresponding optimal cut-off values of 15.8% and 41.7%. Conclusion:Postnatal esophageal deviation index is of value in predicting the need for ECMO support and survival rate in patients with L-CDH.

Research Progress on Efficacy-related Biomarkers of Immunotherapy in Non-small Cell Lung Cancer / 肿瘤防治研究

Lung cancer is one of the most common cancers worldwide, and its mortality rate remains high. In addition to conventional surgery, radiotherapy, and chemotherapy, immunotherapy methods have been developed and used in recent years for the treatment of non-small cell lung cancer (NSCLC). However, only a small number of patients with NSCLC can benefit from immunotherapy strategies, and some patients even have hyperprogression after receiving immunotherapy. Therefore, precision immunotherapy requires effective biomarkers to guide it. In this paper, tissue samples, blood samples, intestinal microbiota, and other biomarkers are reviewed according to different sample sources. Blood samples, including TCR immune repertoire, Tregs cells, cytokines, lactate dehydrogenase, and other markers, are summarized and analyzed to provide reference for clinicians' diagnosis and treatment decisions.

Progress of Research on Immune-related Pneumonia in Non-small Cell Lung Cancer / 肿瘤防治研究

In recent years, immunotherapy has made a breakthrough in the field of non-small cell lung cancer, reshaping the pattern of lung cancer treatment. However, with the wide application of immunotherapy in clinical practice, immune-related adverse events have attracted increasing attention. Immune pneumonia, as one of the immune-related toxic side effects of greatest concern, affects the treatment process and curative effect and can be a threat to life in serious cases. Given that immune pneumonia has a complicated pathogenesis and diverse clinical manifestations, strengthening the understanding of immune pneumonia is urgently needed. The treatment of immune pneumonia is limited, and additional therapeutic medicines are still awaiting exploration. Therefore, this paper summarizes the progress of the research on immune pneumonia in the treatment of non-small cell lung cancer.

Clinical efficacy of entecavir combined with Biejiajian pills and its influence on TCM syndrome scores during the treatment of chronic hepatitis B with hepatic fibrosis and blood stasis syndrome / 中华肝脏病杂志

Objective: To investigate the clinical efficacy of entecavir combined with Biejiajian pills and its influence on TCM syndrome scores during the treatment of chronic hepatitis B with hepatic fibrosis and blood stasis syndrome by prospective, randomized and controlled study. Methods: Patients with chronic hepatitis B with hepatic fibrosis and blood stasis syndrome were selected as the research subjects and randomly divided into a treatment group and a control group. Entecavir plus Biejiajian pills or entecavir plus a simulant of Biejiajian pills were given for 48 weeks. The changes in liver stiffness measurement (LSM) and TCM syndrome scores before and after treatment were compared between the two groups to analyze the correlation. The data between groups were analyzed by t-test/Wilcoxon rank sum test or χ(2) test. Pearson correlation coefficient was used to analyze the correlation between TCM syndrome scores and LSM values. Results: After 48 weeks of treatment, the LSM values of the two groups were significantly lower than those of the baseline (P < 0.001), liver fibrosis was significantly improved, and the LSM values of the treatment group were lower than those of the control group [(8.67 ± 4.60) kPa and (10.13 ± 4.43) kPa, t = -2.011, P = 0.049]. After 48 weeks of treatment, the TCM syndrome scores of the two groups were significantly reduced compared with the baseline (P < 0.001), and the clinical symptoms were significantly relieved, and the total effective rates of the improvement of the TCM syndrome scores in the two groups were 74.19% and 72.97%, respectively, but the differences between the groups were not statistically significant (χ(2) = 0.013, P = 0.910). Correlation analysis showed that there was no obvious trend between TCM syndrome scores and LSM values. There were no serious adverse reactions associated with the drug during the observation period of this study. Conclusion: Based on antiviral treatment with entecavir, regardless of whether it is combined with the Biejiajian pill, it can effectively reduce the LSM value, improve liver fibrosis, reduce TCM syndrome scores, and alleviate symptoms in patients with chronic hepatitis B with liver fibrosis and blood stasis syndrome. Compared with entecavir alone, the combined Biejia pill has greater efficacy in improving liver fibrosis and a favorable safety profile, meriting its implementation and widespread application.

Prevalence of comorbid depression and anxiety and effect of psychological interventions among schistosomiasis patients in China: a meta-analysis / 中国血吸虫病防治杂志

OBJECTIVE@#To investigate the prevalence of comorbid depression and anxiety and to evaluate the effect of psychological interventions among schistosomiasis patients in China, so as to provide insights into improvements of psychological health among schistosomiasis patients.@*METHODS@#Publications pertaining to comorbid depression and anxiety and psychological interventions among Chinese schistosomiasis patients were retrieved in electronic databases, including CNKI, Wanfang Data, PubMed, Web of Science, and Embase. The prevalence of comorbidity, psychological interventions, and scores for the Self-Rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS) before and after psychological interventions among Chinese schistosomiasis patients were extracted. The prevalence of comorbid depression and anxiety was investigated among Chinese schistosomiasis patients using a meta-analysis, and the effect of psychological interventions for depression and anxiety was evaluated.@*RESULTS@#A total of 231 publications were retrieved, and 14 publications that met the inclusion and exclusion criteria were included in the final analysis, including 2 English publications and 12 Chinese publications. Meta-analysis showed that the prevalence rates of comorbid depression and anxiety were 61% [95% confidential interval (CI): (48%, 72%)] and 64% [95% CI: (42%, 81%)] among Chinese schistosomiasis patients. Both the SDS [1.45 points, 95% CI: (1.30, 1.60) points] and SAS scores [2.21 points, 95% CI: (2.05, 2.38) points] reduced among Chinese schistosomiasis patients after psychological interventions than before psychological interventions, and the SDS [-0.47 points, 95% CI: (-6.90, -0.25) points] and SAS scores [-1.30 points, 95% CI: (-1.52, -1.09) points] reduced among Chinese schistosomiasis patients in the case group than in the control group.@*CONCLUSIONS@#The comorbid anxiety and depression are common among Chinese schistosomiasis patients, and conventional psychological interventions facilitate the improvements of anxiety and depression among schistosomiasis patients.

Management of right-sided fetal congenital diaphragmatic hernia with hepatopulmonary fusion: a report of three cases and literature review / 中华围产医学杂志

Objective:To investigate the clinical features and management of right-sided congenital diaphragmatic hernia (RCDH) with hepatopulmonary fusion (HPF).Methods:This retrospective study analyzed the clinical characteristics of three cases of RCDH complicated by HPF that were treated in Guangzhou Women and Children's Medical Center from June to December 2022. Diaphragm defects in the three cases were classified according to the international standard of diaphragm defect classification. Besides, an extensive search of publications was performed including domestic and foreign databases, including CNKI, Wanfang Database, Yiigle, VIP Chinese journals, PubMed, Embase and UpToDate databases from January 1997 to April 2023 using terms including "congenital diaphragmatic hernia" and "hepatopulmonary fusion". Clinical features and prognosis of RCDH complicated by HPF were summarized.Results:(1) Cases in the present study: RCDH was found in case 1 and case 2 during routine prenatal ultrasound examination; antenatal fetal MRI showed partial displacement of the hepatocele into the right hemithorax, right lung hypoplasia, a normal-sized left lung and without left shift of the mediastinum in both cases. Postnatal chest radiographs of case 1 and case 3 showed dense shadow in the left lung and mediastinum shifted to the right. Case 2 had a D-type defect and a slight shift of the mediastinum to the left was observed on the postnatal chest radiograph. Preoperative imaging findings indicated highly suspected HPF in the three cases. Case 1 and case 2 had complete separation of liver and lung and underwent diaphragmatic herniorrhaphy with patch. Partial lung resection was performed in case 2. Both case 1 and case 2 survived (length of hospital stay was 22 d and 23 d, respectively). Case 3 did not undergo hepatopulmonary separation or herniorrhaphy after exploratory operation and died of persistent pulmonary hypertension. (2) Literature review: Only 40 cases of CDH with HPF were retrieved from PubMed. Among the 43 cases including the above three cases, 27 (62.8%) had a right shift or no deviation of the mediastinum before surgery and nine (20.9%) had a left shift of the mediastinum, while the condition of seven patients (16.3%) were not described. There were 26 patients undergoing complete separation of liver and lung and 19 (73.1%) of them survived. Thirteen patients underwent partial separation of liver and lung and six of them survived. Four patients died without receiving separation.Conclusions:HPF should be considered in patients with RCDH, especially in cases with no left shift in the mediastinum in the imaging. Preoperative evaluation for surgery in such cases needs to be managed as if it were a major operation that may require hepatectomy or partial pneumonectomy.

Preparation of mesoporous silica nanoparticles with different sizes and study on the correlation between size and toxicity / 药学学报

To investigate the crucial role of particle size in the biological effects of nanoparticles, a series of mesoporous silica nanoparticles (MSNs) were prepared with particle size gradients (50, 100, 150, 200 nm) with the traditional Stober method and adjusting the type and ratio of the silica source. The correlation between toxicity and size-caused biological effects were then further examined both in vitro and in vivo. The results indicated that the prepared MSNs had a uniform size, good dispersal, and ordered mesoporous structure. Hemolytic toxicity was found to be independent of particle size. At the cellular level, MSNs with smaller particle sizes were more readily internalized by cells, which initiated to more intense oxidative stress, therefor inducing higher cytotoxicity, and apoptosis rate. In vivo studies demonstrated that MSNs primarily accumulated in the liver and kidneys of mice. Pharmacokinetic analysis revealed that larger MSNs were eliminated more efficiently by the urinary system than smaller MSNs. The mice's body weight monitoring, blood tests, and pathological sections of major organs indicated good biocompatibility for MSNs of different sizes. Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Zhejiang Chinese Medical University. Overall, this study prepared MSNs with a particle size gradient to investigate the correlation between toxicity and particle size using macrophages and endothelial cells. The study also examined the biosafety of MSNs with different particle sizes in vivo and in vitro, which could help to improve the safety design strategy of MSNs for drug delivery systems.

The Lived Experience of Frailty in Patients Aged 60 Years and Older with Heart Failure: A Qualitative Study

Purpose@#The prevalence of frailty among patients with heart failure is about 45%. Frailty may result in patients' functional decline, falls, disability, and decreased quality of life. Qualitative studies can explore older patients' perceptions of frailty and help patients cope with it. However, a qualitative approach that explores the experience of frailty in older patients living with heart failure is lacking. This study aimed to explore the lived experience of frailty in older patients with heart failure. @*Methods@#This qualitative study applies Giorgi's phenomenological method. Data were collected from October 2019 to August 2020. Thirteen older patients with heart failure aged at least 60 years were recruited using purposive sampling from a medical center in Taiwan. The participants participated in an in-depth interview using a semistructured interview guide. @*Results@#Seven themes were identified: “being reborn at the end of the road but having difficulty recovering”, “living with a disease with an ineffable feeling”, “feeling like being drained: physical weakness and a dysfunctional body”, “struggling with impaired physical mobility and facing unexpected events”, “suffering from mental exhaustion”, “receiving care from loved ones”, and “turning over a new leaf”. @*Conclusions@#Frailty in older patients with heart failure was obscure and difficult to describe. Frailty could be improved by medical intervention, self-management, and social support but was difficult to reverse. Patients with heart failure should be evaluated for frailty using multidimensional assessment tools at first diagnosis and provided frailty-related information so that patients have proper insight into their disease as early as possible.

Distal Mean Nocturnal Baseline Impedance Predicts Pathological Reflux of Isolated Laryngopharyngeal Reflux Symptoms

Background/Aims@#Diagnosis of isolated laryngopharyngeal reflux symptoms (ILPRS), ie, without concomitant typical reflux symptoms (CTRS), remains difficult. Mean nocturnal baseline impedance (MNBI) reflects impaired mucosal integrity. We determined whether esophageal MNBI could predict pathological esophagopharyngeal reflux (pH+) in patients with ILPRS. @*Methods@#In this cross-sectional study conducted in Taiwan, non-erosive or low-grade esophagitis patients with predominant laryngopharyngeal reflux symptoms underwent combined hypopharyngeal multichannel intraluminal impedance-pH monitoring when off acid suppressants. Participants were divided into the ILPRS (n = 94) and CTRS (n = 63) groups. Asymptomatic subjects without esophagitis (n = 25) served as healthy controls. The MNBI values at 3 cm and 5 cm above the lower esophageal sphincter (LES) and the proximal esophagus were measured. @*Results@#Distal but not proximal esophageal median MNBI values were significantly lower in patients with pH+ than in those with pH– (ILPRS in pH+ vs pH–: 1607 Ω vs 2709 Ω and 1885 Ω vs 2563 Ω at 3 cm and 5 cm above LES, respectively; CTRS in pH+ vs pH–: 1476 vs 2307 Ω and 1500 vs 2301 Ω at 3 cm and 5 cm above LES, respectively, P < 0.05 for all). No significant differences of any MNBI exist between any pH– subgroups and healthy controls. The areas under the receiver operating characteristic curve in the ILPRS group were 0.75 and 0.80, compared to the pH– subgroup and healthy controls (P < 0.001 for both), respectively. Interobserver reproducibility was good (Spearman correlation 0.93, P < 0.0001). @*Conclusion@#Distal esophageal MNBI predicts pathological reflux in patients with ILPRS.

The synergistic effect of withaferin A combined with cisplatin on cervical cancer and its mechanism / 中国药理学通报

Aim To study the synergistic effect of withaferin A (WA) combined with cisplatin (DDP) on cervical cancer and its mechanism. Methods MTT assay was employed to detect the synergistic effect of WA on DDP in cervical cancer cell lines. Annexin V-FITC/PI staining, TUNEL assay and immunoblotting were used to investigate the effect of WA combined with DDP on apoptosis of cervical cancer cells. Immunofluorescence and immunoblotting were used to detect NF-kB/MDR1 pathway related proteins. DCFH-DA and MitoSOX were applied to determine the intracellular reactive oxygen species (ROS) levels. A xenograft model was also used to evaluate the synergistic effect of WA on DDP. Results The combination of WA and DDP could inhibit the survival of cervical cancer cells, promote apoptosis, and inhibit the growth of tumor in mice. WA could inhibit DDP-induced NF-kB/MDR1 signaling pathway and promote ROS production. Conclusions WA plays a synergistic role in anti-cervical cancer by inhibiting DDP-induced NF-kB/MDR1 pathway activation and enhancing DDP induced ROS production.

Application of Worst lacrimal probe combined with modified lacrimal duct threading intubation in anastomosis of complex canalicular laceration / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the application value of Worst lacrimal probe combined with modified lacrimal duct intubation in anastomosis of complex canalicular laceration.METHODS: Retrospective study. A total of 68 cases(68 eyes)with complex traumatic canalicular laceration treated in the ophthalmology department of the Second Affiliated Hospital of Zunyi Medical University from March 1, 2019 to March 31, 2021 were selected. They were divided into two groups according to the surgical methods, with 36 patients(36 eyes)who were treated with the Worst lacrimal probe to find the broken end of lacrimal duct combined with improved lacrimal duct threading intubation in group A, and 32 patients(32 eyes)who were treated with microscope to find the broken end of lacrimal duct and two-way intubation anastomosis canaliculus intubation in group B. The clinical efficacy, success rate of intraoperative search for the broken end of lacrimal duct, searching time, operation time, the degree of pain, postoperative ocular foreign body sensation and complications were compared between the two groups.RESULTS: The total effective rate of clinical efficacy in patients of group A was higher than that in group B(94% vs. 38%), the success rate of intraoperative search for broken end of lacrimal duct was higher than that in group B(100% vs. 47%), the searching time and operation time were shorter than those in group B, and the score of pain degree was lower than that in group B(all P&#x0026;#x003C;0.05). The postoperative follow-up for 6mo-1a showed that the ocular foreign body sensation score, the incidence of lacrimal punctum rupture and morphological change, and the degree of tear overflow in group A were all lower than those in group B(all P&#x0026;#x003C;0.05).CONCLUSION: Worst lacrimal probe combined with modified lacrimal duct intubation for the treatment of complex traumatic canalicular laceration can find the broken end of lacrimal duct more accurately, shorten the operation time, reduce the pain and foreign body sensation of patients, improve clinical efficacy and reduce the incidence of complications.

Validation of Pharyngeal Acid Reflux Episodes Using Hypopharyngeal Multichannel Intraluminal Impedance-pH

Background/Aims@#Hypopharyngeal multichannel intraluminal impedance-pH (HMII-pH) technology incorporating 2 trans-upper esophageal sphincter impedance channels has been developed to detect pharyngeal reflux. We used the HMII-pH technique to validate the candidate pharyngeal acid reflux (PAR) episodes based on the dual-pH tracings and determined the interobserver reproducibility. @*Methods@#We conducted a cross-sectional study in tertiary centers in Taiwan. Ninety patients with suspected laryngopharyngeal reflux and 28 healthy volunteers underwent HMII-pH test when off acid suppressants. Candidate PAR episodes were characterized by pharyngeal pH drops of at least 2 units and reaching a nadir pH of 5 within 30 seconds during esophageal acidification. Two experts manually independently identified candidate PAR episodes based on the dual-pH tracings. By reviewing the HMII-pH tracings, HMII-pH-proven PAR episodes were subsequently confirmed. The consensus reviews of HMII-pH-proven PAR episodes were considered to be the reference standard diagnosis. The interobserver reproducibility was assessed. @*Results@#A total of 105 candidate PAR episodes were identified. Among them 84 (80.0%; 95% CI, 71.0-87.0%) were HMII-pH-proven PAR episodes (82 in 16 patients and 2 in 1 healthy subject). Patients tended to have more HMII-pH-proven PAR episodes than healthy controls (median and percentile values [25th, 75th, and 95th percentiles]: 0 [0, 0, 3] vs 0 [0, 0, 0], P = 0.067). The concordance rate in diagnosing HMII-pH-proven PAR episodes between 2 independent observers was 92.2%. @*Conclusion@#Our preliminary data showed that 80.0% (71.0-87.0%) of the proposed candidate PAR episodes were HMII-pH-proven PAR episodes, among which the interobserver reproducibility was good.

Effect of recombinant human growth hormone on serum Klotho and fibroblast growth factor 23 in children with idiopathic short stature / 中国当代儿科杂志

OBJECTIVES@#To investigate the changes in the serum levels of Klotho, fibroblast growth factor 23 (FGF23), and insulin-like growth factor-1 (IGF-1) in children with idiopathic short stature (ISS) before and after recombinant human growth hormone (rhGH) treatment, as well as the correlation of Klotho and FGF23 with the growth hormone (GH)/IGF-1 growth axis in these children.@*METHODS@#A prospective study was conducted on 33 children who were diagnosed with ISS in the Department of Pediatrics, Hebei Provincial People's Hospital, from March 10, 2021 to December 1, 2022 (ISS group). Twenty-nine healthy children, matched for age and sex, who attended the Department of Child Healthcare during the same period, were enrolled as the healthy control group. The children in the ISS group were treated with rhGH, and the serum levels of Klotho, FGF23, and IGF-1 were measured before treatment and after 3, 6, and 9 months of treatment. A correlation analysis was conducted on these indexes.@*RESULTS@#There were no significant differences in the serum levels of IGF-1, Klotho, and FGF23 between the ISS and healthy control groups (P>0.05). The serum levels of Klotho, FGF23, and IGF-1 increased significantly in the ISS group after 3, 6, and 9 months of rhGH treatment (P<0.05). In the ISS group, Klotho and FGF23 levels were positively correlated with the phosphate level before treatment (P<0.05). Before treatment and after 3, 6, and 9 months of rhGH treatment, the Klotho level was positively correlated with the IGF-1 level (P<0.05), the FGF23 level was positively correlated with the IGF-1 level (P<0.05), and the Klotho level was positively correlated with the FGF23 level (P<0.05), while Klotho and FGF23 levels were not correlated with the height standard deviation of point (P>0.05).@*CONCLUSIONS@#The rhGH treatment can upregulate the levels of Klotho, FGF23, and IGF-1 and realize the catch-up growth in children with ISS. Klotho and FGF23 may not directly promote the linear growth of children with ISS, but may have indirect effects through the pathways such as IGF-1 and phosphate metabolism. The consistent changes in Klotho, FGF23 and IGF-1 levels show that there is a synergistic relationship among them in regulating the linear growth of ISS children.

Efficacy of Biejiajian Pill on Intestinal Microbiota in Patients with Hepatitis B Cirrhosis/Liver Fibrosis: A Randomized Double-Blind Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To analyze the efficacy of Biejiajian Pill (BJJP) on intestinal microbiota in patients with hepatitis B cirrhosis/liver fibrosis, and explore its relationship with liver fibrosis.@*METHODS@#This was a prospective, randomized double-blind controlled trial. Using the stratified block randomization method, 35 patients with hepatitis B liver cirrhosis/liver fibrosis were randomly assigned (1:1) to receive entecavir (0.5 mg/d) combined with BJJP (3 g/time, 3 times a day) or placebo (simulator as control, SC group, simulator 3 g/time, 3 times a day) for 48 weeks. Blood and stool samples were collected from patients at baseline and week 48 of treatment, respectively. Liver and renal functions as well as hematological indices were detected. Fecal samples were analyzed by 16S rDNA V3-V4 high-throughput sequencing, and intestinal microbiota changes in both groups before and after treatment were compared, and their correlations with liver fibrosis were analyzed.@*RESULTS@#Compared with the SC group, there was no significant difference in liver function, renal function and hematology indices in the BJJP group, however, the improvement rate of liver fibrosis was higher in the BJJP group (94.4% vs. 64.7%, P=0.041). Principal coordinate analysis (PCoA) based on weighted Unifrac distance showed significant differences in intestinal microbiota community diversity before and after BJJP treatment (P<0.01 and P=0.003), respectively. After 48 weeks' treatment, the abundance levels of beneficial bacteria (Bifidobacteria, Lactobacillus, Faecalibacterium and Blautia) increased, whereas the abundance levels of potential pathogenic bacteria, including Escherichia coli, Bacteroides, Ruminococcus, Parabacteroides and Prevotella decreased, among which Ruminococcus and Parabacteroides were significantly positively correlated with degree of liver fibrosis (r=0.34, P=0.04; r=0.38, P=0.02), respectively. The microbiota in the SC group did not change significantly throughout the whole process of treatment.@*CONCLUSION@#BJJP had a certain regulatory effect on intestinal microbiota of patients with hepatitis B cirrhosis/liver fibrosis (ChiCTR1800016801).

Diverse genetic spectrum among patients who met the criteria of hereditary breast, ovarian and pancreatic cancer syndrome / 부인종양

Objective@#Genetic high-risk assessment combines hereditary breast, ovarian and pancreatic cancer into one syndrome. However, there is a lack of data for comparing the germline mutational spectrum of the cancer predisposing genes between these three cancers. @*Methods@#Patients who met the criteria of the hereditary breast, ovarian and pancreatic cancer were enrolled and received multi-gene sequencing. @*Results@#We enrolled 730 probands: 418 developed breast cancer, 185 had ovarian cancer, and 145 had pancreatic cancer. Out of the 18 patients who had two types of cancer, 16 had breast and ovarian cancer and 2 had breast and pancreatic cancer. A total of 167 (22.9%) patients had 170 mutations. Mutation frequency in breast, ovarian and pancreatic cancer was 22.3%, 33.5% and 17.2%, respectively. The mutation rate was significantly higher in patients with double cancers than those with a single cancer (p<0.001). BRCA1 and BRCA2 were the most dominant genes associated with hereditary breast and ovarian cancer, whereas ATM was the most prevalent gene related to hereditary pancreatic cancer. Genes of hereditary colon cancer such as lynch syndrome were presented in a part of patients with pancreatic or ovarian cancer but seldom in those with breast cancer. Families with a history of both ovarian and breast cancer were associated with a higher mutation rate than those with other histories. @*Conclusion@#The mutation spectrum varies across the three cancer types and family histories. Our analysis provides guidance for physicians, counsellors, and counselees on the offer and uptake of genetic counseling.

Nicotinamide mononucleotide attenuates ischemia-reperfusion injury induced by donor liver from cardiac death through Sirt3 / 器官移植

Objective To evaluate the effect and mechanism of nicotinamide mononucleotide (NMN) on ischemia-reperfusion injury (IRI) induced by donor liver after cardiac death in rat models. Methods Rat models of orthotopic liver transplantation were established by "magnetic ring + double cuff" method. SD rats were randomly divided into the sham operation group (Sham group), orthotopic liver transplantation group (OLT group), NMN treatment + orthotopic liver transplantation group (NMN group), NMN+sirtuin-3 (Sirt3) inhibitor (3-TYP) + orthotopic liver transplantation group (NMN+3-TYP group), respectively. Pathological changes and hepatocyte apoptosis of the rats were observed in each group. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were determined. Superoxide dismutase (SOD) and malondialdehyde (MDA) contents in liver tissues were detected. The expression levels of Sirt3, microtubule-associated protein 1 light chain 3 (LC3)Ⅱ, PTEN-induced putative kinase 1 (PINK1), Parkin and translocase of the outer mitochondrial membrane 20 (TOMM20) in liver tissues were measured. Postoperative survival of the rats in each group was analyzed. Results Compared with the Sham group, serum ALT and AST levels were higher in the OLT group. Compared with the OLT group, the levels of ALT and AST were decreased in the NMN group. Compared with the NMN group, the levels of ALT and AST were increased in the NMN +3-TYP group (all P < 0.05). The liver tissue structure of rats in the Sham group was basically normal. In the OLT group, pathological changes, such as evident congestion, vacuolar degeneration and hepatocyte necrosis, were observed in the liver tissues. Compared with the Sham group, Suzuki score and apoptosis rate were higher in the OLT group. Suzuki score and apoptosis rate in the NMN group were lower than those in the OLT group. Suzuki score and apoptosis rate in the NMN+3-TYP group were higher compared with those in the NMN group (all P < 0.05). Compared with the Sham group, the SOD content was decreased, whereas the MDA content was increased in the OLT group. Compared with the OLT group, the SOD content was increased, whereas the MDA content was decreased in the NMN group. Compared with the NMN group, the SOD content was decreased, whereas the MDA content was increased in the NMN+3-TYP group (all P < 0.05). Compared with the Sham group, the relative expression levels of Sirt3 and TOMM20 proteins were down-regulated, whereas those of PINK1, Parkin and LC3Ⅱproteins were up-regulated in the OLT group. Compared with the OLT group, the relative expression levels of Sirt3, PINK1, Parkin and LC3Ⅱproteins were up-regulated, whereas that of TOMM20 protein was down-regulated in the NMN group. Compared with the NMN group, the relative expression levels of PINK1, Parkin and LC3Ⅱproteins were down-regulated, whereas that of TOMM20 protein was up-regulated in the NMN+3-TYP group (all P < 0.05). In the Sham group, the 7 d survival rate of rats was 100%, 50% in the OLT group, 75% in the NMN group and 58% in the NMN+3-TYP group, respectively. Conclusions NMN may enhance the antioxidative capacity of the liver, induce PINK1/Parkin-mediated mitochondrial autophagy, and alleviate IRI of the liver by up-regulating Sirt3, thereby playing a protective role in the donor liver after cardiac death.

Research Status of Biomarkers in Early Screening and Early Diagnosis of Lung Cancer / 肿瘤防治研究

Lung cancer is one of the most malignant tumors in the world. In China, the mortality rate of lung cancer has been in the first place for many years. Early screening and early diagnosis of lung cancer is the premise of prolonging the survival time of patients with lung cancer. In recent years, liquid biopsy technology, which is considered to have a bright future, has attracted more and more attention, and its value in the early diagnosis of lung cancer is worth discussing. This paper reviews the application of biomarkers in early screening and early diagnosis of lung cancer, looks for specific biomarkers from multi-omics, and discusses their significance in early diagnosis of lung cancer.

Effect of hippocampal brain derived neurotrophic factor precursor in mice cognitive dysfuction induced by social isolation / 解剖学报

[Abstract] Objective To investigate the effect of hippocampal brain derived neurotrophic factor precursor (proBDNF) in cognitive dysfuction induced by social isolation. Methods Thirty C57BL / 6 J male mice (4-week old) were randomly divided into group house (GH,n = 15) and socially isolated (SI,n = 15) groups. The GH group (5 mice / cage) and SI group (1 mice / cage) were reared separately under the same conditions. The novel object recognition test and the novel place recognition test were used to evaluate the cognitive function. The expression of BDNF mRNA in the hippocampus was detected by Real-time PCR. The expression of BDNF and proBDNF in hippocampus was detected by Western blotting. Matrix metallopeptidase-9 (MMP-9) and tissue plasminogen activator (tPA) were extracellular enzymes that catalyzed the transformation of proBDNF into mature BDNF. Expression of MMP-9 and tPA mRNA in the hippocampus were detected by Real-time PCR. Results Compared with the GH group, the SI group showed significantly reduced discrimination ratio in the novel object recognition test and novel place recognition test. The result of Real-time PCR showed that there was no difference in the expression of BDNF mRNA between SI group and GH group. The result of Western blotting showed that the expression level of proBDNF in the hippocampus of SI group increased significantly compared with the GH group (P<0. 01),and no difference in BDNF expression was found between the two groups; Compared with the GH group, the BDNF/ proBDNF ratio in the hippocampus of SI group decreased. In addition, the result of Real-time PCR showed that the expression level of MMP-9 and tPA mRNA in the hippocampus of SI group decreased significantly compared with the GH group. Conclusion The social isolation-induced cognitive dysfuction in mice may be related to the up-regulation of proBDNF in the hippocampus.