Objective:To analyze the safety and efficacy of PD-1 inhibitors versus chemotherapy or ipilimumab in advanced melanoma.Methods:PubMed,CNKI,VIP and Wanfang databases were searched to collect randomised controlled trials of PD-1 inhibi-tors in treatment of advanced melanoma.The search time was from the establishment of the database to May 1,2022.Two reviewers independently screened the literature,extracted data,and assessed risk of bias of included studies.Meta-analysis was performed using RevMan5.4 and STATA16 software.Results:A total of 7 studies were included.Meta-analysis results show that:①Safety:Compared with chemotherapy,PD-1 inhibitor treatment had fewer adverse events,especially in the blood system;compared with ipilimumab alone,PD-1 inhibitor combined with ipilimumab had more adverse events,especially liver function indicators;there was no signifi-cant difference in the incidence of total adverse events between PD-1 inhibitor monotherapy and ipilimumab monotherapy.②Efficacy:The PFS,OS and ORR of PD-1 inhibitor versus chemotherapy or ipilimumab were HR=0.54,95%CI(0.45,0.62),P<0.05,HR= 0.69,95%CI(0.58,0.80),P=0.03 and OR=3.16,95%CI(2.59,3.86),P<0.05,respectively.Conclusion:PD-1 inhibitors have good efficacy in treatment of advanced melanoma,while different combination methods and different control treatments may have different efficacy.Limited by the quantity and quality of included studies,more research evidence is needed to support this.

Objective:To investigate the clinical phenotype and genetic characteristics of patients with Fabry disease caused by a GLA variant, IVS4+919G>A.Methods:It was a prospective study. Fabry disease screening was conducted among high-risk population in Ninghai from October 2021 to August 2023. Those children with decreased α-galactosidase enzyme activity<2.40 μmol/(L·h) or elavated Lyso-GL-3 level>1.10 μg/L in dried blood spot (DBS) method underwent GLA genetic testing for diagnosis confirmation. Meanwhile, family screening was carried out. A proband and his family members diagnosed with Fabry disease were research subjects. The clinical and genetic characteristics of patients with Fabry disease caused by the GLA variant (IVS4+919G>A) were analyzed.Results:The female proband aged 9.8 years with pain in both lower limbs as the initial symptom was found to have a heterozygous GLA variant IVS4+919G>A among 102 patients. In family screening, there were 4 family members (proband's father, elder sister, elder male cousin and elder female cousin) with Fabry disease and a family member (proband's fifth aunt) with a GLA variant. Among these 4 diagnosed family members, the elder male cousin of the proband, a boy aged 13.2 years had a heterozygous GLA variant, IVS4+919G>A with intermittent pain in both lower limbs as the initial symptom. The proband′s father had knee joint pain. The proband′s elder sister had decreased vision and his elder female cousin had no obvious symptoms. The proband′s fifth aunt with a GLA variant had decreased vision.Conclusions:High-risk screening in children and family screening are helpful for early diagnosis and treatment of Fabry disease. Neuropathic pain may be a early symptom in children with Fabry disease caused by the GLA variant, IVS4+919G>A.

Fatigue is one of the common symptoms in patients with liver cirrhosis, which has a serious impact on the quality of life of patients. This article reviews the influencing factors and intervention strategies of fatigue in patients with cirrhosis, aiming to provide reference for early recognition and intervention of fatigue in patients with cirrhosis.

ObjectiveTo observe the intervention effect of Chaihu and Longgu Mulitang （CLMT） on rat depression model prepared by chronic unpredictable mild stress （CUMS） based on cyclic adenosine monophosphate （cAMP）/protein kinase A （PKA）/cAMP-response element-binding protein （CREB）-brain-derived neurotrophic factor （BDNF） signaling pathway. MethodSixty SD rats were divided into normal group， model group， and CLMT low-， medium- and high-dose groups and fluoxetine group （positive control） according to random number table. They， except the normal group， were treated with CUMS for 49 days to prepare the rat depression model. The CLMT low-， medium- and high-dose groups were given 2.89， 5.78 11.56 g·kg^-1 of CHMD granules， respectively， and the fluoxetine group was given 2.06 mg·kg^-1 of fluoxetine hydrochloride on the 29^th day. The normal group and the model group received equal volume of normal saline for 21 days. The behavioral performance of rats were observed by open field test and forced swim test. The levels of 5-hydroxytryptamine （5-HT）， norepinephrine （NE） and cAMP in rat hippocampus were measured by enzyme-linked immunosorbent assay （ELISA）. The mRNA expressions of PKA， CREB， and BDNF in rat hippocampus were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and the protein expressions of PKA and BDNF were detected by Western blot. Immunohistochemistry was used to determine the expression of CREB， and hematoxylin and eosin （HE） staining and Nissl staining were used to observe the morphological changes of hippocampus. ResultCompared with the conditions in the normal group， the immobility time of the model group in the forced swim test was increased （P<0.01） and the total movement distance， residence time in central area， number of entries in central area and movement distance in central area were decreased （P<0.01）. Additionally， the contents of 5-HT， NE and cAMP in hippocampus of the model group as well as the protein expressions of PKA， BDNF and CRE，the mRNA expressions of BDNF and CREB were lower than those in the normal group （P<0.01）. Compared with the model group， the CLMT groups had reduced immobility time （P<0.01）， elevated total movement distance， residence time in central area， number of entries in central area and movement distance in central area （P<0.05， P<0.01）， up-regulated contents of 5-HT， NE and cAMP in hippocampus （P<0.05， P<0.01）， and up-regulated protein expressions of PKA， BDNF and CREB and mRNA expressions of BDNF and CREB （P<0.01）. HE staining and Nissl staining showed that CLMT significantly improved the neuronal structure in rat hippocampus. ConclusionCLMT alleviates the anxiety and depression of rats. These effects may be mediated by regulating monoamine neurotransmitters 5-HT and NE in hippocampus of depressed rats， activating cAMP/PKA/CREB/BDNF signaling pathway， up-regulating the expression of BDNF and protecting hippocampal structure and function .

Objective:To compare the safety and efficacy of terbutaline and nifedipine for acute intrapartum fetal resuscitation (IUFR).Methods:This was a prospective randomized controlled study involving 110 pregnant women with non-reassuring fetal heart rate tracings (NRFHT) during delivery at Guangzhou Women and Children's Medical Center between January and April 2021. These women were randomly allocated to receive subcutaneous terbutaline sulphate (0.25 mg, terbutaline group) or oral nifedipine (10 mg, nifedipine group), with 55 subjects in each group. Hemodynamic parameters including blood pressure, heart rate, and oxygen saturation before and 5, 15 and 30 min after treatment as well as the success rate of intrapartum resuscitation, the onset time of medication, and the incidence of postpartum hemorrhage were analyzed using t test, Chi-square test or Fisher's exact test. Results:Two groups both showed no significant difference in the mean arterial pressure or oxygen saturation before or after treatment (all P>0.05). The heart rate was not affected in nifedipine group at any time points ( P>0.05). While the patients treated with terbutaline showed accelerated maternal heart rate 5, 15 and 30 min after administration as compared with the baseline[(97.0±20.2), (99.2±13.8), (91.8±12.6) vs (81.7±11.3) bpm, all P<0.001], but it began to decrease at 30 min, with a drop of 6.4 bpm compared with that at 15 min (95% CI: 1.5-11.2, P<0.05). None of the pregnant women had adverse reactions requiring medical intervention. The rates of successful acute resuscitation were similar in the two groups [terbutaline: 78.2% (43/55) vs nifedipine: 70.9% (39/55), χ 2= 0.77, P=0.381]. Terbutaline had a shorter onset time than nifedipine in slowing the frequency of contractions and returning fetal heart rate to class Ⅰ category [2(1-6) vs 6(1-10) min, U=2 348.50, P<0.001]. No significant difference was found between the two groups in terms of NRFHT-indicated cesarean section, assisted vaginal delivery, or second dose of tocolysis within 1 h (all P>0.05) nor in blood loss volume, postpartum hemorrhage rate, low Apgar score, low umbilical artery pH value (pH<7.2), neonatal asphyxia rate, or neonatal intensive care admission rate (all P>0.05). Conclusion:Terbutaline spends less time than nifedipine to take effect and may be an alternative for acute IUFR without significant adverse outcomes.

Objective: To investigate the survival status and influencing factors of HIV/AIDS patients after receiving highly active antiretroviral therapy（HAART）in Shangluo,Shaanxi Province,so as to provide evidence for improving the effect of HAART. Methods: HIV/AIDS patients who received HAART for the first time in Shangluo from 2010 to 2018 were investigated. Life table method was used to analyze the survival rate,mortality rate and median survival time of the subjects. A proportional hazards model was used to analyze the influencing factors for the survival time of HIV/AIDS patients. Results: A total of 286 HIV/AIDS patients were collected,and 27 of them died of AIDS. After HAART,the 1-year,cumulative survival rates of less than 1 year,4 years and 8 years were 93.95%,89.71% and 88.39%,respectively. The results of multivariate proportional hazards regression analysis showed that the patients aged 30 years when first received HAART had higher risk of death than those aged 18-29 years（RR：4.208-24.095,95%CI：1.219-79.491）;patients with AIDS had higher risk of death than those with HIV（RR=38.590, 95%CI：15.451-96.382）;patients by homosexual transmission（RR=3.425,95%CI：1.385-8.470）and non-sexual transmission（RR=10.299,95%CI：3.602-29.446）had higher risk of death than those by heterosexual transmission;patients with baseline CD4+T lymphocytes number of 200/μL and more（RR：0.133-0.170,95%CI：0.048-0.604）had lower risk of death than those with less than 200/μL. Conclusions The survival rate of HIV/AIDS patients in Shangluo after receiving HAART is relatively high. Age at the start of treatment,course of disease,route of infection and the number of CD4+T lymphocytes at baseline are the influencing factors of survival time.

Objective:To explore the effect of continuous quality improvement (CQI) on reducing the incidence of peritoneal dialysis (PD)-related peritonitis in patients within the first year of PD initiation.Methods:The patients who received catheter placement from January 2006 to December 2016 in our hospital were enrolled in this study. All patients were divided into four groups: pre-CQI group patients who initiated PD treatment from 2006 to 2007 (before CQI phase, group A), CQI Ⅰphrase patients who initiated PD treatment from 2008 to 2010 (group B), CQI Ⅱ phrase patients who initiated PD treatment from 2011 to 2013 (group C), and CQI Ⅲ phrase patients who initiated PD treatment from 2014 to 2016 (group D). The method of plan, do, check and act (PDCA) was conducted to decrease the incidence of PDRP. All the patients were followed up for 12 months or until they withdrew from PD in this period. Poisson analysis was used to compare the incidence of PDRP among the groups.Results:There were 2 383 PD patients recruited in this study, including 346 cases in group A, 850 cases in group B, 688 cases in group C and 499 cases in group D, with an age of (47.1±15.8) years, among whom 59.1% of the patients were male, and 21.4% with diabetes. The follow-up time was (10.9±2.8) months. Compared with group A, the incidence of PDRP was lower than that in group C (0.156 episodes/patient year vs 0.234 episodes/patient year, P=0.020); the incidence of gram positive PDRP decreased (0.052, 0.049, 0.054 episodes/patient year vs 0.104 episodes/patient year, all P<0.05) in group B, C, D; the incidence of gram negative PDRP increased in group B, then decreased in group C and group D (all P>0.05). Cox regression analysis indicated that CQI was independently associated with the incidence of gram positive PDRP ( HR=0.526, 95% CI 0.349-0.792, P=0.002). Conclusion:CQI can effectively reduce the incidence of gram positive PDRP in patients within the first year of PD initiation.

Objective: To evaluate the effectiveness of deep learning model trained on routine CT scans when identity the malignant and benign lung nodule on target CT scans dataset. Methods: This retrospective study enrolled 923 patients with lung nodules found by chest CT scan in Shanghai Chest Hospital from January 2016 to December 2018. A total of 969 nodules with pathological report were analyzed. The deep learning based pulmonary malignant prediction method in a fine-grained classification manner was used to make the prediction, and the AUC (the area under the curve), accuracy, sensitivity and specificity of routine CT scans and target CT scans were compared, and Delong test and IDI (Integrated Discrimination Improvement) were employed to provide statistical results. Furthermore, statistical methods were used to investigate the differences between the benign and malignant classification of nodules on routine CT and on target CT. Results: In the benign and malignant discrimination task, AUC, accuracy, sensitivity and specificity on the routine scans were 0.81, 82.0%, 86.0% and 56.6% respectively, while the AUC, accuracy, sensitivity and specificity on the target scans were 0.84, 85.0%, 88.8% and 60.5% respectively. The IDI was 0.056 (Z test, P<0.05), and there was statistically significant difference in ROC (Delong test, P=0.01). Conclusions The deep learning model trained on the data set of routine CT scans can achieve better diagnostic efficiency in target CT scans data.

Objective To explore the characterization of thyroid stimulating hormone receptor(TSHR) gene mutational spectrum in children with hyperthyroidism from Guangzhou. Methods Ninety children were diagnosed with hyperthyroidism from July 2009 to July 2014 in our institute. Their median age at diagnosis was(7.5± 3.4) years, and there were 28 males and 62 females. Mutational analysis were performed by performing polymerase chain reaction (PCR) and DNA direct sequencing of exon 10 of TSHR gene. TSHR gene mutations from 50 unrelated healthy children were served as controls. The correlation between TSHR gene and hyperthyroidism in children was explored. Results A total of 3 mutations were identified in ninety children who were diagnosed with hyperthyroidism, one synonymous mutations(p.V614V), and two missense mutations( p. R707W and p. D727E). Mutation of p. V614V do not change amino acid and do not influence the structure and function of TSHR, no pathogenicity. p.R707W is a SNP associated with human cancers. The frequency of C allele of the D727E in children with hyperthyroidism was 86.7%, while 55.0% in the controls, significant different between the children with hyperthyroidism and the controls( P＜0. 01). In this study, a very high association between the D727E SNP and hyperthyroidism ( OR=18. 86, P＜0. 01) was found. Conclusion Three different mutations of TSHR gene exon 10 were identified in 90 children with hyperthyroidism, (c.1842A＞G,p.V614V、c.2119C＞T,p.R707W、c.2181G＞C,p.D727E), there were association between p.D727E and hyperthyroidism, nor p. V614V and p. R707W. Finally, p. D727E may be correlated with hyperthyroidism in children.