Immunotherapy with dendritic cells and cytokine-induced killer cells for hepatocellular carcinoma: A meta-analysis

BACKGROUND Hepatocellular carcinoma(HCC) has been revealed as the second most common cause of cancer-related deaths worldwide. The introduction of cell-based immunotherapy, including dendritic cells(DCs) and cytokine-induced killer cells(CIKs), has brought HCC patients an effective benefit. However, the efficacy and necessity of cellular immunotherapy after different interventional therapy remains to be further explored.AIM To investigate the efficacy of cellular immunotherapy, involving DCs and CIKs,combined with different conventional treatments of HCC.METHODS We performed a literature search on PubMed and Web of Science up to February15, 2019. Long-term efficacy(overall survival and recurrence) and short-term adverse effects were investigated to assess the effectiveness of immunotherapy with DCs and/or CIKs. Review Manager 5.3 was used to perform the analysis.RESULTS A total of 22 studies involving 3756 patients selected by eligibility inclusion criteria were forwarded for meta-analysis. Combined with the conventional clinical treatment, immunotherapy with DCs and/or CIKs was demonstrated to significantly improve overall survival at 6 mo [risk ratio(RR) = 1.07;95%confidence interval(CI): 1.01-1.13, P = 0.02], 1 year(RR = 1.12;95%CI: 1.07-1.17, P< 0.00001), 3 years(RR = 1.23;95%CI: 1.15-1.31, P < 0.00001) and 5 years(RR =1.26;95%CI: 1.15-1.37, P < 0.00001). Recurrence rate was significantly reduced by cellular immunotherapy at 6 mo(RR = 0.50;95%CI: 0.36-0.69, P < 0.0001) and 1 year(RR = 0.82;95%CI: 0.75-0.89, P < 0.00001). Adverse effect assessment addressed that immunotherapy with DCs and/or CIKs was accepted as a safe,feasible treatment.CONCLUSION Combination immunotherapy with DCs, CIKs and DC/CIK with various routine treatments for HCC was evidently suggested to improve patients’ prognosis by increasing overall survival and reducing cancer recurrence.

Prevalence and risk factors of organ failure in patients with severe acute pancreatitis

BACKGROUND： This study was undertaken to determine the prevalence of organ failure and its risk factors in patients with severe acute pancreatitis （SAP） .METHODS： A retrospective analysis was made of 186 patients with SAP who were had been hospitalized in the intensive care unit of Jinzhong First People’s Hospital between March 2000 and October 2009. The patients met the diagnostic criteria of SAP set by the Surgical Society of the Chinese Medical Association in 2006. The variables collected included age, gender, etiology of SAP, the number of comorbidit, APACHEII score, contrast-enhanced CT （CECT） pancreatic necrosis, CT severity index （CTSI） , abdominal compartment syndrome （ACS） , the number of organ failure, and the number of death. The prevalence and mortality of organ failure were calculated. The variables were analyzed by unconditional multivariate logistic regression to determine the independent risk factors for organ failure in SAP.RESULTS： Of 186 patients, 96 had organ failure. In the 96 patients, 47 died. There was a significant association among the prevalence of organ failure and age, the number of comorbidity, APACHEII score, CECT pancreatic necrosis, CTSI, and ACS. An increase in age, the number of comorbidity, APACHEII score, CECT pancreatic necrosis were correlated with increased number of organ failure. Age, the number of comorbidity, APACHEII score, CECT pancreatic necrosis, CTSI and ACS were assessed by unconditional multivariate logistic regression.CONCLUSIONS： Organ failure occurred in 51.6% of the 186 patients with SAP. The mortality of SAP with organ failure was 49.0%. Age, the number of comorbidity, APACHEII score, CECT pancreatic necrosis, CTSI and ACS are independent risk factors of organ failure.

地塞米松玻璃体内植入剂联合抗VEGF药物治疗视网膜静脉阻塞

目的:比较地塞米松玻璃体内植入剂联合抗VEGF药物与抗VEGF药物单药治疗视网膜静脉阻塞继发黄斑水肿(RVO-ME)的疗效和安全性。方法:选取2019-06/2020-12在厦门大学附属厦门眼科中心确诊为视网膜中央静脉阻塞(CRVO)或视网膜分支静脉阻塞(BRVO)继发黄斑水肿的患者133例133眼,其中CRVO-ME患者48眼,BRVO-ME患者85眼。将纳入患者随机分组,其中单药治疗组66眼接受每月注射康柏西普1次,连续3mo,之后每月复诊;联合治疗组67眼接受地塞米松玻璃体内植入剂注射1次,1wk后注射康柏西普1次,之后每月复诊。随访6mo,观察两组患者最佳矫正视力(BCVA)和中央视网膜厚度(CRT)改善情况,记录康柏西普注射次数及与玻璃体腔注射治疗相关的眼部及全身不良事件发生情况。结果:治疗后1、2、3、6mo,两组患者BCVA和CRT均较治疗前显著改善,但两组间BCVA和CRT改善程度均无差异(P>0.05)。首次玻璃体腔注射至治疗6mo时,单药治疗组和联合治疗组康柏西普玻璃体腔注射次数分别为3.56±0.12、2.96±0.17次,联合治疗组注射次数显著低于单药治疗组(P=0.004)。随访期间,联合治疗组高眼压和白内障发生率均高于单药治疗组。结论:地塞米松玻璃体内植入剂联合抗VEGF药物是治疗RVO-ME的有效方法,可显著改善视力,降低CRT,该治疗方案可在减少抗VEGF药物注射次数的同时达到与抗VEGF药物单药治疗相似的疗效,但需要监控眼压变化及白内障进展情况。

25G+与27G+玻璃体切割手术治疗玻璃体视网膜疾病的疗效比较

目的:对比观察25G+与27G+微创玻璃体切割手术(MIVS)治疗玻璃体视网膜疾病的疗效分析。方法:回顾性病例对照研究,选取自2018-12/2020-01期间在我院治疗的各种玻璃体视网膜疾病的患者76例76眼,随机分为25G+组和27G+组进行玻璃体切割手术治疗,对比分析两组患者的手术时间,以及术前1d,术后1d,1、4、12、24wk的ETDRS视力、眼压、结膜水肿等变化情况。结果:相对于25G+组,27G+组玻璃体切割时间较长(27.17±5.95 vs 26.71±5.93min),而总的手术时间较短(28.26±6.88 vs 30.37±6.68min),但两组间均无差异(t=0.322,P=0.748;t=-1.353,P=0.180)。两组玻璃体切割术后,视力较术前均有明显提高,但两组间比较无差异(P>0.05)。相对于25G+组,27G+组术后1d(12.58±2.44 vs 10.56±3.21mmHg,t=2.943,P=0.004)和术后1wk(13.48±2.85 vs 12.89±2.01mmHg,t=1.460,P=0.031)的眼压波动范围较低。术后1wk内,25G+组发生一过性低眼压7眼,而在27G+组无低眼压发生,表明27G+MIVS能够更好地稳定术后眼压。结论:27G+MIVS和25G+MIVS治疗玻璃体视网膜疾病安全有效。与25G+MIVS相比,27G+MIVS术后更能够很好地稳定眼压,减少因术后低眼压引起的并发症的发生。

Painlevé property, local and nonlocal symmetries, and symmetry reductions for a (2+1)-dimensional integrable KdV equation

The Painlevé property for a(2+1)-dimensional Korteweg–de Vries(KdV) extension, the combined KP3(Kadomtsev–Petviashvili) and KP4(cKP3-4), is proved by using Kruskal’s simplification. The truncated Painlevé expansion is used to find the Schwartz form, the Bäcklund/Levi transformations, and the residual nonlocal symmetry. The residual symmetry is localized to find its finite Bäcklund transformation. The local point symmetries of the model constitute a centerless Kac–Moody–Virasoro algebra. The local point symmetries are used to find the related group-invariant reductions including a new Lax integrable model with a fourth-order spectral problem. The finite transformation theorem or the Lie point symmetry group is obtained by using a direct method.

Serum Soluble Vascular Endothelial Growth Factor Receptor 1 as a Potential Biomarker of Hepatopulmonary Syndrome

Background and Aims:The results of basic research implicate the vascular endothelial growth factor(VEGF)family as a potential target of hepatopulmonary syndrome(HPS).However,the negative results of anti-angiogenetic therapy in clinical studies have highlighted the need for markers for HPS.Therefore,we aimed to determine whether VEGF family members and their receptors can be potential biomarkers for HPS through clinical and experimental studies.Methods:Clinically,patients with chronic liver disease from two medical centers were enrolled and examined for HPS.Patients were divided into HPS,intrapulmonary vascular dilation[positive contrast-enhanced echocardiography(CEE)and normal oxygenation]and CEE-negative groups.Baseline information and perioperative clinical data were compared between HPS and non-HPS patients.Serum levels of VEGF family members and their receptors were measured.In parallel,HPS rats were established by common bile duct ligation.Liver,lung and serum samples were collected for the evaluation of pathophysiologic changes,as well as the expression levels of the above factors.Results:In HPS rats,all VEGF family members and their receptors underwent significant changes;however,only soluble VEGFR1(sFlt-1)and the sFlt-1/placental growth factor(PLGF)ratio were changed in almost the same manner as those in HPS patients.Furthermore,through feature selection and internal and external validation,sFlt-1 and the sFlt-1/PLGF ratio were identified as the most important variables to distinguish HPS from non-HPS patients.Conclusions:Our results from animal and human studies indicate that sFlt-1 and the sFlt-1/PLGF ratio in serum are potential markers for HPS.

Ultrasonographic evaluation of the rete testis thickness:a promising approach to differentiate obstructive from nonobstructive azoospermia

This study aimed to evaluate the ability of rete testis thickness(RTT)and testicular shear wave elastography(SWE)to differentiate obstructive azoospermia(OA)from nonobstructive azoospermia(NOA).We assessed 290 testes of 145 infertile males with azoospermia and 94 testes of 47 healthy volunteers at Shanghai General Hospital(Shanghai,China)between August 2019 and October 2021.The testicular volume(TV),SWE,and RTT were compared among patients with OA and NOA and healthy controls.The diagnostic performances of the three variables were evaluated using the receiver operating characteristic curve.The TV,SWE,and RTT in OA differed significantly from those in NOA(all P≤0.001)but were similar to those in healthy controls.Males with OA and NOA were similar at TVs of 9–11 cm^(3)(P=0.838),with sensitivity,specificity,Youden index,and area under the curve of 50.0%,84.2%,0.34,and 0.662(95%confidence interval[CI]:0.502–0.799),respectively,for SWE cut-off of 3.1 kPa;and 94.1%,79.2%,0.74,and 0.904(95%CI:0.811–0.996),respectively,for RTT cut-off of 1.6 mm.The results showed that RTT performed significantly better than SWE in differentiating OA from NOA in the TV overlap range.In conclusion,ultrasonographic RTT evaluation proved a promising diagnostic approach to differentiate OA from NOA,particularly in the TV overlap range.

Novel mutation in ODF2 causes multiple morphological abnormalities of the sperm flagella in an infertile male

Numerous genes have been associated with multiple morphological abnormalities of the sperm flagella(MMAF),which cause severe asthenozoospermia and lead to male infertility,while the causes of approximately 50%of MMAF cases remain unclear.To reveal the genetic causes of MMAF in an infertile patient,whole-exome sequencing was performed to screen for pathogenic genes,and electron microscope was used to reveal the sperm flagellar ultrastructure.A novel heterozygous missense mutation in the outer dense fiber protein 2(ODF2)gene was detected,which was inherited from the patient’s mother and predicted to be potentially damaging.Transmission electron microscopy revealed that the outer dense fibers were defective in the patient’s sperm tail,which was similar to that of the reported heterozygous Odf2 mutation mouse.Immunostaining of ODF2 showed severe ODF2 expression defects in the patient’s sperm.Therefore,it was concluded that the heterozygous mutation in ODF2 caused MMAF in this case.To evaluate the possibility of assisted reproductive technology(ART)treatment for this patient,intracytoplasmic sperm injection(ICSI)was performed,with the help of a hypo-osmotic swelling test and laser-assisted immotile sperm selection(LAISS)for available sperm screening,and artificial oocyte activation with ionomycin was applied to improve the fertilization rate.Four ICSI cycles were performed,and live birth was achieved in the LAISS-applied cycle,suggesting that LAISS would be valuable in ART treatment for MMAF.

A de novo frameshift mutation of the SRY gene leading to a patient with 46,XY complete gonadal dysgenesis

Dear Editor,Sex in mammals is genetically determined and defined at the cellular level by the sex chromosome constitution(XY males and XX females)and at the phenotypic level by the development of genderspecific anatomy,physiology,and behavior.146,XY complete gonadal dysgenesis(46,XY CGD),first reported by Swyer in 1955,^2 is a rare congenital condition with completely or partially disordered gonadal development,leading to discordance between the genetic,gonadal,and phenotypic sex.Affected patients have a 46,XY karyotype,a female phenotype,normal female external genitalia,and CGD("streak gonads")without sperm production and follicular or steroid function.

Novel deletion mutations of the PIH1D3 gene in an infertile young man with primary ciliary dyskinesia and his cousin with Kartagener’s syndrome

Dear Editor,Male infertility is defined as the inability to achieve pregnancy in a fertile female partner even after 12 months of unprotected intercourse.In humans,it accounts for 40%-50%of cases of infertility,1 and it occurs most often due to problems with sperm production or sperm delivery.Male infertility is commonly due to deficiencies in semen,and semen quality is used as a surrogate measure of male fecundity.Primary ciliary dyskinesia(PCD)is a rare cause of male infertility.2,3 It is an autosomal recessive genetic condition that causes abnormal function of cilia.Cilia are microscopic finger-like projections on the surface of the cells.

SoySNP618K array:A high-resolution single nucleotide polymorphism platform as a valuable genomic resource for soybean genetics and breeding

Innovations in genomics have enabled the development of low-cost,high-resolution,single nucleotide polymorphism(SNP)genotyping arrays that accelerate breeding progress and support basic research in crop science.Here,we developed and validated the Soy SNP618 K array(618,888 SNPs)for the important crop soybean.The SNPs were selected from whole-genome resequencing data containing 2,214 diverse soybean accessions;29.34%of the SNPs mapped to genic regions representing 86.85%of the 56,044annotated high-confidence genes.Identity-by-state analyses of 318 soybeans revealed 17 redundant accessions,highlighting the potential of the Soy SNP618 K array in supporting gene bank management.The patterns of population stratification and genomic regions enriched through domestication were highly consistent with previous findings based on resequencing data,suggesting that the ascertainment bias in the Soy SNP618 K array was largely compensated for.Genome-wide association mapping in combination with reported quantitative trait loci enabled fine-mapping of genes known to influence flowering time,E2 and Gm PRR3 b,and of a new candidate gene,Gm VIP5.Moreover,genomic prediction of flowering and maturity time in 502 recombinant inbred lines was highly accurate(>0.65).Thus,the Soy SNP618 K array is a valuable genomic tool that can be used to address many questions in applied breeding,germplasm management,and basic crop research.