Pancreatic cancer is a kind of highly malignant tumor with a low survival rate and poor prognosis. The effectiveness of gemcitabine as a first-line chemotherapy drug is limited; however, it can activate dendritic cells and improve antigen presentation which increase the sensitivity of tumor cell to immunotherapy. Although immunotherapy has made some advancements in cancer treatment, the therapeutic benefit of programmed cell death receptor 1/programmed death receptor-ligand 1 (PD-1/PD-L1) blockade therapy remains relatively low. The chemokine C-X-C chemokine ligand 12 (CXCL12) contributes to an immunosuppressive tumor microenvironment by recruiting immunosuppressive cells. The receptor C-X-C motif chemokine receptor 4 (CXCR4), highly expressed in various tumors including pancreatic cancer, plays a crucial role in tumor development and progression. In this study, the anti-tumor immune response of human peripheral blood mononuclear cell (hPBMC) was enhanced using the combination of BsNb PX4 (anti-PD-L1&CXCR4 bispecific nanobody) and gemcitabine. In a co-culture system of gemcitabine-pretreated hPBMCs with tumor cells, the BsNb PX4 synergized gemcitabine to improve the cytotoxic activity of hPBMCs against tumor cells. Flow cytometry analysis confirmed increased ratio of CD8⁺ to CD4⁺ T cells in combination treatment. In NOD/SCID mice bearing pancreatic cancer, the combination treatment exhibited more infiltration of CD8⁺ T cells into tumor tissues, contributing to an effective anti-tumor response. This study presents potential new therapies for the treatment of pancreatic cancer. Ethical approval was obtained for collection of hPBMC samples from the Local Ethics Committee of Shanghai Jiao Tong University. All animal experiments were approved by the Animal Ethic Committee of Shanghai Jiao Tong University (authorizing number: A2024246).

Objective To investigate the clinical efficacy of Guiyuan Shujin Mixture in the treatment of patients with lumbar disc herniation(LDH)and to explore its possible therapeutic mechanism.Methods Sixty-eight patients with LDH of qi stagnation and blood stasis syndrome were randomly divided into trial group and control group,with 34 cases in each group.The control group was treated with Celecoxib Tablets and Mecobalamin Tablets orally,and the trial group was treated with Guiyuan Shujin Mixture on the basis of treatment for the control group.The course of treatment lasted for 4 weeks.Before and after treatment,the two groups were observed in the changes of the Visual Analogue Scale(VAS)score of low back pain and lower limb pain,Oswestry Disability Index(ODI)score,modified Japanese Orthopedic Association(JOA)score,serum levels of inflammatory factors of tumor necrosis factor α(TNF-α),interleukin 6(IL-6)and interleukin 1β(IL-1β),and serum nuclear factor-κB p65(NF-κB p65)level.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)During the trial,one case fell off in the trial group and 3 cases fell off in the control group.Eventually,33 cases in the trial group and 31 cases in the control group were included for the efficacy statistics.(2)After 4 weeks of treatment,the total effective rate of the trial group was 96.97%(32/33),and that of the control group was 87.10%(27/31).The intergroup comparison(tested by rank sum test)showed that the curative effect of the trial group was significantly superior to that of the control group(P＜0.05).(3)After treatment,the VAS score and ODI score of low back pain and lower limb pain in the two groups were lower than those before treatment(P＜0.05 or P＜0.01),and the modified JOA score was higher than that before treatment(P＜0.01).The decrease of VAS score and ODI score of low back pain and lower limb pain and the increase of modified JOA score in the trial group were significantly superior to those in the control group(P＜0.05 or P＜0.01).(4)After treatment,the serum levels of inflammation-related indicators of TNF-α,IL-6,IL-1β and NF-κB p65 in the two groups were lower than those before treatment(P＜0.01),and the decrease in the trial group was significantly superior to that in the control group(P＜0.01).(5)During the treatment,the incidence of adverse events in the trial group was 2.94%(1/34)and that in the control group was 8.82%(3/34),and the difference between the two groups was not significant(P＞0.05).Conclusion Guiyuan Shujin Mixture exerts certain effect in the treatment of LDH patients with qi stagnation and blood stasis syndrome.It can effectively relieve the pain symptoms of patients,improve the lumbar function of patients,and reduce the expression levels of serum inflammatory factors and NF-κB p65.The mechanism may be related with the decrease of the level of inflammatory factors and with the inhibition of the activation of NF-κB signaling pathway.

Objective To elucidate the molecular genetic etiology of patients with disorders of sex development(DSD)using whole exome sequencing(WES),thereby enhancing our understanding of the underlying mechanisms of sexual development abnormalities.Methods Retrospective analysis was conducted on clinical data of 60 DSD patients diagnosed in the First People's Hospital of Yunnan Province between March 2008 and August 2021,with an additional family study for one proband.Genomic DNA was extracted from patients for WES analysis.Single nucleotide polymorphism(SNP)and insertions/deletion(InDel)tests were identified using SAMtools software in conjunction with established SNP and InDel databases.Copy number variations(CNVs)at the exon level were detected using ExomeDepth,while the potential pathogenicity of mutations was predicted with PolyPhen-2,Mutation taster and PyMol software,with Sanger sequencing employed for confirmation.Results The study included 22 patients with 46,XX DSD and 38 with 46,XY DSD.Among the 46,XX DSD patients,the SRY gene was detected in 14 patients.In the remaining 8 patients and a proband's families,single nucleotide site variations(SNVs)of NR5A1,PROKR2 and ANOS1 genes were identified in 2 patients,and CNVs in CYP21A2 gene were found in 4 patients.The pathogenicity of CYP21A2 EX1 Dup has been previously reported,while the remaining 3 CNVs were of uncertain significance,and no DSD-related mutations were detected in 2 patients.In the WES analysis of 46,XY DSD patients,10 pathogenic or likely pathogenic SNVs across 5 genes(SRY,AR,SRD5A2,CYP17A1,and NR5A1)were identified in 14 patients.Additionally,5 likely pathogenic CNVs involving the CYP21A2,AKR1C2,CBX2,and NR5A1 genes were detected in 5 patients,comprising 3 deletions and 2 duplications.Novel SNVs in NR5A1(c.722G>T,c.48C>G)and ANOS1 c.564A>T were identified,with no prior reports in relevant databases.The pathogenicity of CYP21A2 EX1 Dup is documented in related databases,while the remaining CNVs have not been previously reported.Conclusion The utilization of WES technology has enhanced the diagnostic potential for DSD,broadened the spectrum of known DSD-related gene mutations,and deepened our comprehension of DSD pathogenesis,offering valuable support for genetic counseling.

Objective To compare the repair effects of different doses of human umbilical cord mesenchymal stem cells(hUC-MSCs)on white matter injury(WMI)in neonatal rats.Methods Two-day-old Sprague-Dawley neonatal rats were randomly divided into five groups:sham operation group,WMI group,and hUC-MSCs groups(low dose,medium dose,and high dose),with 24 rats in each group.Twenty-four hours after successful establishment of the neonatal rat white matter injury model,the WMI group was injected with sterile PBS via the lateral ventricle,while the hUC-MSCs groups received injections of hUC-MSCs at different doses.At 14 and 21 days post-modeling,hematoxylin and eosin staining was used to observe pathological changes in the tissues around the lateral ventricles.Real-time quantitative polymerase chain reaction was used to detect the quantitative expression of myelin basic protein(MBP)and glial fibrillary acidic protein(GFAP)mRNA in the brain tissue.Immunohistochemistry was employed to observe the expression levels of GFAP and neuron-specific nuclear protein(NeuN)in the tissues around the lateral ventricles.TUNEL staining was used to observe cell apoptosis in the tissues around the lateral ventricles.At 21 days post-modeling,the Morris water maze test was used to observe the spatial learning and memory capabilities of the neonatal rats.Results At 14 and 21 days post-modeling,numerous cells with nuclear shrinkage and rupture,as well as disordered arrangement of nerve fibers,were observed in the tissues around the lateral ventricles of the WMI group and the low dose group.Compared with the WMI group,the medium and high dose groups showed alleviated pathological changes;the arrangement of nerve fibers in the medium dose group was relatively more orderly compared with the high dose group.Compared with the WMI group,there was no significant difference in the expression levels of MBP and GFAP mRNA in the low dose group(P＞0.05),while the expression levels of MBP mRNA increased and GFAP mRNA decreased in the medium and high dose groups.The expression level of MBP mRNA in the medium dose group was higher than that in the high dose group,and the expression level of GFAP mRNA in the medium dose group was lower than that in the high dose group(P＜0.05).Compared with the WMI group,there was no significant difference in the protein expression of GFAP and NeuN in the low dose group(P＞0.05),while the expression of NeuN protein increased and GFAP protein decreased in the medium and high dose groups.The expression of NeuN protein in the medium dose group was higher than that in the high dose group,and the expression of GFAP protein in the medium dose group was lower than that in the high dose group(P＜0.05).Compared with the WMI group,there was no significant difference in the number of apoptotic cells in the low dose group(P＞0.05),while the number of apoptotic cells in the medium and high dose groups was less than that in the WMI group,and the number of apoptotic cells in the medium dose group was less than that in the high dose group(P＜0.05).Compared with the WMI group,there was no significant difference in the escape latency time in the low dose group(P＞0.05);starting from the third day of the latency period,the escape latency time in the medium dose group was less than that in the WMI group(P＜0.05).The medium and high dose groups crossed the platform more times than the WMI group(P＜0.05).Conclusions Low dose hUC-MSCs may yield unsatisfactory repair effects on WMI in neonatal rats,while medium and high doses of hUC-MSCs have significant repair effects,with the medium dose demonstrating superior efficacy.[Chinese Journal of Contemporary Pediatrics,2024,26(4):394-402]

The determinations of the operation mode and basic performance conformity for evaluating the electromagnetic compatibility of brain-computer interface rehabilitation robots were described based on relevant standards of the electromag-netic compatibility of medical electrical equipment.The performance deviations and their causes during the electromagnetic compatibility evaluation of brain-computer interface rehabilitation robots were analyzed with case studies,and some improve-ment suggestions were proposed accordingly.Technical references were provided for the manufacturers of brain-computer interface rehabilitation robots.[Chinese Medical Equipment Journal,2024,45(9):84-88]

Objective To investigate the therapeutic effect and mechanism of Jianwei Xiaozhang Tablets on rats with precancerous lesions of gastric cancer(PLGC).Methods Forty male SD rats were randomly divided into the normal group,the model group,the folic acid group and the Jianwei Xiaozhang Tablets group,with 10 rats in each group.In addition to the normal group,the other three groups of rats were prepared by gavage with Ranitidine Aqueous Solution combined with N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)solution drinking method for the preparation of PLGC model.After successful modeling,drugs were administered accordingly for 7 weeks.The changes in body mass of rats during modeling and drug administration were recorded,the gross view of the stomach was observed and scored pathologically,the coefficients of spleen and liver were determined,the pathological changes in gastric tissue were observed by hematoxylin-eosin(HE)staining,enzyme-linked immunosorbent assay(ELISA)was used to measure serum gastrin(GAS),motilin(MTL)and glucagon(GC),Alisin Blue-Periodic Acid Schiff's(AB-PAS)staining was used to observe the thickness of the mucosal layer of gastric tissues,the expressions of phosphatidylinositol 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(Akt),phosphorylated Akt(p-Akt),and endothelial-type nitric oxide synthase(eNOS)proteins in gastric tissues were detected by protein immunoblotting(Western Blot),and the expression of vascular endothelial growth factor A(VEGFA)protein in gastric tissues was detected by immunofluorescence staining.Results Compared with the normal group,the body mass of rats in the model group grew slowly during the experimental period,gastric macroscopic pathological scores were significantly increased(P＜0.01),splenic coefficient and hepatic coefficient were significantly decreased(P＜0.01),the gastric tissues showed cuprocyte hyperplasia and intestinal chemotaxis,gastric tissues'inflammation scores were significantly increased(P＜0.01),the serum GAS content was significantly increased(P＜0.01),and the MTL,GC contents were significantly reduced(P＜0.05),and the thickness of the mucous membrane layer of gastric tissue was significantly reduced(P＜0.05),the protein expression levels of PI3K,p-PI3K,Akt,p-Akt and eNOS were reduced(P＜0.01),and the protein expression level of VEGFA was reduced(P＜0.01);compared with the model group,the above indexes of the Jianwei Xiaozhang Tablets group and the folic acid group were all significantly improved(P＜0.05 or P＜0.01),among which,the Jianwei Xiaozhang Tablets group had a better improvement effect in the proliferation of cup cells and intestinal chemotaxis in gastric tissues,the content of serum GAS,and the thickness of the mucous layer in gastric tissues.Conclusion The mechanism of the improvement of PLGC in rats by Jianwei Xiaozhang Tablets may be related to the activation of the PI3K-Akt-eNOS pathway,which in turn promotes the angiogenesis and repair of gastric damaged tissues.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To investigate the effect of enhanced Dulbecco's modified Eagle's medium(DMEM)on the cultivation of Blastocystis hominis.Methods A total of 329 clinical samples were selected to compare the growth of B.hominis using enhanced DMEM and the iodine solution direct smear method.The morphology,minimum detection limit and growth curve of B.hominis were compared between the conventional DMEM culture medium and the enhanced DMEM culture method.Results In 329 clinical specimens,the positive rate for B.hominis was 5.17％(17/329)in the enhanced DMEM culture and 1.52％(5/329)in the iodine solution stained smears;the difference was statistically significant(P＜0.01).Conclusion The enhanced DMEM culture method can be used for the proliferation and culture of B.hominis in vitro.

Clonorchis sinensis(hookworm)is a foodborne parasite.Infection is caused by consuming raw or semi-raw freshwater fish and shrimp containing metacercariae.It is often misdiagnosed or overlooked because of its hidden onset and atypical clinical symptoms.In the present study,the diagnosis and treatment of two cases of light clonorchiasis infection were reported,and epidemiological investigations were performed.Clinical symptoms,laboratory diagnostic characteristics,epidemiological characteristics,and pathogenic agents of clonorchiasis were analyzed by clinicians to improve the diagnosis and treatment of clonorchiasis and to achieve early prevention,diagnosis,and treatment.