Objective To investigate the synergistic therapeutic effects of HER2 antibody-drug conjugate(HER2-ADC)combined with anti-PD-1 antibody(anti-PD-1)on HER2-expressing bladder cancer and elucidate its regulatory mechanisms on the tumor immune microenvironment.Methods Orthotopic tumor models were established in 40 female C57BL/6 mice(6～8 weeks old,body mass 18～22 g)using MB49 bladder cancer cells overexpressing human HER2.When tumors reached 100 mm3,the mice were randomized into(n=10)control(intraperitoneal injection of 1.0 mL PBS),anti-PD-1(200 μg per mouse every 3 d),HER2-ADC(2.5 mg/kg once weekly),and combination groups(same regimens as above monotherapy).Tumor volume and body mass were measured every 3 d during 28-day treatment.Tumor growth kinetics and survival rates were analyzed.Post-treatment survival was monitored until natural death to determine median survival time(n=5).At day 28,blood and tumor samples(n=5)were collected to detect myeloid-derived suppressor cells(MDSCs;CD11b?Gr1?)and regulatory T cells(Tregs;CD4?CD25?FOXP3?)with flow cytometry,tumor-infiltrating CD3?T,CD8?T,and FOXP3?T cells with immunohistochemical assasy,and liver/kidney functions[alanine aminotransferase(ALT),aspartate aminotransferase(AST),blood urea nitrogen(BUN),creatinine(CRE)]and tissue damage indicators[lactate dehydrogenase isoenzyme(LDH-L)].Results In 28 d after treatment,the combination group obtained significantly smallest tumor volume than the control group and the 2 monotherapy groups(all P<0.01).The longest median survival was observed in the combination group(65 d,P<0.01),followed by the HER2-ADC group(55 d),anti-PD-1 group(53 d)and control group(41 d).After 28 d of treatment,the combination group exhibited obviously the smallest peripheral proportions of MDSCs/Tregs,most tumor-infiltrating CD3?T/CD8?T cells,and less FOXP3?T cells when compared with the 2 monotherapy groups and control group(all P<0.05).While,the 2 monotherapy groups had smaller MDSCs/Tregs proportions than the control group(P<0.05).No significant differences were observed among the 4 groups in serum ALT,AST,BUN,CRE,or LDH-L levels,and all of them were within normal ranges.Conclusion HER2-ADC combined with anti-PD-1 suppresses the growth of orthotopic bladder tumor,probably through their synergic effects on down-regulating MDSCs/Treg and enhancing CD8?T cell infiltration.

Objective To examine the effect of ground cage use on Oncomelania hupensis spread, so as to provide insights into precision snail control. Methods Twenty ground cages that were frequently used to capture rice field eels were purchased, including 11 packaging tape-made cages, 7 plastic cages and 2 nylon rope-made cages. The eel-capturing activity was mimicked, and 20 ground cages were assigned in settings with relatively high (1.00 snail/0.1 m² and higher) and low snail densities (< 1.00 snail/0.1 m²) in Xindai Township, Pinghu City, Zhejiang Province during the period from 15 : 00 to 8 : 00 of the following day on April 13, 26 and 28. The numbers of snails carried by different types of ground cages were compared in settings with different types of snail densities using the rank-sum test. Results A total of 11 cage-times were assigned in settings with a high snail density, and a total of 77 snails were captured, with a mean number of 7 snails in each cage-time and 2.15 snails in 0.1 m² ground cage. The mean numbers of snails carried by packaging tape-made and plastic cages were 2.47 snails/0.1 m² cage and 0.37 snails/0.1 m² cage, respectively. A total of 24 cage-times were assigned in settings with a low snail density, and a total of 8 snails were captured, with a mean number of 0.33 snails in each cage-time and 0.09 snails in 0.1 m² ground cage. The mean numbers of snails carried by packaging tape-made cages were 0.12 snails/0.1 m² cage; however, no snails were carried by plastic or nylon rope-made cages. The number of snails carried by ground cages was higher in settings with a high snail density than in settings with a low snail density (Z = −4.019, P < 0.01), and the number of snails carried by packaging tape-made cages was higher in settings with a high snail density than in settings with a low snail density (Z = −4.086, P < 0.01). No significant differences were found in the numbers of snails carried by different types of ground cages. Conclusion The use of ground cage in snail habitats is a contributor to snail spread.

We report a case of a male patient who developed persistent fever and central nervous system symptoms after eating raw snails for 10 days. The patient was diagnosed with Angiostrongyliasis depended on the clinical presentation, epidemiological history, and etiological results. The patient recovered after receiving albendazole anthelmintic and dexamethasone anti-inflammatory therapy. This article incorporates literature review to sort out the diagnosis and treatment of this patient, in order to provide feasible reference for clinicians.

We report a case of a male patient who developed persistent fever and central nervous system symptoms after eating raw snails for 10 days. The patient was diagnosed with Angiostrongyliasis depended on the clinical presentation, epidemiological history, and etiological results. The patient recovered after receiving albendazole anthelmintic and dexamethasone anti-inflammatory therapy. This article incorporates literature review to sort out the diagnosis and treatment of this patient, in order to provide feasible reference for clinicians.

Objective:To study the changes in serum small molecule metabolites after brucella infection in humans using untargeted metabolomics methods, and screening representative biomarkers. Methods:A total of 109 serum samples collected from January 2019 to December 2021 at the Brucellosis Clinic of the Baotou Center for Disease Control and Prevention were divided into acute phase group ( n = 40), chronic phase group ( n = 35) of brucellosis, and healthy group ( n = 34) based on clinical diagnosis. Ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry technology was used to test serum samples and screen for differential metabolites. Receiver operating characteristic curve was used to evaluate the predictive ability of differential metabolites for brucellosis. Enriched pathways were screened using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway to identify metabolic pathways significantly affected. Results:A total of 17 differential metabolites were screened between the acute phase group and the healthy group, and 12 differential metabolites were screened between the chronic phase group and the healthy group. There were a total of 5 differential metabolites (oleamide, linoleamide, stearamide, palmitoleic acid, α-linolenic acid) statistically significant among the three groups ( F = 16.84, 17.52, 14.31, 13.01, 20.76, P < 0.05). KEGG pathway analysis showed that the differential metabolites in the acute phase group were enriched in metabolic pathways such as ether lipid metabolism, glycerophosphate metabolism, sphingolipid signal and sphingolipid metabolism. The differential metabolites in the chronic phase group were enriched in metabolic pathways such as glycerophosphate metabolism, ether lipid metabolism, protein digestion and absorption metabolism. Conclusion:Untargeted metabolomics methods can screen out serum small molecule metabolites that undergo changes after brucella infection in the human body, including oleamide, linoleamide, stearamide, palmitoleic acid, α-linolenic acid can serve as potential biomarkers to distinguish brucellosis patients from healthy people.

Objective:To develop the Suicide Outcomes Scale for Undergraduates with Suicidal Ideation(SO-SUSI)and test its validity and reliability.Methods:Based on semi-structured interview,literature review and expert discussion,main aspects and indicator system were defined.The initial version of SOSUSI was formed,and items were either modified from existing scales targeting the relevant constructs,or compiled according to previous inter-view results.A total of 607 undergraduates with suicidal ideation were enrolled.The sample was randomly divided in half,one half(n=317)was used for item analysis and exploratory factor analysis,and another half(n=290)for confirmatory factor analysis.All data were used for reliability analysis.The Self-rating Depression Scale(SDS)and Suicidal Intent(SI)were used for criterion validity.Results:The SOSUSI included 39 items in 4 dimensions(nega-tive reinforcement of suicide,negative consequences of suicide,loss of suicide,and positive reinforcement of sui-cide)which explained 50.10％of the total variance.Confirmatory factor analysis showed that the four-factor struc-ture model fitted well(x2/df=3.27,CFI=0.92,TLI=0.91,IFI=0.92,SRMR=0.09).The scores of negative re-inforcement and positive reinforcement of suicide were positively correlated with the SDS and SI scores(ICC=0.15-0.33,Ps＜0.05),while the scores of negative consequences and loss of suicide were negatively correlated with the SI scores(ICC=-0.42--0.56,Ps＜0.05).The Cronbach's α coefficients of each dimension ranged from 0.79 to 0.91.Conclusion:The Suicide Outcomes Scale for Undergraduates with Suicidal Ideation(SOSUSI)has good validity and internal consistency reliability.

Objective To investigate the value of proxies for insulin resistance in evaluating non-alcoholic fatty liver disease visceral fat index(VAI)(OR=3.777,95%CI:1.554-9.180)were the influencing factors of NAFLD in T2DM patients(all P<0.05).Receiver operating character(ROC)curve showed that the sensitivities of HOMA-IR,TG/HDL-C,TyG,TyG-BMI and VAI in predicting NAFLD in T2DM patients was 71.43%,74.79%,71.43%,73.95%and 70.59%,specificity were 70.73%,80.49%,73.17%,79.27%and 70.73%,and AUC values were 0.744,0.758,0.742,0.777 and 0.724,respectively.The levels of HOMA-IR,TG/HDL-C,TyG and TyG-BMI in the progressive liver fibrosis group were higher than those in the non-progressive liver fibrosis group(all P<0.05).Conclusion Homa-IR,TG/HDL-C,TyG,TyG-BMI and VAI are associated with NAFLD in T2DM patients.Insulin resistance proxies show good efficacy in predicting NAFLD in T2DM patients,and it may be related to the severity of NAFLD.

ObjectiveTo investigate the regulatory effect and molecular mechanism of berberine （BBR） on lipophagy in the prevention and treatment of atherosclerotic （AS） lesions in mice. MethodFifty apolipoprotein E-knockout （ApoE^-/-） mice were randomly divided into an AS model group， an atorvastatin group （5 mg·kg^-1）， and low-， medium-， and high-dose BBR groups （2.5， 5， 10 mg·kg^-1）. Ten C57BL/6J mice were assigned to the control group. After 12 weeks， hematoxylin-eosin （HE） and oil red O staining were performed to assess the histopathological changes of AS plaques in the aorta. Biochemical analysis was used to measure serum lipid levels， and enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of inflammatory cytokines interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α）， oxidative stress marker reactive oxygen species （ROS）， and serum lipophagy marker Beclin1 and microtubule-associated protein 1 light chain 3 Ⅱ （LC3Ⅱ）. The xanthine oxidase method was used to measure serum superoxide dismutase （SOD） activity. Immunohistochemistry （IHC） was used to detect the distribution of wingless-type MMTV integration site family member 5a （Wnt5a） and Nieman Pick type C1 （NPC1） in the aorta， and Western blot was used to determine the protein expression of Wnt5a and NPC1 in the aorta. ResultCompared with the control group， the AS model group showed significant AS plaque formation， significantly elevated levels of serum total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， IL-6， TNF-α， and ROS， aortic Wnt5a distribution and protein expression （P<0.01）， and significantly reduced levels of serum high-density lipoprotein cholesterol （HDL-C）， SOD， Beclin1， LC3Ⅱ， and aortic NPC1 distribution and protein expression （P<0.01）. Compared with the AS model group， the atorvastatin group， and high- and medium-dose BBR groups showed a significant reduction in AS plaque area （P<0.05， P<0.01）， significantly decreased levels of serum TC， TG， LDL-C， IL-6， TNF-α， ROS， and aortic Wnt5a distribution and protein expression （P<0.05， P<0.01）， and significantly increased levels of serum HDL-C， SOD， Beclin1， LC3Ⅱ， and aortic NPC1 distribution and protein expression （P<0.05， P<0.01）. There was no statistically significant difference in the above indicators between the atorvastatin group and the medium-dose BBR group. ConclusionBBR can competitively bind to Wnt5a to activate NPC1 expression， upregulate lipophagy levels， reduce blood lipids， and inhibit the release of inflammatory mediators and oxidative stress damage， thereby exerting a preventive and therapeutic effect on AS.

Gelsemium elegans is a traditional Chinese herb of medicinal importance, with indole terpene alkaloids as its main active components. To study the expression of the most suitable housekeeping reference genes in G. elegans, the root bark, stem segments, leaves and inflorescences of four different parts of G. elegans were used as materials in this study. The expression stability of 10 candidate housekeeping reference genes (18S, GAPDH, Actin, TUA, TUB, SAND, EF-1α, UBC, UBQ, and cdc25) was assessed through real-time fluorescence quantitative PCR, GeNorm, NormFinder, BestKeeper, ΔCT, and RefFinder. The results showed that EF-1α was stably expressed in all four parts of G. elegans and was the most suitable housekeeping gene. Based on the coexpression pattern of genome, full-length transcriptome and metabolome, the key candidate targets of 18 related genes (AS, AnPRT, PRAI, IGPS, TSA, TSB, TDC, GES, G8H, 8-HGO, IS, 7-DLS, 7-DLGT, 7-DLH, LAMT, SLS, STR, and SGD) involved in the Gelsemium alkaloid biosynthesis were obtained. The expression of 18 related enzyme genes were analyzed by qRT-PCR using the housekeeping gene EF-1α as a reference. The results showed that these genes' expression and gelsenicine content trends were correlated and were likely to be involved in the biosynthesis of the Gelsemium alkaloid, gelsenicine.
Genes, Essential ; Gelsemium/genetics* ; Peptide Elongation Factor 1/genetics* ; Transcriptome ; Gene Expression Profiling/methods* ; Alkaloids ; Real-Time Polymerase Chain Reaction/methods* ; Reference Standards

Podocyte infolding glomerulopathy (PIG) is a pathologic type of podocyte glomerulopathy reported recently. The characteristic is that the ultrastructure related to podocytes, such as microspheres and microtubules, are folded into the glomerular basement membrane (GBM) under electron microscope. At present, there are few reports about this disease at home and abroad, and most of them are concentrated in Japan. The clinical characteristics and pathogenesis of PIG are still unclear. In this paper, we report a case of clinical manifestations of nephrotic syndrome, renal biopsy indicated PIG, after the treatment of glucocorticoid, hydroxychloroquine and tacrolimus, the patient's clinical symptoms were relieved and urinary protein decreased.