Objective:To investigate GPRC5D expression on myeloma cells in newly diagnosed multiple myeloma (NDMM) patients and evaluate its prognostic significance.Methods:This study retrospectively analyzed the clinical data of 65 patients with NDMM treated at the Affiliated Hospital of Xuzhou Medical University from April 2023 to April 2024. The expression of GPRC5D on the surface of myeloma cells in all patients was detected with flow cytometry before induction therapy, and patients were stratified into high and low GPRC5D expression groups based on the median GPRC5D positivity rate. Clinical characteristics, immune status, treatment response after induction therapy, and prognosis were compared between the two groups.Results:The median positive rate of GPRC5D in the plasma cells of 65 patients with NDMM was 32.68%. Based on this threshold, patients were categorized into the high (33 cases, GPRC5D positive rate ≥ 32.68%) and low (32 cases, GPRC5D positive rate <32.68%) GPRC5D expression groups. Compared with the low GPRC5D expression group, the high GPRC5D expression group demonstrated a higher proportion of 1q21 gain (78.8% vs 43.8%, P=0.004), a higher incidence of immunoparesis involving ≥2 uninvolved immunoglobulins (87.9% vs 62.5%, P=0.018), and severe immunoparesis (59.4% vs 33.3%, P=0.046). Further, CD16 +CD56 + cell levels were lower in the high GPRC5D expression group [ (16.60±8.70) % vs (27.78±15.78) %, P=0.005]. No significant difference was observed in the overall response rate between the high and low GPRC5D expression groups (78.8% vs 93.8%, P=0.165). However, the high GPRC5D expression group exhibited a significantly lower rate of achieving very good partial remission or better (42.4% vs 78.2%, P=0.003) and a lower MRD negativity rate (30.0% vs 68.8%, P=0.002). Compared with the low GPRC5D expression group, patients with high expression demonstrated a significantly shorter median progression-free survival (11.2 months vs not reached, P=0.002), whereas the median overall survival was not reached in either group, with no statistically significant difference ( P=0.069) . Conclusions:The GPRC5D positivity rate in the plasma cells of patients with NDMM is associated with 1q21 gain and immune status. High GPRC5D expression at diagnosis may predict poor response to induction therapy and an unfavorable prognosis.

Objective To investigate the correlation and clinical prognostic value between the expression of polypeptide N-acety lgalactosaminyltransferases 1(GALNT1),lysosomal adaptor MTOR activator 5(LAMTOR5),and epithelial mesenchymal transition(EMT)in gastric cancer.Methods 102 gastric cancer patients admitted to Nantong Tumor Hospital from January 2018 to January 2020 were selected.Immunohistochemistry(IHC)and real-time fluorescence quantitative PCR(RT-PCR)were used to detect the expression of GALNT1,LAMTOR5 mRNA and protein,as well as the expression of EMT indicators Snail mRNA,N-cad mRNA and Vimentin mRNA in cancer and adjacent tissues.Pearson correlation analysis was performed to investigate the correlation between markers.Kaplan Meier curve analysis was used to investigate the relationship between GALNT1 mRNA,LAMTOR5 mRNA and the prognosis of gastric cancer patients.COX regression analysis was used to identify factors that affect the prognosis of gastric cancer patients.Results GALNT1 mRNA(3.38±0.29)and LAMTOR5 mRNA(3.17±0.26)in gastric cancer tissue were higher than those in adjacent tissues(0.72±0.16,0.65±0.13),and the differences were statistically significant(t=81.111,87.553,all P<0.001).The positive rates of GALNT1(92.16%),LAMTOR5(90.20%)proteins in gastric cancer tissues were higher than those in adjacent tissues(7.84%,11.76%),and the differences were statistically significant(χ2=145.020,125.538,P<0.001).The expression of GALNT1 mRNA and LAMTOR5 mRNA in gastric cancer was positively correlated(r=0.757,P<0.001).The expression of GALNT1 mRNA and LAMTOR5 mRNA in gastric cancer was significantly positively correlated with Snail mRNA,N-cad mRNA and Vimentin mRNA expression(r=0.654,0.712,0.689;0.706,0.645,0.723,all P<0.001).The expression of GALNT1 mRNA and LAMTOR5 mRNA was correlated with TNM stage and lymph node metastasis in gastric cancer patients.The expression of GALNT1 mRNA and LAMTOR5 mRNA in cancer tissues with TNM stage III and lymph node metastasis was higher than that in TNM stage I～II and no lymph node metastasis,and the differences were statistically significant(χ2=29.417～290.104,all P<0.001).The 3-year overall survival rate of the high expression group of GALNT1 mRNA was 40.00%(20/50),which was lower than 76.92%(40/52)of the low expression group,the 3-year overall survival rate of the high expression group of LAMTOR5 mRNA was 38.78%(19/49),which was lower than the 77.36%(41/53)of the low expression group,and the differences were statistically significant(Log-Rank χ2=7.327,5.197,P=0.009,0.023).TNM stage III,lymph node metastasis,GALNT1 mRNA was highly expressed,and high LAMTOR5 mRNA was highly expressed were risk factors affecting the prognosis of gastric cancer(Wald χ2=6.409～16.805,all P<0.001).Conclusion The expression of GALNT1 and LAMTOR5 are elevated in gastric cancer tissues.Both of them are related to EMT indicators and adverse clinicopathological features.They are biomarkers for evaluating the prognosis of gastric cancer patients.

Objective:To investigate GPRC5D expression on myeloma cells in newly diagnosed multiple myeloma (NDMM) patients and evaluate its prognostic significance.Methods:This study retrospectively analyzed the clinical data of 65 patients with NDMM treated at the Affiliated Hospital of Xuzhou Medical University from April 2023 to April 2024. The expression of GPRC5D on the surface of myeloma cells in all patients was detected with flow cytometry before induction therapy, and patients were stratified into high and low GPRC5D expression groups based on the median GPRC5D positivity rate. Clinical characteristics, immune status, treatment response after induction therapy, and prognosis were compared between the two groups.Results:The median positive rate of GPRC5D in the plasma cells of 65 patients with NDMM was 32.68%. Based on this threshold, patients were categorized into the high (33 cases, GPRC5D positive rate ≥ 32.68%) and low (32 cases, GPRC5D positive rate <32.68%) GPRC5D expression groups. Compared with the low GPRC5D expression group, the high GPRC5D expression group demonstrated a higher proportion of 1q21 gain (78.8% vs 43.8%, P=0.004), a higher incidence of immunoparesis involving ≥2 uninvolved immunoglobulins (87.9% vs 62.5%, P=0.018), and severe immunoparesis (59.4% vs 33.3%, P=0.046). Further, CD16 +CD56 + cell levels were lower in the high GPRC5D expression group [ (16.60±8.70) % vs (27.78±15.78) %, P=0.005]. No significant difference was observed in the overall response rate between the high and low GPRC5D expression groups (78.8% vs 93.8%, P=0.165). However, the high GPRC5D expression group exhibited a significantly lower rate of achieving very good partial remission or better (42.4% vs 78.2%, P=0.003) and a lower MRD negativity rate (30.0% vs 68.8%, P=0.002). Compared with the low GPRC5D expression group, patients with high expression demonstrated a significantly shorter median progression-free survival (11.2 months vs not reached, P=0.002), whereas the median overall survival was not reached in either group, with no statistically significant difference ( P=0.069) . Conclusions:The GPRC5D positivity rate in the plasma cells of patients with NDMM is associated with 1q21 gain and immune status. High GPRC5D expression at diagnosis may predict poor response to induction therapy and an unfavorable prognosis.

Objective To investigate the correlation and clinical prognostic value between the expression of polypeptide N-acety lgalactosaminyltransferases 1(GALNT1),lysosomal adaptor MTOR activator 5(LAMTOR5),and epithelial mesenchymal transition(EMT)in gastric cancer.Methods 102 gastric cancer patients admitted to Nantong Tumor Hospital from January 2018 to January 2020 were selected.Immunohistochemistry(IHC)and real-time fluorescence quantitative PCR(RT-PCR)were used to detect the expression of GALNT1,LAMTOR5 mRNA and protein,as well as the expression of EMT indicators Snail mRNA,N-cad mRNA and Vimentin mRNA in cancer and adjacent tissues.Pearson correlation analysis was performed to investigate the correlation between markers.Kaplan Meier curve analysis was used to investigate the relationship between GALNT1 mRNA,LAMTOR5 mRNA and the prognosis of gastric cancer patients.COX regression analysis was used to identify factors that affect the prognosis of gastric cancer patients.Results GALNT1 mRNA(3.38±0.29)and LAMTOR5 mRNA(3.17±0.26)in gastric cancer tissue were higher than those in adjacent tissues(0.72±0.16,0.65±0.13),and the differences were statistically significant(t=81.111,87.553,all P<0.001).The positive rates of GALNT1(92.16%),LAMTOR5(90.20%)proteins in gastric cancer tissues were higher than those in adjacent tissues(7.84%,11.76%),and the differences were statistically significant(χ2=145.020,125.538,P<0.001).The expression of GALNT1 mRNA and LAMTOR5 mRNA in gastric cancer was positively correlated(r=0.757,P<0.001).The expression of GALNT1 mRNA and LAMTOR5 mRNA in gastric cancer was significantly positively correlated with Snail mRNA,N-cad mRNA and Vimentin mRNA expression(r=0.654,0.712,0.689;0.706,0.645,0.723,all P<0.001).The expression of GALNT1 mRNA and LAMTOR5 mRNA was correlated with TNM stage and lymph node metastasis in gastric cancer patients.The expression of GALNT1 mRNA and LAMTOR5 mRNA in cancer tissues with TNM stage III and lymph node metastasis was higher than that in TNM stage I～II and no lymph node metastasis,and the differences were statistically significant(χ2=29.417～290.104,all P<0.001).The 3-year overall survival rate of the high expression group of GALNT1 mRNA was 40.00%(20/50),which was lower than 76.92%(40/52)of the low expression group,the 3-year overall survival rate of the high expression group of LAMTOR5 mRNA was 38.78%(19/49),which was lower than the 77.36%(41/53)of the low expression group,and the differences were statistically significant(Log-Rank χ2=7.327,5.197,P=0.009,0.023).TNM stage III,lymph node metastasis,GALNT1 mRNA was highly expressed,and high LAMTOR5 mRNA was highly expressed were risk factors affecting the prognosis of gastric cancer(Wald χ2=6.409～16.805,all P<0.001).Conclusion The expression of GALNT1 and LAMTOR5 are elevated in gastric cancer tissues.Both of them are related to EMT indicators and adverse clinicopathological features.They are biomarkers for evaluating the prognosis of gastric cancer patients.

There is increasing evidence that the activation of glucagon-like peptide-1 receptor(GLP-1R)can be used as a therapeutic intervention for cognitive disorders.Here,we have screened GLP-1 R targeted com-pounds from Scutellaria baicalensis,which revealed baicalein is a potential GLP-1 R small-molecule agonist.Mitophagy,a selective autophagy pathway for mitochondrial quality control,plays a neuro-protective role in multiple cognitive impairment diseases.We noticed that Glp1r knock-out(KO)mice present cognitive impairment symptoms and appear worse in spatial learning memory and learning capacity in Morris water maze(MWM)test than their wide-type(WT)counterparts.Our mechanistic studies revealed that mitophagy is impaired in hippocampus tissue of diabetic mice and Glp1r KO mice.Finally,we verified that the cognitive improvement effects of baicalein on diabetic cognitive dysfunction occur through the enhancement of mitophagy in a GLP-1 R-dependent manner.Our findings shed light on the importance of GLP-1 R for cognitive function maintenance,and revealed the vital significance of GLP-1R for maintaining mitochondrial homeostasis.Furthermore,we identified the therapeutic potential of baicalein in the treatment of cognitive disorder associated with diabetes.

Objective To evaluate the effectiveness of tumor cell Vimentin combined with endoscopic ultrasound-guided fine-needle biopsy(EUS-FNB)in diagnosing solid pancreatic tumors.Methods Clinical data from 110 patients who underwent EUS-FNB from October 2021 to December 2023 were retrospectively analyzed.Solid pancreatic tumors including but not limited to pancreatic cancer and pancreatic neuroendocrine tumors.The sensitivity,specificity,and accuracy of EUS-FNB were assessed by comparing its results with the final pathological diagnoses.Result Clear histopathological diagnoses were obtained in 106 cases,accounting for 96.37%.Among them,87 cases were definitively diagnosed as adenocarcinoma or pancreatic ductal adenocarcinoma.Immunohistochemical staining showed that Vimentin was expressed in the tumor cells.There was no statistically significant difference in positive rates among biopsies from different anatomical sites(P>0.05),but significant differences were observed in lesions of different diameters(P<0.05).Immunohistochemical staining suggested that Vimentin expression levels might be associated with the nature of the lesions.The overall diagnostic accuracy,sensitivity,and specificity of Vimentin combined with EUS-FNB for pancreatic masses were 86.09%,84.57%,and 100.00%,respectively.Specifically,for solid masses,the diagnostic accuracy,sensitivity,and specificity were 87.67%,86.55%,and 100.00%,respectively.For pancreatic cystic tumors,the diagnostic accuracy,sensitivity,and specificity were 65.42%,69.79%,and 100.00%,respectively.Conclusion The combination of tumor cell Vimentin and EUS-FNB demonstrates high diagnostic accuracy for solid pancreatic tumors,making it a valuable tool for clinical application.

Background::Growth differentiation factor-15 (GDF-15) is a stress response protein and is related to cardiovascular diseases (CVD). This study aimed to investigate the association between GDF-15 and pre-eclampsia (PE).Method::The study involved 299 pregnant women, out of which 236 had normal pregnancies, while 63 participants had PE. Maternal serum levels of GDF-15 were measured by using enzyme-linked immunosorbent assay kits and then translated into multiple of median (MOM) to avoid the influence of gestational week at blood sampling. Logistic models were performed to estimate the association between GDF-15 MOM and PE, presenting as odd ratios (ORs) and 95% confidence intervals (CIs).Results::MOM of GDF-15 in PE participants was higher compared with controls (1.588 vs. 1.000, p < 0.001). In the logistic model, pregnant women with higher MOM of GDF-15 (>1) had a 4.74-fold (95% CI= 2.23-10.08, p < 0.001) increased risk of PE, adjusted by age, preconceptional body mass index, gravidity, and parity. Conclusions::These results demonstrated that higher levels of serum GDF-15 were associated with PE. GDF-15 may serve as a biomarker for diagnosing PE.

Background::Growth differentiation factor-15 (GDF-15) is a stress response protein and is related to cardiovascular diseases (CVD). This study aimed to investigate the association between GDF-15 and pre-eclampsia (PE).Method::The study involved 299 pregnant women, out of which 236 had normal pregnancies, while 63 participants had PE. Maternal serum levels of GDF-15 were measured by using enzyme-linked immunosorbent assay kits and then translated into multiple of median (MOM) to avoid the influence of gestational week at blood sampling. Logistic models were performed to estimate the association between GDF-15 MOM and PE, presenting as odd ratios (ORs) and 95% confidence intervals (CIs).Results::MOM of GDF-15 in PE participants was higher compared with controls (1.588 vs. 1.000, p < 0.001). In the logistic model, pregnant women with higher MOM of GDF-15 (>1) had a 4.74-fold (95% CI= 2.23-10.08, p < 0.001) increased risk of PE, adjusted by age, preconceptional body mass index, gravidity, and parity. Conclusions::These results demonstrated that higher levels of serum GDF-15 were associated with PE. GDF-15 may serve as a biomarker for diagnosing PE.

Objective To explore the association between iron metabolism indexes and the risk of gestational diabetes mellitus(GDM)in pregnant women with advanced age.Methods A total of 292 pregnant women,whose age were≥35 years old and gave birth in Taicang First People's Hospital from April 2021 to April 2023,were retrospectively included and divided into GDM group and non-GDM group.The differences of iron metabolism indexes[serum ferritin(SF),serum iron(SI)and hemoglobin(Hb)]measured from the 20 to 24 weeks of gestation were compared between the two groups.Multivariable Logistic regression model was used to explore the association of SF,SI and Hb with GDM.Based on the data of single nucleotide polymorphism from IEU OpenGWAS(http://gwas.mr-cieu.ac.uk/)and FinnGen datasets,two samples Mendelian randomization analysis were conducted to explore the causal relationship between iron metabolism indexes and GDM by using the methods of Inverse Variance Weighted(IVW).Results In the maximally ad-justed multi-factor logistic models,the statistically significant association between SF measured from 20 to 24 weeks of gestation and the risk of GDM was found[odds ratio(95％confident interval)=1.02(1.01-1.04),P=0.001].The association between Hb and GDM was marginally significant[odds ratio(95％confident interval)=1.04(1.00-1.07),P=0.044],but no association between SI and GDM reached statistical significance.However,Mendelian randomization analysis showed there was no significant evidence for causal association between SF,Hb and GDM.Conclusion SF examined at 20 to 24 weeks of gestation could be used as a biomarker of GDM in the pregnant women with advanced age,but no evidence supported the causal association between SF and GDM.

Objective:To compare the result of nucleic acid detection between anal swabs and nasal swabs in confirmed cases of COVID-19.Methods:The result of nucleic acid detection between anal swabs and nasal swabs collected simultaneously at various time points after illness onset were analyzed retrospectively.Results:Totally, 46 matched result of anal swabs and nasal swabs in confirmed cases of COVID-19 collected at various intervals after illness onset in 31 patients were analyzed. All the result of nucleic acid detection were positive for anal swabs. The highest concordance rate of nucleic acid positive of COVID-19 (80%) between anal swabs and nasal swabs was observed 0-3 days after illness onset; while the value declined to 28.57% ≥16 days after illness onset. The longer the interval between sampling and illness onset, the lower the concordance rate.Conclusions:Besides two negative result from respiratory tract specimens, the negative result of anal swabs should be added as an important reference of releasing from quarantine.