Based on the concept of "blood exhaustion" from The Inner Canon of Yellow Emperor （《黄帝内经》）， a three-stage syndrome differentiation and treatment strategy for cancer-related anorexia-cachexia syndrome is proposeed. In the cancer-induced anorexia stage， the pathogenesis is characterized by cancer consuming the spleen and stomach， leading to stagnation of transportation and transformation in the middle jiao （焦）. Treatment should focus on strengthening the spleen， promoting appetite， dispersing accumulation， and aiding digestion， with modified Zisheng Pills （资生丸） in Extensive Notes on Medicine from Xian Xing Studio （《先醒斋医学广笔记》） or Zisheng Decoction （资生汤） in Records of Chinese Medicine with Reference to Western Medicine （《医学衷中参西录》）. In the pre-cachectic stage of malnutrition， the pathogenesis involves insufficient nourishment of blood and qi with essence depletion hindering production. Treatment should focus on nourishing blood and harmonizing ying （营）， warming yang and supplementing qi， and modified Huangqi Jianzhong Decoction （黄芪建中汤） can be used. In the cachectic stage， the pathogenesis involves blood deficiency and essence exhaustion， with blood stasis obstructing the collaterals. The therapeutic approach should focus on tonifying deficiency and replenishing essence， unblocking collaterals， and removing stasis， and modified Buzhong Yiqi Decoction （补中益气汤） and Zuo Gui Beverage （左归饮） are suggested.

OBJECTIVE To explore the mechanism of Qingwen Baidu Drink in treating sepsis-induced lung injury.METHODS One hundred C57BL/6 mice were randomly divided into blank group,model group,Qingwen Baidu Drink low-dose group,Qingwen Baidu Drink medium-dose group,and Qingwen Baidu Drink high-dose group,with 20 mice in each group.HE staining was used to examine the pathological changes of lung tissues.ELISA was used to detect the expression levels of serum interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),chemokine ligand 10(CXCL10)and plasma coagulation factor Ⅲ(F3).qPCR was used to detect the mRNA expression levels of monocyte chemoattractant protein-1(MCP-1),cyclooxygenase-2(COX-2)and interferon-γ(IFN-γ)in lung tissues.The number of platelets(PLT)in plasma was analyzed by routine blood analysis instrument.Immunofluorescence a-nalysis was used to detect vascular endothelial cadherin(VE-cadherin),endothelial adhesion junction marker occludin 5(CLDN5)and pericyte marker neuronal collagen antigen 2(NG2)in alveolar capillary endothelial cells.Western blot was used to detect the pro-tein expression levels of cysteine-containing aspartate proteinase 11(Caspase11),GSDMD and GSDMD-N in mouse lung tissues.RESULTS Compared with the blank group,the lung tissue of the mice in the model group showed obvious pathological dam-age.The levels of serum IL-1β,TNF-α,and CXCL10 and the mRNA expression levels of MCP-1,COX-2,and IFN-γ in lung tis-sue were significantly increased(P<0.01),and the number of PLT and the content of F3 in plasma were significantly decreased(P<0.01).The fluorescence expression of VE-cadherin,CLDN5,and NG2 proteins in lung tissue was significantly enhanced(P<0.01),while the expression of Caspase11 and GSDMD-N proteins was increased(P<0.01).Compared with the model group,the pathological damage of the lung tissue of the mice in all doses of Qingwen Baidu Drink groups was alleviated,the levels of serum IL-1β,TNF-α,and CXCL10 and the mRNA expression levels of MCP-1,COX-2,and IFN-γ in lung tissue were significantly decreased(P<0.05,P<0.01),and the number of PLT and the content of F3 in plasma were increased(P<0.05,P<0.01);the fluorescence expression of VE-cadherin,CLDN5,and NG2 proteins in lung tissues was weakened(P<0.05,P<0.01),and the expression of Caspase11 and GSDMD-N/GSDMD proteins was reduced(P<0.05,P<0.01).CONCLUSION Qingwen Baidu Drink can inhibit the activation of GSDMD-N and Caspase11,reduce the release of inflammatory factors,decrease blood loss and damage to vascular barrier function,and thus improve the lung injury caused by sepsis.

The complement component 4 binding protein alpha(C4BPA)gene is the alpha chain of complement binding protein 4.As a plasma protein involved in the complement and coagulation systems,it can influence immune responses and lipid metabolism.In order to study the polymor-phism of C4BPA gene and its correlation with milk quality traits in Chinese Holstein cows,genom-ic DNA was extracted from blood samples of 92 Chinese Holstein cows,and the target fragment of C4BPA gene was amplified by PCR,and the association analysis was performed by using direct se-quencing to obtain the SNP loci and milk quality traits.The results showed that among the four SNPs found at the third intron of the C4BPA gene,I3-11 G＞A was highly significantly correlated with milk protein and urea nitrogen(P＜0.05),I3-291 T＞G was significantly correlated with lac-tose(P＜0.05),I3-374 C＞T was highly significantly correlated with lactose and urea nitrogen(P＜0.05),and I3-375 T＞G was highly significantly correlated with lactose(P＜0.05),milk pro-tein and urea nitrogen.The chi-square test values for each point indicated that the population was in genetic equilibrium.Individuals of haplotype combination H1 H1 had the highest lactose content,and haplotype combination H1H2 can be used as the best haplotype combination in the molecular selection work of dairy cows.

OBJECTIVE To explore the mechanism of Qingwen Baidu Drink in treating sepsis-induced lung injury.METHODS One hundred C57BL/6 mice were randomly divided into blank group,model group,Qingwen Baidu Drink low-dose group,Qingwen Baidu Drink medium-dose group,and Qingwen Baidu Drink high-dose group,with 20 mice in each group.HE staining was used to examine the pathological changes of lung tissues.ELISA was used to detect the expression levels of serum interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),chemokine ligand 10(CXCL10)and plasma coagulation factor Ⅲ(F3).qPCR was used to detect the mRNA expression levels of monocyte chemoattractant protein-1(MCP-1),cyclooxygenase-2(COX-2)and interferon-γ(IFN-γ)in lung tissues.The number of platelets(PLT)in plasma was analyzed by routine blood analysis instrument.Immunofluorescence a-nalysis was used to detect vascular endothelial cadherin(VE-cadherin),endothelial adhesion junction marker occludin 5(CLDN5)and pericyte marker neuronal collagen antigen 2(NG2)in alveolar capillary endothelial cells.Western blot was used to detect the pro-tein expression levels of cysteine-containing aspartate proteinase 11(Caspase11),GSDMD and GSDMD-N in mouse lung tissues.RESULTS Compared with the blank group,the lung tissue of the mice in the model group showed obvious pathological dam-age.The levels of serum IL-1β,TNF-α,and CXCL10 and the mRNA expression levels of MCP-1,COX-2,and IFN-γ in lung tis-sue were significantly increased(P<0.01),and the number of PLT and the content of F3 in plasma were significantly decreased(P<0.01).The fluorescence expression of VE-cadherin,CLDN5,and NG2 proteins in lung tissue was significantly enhanced(P<0.01),while the expression of Caspase11 and GSDMD-N proteins was increased(P<0.01).Compared with the model group,the pathological damage of the lung tissue of the mice in all doses of Qingwen Baidu Drink groups was alleviated,the levels of serum IL-1β,TNF-α,and CXCL10 and the mRNA expression levels of MCP-1,COX-2,and IFN-γ in lung tissue were significantly decreased(P<0.05,P<0.01),and the number of PLT and the content of F3 in plasma were increased(P<0.05,P<0.01);the fluorescence expression of VE-cadherin,CLDN5,and NG2 proteins in lung tissues was weakened(P<0.05,P<0.01),and the expression of Caspase11 and GSDMD-N/GSDMD proteins was reduced(P<0.05,P<0.01).CONCLUSION Qingwen Baidu Drink can inhibit the activation of GSDMD-N and Caspase11,reduce the release of inflammatory factors,decrease blood loss and damage to vascular barrier function,and thus improve the lung injury caused by sepsis.

The complement component 4 binding protein alpha(C4BPA)gene is the alpha chain of complement binding protein 4.As a plasma protein involved in the complement and coagulation systems,it can influence immune responses and lipid metabolism.In order to study the polymor-phism of C4BPA gene and its correlation with milk quality traits in Chinese Holstein cows,genom-ic DNA was extracted from blood samples of 92 Chinese Holstein cows,and the target fragment of C4BPA gene was amplified by PCR,and the association analysis was performed by using direct se-quencing to obtain the SNP loci and milk quality traits.The results showed that among the four SNPs found at the third intron of the C4BPA gene,I3-11 G＞A was highly significantly correlated with milk protein and urea nitrogen(P＜0.05),I3-291 T＞G was significantly correlated with lac-tose(P＜0.05),I3-374 C＞T was highly significantly correlated with lactose and urea nitrogen(P＜0.05),and I3-375 T＞G was highly significantly correlated with lactose(P＜0.05),milk pro-tein and urea nitrogen.The chi-square test values for each point indicated that the population was in genetic equilibrium.Individuals of haplotype combination H1 H1 had the highest lactose content,and haplotype combination H1H2 can be used as the best haplotype combination in the molecular selection work of dairy cows.

Objective To investigate the mechanism by which conbercept reverses transforming growth factor-β2(TGF-β2)-induced epithelial-mesenchymal transition(EMT)in human lens epithelial cells(HLECs).Methods Cultured HLEC SRA01/04 cells were treated with TGF-β2,conbercept,or both,and the changes in cell proliferation,apoptosis,and migration were observed using MTT assay,flow cytometry,scratch assay,and Transwell assay.Western blotting and qRT-PCR were used to detect the changes in the expression of EMT-related epithelial cell markers(E-Cadherin,α-SMA,and Snail),extracellular matrix components,and genes related to the TGF-β/Smad signaling pathway.Results Conbercept significantly reduced TGF-β2-induced EMT of SRA01/04 cells,decreased the expression levels of mesenchymal and extracellular matrix markers α-SMA,Snail,collagen I,collagen IV,and FN1,and upregulated the protein and mRNA expressions of E-cadherin(P<0.05).Transwell assay showed significantly lower cell migration ability in TGF-β2+conbercept group than in TGF-β2 group(P<0.05).Conbercept also inhibited the increase in Smad2/3 phosphorylation levels in HLEC-SRA01/04 cells with TGF-β2-induced EMT(P<0.01).Conclusion Conbercept inhibits TGF-β2 induced EMT by downregulating the expression of pSmad2/3 in TGF-β/Smad signaling pathway,indicating a potential therapeutic strategy against visual loss induced by posterior capsule opacification.

Objective To investigate the mechanism by which conbercept reverses transforming growth factor-β2(TGF-β2)-induced epithelial-mesenchymal transition(EMT)in human lens epithelial cells(HLECs).Methods Cultured HLEC SRA01/04 cells were treated with TGF-β2,conbercept,or both,and the changes in cell proliferation,apoptosis,and migration were observed using MTT assay,flow cytometry,scratch assay,and Transwell assay.Western blotting and qRT-PCR were used to detect the changes in the expression of EMT-related epithelial cell markers(E-Cadherin,α-SMA,and Snail),extracellular matrix components,and genes related to the TGF-β/Smad signaling pathway.Results Conbercept significantly reduced TGF-β2-induced EMT of SRA01/04 cells,decreased the expression levels of mesenchymal and extracellular matrix markers α-SMA,Snail,collagen I,collagen IV,and FN1,and upregulated the protein and mRNA expressions of E-cadherin(P<0.05).Transwell assay showed significantly lower cell migration ability in TGF-β2+conbercept group than in TGF-β2 group(P<0.05).Conbercept also inhibited the increase in Smad2/3 phosphorylation levels in HLEC-SRA01/04 cells with TGF-β2-induced EMT(P<0.01).Conclusion Conbercept inhibits TGF-β2 induced EMT by downregulating the expression of pSmad2/3 in TGF-β/Smad signaling pathway,indicating a potential therapeutic strategy against visual loss induced by posterior capsule opacification.

Objective:To evaluate the efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with Ph-like acute lymphoblastic leukemia (Ph-ALL) .Methods:Patients with Ph-ALL who underwent CAR-T therapy followed by allo-HSCT from March 2018 to August 2023 at the First Affiliated Hospital of Soochow University were included, and their clinical data were retrospectively analyzed.Results:Of the 21 patients, 14 were male and 7 were female. The median age at the time of CAR-T therapy was 22 (6-50) years. Seven patients had ABL1-like rearrangements, and 14 had JAK-STAT rearrangements. Prior to CAR-T therapy, 12 patients experienced hematologic relapse; 7 were multiparameter flow cytometry minimal residual disease (MFC-MRD) -positive and 2 were MFC-MRD-negative. CAR-T cells were derived from patients’ autologous lymphocytes. Nine patients were treated with CD19 CAR-T cells, and 12 were treated with CD19/CD22 CAR-T cells. After assessment on day 28 after CAR-T therapy, 95.2% of the patients achieved complete remission, with an MRD-negative remission rate of 75%. Nineteen patients developed grade 0–2 cytokine release syndrome (CRS) and 2 patients suffered grade 3 CRS, all cases of which resolved after treatment. All patients underwent allo-HSCT after CAR-T therapy. The median time from CAR-T therapy to allo-HSCT was 63 (38-114) days. Five patients experienced relapse after CAR-T therapy, including four with hematologic relapse and one with molecular relapse. The 3-year overall survival (OS) rates in the ABL1 and JAK-STAT groups were (83.3±15.2) % and (66.6±17.2) %, respectively ( P=0.68) . The 3-year relapse-free survival (RFS) rates were (50.0±20.4) % and (55.6±15.4) % in the ABL1 and JAK-STAT groups, respectively. There was no significant difference in 3-year OS or RFS between the two groups. Conclusions:CAR-T therapy followed by allo-HSCT leads to rapid remission in most patients with Ph-ALL and prolongs leukemia-free survival.

The development of liver inflammatory diseases is associated with autoimmunity and inflammatory response. As a negative feedback regulator of cell signal, suppressor of cytokine signaling 1 (SOCS1) plays a key role in the development and progression of inflammatory diseases. This article mainly introduces the mechanism of action of SOCS1 in autoimmunity and inflammatory response and briefly describes its role in the development and progression of liver inflammatory diseases such as viral hepatitis and nonalcoholic steatohepatitis. The analysis shows that the abnormal expression of SOCS1 in inflammatory response is associated with the regulation of cytokine receptor, Toll-like receptor, and hormone receptor signal, which leads to the development of inflammatory diseases. Therefore, SOCS1 has potential prospects as an auxiliary means for the diagnosis and treatment of liver inflammatory diseases.

Objective:To explore the association between polygenic risk score (PRS) and age at onset and early-onset risk of gastric cancer (GC).Methods:Gastric cancer cases from existing genome-wide association study were included, and 112 single nucleotide polymorphisms associated with GC risk were used to derive individual PRS. Analysis of variance and Pearson correlation test was used to depict the relationship between PRS and GC onset age. Cases diagnosed before 50 years old were defined as early-onset gastric cancer. Cox proportional hazard model was used to test the association between PRS and early-onset GC risk with early-onset age as the timescale and low genetic risk (PRS ≤20%) as the reference group.Results:A total of 8 629 cases, including 6 284 males (72.82%) and 2 345 females (27.18%), were included, and the mean age was (60.61±10.80) years old. The PRS was negatively correlated with age of GC onset ( r=-0.05, P<0.001). The mean age of gastric cancer cases with low, intermediate, and high genetic risk were (61.68±10.33), (60.53±10.79), (59.80±11.20), respectively. PRS was significantly associated with the risk of early-onset GC in a dose-response manner (intermediate genetic risk: HR=1.19, 95% CI: 1.03-1.39, P=0.022; high genetic risk: HR=1.44, 95% CI: 1.20-1.71, P<0.001). Conclusions:PRS may contribute to the risk of both GC and early-onset GC. PRS can be used as a measurable indicator for risk prediction for occurrence and early-onset of GC.