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 observe the clinical efficacy and safety of acupuncture combined with blade needle therapy for knee osteoarthritis (KOA). METHODS: A total of 60 patients with KOA were randomly divided into an observation group and a control group, 30 cases each group. The control group received acupuncture at Neixiyan (EX-LE4)，Dubi (ST35), Yinlingquan (SP9), Liangqiu (ST34), Xuehai (SP10), Yanglingquan (GB34) and Zusanli (ST36) on the affected side, once every other day, 3 times a week. The observation group received blade needle therapy on the basis of the treatment in the control group, once every 3 days, 2 times a week. Both groups were treated for 4 weeks. Before treatment, after 2, 4 weeks of treatment, and after 1 month of treatment completion (in follow-up), the scores of pain visual analogue scale (VAS), Western Ontario and McMaster Universities osteoarthritis index (WOMAC) and Lequesne index were observed in the two groups, and the clinical efficacy and safety were evaluated. RESULTS: After 2, 4 weeks of treatment and in follow-up, the pain VAS scores, Lequesne index scores, and pain, stiffness, function scores of WOMAC in both groups were decreased compared with those before treatment (P<0.05), and the VAS scores, Lequesne index scores and pain, function scores of WOMAC in the observation group were lower than those in the control group (P<0.05). The effective response rate in the observation group was 76.7% (23/30), while that in the control group was 70.0% (21/30), there was no statistically significant difference in the effective response rates between the two groups (P>0.05). No adverse reactions were observed in either group. CONCLUSION Acupuncture combined with blade needle therapy could alleviate pain and promote functional recovery in KOA patients, and achieve long-lasting improvements.
Humans ; Osteoarthritis, Knee/physiopathology* ; Acupuncture Therapy/instrumentation* ; Male ; Female ; Middle Aged ; Aged ; Acupuncture Points ; Treatment Outcome ; Adult ; Needles ; Combined Modality Therapy

Objective This study aimed to investigate the tumorigenic properties of MMTV-PyMT breast cancer transgenic mice at different ages(in weeks)and the changes in the composition of immune cells in the tumor microenvironment.Methods Eight groups of 4,6,8,10,12,14,16 and 18 weeks of age MMTV-PyMT female mice(FVB mice as the background)and one group of 8 weeks of FVB female mice were prepared for routine blood testing,the pathological changes of the mammary gland and lung metastases were observed by histopathological sections,and the immune cells in blood,spleen,and tumor were analyzed by flow cytometry.Results MMTV-PyMT mice showed adenular ductal lesions at 4～6 weeks of age;the ductal portion expanded to the growth boundary at 8～9 weeks of age,and then gradually broke through the glandular boundary to form early breast cancer at 8～12 weeks of age,and advanced breast cancer at 10～14 weeks of age.At 12 weeks of age,metastases were visible in the lungs of some mice,and at 14 weeks of age,the number of metastases in the lungs increased significantly.As the age of the mice increased,the number of white blood cells,neutrophils,and platelets in their blood increased gradually,while the lymphocytes and erythrocytes showed a gradual downward trend.Flow cytometry showed that with the increase in age,the proportion of T cells in the spleen and tumor gradually decreased,the MDSCs in the blood,spleen,and tumor gradually increased,and the NK cells in the tumor also gradually increased.Conclusions This study analyzed routine blood tests,pathology,and immune cells in the tissues of MMTV-PyMT mouse models of different weeks of age,providing a novel perspective on the dynamic alterations of the tumor immune microenvironment during the malignant progression of breast cancer.

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.

OBJECTIVE To observe the effect of Shixiang plaster on promoting the wound healing of diabetic foot ulcer.METHODS Totally 50 male SPF grade SD rats were prepared to establish the diabetic models by feeding with high glucose and high fat forage and intraperitoneal injection of streptozotocin,the rats models that were es-tablished successfully were randomly divided into the model group,the Shixiang plaster group and the Kangfuxin solution group.The models of diabetic ulcers were established.The Shixiang plaster group was treated with exter-nal Shixiang plaster,the Kangfuxin solution group was given external Kangfuxin solution,and the model group was treated with coverage with sterile gauze.The wound healing status of the rats was observed,the wound tis-sues were collected for bacterial culture and hematoxylin-eosin(HE)staining after drug administration for 14 and 28 days,respectively.The expression levels of nuclear factor-red cell-2-related factor 2(Nrf-2),heme oxygenase-1(HO-1),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and vascular endothelial growth factor(VEGF)were detected by immunohistochemistry(IHC),the expression levels of Nrf-2 and HO-1 were detected with the use of Western Blot,and the levels of serum malondialdehyde(MDA),superoxide dismutase(SOD)and reactive oxygen species(ROS)were detected by enzyme-linked immunosorbent assay(ELISA).RESULTS After the drug administration for 14 and 28 days,the wound healing rates of the Shixiang plaster group were(62.15±3.82)％and(81.68±3.83)％,respectively,higher than(47.14±2.80)％and(69.96±6.49)％of the Kangfuxin solu-tion group and(29.14±9.52)％and(57.91±6.63)％of the model group,and there were significant differences(F=21.716,12.626,P=0.002,0.007).The bacterial colony counts of the Shixiang plaster group were less than those of the Kangfuxin solution group and the model group after the drug administration for 14 and 28 days(P＜0.05).The result of HE staining showed that the Shixiang plaster group had a better wound healing.The result of IHC indicated that the expression levels of Nrf-2,HO-1 and VEGF of the Kangfuxin solution group and the Shix-iang plaster group were up-regulated after the drug administration for 28 days,while the expression levels of TNF-α and IL-6 were down-regulated.The expression levels of Nrf-2 and HO-1 proteins of the Shixiang plaster group were higher than those of the Kangfuxin solution group and the model group after the drug administration for 14 and 28 days,the levels of serum MDA and ROS of the Shixiang plaster group were lower than those of the Kangfuxin solution group and the model group,and the serum SOD level of the Shixiang plaster group was higher than that of the model group(P＜0.05).CONCLUSIONS Shixiang plaster can effectively promote the wound heal-ing of the rats with diabetic foot ulcers and reduce the bacterial colony counts of wound surfaces.The mechanism may be associated with the alleviation of oxidative stress injury by mediating the Nrf-2/HO-1 signaling pathways,promotion of angiogenesis and inhibition of excessive inflammatory reactions.

Objective This study aimed to investigate the tumorigenic properties of MMTV-PyMT breast cancer transgenic mice at different ages(in weeks)and the changes in the composition of immune cells in the tumor microenvironment.Methods Eight groups of 4,6,8,10,12,14,16 and 18 weeks of age MMTV-PyMT female mice(FVB mice as the background)and one group of 8 weeks of FVB female mice were prepared for routine blood testing,the pathological changes of the mammary gland and lung metastases were observed by histopathological sections,and the immune cells in blood,spleen,and tumor were analyzed by flow cytometry.Results MMTV-PyMT mice showed adenular ductal lesions at 4～6 weeks of age;the ductal portion expanded to the growth boundary at 8～9 weeks of age,and then gradually broke through the glandular boundary to form early breast cancer at 8～12 weeks of age,and advanced breast cancer at 10～14 weeks of age.At 12 weeks of age,metastases were visible in the lungs of some mice,and at 14 weeks of age,the number of metastases in the lungs increased significantly.As the age of the mice increased,the number of white blood cells,neutrophils,and platelets in their blood increased gradually,while the lymphocytes and erythrocytes showed a gradual downward trend.Flow cytometry showed that with the increase in age,the proportion of T cells in the spleen and tumor gradually decreased,the MDSCs in the blood,spleen,and tumor gradually increased,and the NK cells in the tumor also gradually increased.Conclusions This study analyzed routine blood tests,pathology,and immune cells in the tissues of MMTV-PyMT mouse models of different weeks of age,providing a novel perspective on the dynamic alterations of the tumor immune microenvironment during the malignant progression of breast cancer.

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 observe the effect of Shixiang plaster on promoting the wound healing of diabetic foot ulcer.METHODS Totally 50 male SPF grade SD rats were prepared to establish the diabetic models by feeding with high glucose and high fat forage and intraperitoneal injection of streptozotocin,the rats models that were es-tablished successfully were randomly divided into the model group,the Shixiang plaster group and the Kangfuxin solution group.The models of diabetic ulcers were established.The Shixiang plaster group was treated with exter-nal Shixiang plaster,the Kangfuxin solution group was given external Kangfuxin solution,and the model group was treated with coverage with sterile gauze.The wound healing status of the rats was observed,the wound tis-sues were collected for bacterial culture and hematoxylin-eosin(HE)staining after drug administration for 14 and 28 days,respectively.The expression levels of nuclear factor-red cell-2-related factor 2(Nrf-2),heme oxygenase-1(HO-1),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and vascular endothelial growth factor(VEGF)were detected by immunohistochemistry(IHC),the expression levels of Nrf-2 and HO-1 were detected with the use of Western Blot,and the levels of serum malondialdehyde(MDA),superoxide dismutase(SOD)and reactive oxygen species(ROS)were detected by enzyme-linked immunosorbent assay(ELISA).RESULTS After the drug administration for 14 and 28 days,the wound healing rates of the Shixiang plaster group were(62.15±3.82)％and(81.68±3.83)％,respectively,higher than(47.14±2.80)％and(69.96±6.49)％of the Kangfuxin solu-tion group and(29.14±9.52)％and(57.91±6.63)％of the model group,and there were significant differences(F=21.716,12.626,P=0.002,0.007).The bacterial colony counts of the Shixiang plaster group were less than those of the Kangfuxin solution group and the model group after the drug administration for 14 and 28 days(P＜0.05).The result of HE staining showed that the Shixiang plaster group had a better wound healing.The result of IHC indicated that the expression levels of Nrf-2,HO-1 and VEGF of the Kangfuxin solution group and the Shix-iang plaster group were up-regulated after the drug administration for 28 days,while the expression levels of TNF-α and IL-6 were down-regulated.The expression levels of Nrf-2 and HO-1 proteins of the Shixiang plaster group were higher than those of the Kangfuxin solution group and the model group after the drug administration for 14 and 28 days,the levels of serum MDA and ROS of the Shixiang plaster group were lower than those of the Kangfuxin solution group and the model group,and the serum SOD level of the Shixiang plaster group was higher than that of the model group(P＜0.05).CONCLUSIONS Shixiang plaster can effectively promote the wound heal-ing of the rats with diabetic foot ulcers and reduce the bacterial colony counts of wound surfaces.The mechanism may be associated with the alleviation of oxidative stress injury by mediating the Nrf-2/HO-1 signaling pathways,promotion of angiogenesis and inhibition of excessive inflammatory reactions.

Epidural labor analgesia aims to provide effective medical services to alleviate labor pain in parturients, while adhering to the principles of voluntary participation and clinical safety. In 2018, Peking Union Medical College Hospital(PUMCH)became one of the first pilot units for labor analgesia in China, and has achieved satisfactory results in high-quality development of labor analgesia. This article mainly introduces the achievements and experience of labor analgesia at PUMCH, including: (1) prioritizing maternal and infant safety, arranging personnel rationally, and developing standardized treatment processes through multidisciplinary collaboration to ensure safe and comfortable childbirth; (2) leveraging the hospital's comprehensive capabilities in emergency treatment, and improving collaborative rescue plans for critically ill parturients and newborns; (3) implementing advanced teaching methods to effectively train and conduct simulated drills for labor analgesia and rescue of critically ill parturients; (4) conducting patient education and informative lectures to help parturients acquire a scientific understanding of labor analgesia. We hope that this experience can provide reference and inspiration for other hospitals.