Objective:To investigate the efficacy and safety of anlotinib combined with GP (gemcitabine+cisplatin) regimen in the treatment of advanced triple-negative breast cancer refractory to anthracyclines and taxanes chemotherapy.Methods:A retrospective cohort study was conducted. Fifty two patients with advanced triple-negative breast cancer refractory to anthracyclines and taxanes chemotherapy in Affiliated Jiangyin Hospital of Nantong University from January 2019 to June 2022 were selected. According to follow-up treatment methods, they were divided into the treatment group of anlotinib combined with GP regimen (observation group) and the treatment group of GP regimen alone (control group), with 26 cases in each group. The short-term efficacy was evaluated according to the Response Evaluation Criteria in Solid Tumors 1.1 after 2 cycles of treatment, and the adverse reactions were assessed according to the Common Terminology Criteria for Adverse Events 4.0 after each treatment cycle. Kaplan-Meier method was used for analysis of progression-free survival (PFS) and overall survival (OS), and log-rank test was performed for inter group comparison. The scores of various dimensions of SF-36 quality of life scale before and after treatment were compared.Results:All 52 enrolled patients were able to evaluate the therapeutic effect. The objective response rate (ORR) of the observation group was 38.5% (10/26), and the disease control rate (DCR) was 84.6% (22/26). The ORR of the control group was 19.2% (5/26), and the DCR was 57.7% (15/26). The ORR and DCR of the observation group were higher than those in the control group, and the differences were statistically significant ( χ2 values were 10.82 and 7.18, respectively, both P < 0.05). The PFS [median PFS time, 5.4 months (95% CI: 5.0-5.8 months) vs. 3.9 months (95% CI: 3.6-4.2 months)] and OS [median OS time, 14.0 months (95% CI: 12.1-17.8 months) vs. 9.2 months (95% CI: 7.9-11.3 months)] of the observation group were better than those of the control group, and the differences were statistically significant (both P < 0.05). Compared with the control group, the incidence of hypertension [57.7% (15/26) vs. 3.8% (1/26)] and hand-foot syndrome [23.1% (6/26) vs. 0 (0/26)] in the observation group was higher (both P < 0.05), while there was no statistically significant difference in the incidence of nausea and vomiting, neutropenia, thrombocytopenia, anemia, bleeding, hyperbilirubinemia, fatigue, oral mucositis, and alopecia between the two groups (all P > 0.05). The scores of each dimension of the SF-36 quality of life scale in both groups of patients after treatment were higher than those before treatment (all P < 0.05), and the scores of each dimension in the observation group were higher than those in the control group after treatment (all P < 0.05). Conclusions:Anlotinib combined with GP regimen is effective in the treatment of advanced triple-negative breast cancer refractory to anthracyclines and taxanes chemotherapy, this regimen will not significantly increase the adverse reactions of chemotherapy and can improve the prognosis and the quality of life of patients.

Objective:To investigate the efficacy and safety of anlotinib combined with GP (gemcitabine+cisplatin) regimen in the treatment of advanced triple-negative breast cancer refractory to anthracyclines and taxanes chemotherapy.Methods:A retrospective cohort study was conducted. Fifty two patients with advanced triple-negative breast cancer refractory to anthracyclines and taxanes chemotherapy in Affiliated Jiangyin Hospital of Nantong University from January 2019 to June 2022 were selected. According to follow-up treatment methods, they were divided into the treatment group of anlotinib combined with GP regimen (observation group) and the treatment group of GP regimen alone (control group), with 26 cases in each group. The short-term efficacy was evaluated according to the Response Evaluation Criteria in Solid Tumors 1.1 after 2 cycles of treatment, and the adverse reactions were assessed according to the Common Terminology Criteria for Adverse Events 4.0 after each treatment cycle. Kaplan-Meier method was used for analysis of progression-free survival (PFS) and overall survival (OS), and log-rank test was performed for inter group comparison. The scores of various dimensions of SF-36 quality of life scale before and after treatment were compared.Results:All 52 enrolled patients were able to evaluate the therapeutic effect. The objective response rate (ORR) of the observation group was 38.5% (10/26), and the disease control rate (DCR) was 84.6% (22/26). The ORR of the control group was 19.2% (5/26), and the DCR was 57.7% (15/26). The ORR and DCR of the observation group were higher than those in the control group, and the differences were statistically significant ( χ2 values were 10.82 and 7.18, respectively, both P < 0.05). The PFS [median PFS time, 5.4 months (95% CI: 5.0-5.8 months) vs. 3.9 months (95% CI: 3.6-4.2 months)] and OS [median OS time, 14.0 months (95% CI: 12.1-17.8 months) vs. 9.2 months (95% CI: 7.9-11.3 months)] of the observation group were better than those of the control group, and the differences were statistically significant (both P < 0.05). Compared with the control group, the incidence of hypertension [57.7% (15/26) vs. 3.8% (1/26)] and hand-foot syndrome [23.1% (6/26) vs. 0 (0/26)] in the observation group was higher (both P < 0.05), while there was no statistically significant difference in the incidence of nausea and vomiting, neutropenia, thrombocytopenia, anemia, bleeding, hyperbilirubinemia, fatigue, oral mucositis, and alopecia between the two groups (all P > 0.05). The scores of each dimension of the SF-36 quality of life scale in both groups of patients after treatment were higher than those before treatment (all P < 0.05), and the scores of each dimension in the observation group were higher than those in the control group after treatment (all P < 0.05). Conclusions:Anlotinib combined with GP regimen is effective in the treatment of advanced triple-negative breast cancer refractory to anthracyclines and taxanes chemotherapy, this regimen will not significantly increase the adverse reactions of chemotherapy and can improve the prognosis and the quality of life of patients.

To summarize the nursing experience of a patient with schizophrenia complicated by severe neurodeptic malignant syndrome.Nursing points include:to emphasize monitoring of antipsychotic medications to detect the onset of neurodeptic malignant syndrome as early as possible;to leverage the multidisciplinary team for rapid initiation of acute phase management interventions;to combine multimodal cooling to help rewarm the patient;to implement the stepwise intervention program to promote recovery of bowel function;to emphasize family supportive therapy to restore social functioning;to continue case management by developing a multidisciplinary follow-up plan.After careful management and care by the multidisciplinary team,the patient was successfully discharged from the hospital after a total stay of 47 days.After 3 months of follow-up,the patient's daily life was basically back to normal.

Objective To establish a high-throughput screening system to obtain key Staphylococcus aureus (S.aureus)secretory proteins which required for S.aureus survival in macrophages.Methods Based on our validated eukaryotic expression vector library of S.aureus secretory proteins,DNA transfection was used to obtain an RAW264.7 macrophage array expressing S.aureus secretory proteins.After the RAW264.7 cells were infected with S.aureus,the extracellular bacteria were removed to observe the intracellular surviving situation of S.aureus.Finally,the screening results were validated by the overexpression and knockout S.aureus of corresponding secretory proteins.Results The optimal transfection dose (1.0 μg/well)of plasmids for RAW264.7,multiplicity of infection (MOI,1 .0 ),and infection time (4 h after removing extracellular bacteria of S.aureus ) were established respectively.To validate the screening results,the corresponding overexpression and knockout strains were constructed.And hypothetical protein and Serine protease E were found to promote the survival of intracellular S.aureus.Conclusion We successfully construct a screening system for key secreted secretory proteins which required for S.aureus surviving in macrophages,which may advance the study of the intracellular surviving mechanism of S.aureus.

Objective To explore the mechanism which drives nimbolide(NIM)in treating acute pneumonia caused by Staphylococcus aureus(S.auteus).Methods A mouse model of acute pneumonia caused by S.auteus was constructed through endotracheal intubation.After NIM treatment,the survival rate was observed,the amount of bacteria in the lung was tested by plate culture,and the expression of inflammatory cytokines in the lung tissues was detected with ELISA.After primary cultured peritoneal macrophages(PM)were infected with S.auteus,the effect of NIM on the expression of inflammatory cytokines and activation of inflammatory pathway were studied with ELISA and Western blotting,respectively.The effect of RNF114 knockdown by lentiviral shRNA infection on inflammation responses in PM was explored with ELISA and Western blotting.Results Acute infection of S.auteus in the lung could cause acute death in the mice,while NIM treatment significantly improved the survival rate and down-regulated the levels of inflammatory cytokines in the lung.However,it had no effect on the lung colonization of S.auteus in the short term.The results of in vitro experiments indicated that NIM may regulate RNF114 function to down-regulate the phosphorylation level of ERK,inhibit the activation of MAPK pathway,and thus suppress the expression of inflammatory cytokines.Conclusion NIM may inhibit the activation of MAPK pathway by regulating the function of RNF114,and thus suppress the expression of inflammatory cytokines in the lung,and finally inhibit the death of mice with acute pulmonary hyperinflammation caused by S.auteus.

Vaccination is the most effective measure for reducing and preventing influenza and related complications. In this study, we analyzed the mutation trend and the antigen dominant site changes of the amino acid sequence of hemagglutinin subunit 1 (HA1) of human influenza A virus (IAV) in the northern hemisphere from 2012 to 2022. According to the HA1 sequences of A/Darwin/6/2021 (H3N2) and A/Wisconsin/588/2019 (H1N1) recommended by the World Health Organization in the 2022 influenza season in northern hemisphere, we employed the mosaic algorithm to design three Mosaic-HA1 antigens through stepwise substitution. Mosaic-HA1 was expressed and purified in 293F cells and then mixed with the alum adjuvant at a volume ratio of 1:1. The mixture was used to immunize BALB/c mice, and the immunogenicity was evaluated. Enzyme-linked immunosorbent assay showed that Mosaic-HA1 induced the production of IgG targeting two types of HA1, the specific IgG titers for binding to H3 protein and H1 protein reached 10⁵ and 10³ respectively. The challenge test showed that Mosaic-HA1 protected mice from H3N2 or H1N1. This study designs the vaccines by recombination of major antigenic sites in different subtypes of IAV, giving new insights into the development of multivalent subunit vaccines against influenza.
Animals ; Influenza A Virus, H1N1 Subtype/genetics* ; Influenza A Virus, H3N2 Subtype/genetics* ; Mice, Inbred BALB C ; Mice ; Influenza Vaccines/genetics* ; Hemagglutinin Glycoproteins, Influenza Virus/genetics* ; Humans ; Antibodies, Viral/blood* ; Antigens, Viral/genetics* ; Immunoglobulin G/immunology* ; Female ; Orthomyxoviridae Infections/prevention & control* ; HEK293 Cells

Objective To investigate the regulatory effect and mechanism of new skeleton small molecule compound ZHZ-33-1 on the inflammatory response induced by primary macrophages in mice infected by Staphylococcus aureus.Methods qRT-PCR was used to detect the mRNA expression levels of inflammatory factors Tnf,Illb,116,Il12p40 in macrophages cells.The protein levels of TNF-α,IL-1 β,IL-6 and IL-12 in cell supernatant were determined by ELISA.Western blot was used to analyze the phosphorylation of key signaling pathway proteins such as NF-κB and MAPK.CCK8 detection was used to evaluate the effect of ZHZ-33-1 on macrophages activity.The OD600nm method was used to investigate the effect of ZHZ-33-1 on the growth of Staphylococcus aureus.Results 80 pmol/L ZHZ-33-1 had no significant effect on bacterial proliferation(P＞0.05)and cytotoxicity of macrophages(P＞0.05).Compared with the DMSO group,ZHZ-33-1 significantly inhibited the transcription and expression levels of inflammatory cytokines(TNF-α,IL-iβ,IL-6,and IL-12)in primary macrophages infected by Staphylococcus aureus(USA300)(P＜0.05).Further studies showed that ZHZ-33-1 was able to inhibit the NF-κB and MAPK pathways of wild macrophages,but was not TLR2-/-macrophages.Conclusion Through inhibiting NF-κB and MAPK signaling pathways,ZHZ-33-1 may inhibit the macrophages inflammatory response caused by Staphylococcus aureus.Therefore,ZHZ-33-1 is expected to become a new drug candidate for the treatment of Staphylococcus aureus-induced hyperinflammatory response.

Objective To investigate the regulatory effect and mechanism of new skeleton small molecule compound ZHZ-33-1 on the inflammatory response induced by primary macrophages in mice infected by Staphylococcus aureus.Methods qRT-PCR was used to detect the mRNA expression levels of inflammatory factors Tnf,Illb,116,Il12p40 in macrophages cells.The protein levels of TNF-α,IL-1 β,IL-6 and IL-12 in cell supernatant were determined by ELISA.Western blot was used to analyze the phosphorylation of key signaling pathway proteins such as NF-κB and MAPK.CCK8 detection was used to evaluate the effect of ZHZ-33-1 on macrophages activity.The OD600nm method was used to investigate the effect of ZHZ-33-1 on the growth of Staphylococcus aureus.Results 80 pmol/L ZHZ-33-1 had no significant effect on bacterial proliferation(P＞0.05)and cytotoxicity of macrophages(P＞0.05).Compared with the DMSO group,ZHZ-33-1 significantly inhibited the transcription and expression levels of inflammatory cytokines(TNF-α,IL-iβ,IL-6,and IL-12)in primary macrophages infected by Staphylococcus aureus(USA300)(P＜0.05).Further studies showed that ZHZ-33-1 was able to inhibit the NF-κB and MAPK pathways of wild macrophages,but was not TLR2-/-macrophages.Conclusion Through inhibiting NF-κB and MAPK signaling pathways,ZHZ-33-1 may inhibit the macrophages inflammatory response caused by Staphylococcus aureus.Therefore,ZHZ-33-1 is expected to become a new drug candidate for the treatment of Staphylococcus aureus-induced hyperinflammatory response.

Objective To discussion the effect of endoscopic single nostril transsphenoidal pituitary tumor resection on improving clini-cal symptoms and related quality of life of patients. Methods Selected 114 cases of patients with pituitary tumors in our hospital from August 2013 to August 2015, and randomly divided them into the nasal endoscopic group and the microscopic group according to the random number table,with 57 patients in each group. Patients of the 2 groups were treated with nasal endoscopic and microscopic single nostril transsphenoi-dal pituitary tumor resection respectively. The operation situation,hormone decline,incidence of complications after surgery and SNOT-20 and VAS score of the two groups were compared. Results Operative time of nasal endoscopic group was significantly higher than that in the mi-croscopic group,whlie the blood loss,length of hospital stay in endoscopic group was significantly lower than the microscopic group,and the difference was statistically significant (P<0. 05). The total resection rate of pituitary tumor of the two groups were of no statistically signifi-cance (P>0. 05). One week after operation,cerebrospinal fluid cell count,cerebrospinal fluid protein,adrenocorticotropic hormone,serum chloride,sodium, growth hormone,and prolactin levels of the nasal endoscopic group were lower than the microscopic group (P<0. 05). The complication rate was 14. 9% in the nasal endoscopic group,which was obviously lower than 59. 6% in the microscopic group (P<0. 05). One week after operation,the SNOT-20 scores and VAS scores were increased in both of the two groups,but the microscopic group increased more significantly (P<0. 05). Conclusion Endoscopic single nostril transsphenoidal pituitary tumor resection surgery cost longer operation time,but it lead to less trauma and less postoperative complications,which may delay the decline of patients’ quality of life and promote the improvement of prognosis.

Objective To discuss the efficacy and safety of endoscopic endonasal transsphenoidal surgery for sympatomatic Rathke' s cleft cysts.Methods The clinical manifestations, imaging features, surgical methods, pathology features, postoperative complications, postoperative recurrence and outcomes of 24 patients with Rathke's cleft cysts, admitted to our hospital from January 2007 to December 2014, were reviewed retrospectively.Results Total resection was achieved in 0 patient and subtotal resection was achieved in 24 patients.In the 16 patients with headache, 4 got relief and 12 achieved cure.In the 9 patients with hypopsia, 3 recovered to normal, 5 got improvement and one enjoyed no obvious changes.In the 21 patients with endocrine function disorder, 2 recovered to normal, 2 got improvement and one had transient diabetes insipidus.One patient appeared transient diabetes insipidus.Nine patients had transient decreased thyroid hormones, and those patients with progesterone, follicle stimulating hormone, luteinizing hormone, growth hormone and prolactin disorders recovered to normal;one patient got postoperative recurrence and accepted surgery for the second time.Conclusion Endoscopic endonasal transsphenoidal surgery is a rational choice for sympatomatic Rathke' s cleft cysts, which can effectively perform the cyst drainage and resection of the capsule wall, enjoying small trauma, safety and low postoperative recurrence rate.