Unraveling the potential biomarkers of immune checkpoint inhibitors in advanced ovarian cancer: a comprehensive review.

The ongoing research on the role of immunotherapy in advanced ovarian cancer (OC) and current clinical trials indicate that patients shown limited response to immune checkpoint inhibitor (ICI) monotherapy. When combined with other treatments or drugs, the efficacy of immunotherapy will be significantly improved. Biomarkers can be used to identify patients with better responses, thereby improving the precision and efficacy of immunotherapy. Key biomarkers for advanced OC include homologous repair deficiency, programmed death-ligand (PD-L) 1 expression, chemokines, and tumor infiltrating lymphocytes. These biomarkers could be applied in the future to select the most suitable patient populations. This review comprehensively examines the research and development of biomarkers in OC immunotherapy from three omics perspectives: genomics, transcriptomics, and proteomics, which may provide guidance for the effectiveness of OC immunotherapy strategies.

Authentic leadership and innovation behaviour among nurses in China: A mediation model of work engagement.

AIM: The purpose of this study was to explore the effect of authentic leadership on nurses' innovation behaviour and the mediating role of work engagement. BACKGROUND: Encouraging nurses to generate more innovation behaviours has become an important development direction for improving the quality of nursing services. METHOD: We employed a self-report questionnaire to collect data in Jinan City, China. A total of 2018 valid surveys were obtained. Hierarchical multiple regression model analysis was conducted to test the study hypothesis. RESULT: The mean values of authentic leadership were 55.72 and 35.29, respectively. It shows that nurses can perceive the authenticity of managers, and their innovation behaviours need to be improved. Work engagement was found to have partially mediating effect on the relationship between authentic leadership and innovation behaviour. CONCLUSION: Results suggest the importance of developing nurse managers' authentic leadership to foster nurses' work engagement and innovation behaviour. IMPLICATIONS FOR NURSING MANAGEMENT: Hospitals should enhance authentic leadership by designing leadership training programmes and establishing authentic culture. In addition, nursing managers can also foster nursing innovation through improvements in work engagement. The study data were collected via questionnaires, and we sent out questionnaires with informed consent forms to the study subjects. All valid subjects signed the consent forms and agreed to join this study. In addition, the questionnaires were collected anonymously, and all the subjects' information is strictly confidential. More importantly, the data are only used for research and do not involve any commercial interests.

Organisational innovation climate and innovation behaviour among nurses in China: A mediation model of psychological empowerment.

AIM: This study aimed to explore the effect of organisational innovation climate on nurse innovation behaviour and the mediating role of psychological empowerment. BACKGROUND: Encouraging nurses to generate more innovative behaviours has become an important development direction for improving the quality of nursing services. METHOD: We employed a self-report questionnaire to collect data in Jinan City, China. A total of 2018 valid surveys were obtained. Hierarchical multiple regression model analysis was conducted to test the study hypothesis. RESULT: The mean values of innovation behaviour and organisational innovation climate were 35.29 and 83.30, respectively. Psychological empowerment was found to have partially mediating effect on the relationship between organisational innovation climate and innovation behaviour. CONCLUSION: Organisational innovation climate has significant impact on innovation behaviour, and it can indirectly affect innovation behaviour via the mediating role of psychological empowerment. IMPLICATIONS FOR NURSING MANAGEMENT: Nursing managers should enhance innovation climate through formal rules, procedures and training activities. They can establish resource guarantee system and information sharing platform, and strengthen work autonomy for nurses to improve their psychological empowerment.

SET and MYND Domain-Containing Protein 3 (SMYD3) Polymorphism as a Risk Factor for Susceptibility and Poor Prognosis in Ovarian Cancer.

BACKGROUND We investigated the relationship of the polymorphisms of SET and MYND domain-containing protein 3 (SMYD3) with risk and prognosis of ovarian cancer. MATERIAL AND METHODS The polymerase chain reaction (PCR) amplification method was applied to detect the polymorphisms of variable number of tandem repeats (VNTR) in the SMYD3 gene promoter region for 156 patients with ovarian cancer (case group) and 174 healthy people (control group). Quantitative reverse transcription polymerase chain reaction and Western blot were applied to detect SMYD3 mRNA and protein expressions. RESULTS The frequencies of VNTR genotype 3/3 and allele genotype 3 in the case group were significantly higher than those in the control group, while the frequency of genotype 2/2 in the control group was significantly higher than that in case group (all P<0.05). The proportion of poorly differentiated patients carrying VNTR genotype 3/3 was significantly higher than the proportion of poorly differentiated patients carrying VNTR genotype 2/2+2/3, while the proportion of patients carrying genotype 3/3 with International Federation of Gynecology and Obstetrics (FIGO) stage III-IV disease was significantly higher than the proportion of patients carrying genotype 2/2 +2/3 with FIGO stage III-IV disease (all P<0.05). SMYD3 mRNA and protein expressions were higher in the patients carrying genotype 3/3 than they were in the patients with the 2/2+2/3 genotype (all P<0.05). The 5-year survival rate for patients carrying VNTR genotype 3/3 was significantly lower than that of patients carrying genotype 2/2+2/3, and Cox regression analysis showed that VNTR genotype 3/3 was an independent risk factor for ovarian cancer prognosis (all P<0.05). CONCLUSIONS VNTR genotype 3/3 of the SMYD3 gene was associated with the risk of ovarian cancer. The polymorphism of VNTR genotype could be recognized as an indicator for the poor prognosis of patients with ovarian cancer.

[Effect of Baichanting Compound on Dopamine Contents in Parkinson's Disease Model Mice].

OBJECTIVE: To observe the effect of Baichanting Compound (BC) on dopamine (DA) in striatum of Parkinson's disease (PD) mice, and to screen the optimal component proportion. METHODS: The PD model was established in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced C57BL/6 mice. By using uniform design, they were intervened by three extracts of BC in different proportions [Acanthopanax senticosus extract (X1): white peony root extract (X2): Uncaria rhynchophylla extract (X3) = 30.00: 34.92: 82.50, 48.00: 19.98: 72.19, 18.00: 44.88: 61.88, 36.00: 29.94: 51.56, 54.00: 15.00: 41.25, 24.00: 39.90: 30.94, 42.00: 24.96: 20.63). Equal volume of 5% carboxymethylcellulose sodium was administered to mice in the model group and the normal group by gastrogavage. All medication was lasted for 20 successive days. The dopamine (DA) content was determined by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS). Except 10 in the normal group, 20 PD model mice were screened and divided into the model group and the BC group (with the optimal proportion) according to random digit table. BC extract in optimal proportion was administered to mice in the BC group by gastrogavage, while equal volume of 5% carboxymethylcellulose sodium was administered to mice in the model group and the normal group by gastrogavage. All medication was lasted for 20 successive days. Praxiology was observed in each group. DA content in striatum was also detected. Results Compared with the normal group, the DA content in striatum decreased significantly in the model group (P < 0.01), suggesting a successful PD modeling. Compared with the model group, the DA content in striatum increased significantly in 1 and 2 groups (P<0.05). According to results of quadratic polynomial stepwise regression statistics, the regression equation obtained was: Y = 0.265 + 0.026 X 2 - 0.056 X 3 + 0.334 x 10(-3) x X1 x X3 + 0.691 x 10(-3) X X3(2). X3 extract was the main factor influencing the effectiveness (P < 0.01). The optimal proportion of BC was predicted by the regression equation: X1 = 54.00 mg/(kg x d), X2 = 44.88 mg/(kg x d), the X3 = 82.50 mg/(kg x d). The pole climbing time was shortened, times of autonomic activities increased, DA content was elevated, all with statistical difference in BC groups (P < 0.01, P < 0.05). CONCLUSION: BC could increase DA content in PD model mice with the optimal proportion as 54.00: 44.88: 82.50.

[Enzymatic cyclization of peptides using immobilized sortase A].

Peptide cyclization, a pivotal approach to modifying linear precursors of proteins and pepticles, has been used to enhance their biological activities and serum stabilities. Recently, sortase A (SrtA) from Staphyloccus aureus becomes a promising new technology for efficiently incorporating site specific modifications into proteins, conjugating the cell surface and cyclizing the linear peptides. In this study, we constructed two recombinant expression systems, one with chitin binding domain and the other with six-histidine tag and chitin binding domain on the N-terminal of SrtA, separately. The results of enzymatic kinetics indicate that the two recombinant tags do not impair the transpeptidase activity of SrtA compared with the standard reaction reported under the same reaction condition. The two synthesized peptides with N-ternimal three glycines and C-terminal penta-amino acid motif, LPETG, were cyclized using immobilized and recycled SrtA. The SrtA-based cyclization promises to represent a simple method for easy and efficient enzymatic synthesis of large cyclic peptides.

Systematic review of high-dose and standard-dose chemotherapies in the treatment of primary well-differentiated osteosarcoma.

The objective of this study is to evaluate whether high-dose chemotherapy is more efficacious than standard-dose chemotherapy in the treatment of primary well-differentiated osteosarcoma. The Cochrane systematic evaluation method was adopted. A database search was conducted in MEDLINE, Embase, OVID, the Cochrane Central Register of Controlled Trials database and the Chinese Biomedical Literature CD-ROM Database. The quality of the included studies was jointly evaluated by two reviewers, and homogeneous studies were included for meta-analysis. A total of five studies were included in this meta-analysis, with 1,415 subjects with primary, nonmetastatic, well-differentiated osteosarcoma in the limbs. No statistically significant differences were found between the high-dose chemotherapy group and the low-dose group in 5-year event-free survival [RR 1.04, 95 %CI (0.95, 1.13)], 5-year overall survival [RR 1.02, 95 %CI (0.95, 1.10)], local recurrence rate [RR 0.90, 95 %CI (0.59, 1.39)], proportion of subjects with good histological response [RR 0.93, 95 %CI (0.81, 1.07)], or limb salvage rate [RR 0.97, 95 %CI (0.92, 1.02)]. A statistically significant difference was observed in the 5-year event-free survival between the subjects with good histological response to preoperative chemotherapy and the subjects with poor histological response [RR 1.55, 95 %CI (1.19, 2.00), P < 0.001]. High-dose chemotherapy did not show superior efficacy to low-dose chemotherapy in the treatment of primary well-differentiated osteosarcoma. Further high-quality randomized controlled trials are needed to provide additional reliable evidence for our observation.

Fibroblast growth factor receptor 4 as a potential prognostic and therapeutic marker in colorectal cancer.

The purpose of the study was to explore the significance of FGFR4 protein expression in colorectal cancer. Immunohistochemistry showed 46.8% (148/316) tumors positive for FGFR4 and 7.3% (23/316) for adjacent normal specimens. FGFR4 positivity was correlated with shortened disease free survival (DFS) and overall survival (OS). Multivariate analysis revealed that FGFR4 was an independent prognostic factor. FGFR4 silencing markedly reduced the migration and invasion capacity of colorectal cancer cell lines. These results suggest FGFR4 is a potential prognostic and therapeutic marker for colorectal cancer.

[A cyclotide against influenza A H1N1 virus from Viola yedoensis].

Three cyclotides were isolated from the whole plant of Viola yedoensis in this study. The two, vary peptide E and cycloviolacin Y5, were previously reported, and a novel cycloviolacin VY1 was characterized according to the interpretation of MS/MS fragmentation of peptides which were produced from the reduced and alkylated parent peptide with the digestion of Endo Lys-C, trypsin and chymotrypsin, separately. The stability of remarkable resistance to proteolytic degradation by trypsin and chymotrypsin, and that of thermal denaturation was confirmed again. Besides, the IC50 value of cycloviolacin VY1 against influenza A H1N1 virus was (2.27 +/- 0.20) microg x mL(-1). It is the first cyclotide reported with anti-influenza A H1N1 virus activity in vitro assay.

Pulmonary tumor thrombotic microangiopathy: Two case reports and literature review.

RATIONALE: Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare but serious complication in patients with malignancy; its main manifestation includes acute pulmonary hypertension with severe respiratory distress. More than 200 cases have been reported since it was first identified in 1990. PTTM accounts for approximately 0.9% to 3.3% of deaths due to malignancy, but only a minority of patients are diagnosed ante-mortem, with most patients having a definitive diagnosis after autopsy. PATIENT CONCERNS: Two middle-aged women both died within a short period of time due to progressive dyspnea and severe pulmonary hypertension. DIAGNOSES: One patient was definitively confirmed as a gastrointestinal malignant tumor by liver puncture biopsy pathology. Ultimately, the clinical diagnosis was pulmonary tumor thrombotic microangiopathy. INTERVENTIONS: The patient was treated symptomatically with oxygen, diuresis, and anticoagulation, while a liver puncture was perfected to clarify the cause. OUTCOMES: Two cases of middle-aged female patients with rapidly progressive pulmonary hypertension and respiratory failure resulted in death with malignant neoplasm. LESSONS: PTTM has a rapid onset and a high morbidity and mortality rate. Our clinicians need to be more aware of the need for timely diagnosis through a targeted clinical approach, leading to more targeted treatment and a better prognosis.

A comparative study of virus nucleic acid re-positive and non-re-positive patients infected with SARS-CoV-2 Delta variant strain in the Ningxia Hui Autonomous Region.

Objective: This study aimed to provide a basis for epidemic prevention and control measures as well as the management of re-positive personnel by analyzing and summarizing the characteristics of re-positive patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant infections discharged from a hospital in the Ningxia Hui Autonomous Region in 2021. Methods: This case-control study included a total of 45 patients with Delta variant infections diagnosed in the Fourth People's Hospital of the Ningxia Hui Autonomous Region between October 17 and November 28, 2021. Based on the nucleic acid test results post-discharge, the patients were dichotomized into re-positive and non-re-positive groups. Based on the time of the first re-positive test, the re-positive group was further divided into <7 and ≥7 days groups to compare their clinical characteristics and explore the possible influencing factors of this re-positivity. Results: Of the 45 total patients, 16 were re-positive (re-positivity rate: 35.6%), including four patients who were re-positive after 2 weeks (re-positivity rate: 8.8%). The median time of the first re-positive after discharge was 7 days (IQR: 14-3). The re-positive group was younger than the non-re-positive group (35 vs. 53, P < 0.05), had a higher proportion of patients who were not receiving antiviral therapy (56.2 vs. 17.2%, P < 0.05). The median CT value of nucleic acid in the re-positive group was considerably greater than that at admission (36.7 vs. 22.6 P < 0.05). The findings demonstrated that neutralizing antibody treatment significantly raised the average IgG antibody level in patients, particularly in those who had not received COVID-19 vaccine (P < 0.05). The median lowest nucleic acid CT value of the ≥7 days group during the re-positive period and the immunoglobulin G (IgG) antibody level at discharge were lower than those in the <7 days group (P < 0.05). When compared to the non-positive group, patients in the ≥7 days group had a higher median virus nucleic acid CT value (27.1 vs. 19.2, P < 0.05) and absolute number of lymphocytes at admission (1,360 vs. 952, P < 0.05), and a lower IgG antibody level at discharge (P < 0.05). Conclusions: In conclusion, this study found that: (1) The re-positivity rate of SARS-CoV-2 Delta variant infection in this group was 35.6%, while the re-positivity rate was the same as that of the original strain 2 weeks after discharge (8.0%). (2) Young people, patients who did not use antiviral therapy or had low IgG antibody levels at discharge were more likely to have re-positive. And the CT value of nucleic acid at the time of initial infection was higher in re-positive group. We speculated that the higher the CT value of nucleic acid at the time of initial infection, the longer the intermittent shedding time of the virus. (3) Re-positive patients were asymptomatic. The median CT value of nucleic acid was > 35 at the re-positive time, and the close contacts were not detected as positive. The overall transmission risk of re-positive patients is low.

[Advances in functional studies of nonstructural proteins and development of antiviral agents for enterovirus 71].

Human enterovirus 71 (EV71) is one of the major etiological agents for the hand, foot, and month disease (HFMD) and is causing frequent, widespread occurrence in the mainland of China. The single positive-stranded RNA genome of EV71 is translated into a single polyprotein which is autocleavaged into structural and nonstructural proteins. The functions of many nonstructural proteins characterized in the life cycle of virus are potential targets for blocking viral replication. This article reviews the studies of the structures and functions of nonstructural proteins of EV71 and the anti-enterovirus 71 drugs targeting on these nonstructural proteins.

[Elucidating the structure of two cyclotides of Viola tianshanica maxim by MALDI TOF/TOF MS analysis].

The cyclotides are a family of cyclic "mini" proteins that occur in Violaceae, Rubiaceae and Cucurbitaceae plant families and contain a head-to-tail cyclic backbone and a cystine knot arranged by three disulfide bonds. To study the natural cyclotides of V tianshanica, dried herb was extracted with 50% ethanol, and the concentrated aqueous extract was subjected to a solvent-solvent partitioning between water and hexane, ethyl acetate and n-butanol, separately. The n-butanol extract containing cyclotides was subjected to column chromatography over Sephadex LH-20, eluted with 30% methanol. The subfractions were directly reduced by DTT and analyzed by reverse-phase HPLC. The peaks with different retention times were shown on the profile of RP-HPLC and collected. The cyclotides were speculated based on masses range from 3 000 to 3 500 Da. The purified cyclotides were reduced with DTT, alkylated with iodoacetamide, and then were cleaved with endoproteinase Glu-C, endoproteinase Lys-C and Trypsin, separately. The digested peptides were purified on RP-HPLC and analyzed on MALDI TOF/TOF analyzer. A new cyclotide, cycloviolacin T1 and a reported cyclotide varv E were systemically determined using MALDI TOF/TOF system. So the method for the isolation and characterization of cyclotides was quickly built up in succession.

2-Fluoro-N'-(2-hy-droxy-benzyl-idene)benzohydrazide.

In the title compound, C(14)H(11)FN(2)O(2), an intra-molecular O-H⋯N hydrogen bond influences the mol-ecular conformation; the two benzene rings form a dihedral angle of 18.4 (3)°. The F atom is disordered over two positions in a 0.717 (5):0.283 (5) ratio. In the crystal, inter-molecular N-H⋯O hydrogen bonds link the mol-ecules into chains extending along the c axis.

2-Fluoro-N'-(2-meth-oxy-benzyl-idene)benzohydrazide.

The mol-ecule of the title compound, C(15)H(13)FN(2)O(2), exists in a trans configuration with respect to the methyl-idene unit. The two benzene rings form a dihedral angle of of 64.7 (2)°. In the crystal, mol-ecules are linked through N-H⋯O hydrogen bonds into chains propagating along the c axis.

[cDNA cloning, heterologous overexpression and activity analysis of cytochrome P450 reductase of Taxus chinensis].

NADPH-cytochrome P450 reductase (CPR), a partner for P450 monooxygenases, serves as the electron donor to almost all eukaryotic cytochrome P450s. One cDNA (TchCPR) encoding cytochrome P450 reductase of T. chinensis was isolated from callus cells. The cDNA contains an open reading frame of 2154 nucleotides which encodes a protein of 717 amino acid residues. The TchCPR has higher similarity to other CPRs of gumnosperms (>82%) than that of angiosperms (<74%). The recombinant full-length TchCPR and a series of N-terminal truncated constructs with N-terminal fusion of His Tag were obtained and induced to express in E. coli B121(DE3), and then purified using affinity chromatography. The truncated forms of N-terminal more than 61 amino acid residues could be efficiently expressed while the truncated mutant of N-terminal 48 amino acid residues and the wild-type TchCPR were not successfully expressed in E. coli cells. The activity of the truncated TchCPR was assayed by measuring the reduction of cytochrome C. The electron transfer activity of the recombinantly purified CPRT61 was 1.6057 nmol of cytochrome C reduced per min per microg TchCPR reductase, and it is higher than that of the other four truncated forms.

Using Healthcare Failure Mode and Effect Analysis to Reduce Intravenous Chemotherapy Errors in Chinese Hospitalized Patients.

BACKGROUND: Intravenous chemotherapy administration is a high-risk process; attention must be paid to preventing errors that might occur during the administration of chemotherapy. OBJECTIVE: The aim of this study is to investigate whether the healthcare failure mode and effect analysis (HFMEA) is a valid proactive method to apply to chemotherapy administration in the Chinese oncology inpatient setting. METHODS: A multidisciplinary team created a flow diagram of the chemotherapy administration process and potential failure modes were identified and evaluated using a hazard-scoring matrix. Using a decision tree, failure mode recommendations were made. Chemotherapy error rates before and after the HFMEA were compared. RESULTS: A total of 5 failure modes were identified with high hazard scores, and 15 recommendations were made. After the intervention, the chemotherapy error rate decreased significantly from 2.05% to 0.17%. CONCLUSIONS: The complexity of intravenous chemotherapy makes it vulnerable to error, and with serious consequences. Multiple errors can occur during ordering, preparing, compounding, dispensing, and administering the chemotherapy. The process of HFMEA helped reduce the chemotherapy error rate in Chinese hospitalized patients. IMPLICATIONS FOR PRACTICE: Clinicians in oncology can take effective measures to avoid chemotherapy errors using the HFMEA.

Ifosfamide, Cisplatin or Carboplatin, and Etoposide (ICE)-based Chemotherapy for Mobilization of Autologous Peripheral Blood Stem Cells in Patients with Lymphomas.

BACKGROUND: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a promising approach for lymphomas. This study aimed to evaluate the effect of ifosfamide, cisplatin or carboplatin, and etoposide (ICE)-based regimen as a mobilization regimen on relapsed, refractory, or high-risk aggressive lymphoma. METHODS: From June 2001 to May 2013, patients with lymphomas who mobilized by ICE-based regimen for ASCT were analyzed in this retrospective study. The results of the autologous peripheral blood stem cells collection, toxicity, engraftment after ICE-based mobilization regimen were analyzed in this study. Furthermore, risk factors for overall survival (OS) and progression free survival (PFS) were evaluated by univariate analysis. RESULTS: The stem cells were mobilized using ICE-based regimen plus rituximab or ICE-based regimen alone in 12 patients and 54 patients, respectively. The results of stem cell mobilization were excellent. Ninety-seven percentages of the patients had the stem cell collection of at least 2.0 × 10 6 CD34 + cells/kg and 68% had at least 5 × 10 6 CD34 + cells/kg. Fifty-eight percentage of the patients experienced Grade 4 neutropenia, 20% developed febrile neutropenia, and only 12% had Grade 4 thrombocytopenia. At a median follow-up of 63.8 months, the 5-year PFS and OS were 64.4% and 75.3%, respectively. CONCLUSION: ICE is a powerful regimen for stem cell mobilization in patients with lymphomas.

Effects of nurse-led telephone follow-up for discharged patients treated with chemotherapy.

OBJECTIVE: Nurse-led telephone follow-up is effective in meeting information and psycho-social needs. We explored the potential effects of nurse-led telephone follow-up for patients treated with chemotherapy in China. METHODS: A quasi-experimental study was employed in the research. 300 cases of cancer inpatients in a cancer hospital in Beijing during July-October 2012 were selected by convenience sampling. To compare the satisfaction and response regarding to chemotherapy adverse side effects, patients who discharged on Monday and Friday were provided with telephone follow-up. Patients who discharged on Tuesday, Wednesday and Thursday received routine care. RESULTS: Via telephone follow-up, patient satisfaction relating to nursing care increased. Moreover, their response to chemotherapy adverse side effects showed a significant difference. CONCLUSION: Telephone follow-up by specialist nurses may be a feasible option. It was well received by patients, with no physical or psychological disadvantage.

Quinoid glycosides from Forsythia suspensa.

Phytochemical investigation on Forsythia suspensa (Thunb.) Vahl afforded 10 compounds, including quinoid glycosides, lignan glycosides, phenylethanoid glycoside and allylbenzene glycoside together with 13 known ones. Their structures were established based on extensive spectroscopic data analyses, including IR, UV, HRESIMS, 1D NMR and 2D NMR. Absolute configurations were determined by ECD calculation method and chemical degradation. In addition, all compounds were evaluated for their antiviral activity against influenza A (H1N1) virus and several were further evaluated against respiratory syncytial virus (RSV) in vitro. Among them, two previously known compounds showed significant activities against RSV with EC50 values of 3.43 and 6.72 µM.