[The influence of different blood pressure management schemes on the quality of postoperative anesthesia recovery in elderly patients undergoing long-time gynecological laparoscopic tumor surgery].

Objective: To investigate the effect of different blood pressure management schemes on the quality of postoperative anesthesia recovery in elderly patients undergoing long-term gynecological laparoscopic tumor surgery. Methods: A total of 57 patients who underwent gynecological tumor surgery in Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine from May to October 2022 were prospectively included. The patients were randomly divided into two groups: the precise blood pressure management group [group P, n=28, aged (69.9±3.6) years] and the control group [group C, n=29, aged (68.6±3.1) years]. Group P adopted a precise blood pressure management scheme, and systolic blood pressure (SBP) fluctuated within±10% of basal blood pressure during operation, while group C adopted a routine blood pressure management scheme, which maintained SBP fluctuation within±20% of basal blood pressure during operation, and SBP≥90 mmHg (1 mmHg=0.133 kPa). The main outcome measures were the quality of anesthesia recovery (QoR-40) scores of the two groups 24 hours after the operation. The secondary outcome measures included lactate clearance rate and blood glucose change 2 hours after the beginning of the operation and immediately after the operation, post anesthesia recovery score (PARS) and sedation-agitation scale (SAS) 5 min after extubation, intraoperative norepinephrine dosage, volume of fluid administered, blood loss and urine volume, creatinine clearance rate and urea nitrogen clearance rate 24 hours after the operation, anesthesia satisfaction score, length of hospital stay and hospitalization cost, etc. Results: The QoR-40 score of group P [M (Q1, Q3)] 24 hours after operation was 192 (190, 195), which was higher than that of group C [170 (163, 178)] (P<0.001). The lactate clearance rates 2 hours after the beginning of the operation and immediately after the operation in group P [M (Q1, Q3)] were 31.0% (14.9%, 43.3%) and 21.1% (3.1%, 38.2%), which were higher than those in group C [-12.5% (-43.1%, 11.8%) and -22.2% (-61.3%, -11.1%)] (both P<0.05). The changes in blood glucose 2 hours after the beginning of the operation and immediately after the operation in group P [M (Q1, Q3)] were [1.1 (0.9, 1.4) mmol/L and 1.4 (0.9, 1.9) mmol/L], which were higher than those in group C [0.2 (-0.2, 0.5) mmol/L and 0.2 (-0.2, 0.5) mmol/L] (both P<0.05). The intraoperative urine volume, PARS score and SAS score 5 min after extubation, and anesthesia satisfaction score in group P [M (Q1, Q3)] were 400 (300, 500) ml, 8 (8, 9), 4 (4, 4) and 8 (8, 9), respectively, which were higher than those in group C [200 (100, 300) ml, 7 (7, 8), 3 (3, 3) and 6 (6, 7), respectively] (all P<0.05). There were no statistically significant differences in norepinephrine dosage, volume of fluid administered, blood loss, creatinine clearance rate, urea nitrogen clearance rate, length of hospital stay and hospitalization cost between the two groups (all P>0.05). Conclusion: The precise blood pressure management scheme of maintaining SBP fluctuation within±10% of basal blood pressure in elderly patients undergoing long-time gynecological laparoscopic tumor surgery can significantly enhance the quality of postoperative anesthesia recovery, improve the patients' satisfaction, and facilitate the patients' postoperative rehabilitation.

Association of rs35006907 Polymorphism with Risk of Dilated Cardiomyopathy in Han Chinese Population.

Background: Several investigations have demonstrated the association of MTSS1 with left ventricular (LV) structure and function. A recently published study has even revealed that rs35006907 was associated with both MTSS1 expression and the risk of dilated cardiomyopathy (DCM). Objective: Our study intended to investigate the relationship between rs35006907 and the risk of DCM in the Han Chinese population. Methods: A total of 529 DCM and 600 healthy controls were recruited. We conducted genotyping for rs35006907 in all participants. Gene association studies were performed to assess the association between rs35006907 and the risk of DCM. A series of functional assays including western blot, realtime PCR and firefly luciferase reporter gene assays were conducted to illuminate the underlying mechanism. Results: We found that rs35006907-A allele was significantly associated with reduced risk of DCM in additive (p= 0.004; OR=0.78; 95% CI=0.66-0.93) and recessive models (p= 0.0005; OR=0.56; 95%CI=0.41-0.78) when compared with the rs35006907-C allele. There were significant differences in the left ventricular end-diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) between rs35006907-CC/AC and AA genotypes. Furthermore, the variant rs35006907-A allele presented lower reporter gene activity, reduced mRNA and protein expression levels when compared with the C allele. Conclusions: Our findings demonstrated that rs35006907-C allele increased the risk of DCM in Han Chinese population. Besides, rs35006907-C displayed higher reporter gene activity and increased MTSS1 expression in human samples.

The role of infant attention and parental sensitivity in infant cognitive development in the Netherlands and China.

Infant attention and parental sensitivity are important predictors of later child executive function (EF). However, most studies have investigated infant and parent factors in relation to child EF separately and included only mothers from Western samples. The current study examined whether both infant attention at 4 months and parental sensitivity at 4 and 14 months were related to infant EF (i.e., inhibition, working memory, and cognitive flexibility) at 14 months among 124 Dutch and 63 Chinese first-time mothers and fathers and their infants. Findings revealed that parental sensitivity at 4 months was not correlated with infant EF abilities at 14 months. However, infant attention at 4 months was significantly related to 14-month working memory, but not to inhibition and cognitive flexibility. Maternal sensitivity at 14 months was significantly related to 14-month inhibition, but not to working memory and cognitive flexibility. No country differences were found in the relation among 4-month infant attention, parental sensitivity, and EF outcomes. Results show that both infant and parent factors are associated with early EF development and that these correlates of early EF skills may be similar in Western and non-Western samples.

Regulator of cullins-1 (ROC1) negatively regulates the Gli2 regulator SUFU to activate the hedgehog pathway in bladder cancer.

BACKGROUND: The regulator of cullins-1 (ROC1) is an essential subunit in the cullin-RING ligase (CRL) protein complex and has been shown to be critical in bladder cancer cell survival and progression. This study aimed to explore the molecular mechanism of ROC1 action in the malignant progression of bladder cancer. METHODS: This study utilized ex vivo, in vitro, and in vivo nude mouse experiments to assess the underlying mechanisms of ROC1 in bladder cancer cells. The expression of the components of the sonic hedgehog (SHH) pathway was determined by western blot analysis. ROC1 expression in human tumors was evaluated by immunohistochemistry. RESULTS: ROC1 overexpression promoted the growth of bladder cancer cells, whereas knockdown of ROC1 expression had the opposite effect in bladder cancer cells. Mechanistically, ROC1 was able to target suppressor of fused homolog (SUFU) for ubiquitin-dependent degradation, allowing Gli2 release from the SUFU complex to activate the SHH pathway. Furthermore, knockdown of SUFU expression partially rescued the ROC1 knockdown-suppressed SHH activity as well as cancer cell growth inhibition. In ex vivo experiments, tissue microarray analysis of human bladder cancer specimens revealed a positive association of ROC1 expression with the SHH pathway activity. CONCLUSION: This study demonstrated that dysregulation of the ROC1-SUFU-GLI2 axis plays an important role in bladder cancer progression and that targeting ROC1 expression is warranted in further investigations as a novel strategy for the future control of bladder cancer.

The diagnostic accuracy of dermoscopy and reflectance confocal microscopy for amelanotic/hypomelanotic melanoma: a systematic review and meta-analysis.

BACKGROUND: Dermoscopy and reflectance confocal microscopy (RCM) are noninvasive techniques for the diagnosis of skin lesions. Their accuracy for amelanotic/hypomelanotic melanoma (AHM) has not been systematically studied. OBJECTIVES: We aimed to investigate systematically the accuracy of dermoscopy and RCM and to compare the accuracy between them for diagnosing AHM. METHODS: We searched the PubMed, Web of Science, Embase and Cochrane Library databases for eligible studies about dermoscopy, RCM and AHM from inception to 31 June 2019. The quality of the studies was assessed with the Quality Assessment of Diagnostic Accuracy Studies tool. The pooled results were calculated using a random effects model in Stata 14, Meta-DiSc, RevMan 5·3 and SAS 9·4. We also explored the sources of heterogeneity by sensitivity analysis. RESULTS: Seven studies with a total of 1111 lesions were included. The pooled sensitivity and specificity of dermoscopy for the diagnosis of AHM were 61% [95% confidence interval (CI) 0·37-0·81] and 90% (95% CI 0·74-0·97), respectively. The corresponding respective values of RCM for the diagnosis of AHM were 67% (95% CI 0·51-0·81) and 89% (95% CI 0·86-0·92). In three studies including the performance of both RCM and dermoscopy, the relative diagnostic odds ratio of RCM over dermoscopy was 4·69 (95% CI 0·81-27·3) (P = 0·068). CONCLUSIONS: Our study demonstrates that both dermoscopy and RCM offer good diagnostic accuracy with high specificity and moderate sensitivity in the diagnosis of AHM. RCM is more accurate than dermoscopy in diagnosing AHM but the comparison needs to be confirmed. What's already known about this topic? Amelanotic/hypomelanotic melanoma (AHM) is the most lethal skin cancer. The diagnosis of AHM is a great challenge because of its nonspecific clinical manifestation. Early diagnosis can improve the prognosis. Dermoscopy and reflectance confocal microscopy (RCM) have high diagnostic accuracy for pigmented melanoma. What does this study add? Both dermoscopy and RCM offer good diagnostic accuracy with high specificity and moderate sensitivity for AHM. RCM might be more accurate than dermoscopy for diagnosis of AHM. More research on the diagnostic accuracy of dermoscopy and RCM for AHM is required in support of these findings.

Increased risk of osteoporotic vertebral fracture in rheumatoid arthritis patients with new-onset cardiovascular diseases: a retrospective nationwide cohort study in Taiwan.

INTRODUCTION: Both cardiovascular diseases (CVD) and osteoporosis are common comorbidities in rheumatoid arthritis (RA) patients. Although accumulating evidence indicates a link between CVD and osteoporotic fracture, whether CVD contributes to osteoporotic fracture risk in RA has yet to be explored. We examined the incidence rate and risk factors of osteoporotic vertebral fracture in RA patients with new-onset CVD (RA-CVD) and evaluated the effects of medications on such fracture risk. METHODS: A retrospective study was conducted using a nationwide database from 2000 to 2010: 1267 RA-CVD and 1267 non-CVD patients were enrolled from 30,507 patients with newly diagnosed RA. The main outcome was the development of osteoporotic vertebral fracture. After being adjusted for age, gender, and comorbidities, the Cox proportional hazard model was used to identify independent factors contributing to osteoporotic vertebral fracture. RESULTS: The adjusted hazard ratio (aHR) of developing osteoporotic vertebral fracture was 1.47-fold greater in RA-CVD group than in non-CVD group (95% confidence interval 1.19-1.81, p < 0.001). Both the age above 40 years and female gender were significant risk factors for developing osteoporotic vertebral fracture in RA-CVD patients. Using patients not taking medication as a reference group, the aHR of osteoporotic vertebral fracture was significantly lower in those receiving statins (0.50), low-dose corticosteroids (0.57), or hydroxychloroquine (0.12). CONCLUSIONS: The risk of osteoporotic vertebral fracture was significantly increased in RA-CVD patients, particularly women above 40 years of age, and could be reduced by statin therapy. However, the protective effect of low-dose corticosteroids or hydroxychloroquine on osteoporotic vertebral fracture risk needs further validation.

The effect of the still-face paradigm on infant behavior: A cross-cultural comparison between mothers and fathers.

Most still-face paradigm (SFP) studies have been done in Western families with infant-mother dyads. The present study investigated the SFP pattern in 123 Dutch and 63 Chinese 4-month-old infants with mothers and fathers. The classic SFP effect was found for positive affect and gaze in both countries. For negative affect, Chinese infants showed a different SFP pattern than Dutch infants. With fathers, infants displayed a less pronounced SFP pattern for positive affect and an increase from the still face to the reunion for negative affect. Only a minority of infants showed the expected SFP pattern across episodes. Our findings support that infant emotion expression is influenced by parent gender and cultural context. An interesting avenue for further study is the exploration of the origins of within- and between-gender and culture differences in affective communication between parents and infants.

[Application of modified micro titanium plate for extensor attachment point reconstruction in open-door laminoplasty].

Objective: To observe the effect of modified micro titanium plate for extensor attachment point reconstruction in open-door laminoplasty. Methods: From January 2016 to February 2017, 26 patients with cervical spondylotic myelopathy underwent open-door laminoplasty+modified micro-titanium plate fixation+extensor muscle attachment point reconstruction at Tianjin Hospital were enrolled in this study. There were 14 males and 12 females in this group, aged (59±18) years. The improvement of neurological function based on the Japanese Orthopedic Association (JOA) score and the changes cervical curvature based on the cervical curvature index (CCI), especially the atrophy of the back muscles and the occurrence axial symptoms were recorded and analyzed. Intra-group comparisons were performed by using repeated measures of variance analysis or paired t-test. Results: The operations were performed well without injury to spinal cord. The operation time was (116±32) min with a blood loss of (196±41) ml. The JOA scores was improved form 7.8±2.1 preoperatively to 13.5±3.4 three months after surgery, and 13.9±3.7 at the final follow up (F=30.619, P<0.05). The improvement rate of neurological function was 66%±13%. The CCI decreased from 14.3%±3.9% preoperatively to 13.7%±3.7% three months after surgery and 13.0%±3.3% at the last follow-up (F=0.829, P>0.05). The cross-sectional area of the posterior cervical muscle was (35.9±7.6) cm(2) before surgery, and it was (33.5±6.7) cm(2) at the last follow-up (t=1.208, P>0.05). The spinal cord drift distance was (2.6±0.5) mm. The axial symptoms occurred in three patients, the incidence rate was 11.5%. Conclusion: In the open-door laminectomy, modified micro titanium plate can maintain the stability of the cervical spine, it also can rebuild the extensor attachment points and reduce the atrophy of the posterior cervical muscles, which avoid the occurrence of kyphotic deformity and reduce the occurrence of axial symptoms.

Increased risk of hepatitis B virus reactivation in systemic lupus erythematosus patients receiving immunosuppressants: a retrospective cohort study.

Objective We aimed to investigate risk of hepatitis B virus reactivation in systemic lupus erythematosus patients with different hepatitis B virus infection statuses receiving immunosuppressive therapy. Methods We retrospectively analyzed systemic lupus erythematosus patients with positive hepatitis B surface antigen or anti-hepatitis B core IgG antibody who underwent immunosuppressive therapies from January 2001 to December 2012 at a medical center in Taiwan for evidence of hepatitis B virus reactivation. Results During this period, 906 out of 3125 patients who were diagnosed with systemic lupus erythematosus received screening tests for hepatitis B virus. Thirty-eight patients were identified as hepatitis B surface antigen-positive. Fifteen of 38 (39.5%) hepatitis B surface antigen-positive patients developed hepatitis B virus reactivation, and 53.3% of these patients experienced severe hepatitis flare. Three of 157 hepatitis B surface antigen-negative/anti-hepatitis B core IgG antibody-positive patients (1.9%) experienced hepatitis B surface antigen seroreversion after immunosuppressive therapy. Five patients received prophylactic or preemptive antiviral therapy and none of them developed hepatitis B virus flares. A daily dose of prednisolone greater than 5 mg was a risk factor for hepatitis B reactivation by multivariate logistic analysis. Conclusions The risk of hepatitis B virus reactivation is high in lupus patients receiving immunosuppressive therapy. Antiviral prophylaxis or preemption can effectively reduce the incidence of hepatitis B virus reactivation in lupus patients.

Predicative values of serum microRNA-22 and microRNA-126 levels for non-small cell lung cancer development and metastasis: a case-control study.

Presented study aims to explore the predictive values of serum microRNA-22 (miR-22) and miR-126 levels for non-small cell lung cancer (NSCLC) development and metastasis.A total of 127 NSCLC patients who were admitted in the First People's Hospital of Yancheng City from May, 2013 to May, 2015 were selected as the case group, including 71 cases of adenocarcinoma and 56 cases of squamous cell carcinoma. There were 112 healthy individuals selected as the control group. The qRT-PCR was performed to testify the serum miR-22 and miR-126 levels. Logistic regression analysis was conducted to analyze independent factors influencing NSCLC metastasis and receiver operating characteristic (ROC) curve was drawn to analyze the sensitivity and specificity of serum miR-22 and miR-126 levels in predicting NSCLC developments and metastasis.The serum miR-22 level was significantly higher in the case group than that in the control group, while the serum miR-126 level was lower in the case group as compared with that in the control group. Compared with squamous cell carcinoma patients, serum miR-22 level significantly increased, while serum miR-126 level decreased in patients with adenocarcinoma. Patients at III + IV stage showed increased serum miR-22 level and relatively decreased serum miR-126 level as compared to patients at I + II stage. Serum miR-22 level elevated in patients with metastasis; in contrast serum miR-126 level reduced in comparison to those without metastasis. In patients with familial inheritance, serum miR-22 level increased but serum miR-126 level decreased as compared to those without familial inheritance. The specificity and sensitivity of serum miR-22 and miR-126 levels in predicting NSCLC development were 99.11%, 84.30%, 82.68% and 96.40%, respectively. The specificity and sensitivity of serum miR-22 and miR-126 levels in predicting NSCLC metastasis were 59.74%, 96.00%, 84.00% and 62.30%, respectively.Results indicated that serum miR-22 and miR-126 levels may be used as the predicative biomarkers for NSCLC development and metastasis.

Description of Triplophysa luochengensis sp. nov. (Teleostei: Nemacheilidae) from a karst cave in Guangxi, China.

A new cave-dwelling fish Triplophysa luochengensis is described based on specimens collected from a karst cave in Guangxi Zhuang Autonomous Region, China, that is interconnected to the Hongshui River drainage. The species can be distinguished from its congeners by a combination of characters: eyes degenerated, anal fin with six branched rays, caudal fin with 16-17 branched rays, pectoral-fin length 72·4-95·8% of the distance between pectoral-fin origin and pelvic-fin origin, lateral head length 26·2-28·2% of standard length (LS ), eye diameter 7·5-8·6 of LS , body covered by sparse scales, lateral line complete and 7-8 pre-operculo-mandibular pores. Dark pigments irregularly present on dorsum of head, dorsum and flank.

[Overexpression of TRPV1 after periphery nerve injury attenuates nerve regeneration in rats].

Objective: To observe the effect of the expressive or functional blockage of TRPV1 on nerve regeneration after sciatic trans-section injury. Methods: AMG-517, a kind of TRPV1 inhibitor, was injected into the surrounding area of the ipsilateral lumbar dorsal root ganglia while unilateral sciatic nerve was transected. A total of 24 healthy male Sprague-Dawley rats were divided into 4 groups: control group, injury only group, injury+ AMG-517 150 µg/kg group, injury+ AMG-517 300 µg/kg group. The injury only group was injected the same volume of medium. The release of CGRP from dorsal-horn of spinal cord, the number of axons at proximal stem of sciatic nerve after transection, and the expression of TRPV1 in dorsal root ganglion were detected using the methods of ELISA, Western blot and semi-thin section (1 µm)- toluidine blue staining 2 weeks after injury. Results: The release of CGRP in lumbar spinal dorsal horn was obviously decreased after AMG-517 treatment, which was the evidence of TRPV1 functional inhibition. CGRP in the control group was 0.15 ng/g, the injury only group 0.17 ng/g, AMG-517 150 µg/kg group 0.09 ng/g, and AMG-517 300 µg/kg group 0.11 ng/g(P<0.01). The number of axons which were myelinated or unmyelinated increased after the TRPV1 was inhibited by AMG-517(P<0.01). In addition, the injection of AMG-517 into surrounding dorsal root ganglion decreased the expression of TRPV1 in dorsal root ganglion(P<0.01). Conclusions: Over expression or activation of TRPV1 after periphery nerve injury has negative effect on nerve regeneration in fact; Inhibiting the over-expression or over-activation of TRPV1 after nerve injury facilitates axonal regeneration and nerve repair.

Regulator of cullins-1 expression knockdown suppresses the malignant progression of muscle-invasive transitional cell carcinoma by regulating mTOR/DEPTOR pathway.

BACKGROUND: Regulator of cullins-1 (ROC1) is a key subunit in the cullin-RING ligase (CRL) protein complex. Our previous study indicated that ROC1 was essential for bladder cancer cell survival and that ROC1 knockdown inhibited CRL activity, triggering G2 phase arrest and senescence. However, the role of ROC1 in the malignant progression of bladder cancer remained unknown. METHODS: ROC1 expression in cancer cells was knocked down by siRNA silencing. The effects of ROC1 silencing were evaluated by in vitro assays for cell migration and by an in vivo mouse metastasis model. Epithelial-mesenchymal transition (EMT) induction was evaluated by immunofluorescence staining and western blotting of EMT-associated proteins. ROC1 expression in human tumours was further evaluated by immunohistochemical analysis. RESULTS: ROC1 knockdown suppresses bladder cancer cell migration by inhibiting EMT. ROC1 knockdown inhibited EMT by inhibiting mammalian target of rapamycin (mTOR) activity via the accumulation of the mTOR-inhibitory protein DEPTOR, a CRL substrate. DEPTOR knockdown partially rescued ROC1 knockdown-inhibited EMT and the ROC1-induced inhibition of cancer cell migration. Furthermore, in vivo studies using a nude mouse metastasis model confirmed the in vitro data. Finally, tissue microarray analysis of clinical bladder cancer specimens indicated a positive correlation between ROC1 expression and EMT. CONCLUSIONS: ROC1 has an important role in the malignant progression of bladder cancer via the mTOR/DEPTOR pathway. ROC1 may serve as a novel therapeutic target for the treatment of muscle-invasive transitional cell carcinoma.

[Identification of the Disease-Associated Genes in Periodontitis Using the Co-expression Network].

The aim of this study was to investigate the disease-associated genes in periodontitis. In the present experiments, the topological analysis of the differential co-expression network was proposed. Using the GSE16134 dataset downloaded from the European Molecular Biology Laboratory-European Bioinformatics Institute, a co-expression network was constructed after the differentially expressed genes (DEGs) were identified between the diseased (242 samples) and healthy (69 samples) gingival tissues from periodontitis patients. The topological properties of the modules obtained from the network as well as an analysis of transcription factors (TFs) were used to determine the disease-associated genes. The gene ontology and pathway enrichment analysis was performed to investigate the underlying mechanisms of these disease related genes. A total of 524 DEGs, including 19 TFs were identified and a co-expression network with 2569 edges was obtained. Among the 7 modules gained in the network, the TFs (ZNF215, ZEN273, NFAT5, TRPS1, MEF2C and FLI1) were considered to be important in periodontitis. The functional and pathway enrichment analysis revealed that the DEGs were highly involved in the immune system. The co-expression network analysis and TFs identified in periodontitis may provide opportunities for biomarker development and novel insights into the therapeutics of periodontitis.

Cloning, expression, and polymorphism at the 5'-flanking region of the GnRH gene and their association with laying traits in Muscovy duck (Cairina moschata).

Gonadotropin-releasing hormone (GnRH), a neuropeptide, plays a vital role in the hypothalamus-pituitary-gonadal (HPG) axis. In vertebrates, GnRH is crucial for the onset of sexual development and the entire reproductive process. The purpose of this study was to identify genetic factors associated with egg-laying traits of Muscovy ducks. The full-length cDNA (474 bp) of Muscovy duck GnRH was obtained and characterised. It encodes 92 amino acids containing a 1-amino acid signal peptide cleavage site. Phylogenetic analysis revealed that Muscovy duck GnRH has a close relationship with Anas platyrhynchos GnRH. GnRH showed significantly different expression profiles between 4 developmental periods in the hypothalamus, pituitary, and ovary. The expression of GnRH in the laying period (36 weeks) was higher than at other periods in the three tissues. GnRH was widely expressed in 12 examined tissues of nesting and laying Muscovy ducks. In the hypothalamus, pituitary and gonads, the expression of GnRH was higher than in other tissues. In laying Muscovy ducks, the expression of GnRH in the hypothalamus, pituitary, ovary, muscular stomach, pancreas, heart, duodenum and spleen was significantly higher than in nesting dusks. Differences were detected in the liver and glandular stomach between laying ducks and nesting ducks. Differences between the kidney and lung were not significant. In the pituitary, the GnRH and GnRH receptor (GnRHR) genes shared the same expression profiles during 4 time points. Both genes had the highest expression at 36 weeks of age. A mutation (g.206G > A) in the 5'-flanking region was associated with egg-laying performance. Individuals with genotype GG had better egg-laying performance than the individuals with genotype AA. GnRH may be used as a marker gene for laying performance in the Muscovy duck.

[Sensitivity of colorectal cancer organoids to hyperthermic intraperitoneal chemotherapy with lobaplatin].

Objective: To investigate the sensitivity of tumor organoids derived from samples of colorectal cancer to lobaplatin and oxaliplatin hyperthermic perfusion in vitro and to assist clinical development of hyperthermic intraperitoneal chemotherapy. Method: Tumor samples and relevant clinical data were collected from patients with pathologically confirmed colorectal cancer in the Sixth Affiliated Hospital of Sun Yat-sen University from July 2021 to December 2022. Organoids were cultured and tumor tissue were passaged. In vitro hyperthermic perfusion experiments were performed on organoids with good viability. Firstly, 10 organoids were treated with oxaliplatin and lobaplatin at the following six concentrations: 1 000, 250, 62.5, 15.6, 3.9, and 0.98 µmol/L. The organoids were exposed to oxaliplatin at 42℃ for 30 minutes and to lobaplatin at 42℃ for 60 minutes. Dose-response curves of responses to in vitro hyperthermic perfusion with these two drugs were constructed and evaluated. Clinical doses of oxaliplatin and lobaplatin were further tested on 30 organoids. This testing revealed oxaliplatin was effective at 579 µmol/L at a hyperthermic perfusion temperature of 42℃ for 30 min and lobaplatin was effective at 240 µmol/L at a hyperthermic perfusion temperature of 42℃ for 60 minutes. Result: Thirty-two tumor organoids were cultured from samples of colorectal cancer. The median concentration required for oxaliplatin to eliminate 50% of tumor cells (IC50) was 577.45 µmol/L (IQR: 1846.09 µmol/L). The median IC50 for lobaplatin was 85.04 µmol/L (IQR: 305.01 µmol/L).The difference between the two groups was not statistically significant (Z=1.784, P=0.084). In seven of 10 organoids, lobaplatin showed a greater IC50 after in vitro hyperthermic perfusion than did oxaliplatin. Testing of 30 organoids with clinical doses of oxaliplatin and lobaplatin revealed that oxaliplatin achieved an average inhibition rate of 39.6% (95%CI: 32.1%‒47.0%), whereas the average rate of inhibition for lobaplatin was 89.7% (95%CI: 87.0%‒92.3%): this difference is statistically significant (t=‒15.282, P<0.001). Conclusion: The rate of inhibition achieved by hyperthermic perfusion of lobaplatin in vitro is better than that achieved by hyperthermic perfusion with oxaliplatin. Lobaplatin is more effective than oxaliplatin when administered by hyperthermic intraperitoneal perfusion and therefore has the potential to replace oxaliplatin in this setting.

[Efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation in the treatment of secondary acute myeloid leukemia].

Objective: To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with secondary acute myeloid leukemia (sAML) . Methods: In this multicenter, retrospective clinical study, adult patients aged ≥18 years who underwent allo-HSCT for sAML at four centers of the Zhejiang Hematopoietic Stem Cell Transplantation Collaborative Group from January 2014 to November 2022 were included, and the efficacy and prognostic factors of allo-HSCT were analyzed. Results: A total of 95 patients were enrolled; 66 (69.5%) had myelodysplastic syndrome-acute myeloid leukemia (MDS-AML) , 4 (4.2%) had MDS/MPN-AML, and 25 (26.3%) had therapy-related AML (tAML) . The 3-year CIR, LFS, and overall survival (OS) rates were 18.6% (95% CI 10.2%-27.0%) , 70.6% (95% CI 60.8%-80.4%) , and 73.3% (95% CI 63.9%-82.7%) , respectively. The 3-year CIRs of the M-AML group (including MDS-AML and MDS/MPN-AML) and the tAML group were 20.0% and 16.4%, respectively (P=0.430) . The 3-year LFSs were 68.3% and 75.4%, respectively (P=0.176) . The 3-year OS rates were 69.7% and 75.4%, respectively (P=0.233) . The 3-year CIRs of the groups with and without TP53 mutations were 60.0% and 13.7%, respectively (P=0.003) ; the 3-year LFSs were 20.0% and 76.5%, respectively (P=0.002) ; and the 3-year OS rates were 40.0% and 77.6%, respectively (P=0.002) . According to European LeukmiaNet 2022 (ELN2022) risk stratification, the 3-year CIRs of patients in the low-, intermediate-, and high-risk groups were 8.3%, 17.8%, and 22.6%, respectively (P=0.639) . The three-year LFSs were 91.7%, 69.5%, and 65.6%, respectively (P=0.268) . The 3-year OS rates were 91.7%, 71.4%, and 70.1%, respectively (P=0.314) . Multivariate analysis revealed that advanced disease at allo-HSCT and TP53 mutations were independent risk factors for CIR, LFS, and OS. Conclusion: There was no significant difference in the prognosis of patients who underwent allo-HSCT among the MDS-AML, MDS/MPN-AML, and tAML groups. Advanced disease at transplantation and TP53 mutations were poor prognostic factors. ELN2022 risk stratification had limited value for predicting the prognosis of patients with sAML following allo-HSCT.