OBJECTIVE To develop a prediction model for durable clinical benefit （DCB） in patients with advanced esophageal squamous cell carcinoma （ESCC） receiving programmed death-1 （PD-1） inhibitor. METHODS The clinical data of patients with advanced ESCC who received PD-1 inhibitor in Jieyang People’s Hospital were retrospectively collected between January 2020 to December 2023. Predictors were screened by least absolute shrinkage and selection operator （Lasso） regression， and a multivariable Logistic regression model was developed to predict DCB. A nomogram was constructed based on the model. Internal validation of the prediction model was performed by using the Bootstrap method， and the model was evaluated by the receiver operating characteristic （ROC） curve， calibration curve， and decision curve analysis. RESULTS A total of 91 patients with advanced ESCC were included. The results of Lasso regression combined with Logistic regression analysis indicated that the baseline lymphocyte monocyte ratio （LMR） [odds ratio （OR）＝1.97， 95% confidence interval （CI）： 1.15-3.36， P＝0.013]， albumin （ALB） content （OR＝1.35， 95%CI： 1.13-1.60， P＜0.001）， body mass index （BMI） category 1 [normal vs. low： OR＝ 0.28， 95%CI （0.09-0.96）， P＝0.042]， BMI category 2 [overweight-obesity vs. low： OR＝0.08， 95%CI （0.01-0.59）， P＝0.013]， and treatment regimen [monotherapy vs. monotherapy combination therapy： OR＝0.07， 95%CI （0.01-0.50）， P＝0.008] were predictive factors for patients with advanced ESCC to achieve DCB when treated with PD-1 inhibitor. A prediction model was constructed based on the above indicators. Internal validation of the model using the Bootstrap method showed an area under the curve of 0.831 （95%CI： 0.746-0.904）， with specificity of 74.4% and sensitivity of 75.0%. The Hosmer-Lemeshow test yielded χ2＝ 9.930， P＝0.270， and the calibration curve slope was close to 1. The decision curve analysis demonstrated that the model exhibited good clinical utility within a threshold range of 0.1 to 1.0. CONCLUSIONS The prediction model based on baseline LMR， ALB content， BMI， and treatment regimen demonstrates robust predictive performance and clinical utility for assessing therapeutic efficacy of PD-1 inhibitor in the treatment of advanced ESCC.

Humans ; Antineoplastic Agents/therapeutic use* ; Neoplasms/drug therapy* ; Outcome Assessment, Health Care ; China

Objective To investigate knowledge of cervical cancer,human papillomavirus (HPV) and HPV vaccine and attitude to HPV vaccine among employed urban women in China,and to assess willingness to vaccinate their children.Methods This study was conducted in women from 16 factories or companies in Beijing,Hangzhou,Changsha,Chcngdu and Guangzhou.A questionnaire on cervical cancer,HPV knowledge and HPV vaccine acceptability was administered to participants before and after educational intervention.Results A total of 1 146 women were surveyed from August to November,2011.The awareness rates of cervical cancer,HPV and HPV vaccine were 95.06 ％,27.98 ％ and 12.82 ％,respectively.Only 20.68 ％ knew that HPV was related to cervical cancer.After educatioual instruction,89.26 ％ understood the relationship between HPV and cervical cancer (x2 =93.414,P ＜ 0.001).Only 19.25 ％ women were unwilling to allow their children to be vaccinated.The main reasons were as follows:worried about vaccine safety (23.52 ％),belief that their child was not at risk (21.92 ％),lack of scientific evidence for the vaccine (13.01％),and worricd about vaccine efficacy (12.79 ％).Conclusions In general,there is a high acceptability of HPV vaccine to prevent cervical cancer among employed urban Chinese women after educational intervention.However,some women remain reluctant to vaccinate their children due to concern about vaccine safety and efficacy.

Objective To investigate the effect of bortezomib on the proliferation and apoptosis in leukemia cell line NB_4-R2 in vitro and provide some new evidences for the treatment of acute promyelocytic leukemia APL with ATRA-resistant using bortezomib. Methods NB_4-R2 cells were incubated with bortezomib at different does for 48 h. The proliferation capacity was measured by MTT assay, the morphology of cell apoptosis observed with Hoechst33342 staining by fluorescence microscopy and the percentage of apoptosis calculated by flow cytometry. The expression of apoptosis protein of cleaved (poly ADP-ribose polymerase, PARP) and Caspase-3 were determined by Western blotting. Results The proliferation of NB_4-R2 cells were obviously inhibited by bortezomib in vivo and the role of inhibition was a does-dependant manner within the scope of the bortezomib concentration from 1-5 μg /L.The incidence of inhibition was up to 74.9 % at the bortezomib concentration of 5 μg/L. Within this scope of the bortezomib concentration mentioned above, the role of inhibition of proliferation of NB_4-R2 cells mainly showed an increase of the late apoptosis, and the percentage of apoptosis was up to 78.9 %. In the meaning time, the expressions of the apoptotic protein of cleaved PARP and Caspase-3 were up-regulated in NB_4-R2 cells after treated with bortezomib by Western blotting assay. Conclusion Bortezomib can inhibit the proliferation of NB_4-R2 cells in vivo by inducing cell apoptosis.

Objective To evaluate the therapeutic effects and safety of acitretin for severe inherited keratodermas in children and adolescents. Methods Acitretin was given to 23 children and adolescents with either lamellar ichthyosis, bulbous ichthyosiform erythroderma, pityriasis rubra pillars, progressive sym- metrical erythrokeratoderma, keratitis ichthyosis deafness syndrome, generalized porokeratosis, inflammatory liner verrucous epidermal nevus, ichthyosis hystrix and non-bullous ichthyosiform erythroderma. The thera- peutic dosage was 0.67-1.07 mg/(kg?d),and maintenance dosage 0.08-0.94 mg/(kg?d).The effects on the patients' growth and development of the drug were evaluated based on the changes of body weight and height in the children. The total follow-up period was 6-35 months in an interval of 1-3 months. Results The considerable overall improvement was achieved after 1-6 months' treatment, with an overall clinical cure rate of 82.6%. Only one case responded poorly to the therapy. The excellent responses were observed in patients with bulbous ichthyosiform erythroderma, lamellar ichthyosis, and pityriasis rubra pillars, etc, and the much poor responses in ichthyosis hystrix. The most frequent adverse reaction was mild to moderate dry lips (65.2%),the next were pruritus(39.1%),skin fragility(34.8%),and dry mouth(30.4%).The less frequent adverse reactions were alopecia(13%),anorexia(8.7%),headache (4.3%) and hypoacusis (4.3%).No effects on the growth and development were found in those children during the follow up period. Conclusions The considerable overall improvement is achieved with the acitretin therapy for children and adolescents with inherited keratodermas, with only mild to moderate adverse reactions and no effects on the growth and development in the children.

In order to explore the expansive effect of human placental cell-free suspension (HPCFS) on bone marrow hematopoietic stem/progenitor cells, and to compare the effect of HPFCS with some cytokines and their combination, human marrow CFU-GM, CFU-GEMM and BFU-E were assayed in a semisolid methyl cellulose culture system using HPCFS, IL-3, GM-CSF, and IL-3 + IL-6 + GM-CSF + EPO as colony stimulating factors, respectively. The results showed that HPCFS stimulated the growth of CFU-GM, CFU-GEMM and BFU-E and the optimal concentrations for stimulating effect were 200 - 300 micro g protein/L, and the yield of 3 kinds of colony in HPCFS group was higher than that in IL-3, GM-CSF and IL-3 + IL-6 + GM-CSF + EPO groups. The expansive effect of HPCFS on marrow progenitors was superior to IL-3, GM-CSF and IL-3 + IL-6 + GM-CSF + EPO. Human placental cell-free suspension contained a variety of cytokines to stimulate proliferation of hematopoietic stem/progenitor cells, and it could be used as an efficacious and inexpensive agent to expand hematopoietic stem/progenitor cells in vitro.

AIM: To re-identify the special motif regulating osteoclast(OC)differentiation in receptor activator of nuclear factor kappa B(RANK)to provide evidences for studying the mechanism of OC differentiation.METHODS: Eight amino acids were mutated(from DIIVVYVS into ELLAAFAA)in the fragment between the 533th and the 540th amino acids in RANK cytoplasmic domain.Eight mutant TNFR1/RANK chimeras,each consists of TNFR1(tumor necrosis factor receptor 1)extracellular domain linked to transmembrane domain and cytoplasmic domain of RANK with one amino acid mutated in cytoplasmic domain was constructed by point mutation method.After the eight mutant chimeras were finished,they were packed with plat E cell line to produce the retrovirus expressing mutant TNFR1/RANK.The bone marrow macrophages(BMMs),isolated from TNFR1/R2 double knockout mice,were infected with retrovirus derived from different mutants and infected BMMs which did not differentiated into OCs were inspected after stimulated by TNF-? and M-CSF.The fragment consisted of different amino acids in TNFR1/RANK chimeras,which couldn't induce OC formation after mutated,may be the special motif regulating OC differentiation.RESULTS: We found that all BMMs transfected by TNFR1/RANK-533,TNFR1/RANK-539 or TNFR1/RANK-540 differentiated into OCs,indicating that none of amino acids D533,V539 or S540 had an effect on OC differentiation.A fewer of BMMs transfected by TNFR1/RANK-534 differentiated into OCs,indicating that I534 had a partial effect on OC formation.Most importantly,BMMs transfected TNFR1/RANK-535,TNFR1/RANK-536,TNFR1/RANK-537 or TNFR1/RANK-538 did not differentiated into OCs,indicating each of amino acids I535,V536,V537 and Y538 played a pivotal role in OC differentiation.CONCLUSION: The amino acid fragment consists of I534,I535,V536,V537 and Y538 may be the special motif regulating OC differentiation in RANK.