To summarize Professor WANG Xixing's clinical experience in treating advanced breast cancer with anxiety and depression from the perspective of shaoyang pivot. It is believed that the core pathogenesis of advanced breast cancer with anxiety and depression lies in the dysfunction of shaoyang pivot （referring to the imbalanced regulatory function of the shaoyang meridian system that governs the transportation and transformation of qi， blood， and body fluids）. This dysfunction can lead to abnormal circulation of qi， blood， and body fluids， as well as the intermingling of phlegm and blood stasis， which further promotes the spread and diffusion of cancer toxin. Meanwhile， it disturbs mental activity， resulting in a condition characterized by stagnation of cancer toxin and concurrent disorders of both the physical body and the spirit. Based on this pathogenesis， the basic therapeutic principles of harmonizing shaoyang， regulating the pivot to calm the spirit， and dissipating masses and resolving toxins are proposed. Clinically， the disease is classified into three syndromes for differentiation and treatment. For shaoyang pivot dysfunction syndrome， treatment should use self-prescribed Chaiqin Hengshu Ningxin Decoction （柴芩衡枢宁神汤）； for sanjiao pivot dysfunction syndrome， treatment should prescribe Chaigui Tongshu Dashen Decoction （柴归通枢达神饮）； for gallbladder function disorder syndrome， treatment should apply Wendan Qishu Shoushen Decoction （温胆启枢守神汤）. Throughout the treatment process， the concept of "simultaneous treatment of cancer and depression" is implemented to smooth the shaoyang pivot， block the vicious cycle where cancer toxin and emotional abnormalities mutually reinforce each other.

Objective:To explore the prognostic factors of primary plasma cell leukemia (pPCL) in the era of novel agents.Methods:The clinical data of 66 patients with pPCL treated at the Department of Haematology, Beijing Chao-Yang Hospital, Capital Medical University from 2011 to 2022 were retrospectively collected to analyze their prognostic factors.Results:Among the 66 patients with pPCL, the median age was 59 (range: 29-79) years. The median overall survival (OS) duration was 19.0 (95% CI 10.4-27.6) months, and the median progression-free survival (PFS) duration was 11.0 (95% CI 6.5-15.6) months. The median OS and PFS were significantly longer in patients with the best post-treatment response of very good partial remission (VGPR) or better than in patients with a response of partial remission (PR) or worse (median OS: 33.0 months vs 6.0 months, P<0.001; median PFS: 16.0 months vs 3.0 months, P<0.001). OS was significantly longer in patients who underwent autologous hematopoietic stem cell transplantation than in those who did not undergo transplantation (49.0 months vs 6.0 months, P=0.002), and there was a trend toward a longer PFS in patients who underwent transplantation than in those who did not undergo transplantation (19.0 months vs 8.0 months, P=0.299). The median OS and PFS were significantly longer in patients who received maintenance therapy than in those who did not receive maintenance therapy (median OS: 56.0 months vs 4.0 months, P<0.001; median PFS: 20.0 months vs 2.0 months, P<0.001). Multivariate analysis showed that hypercalcemia was an independent risk factor ( HR=3.204, 95% CI 1.068-9.610, P=0.038) for patients with pPCL, while receiving maintenance therapy ( HR=0.075, 95% CI 0.022-0.253, P<0.001) and post-treatment response of VGPR or better ( HR=0.175, 95% CI 0.048-0.638, P=0.008) were independent protective factors for patients with pPCL. Conclusions:In the era of novel agents, hypercalcemia, receiving maintenance therapy, and post-treatment response of VGPR or better are independent prognostic factors for pPCL.

Objective:To verify the predictive value of the Second Revision of the International Staging System (R2-ISS) in newly diagnosed patients with multiple myeloma (MM) who underwent first-line autologous hematopoietic stem cell transplantation (ASCT) in a new drug era in China.Methods:This multicenter retrospective cohort study enrolled patients with newly diagnosed MM from three centers in China (Beijing Chao-Yang Hospital, Capital Medical University; the First Affiliated Hospital, Sun Yat-Sen University, and the Second Affiliated Hospital of Naval Medical University) from June 2008 to June 2018. A total of 401 newly diagnosed patients with MM who were candidates for ASCT were enrolled in this cohort, all received proteasome inhibitor and/or immunomodulator-based induction chemotherapy followed by ASCT. Baseline and follow-up data were collected. The patients were regrouped using R2-ISS. Progression-free survival (PFS) and overall survival (OS) were analyzed. The Kaplan-Meier method was used to analyze the survival curve and two survival curves were compared using the log-rank test. Cox regression analysis were performed to analyze the relationship between risk factors and survival.Results:The median age of the patients was 53 years (range 25-69 years) and 59.5% (240 cases) were men. Newly diagnosed patients with renal impairment accounted for 11.5% (46 cases). According to Revised-International Staging System (R-ISS), 74 patients (18.5 %) were diagnosed with stage Ⅰ, 259 patients (64.6%) with stage Ⅱ, and 68 patients (17.0%) with stage Ⅲ. According to the R2-ISS, the distribution of patients in each group was as follows: 50 patients (12.5%) in stage Ⅰ, 95 patients (23.7%) in stage Ⅱ, 206 patients (51.4%) in stage Ⅲ, and 50 patients (12.5%) in stage Ⅳ. The median follow-up time was 35.9 months (range, 6-119 months). According to the R2-ISS stage, the median PFS in each group was: 75.3 months for stage Ⅰ; 62.0 months for stage Ⅱ, 39.2 months for stage Ⅲ, and 30.3 months for stage Ⅳ; and the median OS was not reached, 86.6 months, 71.6 months, and 38.5 months, respectively. There were statistically significant differences in PFS and OS between different groups (both P<0.001). Multivariate Cox regression analysis showed that stages Ⅲ and Ⅳ of the R2-ISS were independent prognostic factors for PFS ( HR=2.37, 95% CI 1.30-4.30; HR=4.50, 95% CI 2.35-9.01) and OS ( HR=4.20, 95% CI 1.50-11.80; HR=9.53, 95% CI 3.21-28.29). Conclusions:The R2-ISS has significant predictive value for PFS and OS for transplant-eligible patients with MM in the new drug era. However, the universality of the R2-ISS still needs to be further verified in different populations.

Objective:To discuss the effect of microRNA(miR)-30c-5p on the proliferation,migration,and invasion of the human prostate cancer cells(LNCap),and to clarify its possible mechanism.Methods:The LNCap cells were divided into LNCap group(without plasmid transfection),miR-30c-5p mimic group(transfected with miR-30c-5p mimic),mimic NC group(transfected with miR-30c-5p mimic NC),sh-DNA damage inducible transcript 4(DDIT4)group(transfected with sh-DDIT4),sh-NC group(transfected with sh-DDIT4 NC),miR-30c-5p mimic+pc-DNA3.1-NC group(co-transfected with miR-30c-5p mimic and pc-DNA3.1 empty vector),and miR-30c-5p mimic+pc-DNA3.1-DDIT4 group(co-transfected with miR-30c-5p mimic and pc-DNA3.1-DDIT4 over-expression plasmid).The RWPE-1 cells were cultured normally.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of miR-30c-5p and DDIT4 mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of DDIT4 protein in the cells in various groups;CCK-8 method was used to detect the proliferation rates of the LNCap cells in various groups;Transwell assay was used to detect the numbers of the invasion LNCap cells in various groups;Scratch assay was used to detect the scratch healing rates of LNCap cells in various groups;dual-luciferase reporter assay was used to detect the targeting relationship between miR-30c-5p and DDIT4.In the in vivo tumor formation experiment,18 male BALB/c nude mice were divided randomly into blank group,agomiR-NC group(transfected with agomiR-30c-5p NC),and agomiR-30c-5p group(transfected with agomiR-30c-5p);there were six mice in each group.The mice in agomiR-NC group and agomiR-30c-5p group were subcutaneously injected with LNCap cells,while the mice in blank group were given an equal volume of physiological saline.The volumes of tumor of the mice in various groups were detected.HE staining was used to observe the morphology of prostate cancer tissue the mice of in various groups;RT-qPCR method and immunofluorescence staining were used to detect the expression levels of miR-30c-5p and DDIT4 mRNA and the fluorescence intensities of DDIT4 protein in prostate cancer tissue of the mice in various groups.Results:The In vitro prostate cancer cell experiment results showed that compared with RWPE-1 cells,the expression level of miR-30c-5p in the prostate cancer LNCap cells was decreased(P<0.01),and the expression levels of DDIT4 mRNA and protein were increased(P<0.05 or P<0.01).After 48 of transfection,compared with LNCap group and mimic NC group,the expression level of miR-30c-5p in the LNCap cells in miR-30c-5p mimic group was increased(P<0.01).Compared with LNCap group and sh-NC group,the expression level of DDIT4 mRNA in the LNCap cells in sh-DDIT4 group was decreased(P<0.01).Compared with miR-30c-5p mimic group and miR-30c-5p mimic+pcDNA3.1 NC group,the expression level of miR-30c-5p in The LNCap cells in miR-30c-5p mimic+pc-DNA3.1-DDIT4 group was decreased(P<0.01);compared with miR-30c-5p mimic group and miR-30c-5p mimic+pcDNA3.1 NC group,the expression level of DDIT4 mRNA in the LNCap cells in miR-30c-5p mimic+pc-DNA3.1-DDIT4 group was increased(P<0.01);compared with miR-30c-5p mimic group and miR-30c-5p mimic+pcDNA3.1 NC group,the expression level of DDIT4 protein in the LNCap cells in miR-30c-5p mimic+pc-DNA3.1-DDIT4 group was increased(P<0.05).The CCK-8 method results showed that compared with LNCap group and mimic NC group,the proliferation rate of the LNCap cells in miR-30c-5p mimic group was decreased(P<0.01);compared with LNCap group and sh-NC group,the proliferation rate of the LNCap cells in sh-DDIT4 group was decreased(P<0.01);compared with miR-30c-5p mimic group and miR-30c-5p mimic+pcDNA3.1 NC group,the proliferation rate of the LNCap cells in miR-30c-5p mimic+pc-DNA3.1-DDIT4 group was increased(P<0.01).The Transwell assay results showed that compared with LNCap group and mimic NC group,the number of the invasion LNCap cells in miR-30c-5p mimic group was decreased(P<0.01);compared with LNCap group and sh-NC group,the number of invasion LNCap cells in sh-DDIT4 group was decreased(P<0.01);compared with miR-30c-5p mimic group and miR-30c-5p mimic+pcDNA3.1 NC group,the number of the invasion LNCap cells in miR-30c-5p mimic+pc-DNA3.1-DDIT4 group was increased(P<0.01).The scratch assay results showed that compared with LNCap group and mimic NC group,the scratch healing rate of the LNCap cells in miR-30c-5p mimic group was decreased(P<0.01);compared with LNCap group and sh-NC group,the scratch healing rate of the LNCap cells in sh-DDIT4 group was decreased(P<0.01);compared with miR-30c-5p mimic group and miR-30c-5p mimic+pcDNA3.1 NC group,the scratch healing rate of the LNCap cells in miR-30c-5p mimic+pc-DNA3.1-DDIT4 group was increased(P<0.01).The dual-luciferase reporter assay results showed that compared with the LNCap cells co-transfected with WT-DDIT4 and mimic NC,the luciferase activity of the LNCap cells co-transfected with WT-DDIT4 and miR-30c-5p mimic was decreased(P<0.01).The in vivo nude mouse tumor formation experiment results showed that on the 3 rd,6 th,9 th,12 th,and 15th days after cell injection,compared with blank group and agomiR-NC group,the tumor volumes of the nude mice in agomiR-30c-5p group were decreased(P<0.05).The HE staining results showed that in prostate cancer tissue of the mice in blank group and agomiR-NC group,the cell nuclei were enlarged,and nucleoli were prominent and deformed.In the mice in agomiR-30c-5p group,some regions of prostate cancer tissues results showed neatly arranged cells with normally shaped nuclei.The RT-qPCR and immunofluorescence staining showed that compared with agomiR-NC group,the expression level of miR-30c-5p in prostate cancer tissue of the mice in agomiR-30c-5p group was increased(P<0.01).Compared with blank group and agomiR-NC group,the expression level of DDIT4 mRNA in prostate cancer tissue of the mice in agomiR-30c-5p group was decreased(P<0.01).DDIT4 protein was mainly expressed in the cytoplasm.Compared with blank group and agomiR-NC group,the fluorescence intensity of DDIT4 protein in prostate cancer tissue of the mice in agomiR-30c-5p group was decreased(P<0.01).Conclusion:The expression level of miR-30c-5p in the prostate cancer LNCap cells is decreased,and it inhibits the proliferation,migration,and invasion of the prostate cancer cells by targeting downregulation of DDIT4,thereby participating in the occurrence and development of prostate cancer.

Objective:To investigate the clinical features and prognosis of multiple myeloma(MM)patients who resisted to the combination of bortezomib,lenalidomide and dexamethasone(VRD). Methods:The clinical features and prognosis of 150 patients with newly diagnosed MM in Beijing Chaoyang Hospital who were treated with VRD from January 2015 to January 2020 were retrospectively analyzed by SPSS software. Results:Among a total of 150 MM patients,21 patients resisted to VRD,including 14 patients with primary refractory to VRD and 7 patients with early relapse.In the VRD-resistant group(n=21),the median age of patients was 58 years(37-70 years),and female patients were more common(61.9％);Durie-Salmon stage:17 patients were DS stage Ⅲ,4 patients were DS stage Ⅱ;44.4％of those patients were cytogenetic high risk.CD20 positive rate was higher in the VRD-resistant group(P=0.014).The overall survival(OS)of MM patients in the VRD-resistant group was significantly lower than that in the VRD-nonresistant group(34 months vs not achieved,P＜0.001).In the VRD-resistant group,the median OS of MM patients receiving autologous hematopoietic stem cell transplantation was significantly longer than that of non-transplant patients(34 months vs 16 months,P=0.038).Drug resistance and non-autologous transplantation are independent adverse prognostic factors for newly diagnosed MM patients receiving VRD induction chemotherapy.COX multivariate analysis showed that age＞65,cytogenetic high risk and non-autologous stem cell transplantation may be adverse prognostic factors for VRD-resistant MM patients. Conclusion:Positive CD20 was more common in MM patients with VRD resistence,which may indicate more aggressive biological characteristics in VRD-resistent MM patients.The VRD-resistent MM patients had poor prognosis,they can obtain disease remission from salvage chemotherapy including daratumumab,and the survival of them also can be improved after autologous stem cell transplantation.

Objective:To summarize the clinical and imaging features of pediatric neuroglial heterotopia (NGH) in different locations.Methods:The clinical and preoperative imaging data of 9 patients (6 boys and 3 girls, median age 3 months, range from 1 to13 months) with NGH confirmed by pathology were retrospectively reviewed in Wuhan Children′s Hospital, Tongji Medical College, Huazhong University of Science and Technology from October 2009 to December 2020. All patients underwent preoperative CT or/and MR examination. Follow-up was performed in 12 to 60 months after operation, with a median follow-up time of 24 months. The location, range, size, density/signal intensity of the lesions were reviewed.Results:Of all 9 cases, three cases were located in nose (2 extranasal type and 1 mixed type), with the maximum diameter of 13, 13 and 15 mm; there were 3 lesions in tongue, all of which were located on the dorsum of tongue, with the maximum diameter of 13, 18 and 23 mm; there were also 2 cases located in nasopharynx, maximum diameter of 15 and 22 mm, respectively. One case was in sacrococcygeal area, with the maximum diameter as 18 mm. All lesions presented as solid masses with well-defined margins, displaying slightly low density compared to grey matter. The CT value ranged from 25 to 47 HU. Compared to grey matter or spinal cord, MRI demonstrated isointense or slight hypointense on T 1WI and slight hyperintense on T 2WI. All masses presented homogenous density or signal intensity, with mild homogenous enhancement. During postoperative follow-up, no recurrence was found in 8 cases. One case of nasal NGH with gradeⅡcleft lip recurred at 1 month follow-up after surgery, and no recurrence was found after the second surgery. Conclusions:The NGH in children has typical imaging features, and is mostly located at the extracranial midline structure.It presents as solid mass, with quasi-circular morphology, well-defined margins and homogeneous density or signal intensity similar to gray matter or spinal cord. The postoperative recurrence rate is low.

Objective:To evaluate the prognostic value of CD56 expression in newly diagnosed MM (NDMM).Methods:A total of 332 NDMM patients were enrolled in Beijing Chaoyang Hospital, Capital Medical University from January 1, 2011 to January 1, 2021, with a median age of 60 years and a male to female ratio of 1.2∶1. CD56 expression on myeloma cells was detected by flow cytometry before induction therapy. Overall survival (OS) and progression-free survival (PFS) data were collected. In order to reduce the confounding factors, the propensity score matching technique was used to match CD56 positive versus negative patients at a ratio of 1∶1.Results:Among 332 patients, CD56 positivity rate was 65.1% (216/332). Patients with CD56 expression had significantly longer median OS (58.4 vs. 43.1 months, P=0.024) and PFS (28.7 vs. 24.1 months, P=0.013) than those with negative CD56. Univariate Cox proportional hazards regression analyses showed that CD56 expression was positively correlated with OS ( HR=0.644, 95 %CI 0.438-0.947, P=0.025) and a favorable prognostic factor for PFS ( HR=0.646, 95 %CI 0.457-0.913, P=0.013). The favorable effect of CD56 expression on PFS was confirmed in multivariate analysis ( HR=0.705, 95 %CI 0.497-0.998, P=0.049), but OS was not affected ( P>0.05).In the propensity score matching analysis, 194 patients with 97 in each group were identified. CD56 positivity consistently predicted longer PFS (34.2 vs.25.1 months, P=0.047), but not OS (63.4 vs.43.1 months, P=0.056). Conclusion:These results demonstrate that CD56 expression is a favorable prognostic factor for PFS of newly diagnosed MM patients.

Objective:To examine the characteristics of blood lipid profile and the correlation with clinic-pathological features of pancreatic cancer patients.Methods:The clinical and pathological data of 265 pancreatic cancer patients who received radical surgical treatment at Department of General Surgery,Qilu Hospital,Shandong University from January 2013 to September 2020 were collected and analyzed retrospectively. Among the 265 pancreatic cancer patients,there were 170 males and 95 females,with age of (61.0±9.6)years(range:28 to 86 years). General information,lipid indicators and clinic-pathological information were collected from electronic medical record system,and follow-up information gained by telephone. According to level of serum lipid in pancreatic cancer patients,265 patients were divided into dyslipidemia group( n=115) and normal lipid group( n=150). Pearson χ 2,Student′s t tests, variance analysis or univariate Logistic regression was used to analyze the correlation between dyslipidemia and clinico-pathological characteristics of pancreatic cancer,respectively. Kaplan-Meier survival curve was used to assessed the influence of dyslipidemia on prognosis of pancreatic cancer patients. Results:In 265 pancreatic cancer patients,115(43.4%)of them had dyslipidemias,and the most common form was increase of triglyceride(TG)(72.2%). In pancreatic cancer with dyslipidemias group,patients with body mass index ≥25 kg/m 2 had higher proportion than normal lipid group(36.1%(26/72) vs. 21.2%(21/99),χ2=4.643, P=0.031); The proportion of carcinoma located at head of pancreas(83.5%(96/115) vs. 40.7%(61/150),χ2=49.412, P<0.01), staging of T1/T2(79.1%(91/115) vs. 60.7%(91/150),χ2=10.316, P<0.01) and lymphatic metastasis(36.5%(42/115) vs. 22.7%(34/150),χ2=6.007, P<0.01) were higher. In patients of pancreatic cancer, dyslipidemias were closely associated with tumor location( OR=10.529, P<0.01)and body mass index( OR=3.671, P=0.008). Serum lipid profile results showed that TG,total cholesterol and high-density lipoprotein(HDL) disorders were associated with tumor location( P<0.05). TG disorder had association with body mass index( P<0.05), and HDL disorder had association with tumor stage( P<0.05). Moreover, the result of survival analysis showed that dyslipidemia was not a factor to impact the prognosis of pancreatic cancer patients underwent surgery( P>0.05). Conclusions:In pancreatic cancer patients,TG disorder was the most common type of dyslipidemia. Dyslipidemia has closely association with clinicopathologic features,including tumor location,body mass index,tumor stage. However,dyslipidemia had little effect on prognosis of pancreatic cancer patients.

Objective:To examine the characteristics of blood lipid profile and the correlation with clinic-pathological features of pancreatic cancer patients.Methods:The clinical and pathological data of 265 pancreatic cancer patients who received radical surgical treatment at Department of General Surgery,Qilu Hospital,Shandong University from January 2013 to September 2020 were collected and analyzed retrospectively. Among the 265 pancreatic cancer patients,there were 170 males and 95 females,with age of (61.0±9.6)years(range:28 to 86 years). General information,lipid indicators and clinic-pathological information were collected from electronic medical record system,and follow-up information gained by telephone. According to level of serum lipid in pancreatic cancer patients,265 patients were divided into dyslipidemia group( n=115) and normal lipid group( n=150). Pearson χ 2,Student′s t tests, variance analysis or univariate Logistic regression was used to analyze the correlation between dyslipidemia and clinico-pathological characteristics of pancreatic cancer,respectively. Kaplan-Meier survival curve was used to assessed the influence of dyslipidemia on prognosis of pancreatic cancer patients. Results:In 265 pancreatic cancer patients,115(43.4%)of them had dyslipidemias,and the most common form was increase of triglyceride(TG)(72.2%). In pancreatic cancer with dyslipidemias group,patients with body mass index ≥25 kg/m 2 had higher proportion than normal lipid group(36.1%(26/72) vs. 21.2%(21/99),χ2=4.643, P=0.031); The proportion of carcinoma located at head of pancreas(83.5%(96/115) vs. 40.7%(61/150),χ2=49.412, P<0.01), staging of T1/T2(79.1%(91/115) vs. 60.7%(91/150),χ2=10.316, P<0.01) and lymphatic metastasis(36.5%(42/115) vs. 22.7%(34/150),χ2=6.007, P<0.01) were higher. In patients of pancreatic cancer, dyslipidemias were closely associated with tumor location( OR=10.529, P<0.01)and body mass index( OR=3.671, P=0.008). Serum lipid profile results showed that TG,total cholesterol and high-density lipoprotein(HDL) disorders were associated with tumor location( P<0.05). TG disorder had association with body mass index( P<0.05), and HDL disorder had association with tumor stage( P<0.05). Moreover, the result of survival analysis showed that dyslipidemia was not a factor to impact the prognosis of pancreatic cancer patients underwent surgery( P>0.05). Conclusions:In pancreatic cancer patients,TG disorder was the most common type of dyslipidemia. Dyslipidemia has closely association with clinicopathologic features,including tumor location,body mass index,tumor stage. However,dyslipidemia had little effect on prognosis of pancreatic cancer patients.

Due to good mechanical properties and biocompatibility, tissue engineering scaffolds have become the vital method for repairing and regenerating articular cartilage defects. With the continuous development of tissue engineering technology, many scaffolds preparation and formation methods have been developed and tested in the past decade, however, the preparation of ideal regenerative scaffolds remain controversial. As load-bearing tissue inside the body joints, the matrix structure and cell composition of articular cartilage are hierarchical, and there are several smooth natural gradients from the cartilage surface to the subchondral bone layer, including cell phenotype and number, specific growth factors, matrix composition, fiber arrangement, mechanical properties, nutrient and oxygen consumption. Therefore, in the design of regenerative scaffolds, it is necessary to achieve these gradients to regenerate articular cartilage in situ. In recent studies, many new biomimetic gradient scaffolds have been used to simulate the natural gradient of articular cartilage. These scaffolds show different mechanical, physicochemical or biological gradients in the structure, and have achieved good repair effects. The related articles on tissue engineering for the treatment of articular cartilage defects were retrieved by searching databases with key wordsarticular cartilage injury, cartilage repair and gradient scaffolds. In this work,the structural, biochemical, biomechanical and nutrient metabolism gradients of natural articular cartilage were studied and summarized firstly. Then, the latest design and construction of articular cartilage gradient scaffolds were classified. Besides that, the material composition (such as hydrogels, nanomaterials, etc.) and the preparation process (such as electrospinning, 3D printing, etc.) of grandient scaffolds were further enhanced. Finally, the prospect and challenge of biomimetic gradient scaffolds in cartilage engineering are discussed, which provides a theoretical basis for the successful application of gradient scaffolds in clinical transformation.