Objective To evaluate the patient-reported outcome(PRO)of patients with breast cancer who underwent autologous breast reconstruction and implant breast reconstruction.Methods Patients who underwent breast reconstruction in Shanghai Cancer Center,Fudan University from Jan 2020 to Jun 2021 were selected,including 111 patients who underwent autologous breast reconstruction and 108 patients who underwent implant breast reconstruction.Chinese version Breast-Q2.0 scale,breast cancer specificity scale QLQ-BR23 and EORTC quality of life scale QLQ-C30 were used to investigate the PRO of the two groups 18 months after operation.Results The rate of stage Ⅲ breast cancer in the self-weight construction group was higher than that in the implant reconstruction group(64.9%vs.44.4%,P<0.001).The preoperative neoadjuvant therapy and postoperative radiotherapy in the autologous reconstruction group were higher than those in the implant reconstruction group(P<0.001).Postoperative chemotherapy and endocrine therapy in the autologous reconstruction group were lower than those in the implant reconstruction group(P<0.001).The study based on Breast-Q scale showed that the breast satisfaction of autologous reconstruction group was higher than that of implant reconstruction(59.28±17.20 vs.54.94±14.48,P<0.05).The study based on QLQ-BR23 showed that the self-weight construction group was higher than the implant reconstruction group in the field of arm symptoms(20.02±20.80 vs.12.65±16.18,P<0.05).The study based on QLQ-C30 scale showed that there was no significant difference in all functional areas and symptom areas of patients.There was no significant difference in the number and time of social regression between the two groups.Conclusion Breast reconstruction can improve the PRO of breast cancer patients,and oncology factors will affect the choice of breast reconstruction.Patients with autologous breast reconstruction are more satisfied with breast appearance,but upper limb symptoms such as swelling and pain are more obvious than implant reconstruction,which is related to the higher proportion of axillary lymph node dissection in patients with autologous reconstruction.There is no significant difference in quality of life and social regression between the two groups.

Objective To observe the effect of abdominal massage combined with thumb-tack needling for subcutaeous embedding on sleep homeostasis system in rats with anxiety insomnia.Methods Forty rats were randomly divided into normal group,model group,abdominal massage group,thumb-tack needling for subcutaeous embedding group and abdominal massage plus thumb-tack needling for subcutaeous embedding group,with 8 rats in each group.Except for the normal group,the rats in the other groups were used to replicate the model of anxiety insomnia by multi-factor compound stimulation.After the corresponding intervention,Morris water maze test was used to detect the level of learning and memory.Open field test was used to detect the degree of anxiety stress.Hematoxylin-eosin(HE)staining was used to observe the pathological changes of hypothalamic ventral lateral preoptic nucleus(VLPO)neurons.Immunohistochemistry,real-time quantitative polymerase chain reaction(qRT-PCR)and Western Blot were used to detect the protein and mRNA expression of N-methyl-D-aspartate(NMDA)receptor subunits NR1,NR2B and calmodulin kinase Ⅱ(CaMK Ⅱ)in hypothalamic VLPO area,respectively.Results Compared with the normal group,the daytime anxiety symptoms of the rats in the model group were aggravated,the sleep latency was prolonged and the duration was shortened(P＜0.01).The average total swimming distance and average escape latency of the water maze directional navigation experiment were increased(P＜0.01).The number of crossing the hidden platform and the retention time of the target quadrant in the space exploration experiment were decreased(P＜0.01).The movement distance,the number of central grid crossings and the retention time of the central grid in the open field experiment were significantly reduced(P＜0.01).There was no significant difference in the modification frequency and the number of uprights(P＞0.05).Neurons in the VLPO brain region showed pathological damage.The protein and mRNA expression levels of NR1 and CaMK Ⅱ were decreased(P＜0.01)in VLPO brain region,and the protein and mRNA expression levels of NR2B were increased(P＜0.01).Compared with the model group,the level of learning and memory in the water maze test and the degree of anxiety stress in the open field test were significantly restored in the abdominal massage group,the thumb-tack needling for subcutaeous embedding group and the abdominal massage combined with thumb-tack needling for subcutaeous embedding group(P＜0.05 or P＜0.01),the neuronal damage in the VLPO brain region was improved,the protein and mRNA expression levels of NR1,CaMK Ⅱ were increased(P＜0.05 or P＜0.01),and the protein and mRNA expression levels of NR2B were decreased(P＜0.05 or P＜0.01).The improvement effect of the above indexes in the abdominal massage plus thumb-tack needling for subcutaeous embedding group was superior to that in the abdominal massage group or thumb-tack needling for subcutaeous embedding group(P＜0.05 or P＜0.01).Conclusion Abdominal massage combined with thumb-tack needling for subcutaeous embedding can promote sleep and anti-anxiety in rats with anxiety insomnia.The related mechanism may be related to adjusting the dynamic balance between NR1/NR2B in VLPO brain area and up-regulating the expression level of CaMK Ⅱ,improving the function of neurons in VLPO brain area,and then restoring the regulation of sleep homeostasis system.

Objective To explore the effectiveness of different intervention strategies in response to outbreaks of emerging highly pathogenic respiratory infectious diseases(RIDs)in mega-city in China,and provide decision-ma-king basis for effective response to emerging RIDs.Methods A susceptible-exposed-infectious-recovered(SEIR)transmission dynamics model was constructed,referencing to and combining the pathogenicity and infectivity para-meters of previous emerging RIDs.The outbreak of emerging highly pathogenic RIDs with low,moderate,and high infectivity in a mega-city with a population of 10 million in China was simulated,the development of the epidemic within 100 days after implementing different combinations of non-pharmaceutical interventions(NPIs)in response to the outbreak was compared.Results When highly pathogenic RIDs outbreak occurred,and if its infectivity was low(R0 was about 1.5),it was unnecessary to adopt strict NPIs to control epidemic.If its infectivity was moderate(R0 was about 6),different intensities of NPIs were needed based on its existing infection scale.When the initial num-ber of infected cases was 50,moderate-intensity NPIs could keep the infection and death at a low level within 100 days,and the required bed number in hospital for cases could be kept below the national average reserve level.But when the scale of infection exceeded 100 cases,high-intensity NPIs were needed to control the development of the epidemic.In the case of extremely strong infectivity(R0 was about 10),regardless of the scale of infection,only immediate high-intensity NPIs could control the epidemic,infection and death scale.Conclusion In case of out-breaks of highly pathogenic RIDs,adopting appropriate NPIs as early as possible based on their epidemiological characteristics and infection scale is necessary to minimize the harm to the population.

AIM: To investigate the effect of modified Chufeng Yisun Decoction on ocular surface inflammation after pterygium surgery.METHODS: A total of 60 patients(60 eyes)with primary pterygium who underwent pterygium surgery were randomly divided into control group and study group, with 30 cases(30 eyes)in each group. In the control group, patients were treated with pranoprofen eye drops, tobramycin dexamethasone eye drops, and deproteinized calf blood extract eye gel after the surgery. In the study group, patients were treated by oral modified Chufeng Yisun Decoction in addition to the treatments in the control group. The changes of ocular irritation symptoms, ocular inflammatory signs, tear interleukin 6(IL-6)levels, and tear ferning test(TFT)of patients in the two groups were assessed.RESULTS: The visual analogue scale(VAS)in patients of both groups was significantly lower at 2d and 1wk after the surgery than that at 1d after the surgery(all P<0.01), and the VAS of the study group was significantly better than that of the control group at 2d and 1wk after surgery(P<0.01). The ocular signs integrals(OSI)and TFT results of both groups at 1wk were significantly lower than those at 1d after the surgery(all P<0.01), and the OSI and TFT were also lower in the study group than in the control group at 1wk after the surgery(all P<0.01). In addition, the concentration of tear IL-6 in both groups was significantly lower at 1wk after the surgery than 1d after the surgery(all P<0.01), and it was also significantly lower in the study group than in the control group at 1wk after the surgery(P<0.05).CONCLUSION: The combination of Chufeng Yisun Decoction and conventional treatment of western has a better effect on controlling ocular surface inflammation after pterygium surgery.

OBJECTIVE: To investigate the involvement of endothelial cells (ECs)-derived exosomes in the anti-apoptotic effect of Danhong Injection (DHI) and the mechanism of DHI-induced exosomal protection against postinfarction myocardial apoptosis. METHODS: A mouse permanent myocardial infarction (MI) model was established, followed by a 14-day daily treatment with DHI, DHI plus GW4869 (an exosomal inhibitor), or saline. Phosphate-buffered saline (PBS)-induced ECs-derived exosomes were isolated, analyzed by miRNA microarray and validated by droplet digital polymerase chain reaction (ddPCR). The exosomes induced by DHI (DHI-exo), PBS (PBS-exo), or DHI+GW4869 (GW-exo) were isolated and injected into the peri-infarct zone following MI. The protective effects of DHI and DHI-exo on MI hearts were measured by echocardiography, Masson's trichrome staining, and TUNEL apoptosis assay. The Western blotting and quantitative reverse transcription PCR (qRT-PCR) were used to evaluate the expression levels of miR-125b/p53-mediated pathway components, including miR-125b, p53, Bak, Bax, and caspase-3 activities. RESULTS: DHI significantly improved cardiac function and reduced infarct size in MI mice (P<0.01), which was abolished by the GW4869 intervention. DHI promoted the exosomal secretion in ECs (P<0.01). According to the results of exosomal miRNA microarray assay, 30 differentially expressed miRNAs in the DHI-exo were identified (28 up-regulated miRNAs and 2 down-regulated miRNAs). Among them, DHI significantly elevated miR-125b level in DHI-exo and DHI-treated ECs, a recognized apoptotic inhibitor impeding p53 signaling (P<0.05). Remarkably, treatment with DHI and DHI-exo attenuated apoptosis, elevated miR-125b expression level, inhibited capsase-3 activity, and down-regulated the expression levels of proapoptotic effectors (p53, Bak, and Bax) in post-MI hearts, whereas these effects were blocked by GW4869 (P<0.05 or P<0.01). CONCLUSION DHI and DHI-induced exosomes inhibited apoptosis, promoted the miR-125b expression level, and regulated the p53 apoptotic pathway in post-infarction myocardium.
Mice ; Animals ; Tumor Suppressor Protein p53/metabolism* ; Endothelial Cells/metabolism* ; Exosomes/metabolism* ; bcl-2-Associated X Protein/metabolism* ; Myocardium/metabolism* ; Myocardial Infarction/drug therapy* ; Apoptosis ; MicroRNAs/metabolism*

Multidrug resistance (MDR) is the main cause of clinical treatment failure and poor prognosis in cancer. Targeting P-glycoprotein (P-gp) has been regarded as an effective strategy to overcome MDR. In this work, we reported our preclinical studies of the triazolo[1,5-a]pyrimidine-based compound WS-716 as a highly potent, specific, and orally active P-gp inhibitor. Through direct binding to P-gp, WS-716 inhibited efflux function of P-gp and specifically reversed P-gp-mediated MDR to paclitaxel (PTX) in multiple resistant cell lines, without changing its expression or subcellular localization. WS-716 and PTX synergistically inhibited formation of colony and 3D spheroid, induced apoptosis and cell cycle arrest at G2/M phase in resistant SW620/Ad300 cells. In addition, WS-716 displayed minimal effect on the drug-metabolizing enzyme cytochrome P4503A4 (CYP3A4). Importantly, WS-716 increased sensitivity of both pre-clinically and clinically derived MDR tumors to PTX in vivo with the T/C value of 29.7% in patient-derived xenograft (PDX) models. Relative to PTX treatment alone, combination of WS-716 and PTX caused no obvious adverse reactions. Taken together, our preclinical studies revealed therapeutic promise of WS-716 against MDR cancer, the promising data warrant its further development for cancer therapy.

OBJECTIVE: To explore the prognostic factors of young and middle-aged patients with acute myeloid leukemia (AML) and the predictive value of minimal residual disease (MRD) before consolidation therapy. METHODS: The clinical data of 262 middle-risk young and middle-aged patients with AML treated in our hospital from January 2010 to December 2018 were selected retrospectively. All the patients were reached morphological leukemia-free state (MLFS) after induction chemotherapy, the overall and subgroup clinical data of the selected patients were analyzed. Cox regression model was used to evaluate the independent prognostic factors of middle-risk newly diagnosed young and middle-aged patients. RESULTS: Among the patients less than 40 years old treated by consolidation therapy with PR-CT and allo-HSCT regimens, the 5-year cumulative leukemia-free survival(LFS) rates were 40.92% and 63.51%（P=0.01）respectively, while those over 40 years old were 23.61% and 49.14%（P=0.00）, respectively. The 5-year cumulative LFS rates of the patients treated by chemotherapy and achieved early remission and late remission were 63.51% and 41.33% （P=0.01）, respectively. The 5-year cumulative overall survival(OS) rates of the patients treated by PR-CT and allo-HSCT regimens were 23.65% and 69.32% (P=0.00), respectively, and the 5-year cumulative LFS rates were 26.44% and 52.30% (P=0.01). Among the patients treated by PR-CT consolidation treatment, the MRD-negative and MRD-positive cases were 74 and 60 cases, respectively. The 5-year cumulative incidence of relapse rate in the MRD-negative subgroup was significantly lower than those in the MRD-positive subgroup (P<0.05), the 5-year LFS rate and OS rate of the patients in MRD-negative subgroup were significantly higher than those in MRD-positive subgroup (P<0.05). For the patients treated by allo-HSCT consolidation treatment, the MRD-negative and MRD-positive cases were 66 and 62 cases, respectively. The 5-year cumulative incidence of relapse rate of the patients in MRD-negative subgroup was significantly lower than those in MRD-positive subgroup（P<0.05）, and the 5-year LFS and OS rates of the patients in MRD-negative subgroup were significantly higher than those in MRD-positive subgroup (P<0.05). The univariate analysis results showed that age, chromosome karyotype, MRD status after reaching MLFS, and consolidation treatment regime were all related to the prognosis of patients (P<0.05). The multivariate analysis results showed that age, MRD status after reaching MLFS, and consolidation therapy were the independent factors affecting the cumulative OS rate of the patients (P<0.05). Chromosome karyotype was an independent factor affecting the cumulative LFS rate of the patients (P<0.05). MRD status and consolidation treatment plan after reaching MLFS were the independent factors affecting the cumulative recurrence rate of the patients (P<0.05). CONCLUSION The OS rate of middle-risk young and middle-aged patients with newly diagnosed AML is independently related to age, MRD status after MLFS and consolidation therapy, while chromosome karyotype is independently related to cumulative LFS, and allo-HSCT consolidation therapy is recommended for middle-risk young and middle-aged AML patients after induction chemotherapy for MLFS, especially for those less than 40 years old and MRD positive before consolidation therapy.
Adult ; Consolidation Chemotherapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute ; Middle Aged ; Neoplasm, Residual ; Prognosis ; Retrospective Studies

OBJECTIVE: To discuss the long-term outcome of convex epiphysiodesis in the treatment for congenital scoliosis (CS). METHODS: The clinical data of 22 patients with hemivertebral deformity undergoing convex epiphysiodesis from the October 1998 to Febuary 2008 were respectively analyzed. There were 12 males and 10 females. The whole spine anteroposterior radiographs were taken preoperatively, at 3-month postoperatively and at the final follow-up to measure the main curve and the compensatory curve. The progression rate was calculated for each patient. Observing the correlation between the progression rate and annual progression of the scoliosis and age, gender, hemivertebral number, hemivertebral position, preoperative main curve Cobb angle and compensatory curve Cobb angle, comparing different ages, genders, hemivertebral number and position, and preoperative main curve Cobb angle on the progression of postoperative curve. RESULTS: The mean Cobb angle of main curve changed from (40.5±9.8) ° before surgery to (39.5±11.1) ° at 3 months after surgery, which significantly increased to (46.8±13.9) ° in the final follow-up. Meanwhile the mean Cobb angle of compensatory curve was changed from (20.1±10.8) ° before surgery to (23.0±11.1) °, which significantly increased to (29.9±11.5) ° in the final follow-up. There were no significant differences in the Cobb angle of the main curve and the compensatory curve between postoperative 3 months and before operation (>0.05). The difference between the final follow-up and the preoperative, postoperative 3 months was statistically significant (<0.01). Twenty patients experienced progression of both main curve and compensatory curve, with a mean progression rate of (19.2±17.9)% for main curve and (39.6±37.0)% for compensatory curve. The annual progression volume was (1.5± 1.4) ° for main curve and (1.4±1.3) ° for compensatory curve. Three patients underwent lateral convex orthopedic internal fixation due to postoperative scoliosis progression. The curve progression was significantly correlated with age at the time of surgery and hemivertebral number. There was a significant correlation between the age of the operation, the main curve angle, the preoperative compensatory curve angle and the annual progression volume of the main curve (<0.05). CONCLUSION The convex epiphysiodesis technique cannot effectively prevent curve progression of CS patients in the long-term follow-up. It is not recommended to apply this technique to the treatment of patients with congenital hemivertebrae.

Adult ; Aged ; Antiviral Agents ; administration & dosage ; Betacoronavirus ; Coronavirus Infections ; drug therapy ; Drug Therapy, Combination ; Humans ; Interferon-alpha ; administration & dosage ; Lopinavir ; administration & dosage ; Middle Aged ; Pandemics ; Pneumonia, Viral ; drug therapy ; Randomized Controlled Trials as Topic ; Ribavirin ; administration & dosage ; Ritonavir ; administration & dosage

Background: At the end of 2019, a novel coronavirus outbreak emerged in Wuhan, China, and its causative organism has been subsequently designated the 2019 novel coronavirus (2019-nCoV). The virus has since rapidly spread to all provinces and autonomous regions of China, and to countries outside of China. Patients who become infected with 2019-nCoV may initially develop mild upper respiratory tract symptoms. However, a significant fraction of these patients goes on to subsequently develop serious lower respiratory disease. The effectiveness of adjunctive glucocorticoid therapy uses in the management of 2019-nCoV infected patients with severe lower respiratory tract infections is not clear, and warrants further investigation. Methods: The present study will be conducted as an open-labelled, randomised controlled trial. We will enrol 48 subjects from Chongqing Public Health Medical Center. Each eligible subject will be assigned to an intervention group (methylprednisolone via intravenous injection at a dose of 1-2mg/kg/day for 3 days) or a control group (no glucocorticoid use) randomly, at a 1:1 ratio. Subjects in both groups will be invited for 28 days of follow-up which will be scheduled at 4 consecutive visit points. We will use the clinical improvement rate as our primary endpoint. Secondary endpoints include the timing of clinical improvement after intervention, duration of mechanical ventilation, duration of hospitalization, overall incidence of adverse events, as well as rate of adverse events at each visit, and mortality at 2 and 4 weeks. Discussion: The present coronavirus outbreak is the third serious global coronavirus outbreak in the past two decades. Oral and parenteral glucocorticoids have been used in the management of severe respiratory symptoms in coronavirus-infected patients in the past. However, there remains no definitive evidence in the literature for or against the utilization of systemic glucocorticoids in seriously ill patients with coronavirus-related severe respiratory disease, or indeed in other types of severe respiratory disease. In this study, we hope to discover evidence either supporting or opposing the systemic therapeutic administration of glucocorticoids in severe coronavirus disease 2019 (COVID-19) patients. Trial registration ClinicalTrials.gov, ChiCTR2000029386, http://www.chictr.org.cn/showproj.aspx?proj=48777.