Objectives:To explore the antitumor effects of redox-responsive nanoparticles containing platinum(Ⅳ)—NP@Pt(Ⅳ) in ovarian cancer.Methods:Redox-responsive polymer carriers were synthesized. Polymer carriers and platinum(Ⅳ)—Pt(Ⅳ) can self-assemble into NP@Pt(Ⅳ). Inductively coupled plasma mass spectrometry was performed to detect the platinum release from NP@Pt(Ⅳ) in reducing environment and the platinum content in ovarian cancer cells ES2 treated with cisplatin, Pt(Ⅳ) and NP@Pt(Ⅳ). The proliferation ability of the ovarian cancer cells were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cellular apoptosis was assessed by flow cytometry. Collection of primary ovarian cancer tissues from patients with primary high-grade serous ovarian cancer who were surgically treated at the Cancer Hospital of the Chinese Academy of Medical Sciences from October to December 2022. The high-grade serous ovarian cancer patient-derived xenograft (PDX) mice were intravenously injected with Cy7.5 labeled NP@Pt(Ⅳ) followed by in vivo imaging system. Mice were treated with PBS, cisplatin and NP@Pt(Ⅳ). Tumor volume and weight were measured in each group. Necrosis, apoptosis and cell proliferation of tumor tissues were detected by hematoxylin-eosin (HE) staining, TUNEL fluorescence staining and Ki-67 immunohistochemistry staining. Body weight and HE staining of heart, liver, spleen, lung and kidney of mice in each group were measured.Results:The platinum release of NP@Pt(Ⅳ) after 48 hours in reducing environment was 76.29%, which was significantly higher than that of 26.82% in non-reducing environment ( P<0.001). The platinum content in ES2 cells after 4 hours and 7 hours of treatment with NP@Pt(Ⅳ) (308.59, 553.15 ng/million cells) were significantly higher than those of Pt(Ⅳ) (100.21, 180.31 ng/million cells) and cisplatin (43.36, 50.36 ng/million cells, P＜0.05). The half inhibitory concentrations of NP@Pt(Ⅳ) in ovarian cancer cells ES2, A2780, A2780DDP were 1.39, 1.42 and 4.62 μmol/L, respectively, which were lower than those of Pt(IV) (2.89, 7.27, and 16.74 μmol/L) and cisplatin (5.21, 11.85, and 71.98 μmol/L). The apoptosis rate of ES2 cells treated with NP@Pt(Ⅳ) was (33.91±3.80)%, which was significantly higher than that of Pt(Ⅳ) [(16.28±2.41)%] and cisplatin [(15.01±1.17)%, P＜0.05]. In high-grade serous ovarian cancer PDX model, targeted accumulation of Cy7.5 labeled NP@Pt(Ⅳ) at tumor tissue could be observed. After the treatment, the tumor volume of mice in NP@Pt(IV) group was (130±98) mm 3, which was significantly lower than those in control group [(1 349±161) mm 3, P<0.001] and cisplatin group [(715±293) mm 3, P=0.026]. The tumor weight of mice in NP@Pt(IV) group was (0.17±0.09)g, which was significantly lower than those in control group [(1.55±0.11)g, P<0.001] and cisplatin group [(0.82±0.38)g, P=0.029]. The areas of tumor necrosis and apoptosis in mice treated with NP@Pt(Ⅳ) were higher than those in mice treated with cisplatin. Immunohistochemical staining revealed that there were low expressions of Ki-67 at tumor tissues of mice treated with NP@Pt(Ⅳ) compared with cisplatin. The change in body weight of mice in NP@Pt(Ⅳ) group was not significantly different from that of the control group [(18.56±2.04)g vs.(20.87±0.79)g, P=0.063]. Moreover, the major organs of the heart, liver, spleen, lung, and kidney were also normal by HE staining. Conclusion:Redox-responsive NP@Pt(Ⅳ), produced in this study can enhance the accumulation of cisplatin in ovarian cancer cells and improve the efficacy of ovarian cancer chemotherapy.

Given the systematic, rigorous, and practical characteristics of medical disciplines, ensuring the teaching quality of online courses has become a significant focus. In traditional teaching models, teaching supervision is an important method to guarantee instructional quality, and introducing teaching supervision into online teaching activities is of great significance. This article systematically reviews and summarizes the domestic and international experience of conducting online medical courses. We explore the instructional supervision of online medical courses from the following perspectives: the meaning of supervision, the necessity of online supervision, online supervision methods and technical approaches, the feedback and application of supervision information, and the establishment of a standardized online supervision process.

Objective:To analyze the whole genome sequence and key site mutations of hepatitis B virus (HBV) in patients with different stages of disease progression, and to understand the relationship between HBV genetic characteristics and disease progression.Methods:Serum samples and basic information of hepatitis B patients with asymptomatic HBV carrier, chronic hepatitis B patients, cirrhosis patients and primary hepatocellular carcinoma patients were collected. Nested PCR was used to amplify the samples to obtain HBV whole gene sequences. Phylogenetic trees were constructed to determine the genotype of the samples, and gene mutations of the samples were analyzed combined with reference sequences of each type.Results:A total of 256 samples were successfully amplified, including 68 asymptomatic HBV carrier patients, 118 CHB patients, 15 LC patients and 55 HCC patients, and five genotypes (B, C, D, I and C/D) were detected. The result of comparative analysis showed that the mutation rate of 56 nucleotide sites was significantly different among the four groups ( P<0.05). In addition to the discovery of C105T, A1762T/G1764A and G1899A and other previously reported key site mutations, the mutation rates of T53A, C1485T and C1628T in newly diagnosed HCC group were significantly higher than those in other groups, and the mutation rates of T2150G and T2151C in asymptomatic HBV infection group were significantly higher than those in other groups. A total of 26 sequences were deleted, mainly distributed in the pre-C and pre-S regions. The deletion mutation rate in the HCC group was significantly higher than that in the other groups. Conclusions:The data of this study indicate that some nucleotide substitution mutations and deletion mutations may be closely related to the occurrence and development of HBV-related diseases, and HCC patients are more likely to have gene mutations than non-HCC patients. These result provide a reference for understanding the relationship between viral mutation and the progression of HBV infection-related diseases.

Objective: To investigate the effects of neonatal intensive care unit (NICU)-centered regional neonatal transport network (NTN) on the treatment of retinopathy of prematurity (ROP). Methods: A retrospective analysis was conducted to analyze the transfer, treatment and outcomes of 406 preterm infants with ROP who were transferred to the Bayi Children's Hospital Affiliated to the Seventh Medical Center of PLA General Hospital via the NTN from July 2008 to December 2014. Independent sample t-test, Chi-square test and Mann-Whitney nonparametric test were used for statistical analysis. Results: Among the 406 premature infants who were transferred to our hospital because of ROP, there were 257 males and 149 females with the gestational age of (29.5±1.9) weeks (24⁺⁵-36 weeks) and the birth weight of (1 234.8± 268.9) g (580-2 400 g). The age at transfer was (48.9±18.5) d (15-78 d) and the transport distance was (216.5±78.6) km (10-625 km). No death was reported during the transportation. Very preterm births and very low birth weight infants (VLBWI) accounted for 88.7% (360 cases) and 82.5% (335 cases), respectively. Lesions occurred in 1, 2 and 3 zones were detected in 98 (24.1%), 286 (70.4%) and 22 (5.4%) cases, respectively. Lesions of stage 1-5 were observed in 51 (12.6%), 156 (38.4%), 183 (45.1%), 12 (3.0%) and 4 (1.0%) cases. There were 186 cases (45.8%) with Plus lesions. A total of 252 cases (62.1%) underwent surgery which were achieving treatment standards, including 165 (65.5%) undergoing laser therapy, 93 (36.9%) receiving anti-vascular endothelial growth factor (VEGF) therapy, 16 (6.4%) having vitrectomy and two (0.8%) having scleral buckling. Eighteen infants were diagnosed with retinal structural abnormalities, among which 16 had retinal detachment before admission (12 in phase 4 and four in phase 5). Two without retinal detachment on admission developed to phase 4 after surgery. The incidence of retinal structural dysplasia was 0.9% (2/236) in infants receiving laser and/or anti-VEGF therapy in our hospital. Compared with the cured patients (n=234), those with retinal structural dysplasia (n=18) had a late transfer time [80 (38-270) vs 50 (19-150) d, Z=3.387, P<0.001]. Conclusions The NICU-centered and regional transfer-based ROP treatment network provides timely and effective treatment for infants with ROP.

Objective To investigate the application value of dynamic single-photon emission computed tomography (SPECT) 99m-technetium galactosyl human serum albumin diethylenetriamine pentaacetic acid injection (99 Tcm-GSA) scintigraphy assessing regional liver function changes before and after portal vein embolization (PVE).Methods The retrospective cross-sectional study was conducted.The clinical data of 11 patients with Bismuth Ⅲ a hilar cholangiocarcinoma who were admitted to the General Hospital of People's Liberation Army (10 patients) and Beijing Tsinghua Changgung Hospital (1 patient) from October 2010 to October 2016 were collected.B ultrasound-guided percutaneous transhepatic ipsilateral exbolization was performed before radical resection of hilar cholangiocarcinoma.Dynamic SPECT 99 Tcm-GSA scintigraphy was performed to calculate and compare the changes of functional liver volume (FLV),morphological liver volume (MLV) and functional liver density (FLD) in embolized lobe and non-embolized lobe before PVE and 2 weeks after PVE.Observation indicators:(1) the changes of serum indexes in 2 weeks before and after PVE;(2) the changes of FLV,MLV and FLD in the whole liver,embolized and non-embolized lobes in 2 weeks before and after PVE;(3) surgical and postoperative situations of hilar cholangiocarcinoma;(4) follow-up and survival situations.Follow-up using outpatient examination and telephone interview was performed to detect postoperative serum toal bilirubin (TBil) level,with or without peritoneal effusion and survival up to June 2017.Measurement data with normal distribution were represented as x-±s.The comparisons of pre-and post-operative data were analyzed by the paired t test.Results (1) The changes of serum indexes in 2 weeks before and after PVE:11 patients underwent successful right PVE.The alanine aminotransferase (ALT),TBil,albumin (Alb),Platelets (PLT) and prothrombin time (PT) were respectively (113±20) U/L,(73± 8) μmol/L,(35.0±2.5) g/L,(209±58) × 109/L,(11.4±0.7) seconds in 2 weeks before PVE and (120± 18) U/L,(36± 7) μmol/L,(34.4± 3.2) g/L,(224± 82) × 109/L,(11.2±0.8)seconds in 2 weeks after PVE,with a statistically significant difference in TBil level (t=-10.592,P＜0.05) and no statistically significant difference in ALT,Alb,PLT and PT (t=0.981,-0.350,-0.591,0.533,P＞0.05).(2) The changes of FLV,M LV and FLD in the whole liver,embolized and nonembolized lobes in 2 weeks before and after PVE:the FLV,MLV and FLD of the whole liver were respectively (894±255) mL,(1 552±504) mL,0.59±0.14 in 2 weeks before PVE and (812±206) mL,(1 521±422) mL,0.55±0.16 in 2 weeks after PVE,with no statistically significant difference (t =1.569,0.666,1.980,P＞ 0.05).The FLV,MLV and FLD of the embolized lobe were respectively (623±275) mL,(1 047± 394) mL,0.62±0.14 in 2 weeks before PVE and (375±240) mL,(865±337) mL,0.44±0.24 in 2 weeks after PVE,with statistically significant differences (t =5.909,3.736,3.359,P ＜ 0.05);the descending percentages were respectively 38.1％,9.8％ and 24.6％.The FLV,MLV and FLD of the non-embolized lobe were respectively (274±152)mL,(530±176)mL,0.52±0.21 in 2 weeks before PVE and (436±149) mL,(656±133)mL,0.68± 0.24 in 2 weeks after PVE,with statistically significant differences (t =-6.019,-6.345,-3.933,P＜0.05);the elevated percentages were respectively 80.1％,19.9％ and 23.8％.(3) Surgical and postoperative situations of hilar cholangiocarcinoma:of 11 patients,10 received successful peri-hilar right hemihepatectomy,the right hepatic atrophy and an obvious demarcation line between left and right liver were found intraoperatively;1 stopped operation due to detect intraoperatively peritoneal metastasis of tumor.The operation time,volume of intraoperative blood loss and time of postoperative abdominal drainage-tube removal were respectively (585± 194)minutes,(472± 274)mL and (8±5)days.Of 10 patients undergoing operations,2 were complicated with massive peritoneal effusion at 2 days postoperatively,volume of peritoneal effusion remained more than 500 mL up to 7 days after drainage,and were improved by 1-month conservative treatment;other 8 patients were not complicated with hepatic dysfunction.Duration of hospital stay of 11 patients was (16± 4) days.(4) Follow-up and survival situations:10 patients were followed up for 4-72 months,with a median time of 39 months.During the follow-up,there was no evaluated TBil level and peritoneal effusion in 10 patients.The median survival time,1-,3-and 5-year overall survival rates were 88.8％,74.6％ and 36.8％,respectively.Conclusions The dynamic SPECT 99Tcm-GSA scintigraphy can effectively evaluate liver function changes of embolized and non-embolized lobes before and after PVE.The increased rate of FLV of non-embolized lobe is higher than that of MLV.

Objective To explore clinical efficacy of new types of operation based on perihilar resection to cure hilar cholangiocarcinoma.Methods The retrospective descriptive study was conducted.The clinicopathological data of 4 patients with different Bismuth type of hilar cholangiocarcinoma who were admitted to the Beijing Tsinghua Chunggung Hospital from December 2014 to June 2016 were collected.After preoperative examinations and evaluations,single perihilar resection or combined with central liver segmentectomy were performed.Observation indicators included:(1) intraoperative situations;(2) postoperative pathological examinations;(3) postoperative situations;(4) follow-up.Patients were followed up using outpatient examination up to June 2017.Follow-up included abdominal pain,fever,routine blood test,tumor marker test and imaging examination which detected tumor recurrence and metastasis.Measurement data were represented as average (range).Results (1) Intraoperative situations:4 patients received successful operations,with an average operation time of 512 minutes (range,300-620 minutes).Portal vein was blocked continuously,with an average occlusion time of 70 minutes (range,57-80 minutes),an average volume of intraoperative blood loss was 537 mL (range,200-1 000 mL).Two patients received transfusion of 2 U plasma,4 U plasma + 4 U red blood cell (RBC),respectively.(2) Postoperative pathological examinations:results of postoperative pathological examinations in 4 patients showed that tumor size was respectively 1.5 cm× 1.2 cm× 1.1 cm,1.3 cm× 1.1 cm× 1.0 cm,2.0 cm× 1.7 cm× 1.5 cm and 2.0 cm×2.0 cm× 1.5 cm.Tumor differentiation:1 and 3 patients were respectively detected in moderate-differentiated cholangiocarcinoma and low-differentiated cholangiocarcinoma.Positive nerve plexus invasion was found in all 4 patients and 3 patients had regional lymph node metastasis.Four patients received R0 resection.TNM staging:T2aN1M0 and T2bN1M0 were found in 1 and 3 patients,respectively.(3) Postoperative situations:of 4 patients,1 complicated with biliary leakage was cured by conservative treatment and then discharged from hospital at 67 days;3 had good recovery and then discharged from hospital at day 21,14 and 14,respectively.Patients didn't receive postoperative adjuvant treatment,such as chemoradiotherapy.(4) Follow-up:4 patients were followed up for 12-31 months.During follow-up,4 patients were in good condition,and 1 with transient fever was relieved by conservative treatment.Levels of tumor marker in 4 patients were normal,results of enhanced CT scan showed no signs of tumor recurrence and intrahepatic bile duct dilatation.Conclusion After precisely evaluating the tumor extension among segmental bile duct,single perihilar resection or combined with central segmentectomy can effectively cure hilar cholangiocarcinoma.

Objective To identify the epidemiological changes in invasive fungal infection (IFI) in a neonatal intensive care unit (NICU) to provide information for prevention and treatment of IFI.Methods A total of 102 cases who were diagnosed with IFI among 42 187 neonates hospitalized in the NICU of Affiliated BaYi Children's Hospital,Chinese People's Liberation Army General Hospital from January 1,2009 to December 31,2014 were enrolled in this study.Since January 1,2012,the divisions of our NICU were more specific and intravenous fluconazole was administered as a routine preventive measure for high-risk infants.Clinical information of the IFI cases including general features,incidence,distribution of pathogens and drug (Amphotericin B,Fluconazole,Flucytosin,Itraconazole and Voriconazole) sensitivity were analyzed between former period (January 1,2009 to December 31,2011) and latter period (January 1,2012 to December 31,2014) by Chi-square test.Results The total incidence of IFI was 2.42‰ (102/42 187),and among the 102 IFI cases,73.5％ (75/102) were preterm infants and 75.5％ (77/102) were low birth weight infants.The incidence ofIFI in the latter period was lower than that in the former period [1.8‰ (48/26 046) vs 3.3‰ (54/16 141),x2=9.329,P＜0.01].The incidences of IFI in neonates with gestation age ＜28,≥ 28-＜32 and ≥ 32-＜37 weeks in latter period were decreased as compared with those in former period [10.6 ‰ (3/284) vs 76.9 ‰ (9/117),x2=12.569;6.1‰ (13/2 134) vs 21.9‰ (28/1 277),x2=16.868;1.4‰ (12/8 706) vs 1.9‰ (10/5 256),x2=7.165] (all P＜0.01).Altogether 103 pathogen strains were identified from 102 IFI cases as one Candida parapsilosis strain and one Laurent cryptococcus strain were both isolated from one patient.The most prevalent three pathogens were Candida albicans [51.5％ (53/103)],Candidaparapsilosis [24.3％ (25/103)] and Candida glabrata [8.7％ (9/103)].The isolated rates of Candida albicans and Candida glabrata strains in the latter period were higher than those in the former period [63.3％ (31/49) vs 40.7％ (22/54),x2=5.218;18.4％ (9/49) vs 0.0％ (0/54),x2=10.868],while the isolated rate of Candida parapsilosis strain was lower in the latter period than that in the former period [12.2％(6/49) vs 35.2％(19/54),x2=7.355] (all P＜0.05).All pathogen strains were sensitive strains except one Candida krusei strain which was isolated in the former period and was resistant to Fluconazole.Conclusions Premature infants born at lower gestational ages or with low birth weights are still at high-risk of IFI,but the incidence of IFI has declined in recent years.Routine administration of fluconazole in high-risk infants in NICU could prevente IFI without increasing drug resistance.Candida albicans is the predominant pathogen ofIFI.

TCM higher education has cultivated a large number of high-level TCM professionals in the past sixty years.Against the backdrop of social progress in China,a system of cultivating faculty of TCM higher education has been put in place that features an organic link-up between college,after graduation and continuing education.Academic community serves as a starting point in the system.This paper mainly illustrates our understanding of academic community,life-long education through connecting the three phases and its implementation.

Objective: To investigate the clinical and immunological laboratory features, mutations in SH2D1A gene and SAP protein expression in four children of two families with X-linked lymphoproliferative disease type 1(XLP-1). Method: Four patients (Family A including Patient 1 and Patient 2, Family B including Patient 3 and Patient 4) and their maternal relatives were enrolled in this study. The clinical manifestation, EBV infection status and chest CT scan were analyzed. The absolute and relative numbers of lymphocyte subsets, T lymphocyte proliferative response, SAP protein expression were assessed by flow cytometry. Quantification of signal joint TCR rearrangementexcision circle (sjTRECs), CDR3 spectratyping of TCRvβ and gene mutation of SH2D1A were detected by PCR based on genomic DNA or cDNA. Result: Four male patients from two families were diagnosed with XLP-1. The ages of disease onset were more than 1 year, more than 1 year, more than 1 month and 6 months. The ages at diagnosis were nine years and ten months, sixteen years and eight months, fourteen years and ten months, four years and nine months. All patients had recurrent infections and EBV infection. Patients 1, 2, and 3 had agammaglobulinemia and Patient 4 had hypogammaglobulinemia. Chest CT scan showed all patients had atelectasis and pneumonia, and Patient 3 had bronchiectasis. Patient 3 was diagnosised as Burkitt lymphoma. For immunological function, all patients exhibited reduced CD4/CD8 ratios, increased numbers of exhausted T lymphocyte, decreased number of NK cell. The numbers of total B lymphocyte and naïve B lymphocyte were normal, but the number of memory B lymphocyte declined in all cases. Four patients′ copy numbers of sjTRECs were low and CDR3 spectratypings of TCRvβ showed mildly skewed. But their T lymphocyte proliferative response was normal. SAP protein expression in four cases were measured by flow cytometry. Two patients from Family A were absent and two patients from Family B showed decreased values. SH2D1A gene sequence analysis showed that the patients of Family A harbored a nonsense mutation (c.163 C>T; p.R55X) in exon 2. Their mother and two sisters were carriers. A missense mutation of SH2D1A gene (c.278 G>A; p.G93D) in exon 3 was found in the patients of Family B. The mother was carrier. Four patients remain survived, Patient 3 gave up treatment, other three patients received IVIG therapy. Conclusion Four patients with XLP-1 from two families characterized by agammaglobulinemia have an extreme vulnerability to Epstein-Barr virus (EBV) infection. The functions of T cell, B cell and NK cell are impaired at different stages. The detection of SAP protein and SH2D1A gene are the key methods for diagnosis of XLP-1.

Objective: To investigate the clinical and immunological laboratory features and gene mutation in a female patient who carried a germline gain-of-function mutation in STAT3. Method: A patient with lymphadenopathy and pancytopenia, visited the Department of Rheumatology and Immunology of Children′s Hospital of Chongqing Medical University in May 2016. The clinical and laboratory characteristics, results of immunophenotyping and exome sequencing were analyzed retrospectively and related literature was reviewed. Result: The patient was a four years old girl. The clinical manifestation consisted of autoimmune pancytopenia, lymphadenopathy and recurrent infections. Multiple exams showed that peripheral blood leukocyte count was (2.2-4.9)×10⁹/L, red blood cell count was (2.09-5.75)×10⁹/L, hemoglobin level was 64-165 g/L, platelet count was (52-138) ×10⁹/L. Percentages of lymphocyte subsets showed that CD3⁺ T lymphocyte was 0.716 0 (CD4⁺ T lymphocyte was 0.326 0, CD8⁺ T lymphocyte was 0.323 0 and CD4^- CD8^-T TCRαβ⁺ lymphocyte was 0.029 0), CD19⁺ B lymphocyte was 0.235 0 (transitional B was 0.004 3), NK was 0.032 0. Percentages of CD4⁺ T lymphocyte release IL-4, IFN-γ, IL-17 and IL-21 were 0.014 9, 0.213, 0.024 0 and 0.021 0, respectively. Lymphocyte proliferation function and TCRVβ diversity were normal. The serum immunoglobulin levels were 16.4 g/L (IgG), 1.53 g/L (IgA), 3.99 g/L (IgM) and 3.20 kU/L (IgE). The patient carried a missense variant in the 21^st exon of STAT3, c. 1974G>C, p.K658N, which was previously described as a gain-of-function mutation. The patient was treated with methylprednisolone and prednisone intermittently. There were significant improvements of hepatosplenomegaly, lymphadenopathy and pancytopenia. We searched internal database and literature for cases with gain-of-function mutations in STAT3. A total of 19 cases were identified, all were non-Chinese. Among 16 cases who had clinical data, age of onset of 11 patients was less than 5 years. 14 cases had autoimmune hemolytic anemia, autoimmune thrombocytopenia or autoimmune neutropenia. Twelve patients had lymphadenopathy while 11 had infections and 5 had endocrine abnormalities. Conclusion The patient with Primary immunodeficiency disease (PID) due to gain-of-function mutation in STAT3 gene often has early-onset autoimmune disorders, lymphadenopathy and recurrent infections. Since the routine immunological examination may be normal or slightly abnormal, comprehensive evaluation of immune function should be done. Genetic testing ultimately helps to confirm the diagnosis.