Objective:To explore the genetic etiology for a patient with Alstr?m syndrome (ALMS) presenting as dilated cardiomyopathy.Methods:A 41-year-old male patient who had presented at the Sixth Medical Center of PLA General Hospital on October 20, 2021 was selected as the study subject. Clinical and laboratory examinations were carried out. Whole exome sequencing (WES) was employed for genetic testing, and candidate variants were validated by Sanger sequencing and pathogenicity analysis.Results:The patient had a 14-year medical history characterized by dilated cardiomyopathy, complete atrioventricular block, visual impairment, sensorineural hearing loss, truncal obesity, insulin resistance, type 2 diabetes, hypertension, renal dysfunction, and paranoid delusions. Genetic testing revealed that he has harbored compound heterozygous variants of the ALMS1 gene, namely c. 6823C>T (p.Arg2275Ter) and c. 9442_9445dup (p.Ser3149LysfsTer2). Sanger sequencing confirmed that they were inherited from his father and mother, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PVS1_VeryStrong+ PM2_Supporting+ PM3+ PP3, PVS1_VeryStrong+ PM2_Supporting+ PM3). Literature review indicated that the complete atrioventricular block in the patient was a phenotype unreported previously. Conclusion:The c. 6823C>T (p.Arg2275Ter) and c. 9442_9445dup (p.Ser3149LysfsTer2) compound heterozygous variants of the ALMS1 gene probably underlay the pathogenesis in this patient. Above findings have expanded the phenotypic spectrum of ALMS and provided insights for clinicians dealing with similar cases.

In May 2019, a patient who suffered with multiple foot metatarsus injury with soft tissues defect was treated in the Hand and Foot Microsurgery of Xi'an Fengcheng Hospital, by using chimeric peroneal artery for phase-1 reconstruction of metatarsus with folded fibular flap, foot cross arch and soft tissue defects. After 2 years, the arch of foot as intact without collapse. There was no arthritic lesions. The height, arc and width of metatarsus were very close to the healthy side. The flap and plantar were smooth without abrasion and ulceration. The patient could walk, run and stand with single-foot stand, and able to carry out heavy physical work continuously.

ObjectiveTo explore the underlying mechanism of Gegen Qinliantang （GGQL） in the treatment of ulcerative colitis （UC） in rats and discuss the effects of modification of GGQL on its efficacy. MethodThe UC model was induced in rats by free access to 5% dextran sulfate sodium in saline solution. Male SD rats were randomly divided into a normal group， a model group， a positive control group （sulfasalazine enteric-coated tablets， 350 mg·kg^-1）， a GGQL group （17 g·kg^-1）， a Glycyrrhizae Radix et Rhizoma （GR）-absent GGQL group （17 g·kg^-1）， a Puerariae Lobatae Radix （PLR）-absent GGQL group （17 g·kg^-1）， a GR-PLR group （17 g·kg^-1）， and a Scutellariae Radix （SR）-Coptidis Rhizoma （CR） group （17 g·kg^-1）. The in vitro antioxidant activities of GGQL and its combinations were evaluated by 2，2-diphenyl-1-picrylhydrazyl （DPPH）， 2，2′-azino-bis（3-ethylbenzothiazoline-6-sulfonic acid） （ABTS）， and fluorescence recovery after photobleaching （FRAP） methods. The degree of colonic tissue injury in each group was evaluated based on the weight changes of rats， the length of the colon， the colon sections， and hematoxylin-eosin （HE）-stained histopathologic sections. The serum levels of myeloperoxidase （MPO）， lipid peroxide （LPO）， malondialdehyde （MDA）， total superoxide dismutase （T-SOD）， catalase （CAT）， and reduced glutathione （GSH） were measured by colorimetry. The mRNA and protein expression of nuclear factor-erythroid 2 related factor （Nrf2）， quinone oxidoreductase 1 （NQO1）， and heme oxygenase-1 （HO-1） in colon tissues was detected by real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the normal group， the model group showed colonic mucosal necrosis， inflammatory infiltration， increased serum levels of MPO， LPO， and MDA （P<0.01）， blunted activities of T-SOD， CAT， and GSH （P<0.01）， decreasing trend of mRNA expression of Nrf2， NQO1， and HO-1， reduced expression of Nrf2 protein （P<0.01）， and decreasing trend of expression of NQO1 and HO-1 proteins. Compared with the model group， the GGQL and its combination groups showed improved pathological injury and morphological structure of colon tissues in UC rats， reduced serum levels of MPO， LPO， and MDA （P<0.05）， potentiated T-SOD activity （the PLR-absent GGQL group）， CAT activity （the GR-absent GGQL group and the SR-CR group）， and GSH activity （P<0.01）， and increased mRNA and protein expression of Nrf2， NQO1， and HO-1 in colon tissues. The difference in the GGQL group was significant （P<0.05）. ConclusionGGQL has a restorative effect on the pathological injury of UC rats， and its mechanism may be related to the activation of the Nrf2 signaling pathway and inhibition of oxidative stress response. The absence of PLR or only presence of SR and CR has a great impact on the treatment of UC. The results can provide references for the clinical rational medication of Chinese medicine and the research on the mechanism of compound combinations.

Objective:To improve the understanding of sporadic adult Burkitt lymphoma.Methods:The clinical data of a patient with sporadic adult Burkitt lymphoma who was admitted to the Affiliated Hospital of Chengde Medical College in August 2019 were retrospectively analyzed, and the relevant literature was reviewed.Results:The patient visited the clinic mainly for abdominal pain and abdominal distension, and the disease progressed rapidly. The early pathological examination of an ileocecal mass showed B-cell lymphoma, which was treated with R-CHOP regimen chemotherapy, and the mass disappeared immediately. The patient's symptoms were slightly improved, but the ascites was not significantly improved. The diagnosis of Burkitt lymphoma was confirmed by ascites test, and the treatment was adjusted to R-EPOCH regimen. The patient's condition was stable before the submission of this paper.Conclusion:Burkitt lymphoma is a highly aggressive malignancy, and cytological detection of serosal effusion is of important reference value in the diagnosis of Burkitt lymphoma.

Metastasis is the leading cause of human cancer deaths. Unfortunately, no approved drugs are available for anti-metastatic treatment. In our study, high-throughput sequencing-based high-throughput screening (HTS) and a breast cancer lung metastasis (BCLM)-associated gene signature were combined to discover anti-metastatic drugs. After screening of thousands of compounds, we identified Ponatinib as a BCLM inhibitor. Ponatinib significantly inhibited the migration and mammosphere formation of breast cancer cells in vitro and blocked BCLM in multiple mouse models. Mechanistically, Ponatinib represses the expression of BCLM-associated genes mainly through the ERK/c-Jun signaling pathway by inhibiting the transcription of JUN and accelerating the degradation of c-Jun protein. Notably, JUN expression levels were positively correlated with BCLM-associated gene expression and lung metastases in breast cancer patients. Collectively, we established a novel approach for the discovery of anti-metastatic drugs, identified Ponatinib as a new drug to inhibit BCLM and revealed c-Jun as a crucial factor and potential drug target for BCLM. Our study may facilitate the therapeutic treatment of BCLM as well as other metastases.

Objective: To investigate the effects and mechanism of Holothurian Glycosaminoglycan (hGAG) alone in combination with cisplatin (DDP) on apoptosis of pulmonary adenocarcinoma cell A549. Methods: A549 cells were separately treated with blank, hGAG, DDP and hGAG combined with DDP (hGAG + DDP). The cell morphology in 4 groups was observed using light microscope. CCK8 assay was used to determine the cell viability. Flow cytometry by Hoechst 33258 and AnnexinV-FITC/PI staining was applied to detect cell apoptosis. Western blot was then used to detect the protein expression of Bax, Bcl-2, survivin and caspase-3. Results: After treatment for 24 h, the inhibitory rates of A549 cells in control, hGAG, DDP and hGAG + DDP groups were 0, (19.74±5.39)%, (42.01±2.57)% and (53.89±4.58)%, respectively. Moreover, after treatment for 48 h and 72 h, the inhibitory rates in each group were 0, (23.17±4.78)% and (29.17±4.21 )%, (54.00±7.64)% and (59.35±7.31)%, as well as (77.58±4.26)% and (79.94±4.58)%, respectively. The cell viability was significantly lower in drug treatment groups compared with those in control group at the same time point (P<0.05). Hochest 33258 staining showed that no obvious apoptotic cells were detected in the control group, while apoptotic cells were visible in hGAG, cisplatin and combination groups. Flow cytometry showed that cell apoptotic rates were (2.38±0.59)%, (12.59±4.22)%, (16.36±3.63)% and (44.60±5.45)% in the control, hGAG, DDP and hGAG + DDP groups, respectively. The cell apoptosis was significantly lower in drug treatment groups compared with those in control group at the same time point (P<0.05). Furthermore, western blot results showed that the expression of Bax and caspase-3 protein was increased (P<0.05), whereas Bcl-2 and survivin was decreased (P<0.05) in the hGAG+ DDP group compared with cisplatin alone (P<0.05). Conclusions HGAG can inhibit the proliferation and promote the apoptosis of human lung adenocarcinoma A549 cells. Meanwhile, it can strengthen the chemosensitivity of A549 cells to DDP via up-regulation of Bax, caspase-3 and down-regulation of Bcl-2 and survivin.

Objective: To explore the clinical features, the serotype distribution and drug resistance of the isolates in patient with invasive pneumococcal disease (IPD). Methods: By retrieving the laboratory information system in 18 children′s hospitals from 2012 to 2017, the children with IPD were enrolled. Streptococcus pneumoniae (Spn) must be isolated from the sterile sites (blood, cerebrospinal fluid, hydrothorax and joint effusion etc.). The clinical characteristics, serotype, drug resistance, treatment and prognosis were reviewed and analyzed. According to the telephone follow up results, the patients were divided into death group and recovered group. The index as an independent risk factor of mortality was demonstrated by multivariate logistic regression analysis. Results: There were 1 138 children with IPD, including 684 male and 454 female. The proportion of male to female was 1.5∶1. The age ranged from one day to 16 years. The median age was 1 year 3 month. The majority was under 5 years of age (89.3%, n= 1 016), especially under 2 years of age (61.9%, n=704). In all cases, 88.2% (n=1 004) were community acquired infection. The infections included meningitis (n=446, 39.2%), pneumonia with bacteremia (n=339, 29.8%), and bacteremia without focus (n=232, 20.4%). Underlying diseases were found in 242 cases (21.3%). Co-infections were determined in 62 cases (5.4%) with mycoplasma, 27 cases (2.4%) with adenovirus and 34 cases with influenza virus (3.0%). The penicillin insensitivity (PNSP) rates in meningitis and non-meningitis isolates were 69.5% (276/397) and 35.9% (221/615), respectively. There were 81 strains serotyped, in which 93.8% (76/81) were covered by 13-valent protein-polysaccharide conjugate vaccine (PCV13). In the 965 patients who were followed up by phone call, 156 cases (16.2%) were confirmed dead. The independent risk factors for the death were under 2 years of age (OR=2.143, 95%CI 1.284-3.577, P=0.004), meningitis (OR=3.066, 95%CI 1.852-5.074, P<0.01), underlying disease (OR=4.801, 95%CI 2.953-7.804, P<0.01), septic shock(OR=3.542, 95%CI 1.829-6.859, P<0.01), disseminated intravascular coagulation (DIC) (OR=4.150, 95%CI 1.468-11.733, P=0.007), multiple organ failure (OR=12.693, 95%CI 6.623-24.325, P<0.01) and complications of central nervous system (OR=1.975, 95%CI 1.144-3.410, P=0.015). Conclusions Most children with IPD were under 5 years of age, having underlying diseases and acquired the infection in community. The independent risk factors for death were under two years old, meningitis, underlying diseases and multiple organ failure. The problem of drug resistance was severe. The universal immunization of PCV13 would be effective to prevent IPD in Chinese children.

Objective To investigate the inhibitory effects of radioactive 125I seeds on the growth and apoptosis of human lung adenocarcinoma cells A 549 in nude mice.Methods Human lung adenocarcinoma A549 cells were cultured in vitro and subcutaneously transplanted in BALA/c nude mice.When the tumor size reached(300 ±50)mm3,40 tumor-bearing mice were divided into 4 groups by the random number table method as 0,0.6,0.8 mCi(1 Ci＝3.7×1010Bq)groups and blank control group,with 10 in each group.The 125I seeds of 0,0.6,and 0.8 mCi were implanted into the transplanted tumors in nude mouse,respectively.The blank control group received no treatment.The weight of nude mice was measured regularly every 4 days.The mice were sacrificed on the 32 days after 125I seeds implication.The transplanted tumors were weighed and the weight gain curve for nude mice was plotted.Hematoxylin-eosin(HE)staining was used to observe the histopathological changes of the tumor tissue.Cell apoptosis was detected by TUNEL assay,and the expressions of the P21,Caspase-9,Survivin and Livin proteins were detected by immunohistochemical assay.Results There was no nude mice dead in each group.On the day 28 and 32 after 125I seeds treatment,the body weights of nude mice of 0.6 and 0.8 mCi groups became lighter than those of the blank control group(q＝4.26,9.19,4.11,11.59,P＜0.05),the tumor weights of the 0.6 and 0.8 mCi groups were significantly decreased(q＝5.021,5.692,P＜0.05)with tumor inhibition rates of about 49％and 62％.In the 0.6 and 0.8 mCi groups,a large number of tumor cells degenerated to be necrotic cells.In addition,the apoptotic indexes were(50.00 ±2.58)％and(62.33 ± 4.51)％in the 0.6 and 0.8 mCi groups,respectively,and higher than that of blank control group(27.00 ±4.69)％.The expressions of P21 and Caspase-9 proteins in the 0.6 and 0.8 mCi groups were significantly higher than that in the blank control group(χ2＝11.380,24.310,11.380,20.376,P＜0.05).The expressions of Survivin and Livin proteins in the 0.6 and 0.8 mCi groups was significantly lower than that in the blank control group(χ2＝9.643,23.254,15.429,26.667,P＜0.05).Conclusions Radioactive 125I seeds can inhibit the proliferation of tumor cells and promote the apoptosis of A 549 cells probably by up-regulating the expressions of P21 and Caspase-9 but down-regulating the expressions of Survivin and Livin.

Objective To investigate the expression of guanylate binding protein 5 (GBP5) and ArfGAP with SH3 domain ankyrin repeat and PH domain 1 (ASAP1) genes in pulmonary tuberculosis patients and tuberculosis latent population. Methods Forty pulmonary tuberculosis patients (pulmonary tuberculosis group), 40 latent tuberculosis infection patients (latent tuberculosis infection group) and 40 cases of healthy control (healthy control group) were selected from August 2016 to May 2017. The gene expression was detected in 4 ml peripheral anticoagulant blood by real-time fluorescent quantitative reverse transcription-polymerase chain reaction (RT-PCR) and the relative expression of two genes in three groups were compared. Results The GBP5 gene expression in three groups was significantly differentce (F=7.23, P=0.001). The GBP5 gene relative expression in pulmonary tuberculosis group was significantly higher than that in latent infection group :1.58 ± 0.80 vs. 1.09 ± 0.68, there was significant difference (t=2.93, P=0.004). The GBP5 gene relative expression in pulmonary tuberculosis group was significantly higher than that in healthy control group: 1.58 ± 0.80 vs. 1.04 ± 0.61, there was significant difference (t=3.40, P=0.010). The GBP5 gene relative expression in latent infection group and healthy control group had no significant difference (t=0.39, P=0.700). There was no significant difference in ASAP1 expression among three groups (F=0.26, P=0.770). Conclusions The expression of GBP5 in pulmonary tuberculosis patients, latent tuberculosis infection patients and healthy controls is different, and GBP5 could screen latent tuberculosis infection patients which is expected to be a potential screening marker for latent tuberculosis infection.

Objective To investigate the effect and underlying mechanism of radioactive 125I seed implantation on the angiogenesis of transplanted human lung adenocarcinoma in nude mice.Methods An animal model of transplantd human lung adenocarcinoma was established by subcutaneous implanting A549 cells into nude mice.Twenty four tumor-bearing nude mice were randomly divided into 4 groups with different irradiation doses of blank control (without any treatment) and 0 MBq,22.2 MBq,29.6 MBq and by embedding radioactive 125I seeds with an 18 G implant needle.Tumor volumes were measured every 4 days until all mice were terminated 30 d later and the tumor growth curve was drawn.The microvessel density (MVD) in the tumor tissue was detected by immunohistochemistry S-P assay.The mRNA and protein levels of VEGF and HIF-1α of each group were detected by RT-PCR and Western blot,respectively.Results After embedding of 125I seeds,the tumor volumes of 22.2 MBq group (886 ± 97) and 29.6 MBq group (590 ± 107) were significantly smaller than those of control group (2 297 ± 149) at 54 d after administration (q =14.117,17.075,P ＜ 0.05),but there were no significant differences among 0 MBq group and control group,22.2 MBq and 29.6 MBq groups (P ＞ 0.05).The immunohistochemical CD34-positive staining demonstrated that MVD in 22.2 MBq group (522 ± 119) and 29.6 MBq group (491 ± 121) were decreased significantly compared with control group (922 ± 260) (q =4.826,5.197,P ＜0.05),but there were no significant differences among 0 MBq and control groups,22.2 MBq and 29.6 MBq groups(P ＞0.05).The mRNA expressions of VEGF and HIF-1α in 22.2 MBq group (0.279±0.0659,0.370 ±0.0857) and 29.6 MBq group (0.215 ±0.0620,0.278 ±0.0651) were significantly lower than those in the control group (q VEGFmRNA =18.881,17.211,q HIF-1αmRNA =15.376,14.733,P ＜0.05),but there were no significant differences among 0 MBq and control groups,22.2 MBq and 29.6 MBq groups(P ＞0.05).At the same time,the expression levels of VEGF and HIF-1α protein after 125I seed implantation were also obviously decreased in 22.2 MBq and 29.6 MBq groups (qvEGr =5.848,6.263,q HIF-1α =6.560,7.576,P ＜ 0.05),and no significant difference between 0 MBq and control groups(P ＞ 0.05) and between 22.2 MBq and 29.6 MBq groups (P ＞ 0.05).Conclusions Interstitial implantation with 125I seeds may potently inhibit angiogenesis in human lung adenocarcinoma xenografts of nude mice.