@@

Objective To study the clinical manifestation,diagnosis,differential diagnosis and the essentials of management and treatment of fibrodysplasia ossificans progressiva (FOP).Methods Three cases of FOP were reported.The features of clinical manifestation and radiography were studied.The literature related to FOP was reviewed.Results FOP affected young children′s age of onset was between 10 days and 2 years (mean age 1 3 years).Mean disease duration was 5 3 years (range 2～11 years),and mean age 5 3 years (range 2～11 years) with sex ratio 1∶2 (boy∶girl).Soft tissue swelling in cervical and dorsal regions with or without local pain and warmth,and low fever were the early clinical manifestations.These nodules usually disappeared spontaneously,but some of nodules gradually developed ossification.The X ray features included ectopiac ossification most frequently in the soft tissue of the upper back and neck,next,the loin,chest and extremities.Two cases showed short hallux and hallux valgus.Exacerbation of the two cases was precipitated after muscle biopsy and careless venepuncture.All patients showed progressive extra articular bony ankylosis of most joints of axial and/or appendicular skeleton with severe movement restriction.Conclusion FOP is a rare and disabling genetic disorder of connective tissue.FOP should be diagnosed as early as possible and non invasively,based upon history,clinical and radiological findings.The finding of abnormalities of the great toe is helpful to diagnose FOP so that management can be early and adequate.Manogement principle includes avoiding conditions potentially provocative of abnormal ossification.The disease should be familiar to pediatricians.

Objective To evaluate the effects of post-operation rehabilitation treatment of patients with calcaneus fracture by dynamic plantar pressure analysis,and assess the value of the Footscan system.Methods Sixty-two patients with unilateral calcaneus fracture were randomly divided into a rehabilitation group and a control group.The patients in the rehabilitation group were given early,systemic standard rehabilitation treatment,while those in the control group took functional exercise following the doctors'advice.At 3 months and 6 months after operation,the plantar pressure distribution of the patients in both groups was analyzed with the Footscan system,respectively.Results After 3 months of treatment.there was statistically significant difference between the injured and the uninjured sides in both groups,with regard to the contact time,average plantar pressure and pressure-time integrals at different phases of gait.However,there was no significant difference between the injured and the uninjured sides after 6 months in rehabilitation group.But in control group,there was still statistically significant difference between the two sides with regard to the above parameters.Conclusion Early rehabilitation treatment could significantly improve the function outcome of patients with calcaneus fracture.Footscan System can objectively evaluate the recovery of the calcaneous fracture.

Objective To explore the value of SUV in patients with ascites of unknown cause.Methods A total of 55 patients (24 males,31 females,average age 54.8 years,age range:23-82 years) with ascites of unknown cause who underwent 18F-FDG PET/CT scan were retrospectively enrolled in this study.SUVmax and SUVmean of ascites and liver were measured and their ratios (T/NT) were calculated and compared by two-sample t test.All patients were followed up and had final diagnoses.Sensitivity,specifici ty,accuracy,positive predictive value and negative predictive value were calculated respectively.The diagnostic efficiency was compared among 18F-FDG PET/CT tumor localization alone,ascites radioactivity and ascites cytology examination by x2 test or Fisher exact test.Results Besides the high metabolized primary lesions and/or metastasis,the liver and spleen swamped by ascites with high radioactivity were visualized on MIP images.The SUVmax and SUVmean of malignant ascites were 1.78±0.65 and 1.37±0.38 respectively,which were higher than those of benign ascites (1.11±0.36 and 0.72±0.22; t=4.13,6.82,both P＜0.05).T/NT of malignant ascites was higher than that of benign ascites (SUVmax:0.64±0.20 vs 0.48±0.12,t =3.27,SUVmeax:0.68±0.17 vs 0.38±0.10,t =7.21 ; both P＜0.05).The diagnostic sensitivity,specificity and accuracy of SUV in ascites were 75.0％ (27/36),94.7％ (18/19) and 81.8％ (45/55),respectively.The sensitivity and accuracy of SUV were higher than those of cytological examination (44.4％ (16/36) and 63.6％ (35/55) ; x2 =6.98,4.58,both P＜0.05).The specificity of SUV was higher than that of tumor localization by 18F-FDG PET/CT (63.2％,12/19; x2 =5.70,P＜0.05).Conclusion Significantly higher SUVmax and SUV in malignant ascites than benign ascites were noted,which might play an adjuvant role in patients with ascites of unknown cause.

Objective To study the relationship between the CT value and injury of ultrastructure in posttraumatic acute diffuse brain swelling(PADBS). Methods The change of CT value of brain tissue was analyzed at posttrauma and preoperation in 9 patients, in combination with the ultrastructure in brain parenchyma in 36 specimen taken from operations. The relationship between the descend of CT value and ultrastructure injury was analysed.Results The CT value of brain in preoperation was lower than it in posttrauma first scanning(2.5～4.3 HU).The capillary distention and stenosis and the diffuse edema in pericapillary and intercellular were observed under transmission electron microscopy(TEM). The nucleolus of neuronal cells displaced to membrane or disappeard. Chromation agglutionation, nuclear membrane circuity, perinuclear diffuse lipid drops and blankspace were detected. The mitochondrion swelling, mitochondrial crest blurring or effacement, rough endoplasmic reticulum distension and its’ granules detachmen were also seen under TEM. Axolemma edema, microfilaments and microtubules derangement in axis-cylinder were found too. The similar phenomena existed in astrocyte.Conclusion The descent of CT value in PADBS was relevant to the aggravation of vasogenic cerebral edema, cytotoxic cerebral edema and ultrastructure injury in brain parenchyma.

To study the apoptosis induced by cisplatin in cervical cancer cell line HeLa and its mechanism, cell growth inhibition of cisplatin on HeLa cells was analyzed by MTT assay. Cell apoptosis was examined by cytometry and Hoechst33258 staining after treatment with cisplatin. The ef- fects of cisplatin on transcription of E6 were analyzed by RT-PCR. The protein expressions of E6, p53, p21, Bax and Bcl-2 were studied by Western blotting. Cisplatin inhibited proliferation in a time- and dose-dependant manner. Cytometically, sub-G1 peak showed higher apoptosis rates in the ex- perimental group than those in the control. Hoechst33258staining exhibited apoptosis induced by cis- platin. RT-PCR revealed that cisplatin decreased transcription of E6. Western blotting showed that cisplatin decreased protein expression of E6 and increased protein expression of p53, p21and Bax. It had no effect on protein expression of Bcl-2. It is concluded that cisplatin can induce apoptosis in HeLa cells by suppressing HPV E6 and thereby restoring the function of p53.

Objective To retrospectively analyze the clinical efficacy and safety of VCD (bortezomib/cyclophosphamide/dexamethason) in the treatment of multiple myeloma (MM) patients. Methods Fifty-five consecutive patients with newly diagnosed or relapsed MM were enrolled in the study retrospectively from June 2012 to June 2017. We collected and analyzed the clinical information of all patients treated with VCD.Results Firstly, the patients received therapy of VCD for median 4 cycles (Range : 2 ～8). The overall response rate (ORR) was 85.5％ (45/55). The complete response/near complete response rate (CR/nCR) , very good partial response rate (VGPR) and partial response rate (PR) were 27.3％, 23.6％ and 34.6％, respectively. The ORR of10 patients with renal inadequacy was 80.0％, while 45 cases with normal renal function was 82.2％ (P=0.627).Secondly, with a median follow-up of 13.5 months, the median progression free survival (PFS) , the median duration of response (DOR) and the median overall survival (OS) were 27 (1～61) months, 18 (1～50) months and 49 (1～64) months, respectively. Univariate prognostic analysis showed that abnormal ISS stage Ⅲ, relapse, renal dysfunction and response inferior to VGPR were negative prognostic factors for PFS, while abnormal ISS stageⅢ and renal dysfunction were negative prognostic factors for OS. Moreover, the multivariate prognostic analysis showed that abnormal ISS stage Ⅲ and response inferior to VGPR were independent prognostic factors for PFS, while ISS stage Ⅲ was independent prognostic factors for OS. Thirdly, the VCD treatment is effective and safe.The adverse events were evaluated according to International Myeloma Working Group Uniform Response Criteria.The results showed that the most common grade 3 ～4 non-hematology adverse events (AEs) were infection (20.0％) , peripheral neuropathy (5.5％) and hypertension (5.5％). The most common grade 3～4 hematology AEs were thrombocytopenia (10.9％) , neutropenia (9.0％) and anemia (5.5％). A total of 2 patients (3.6％) discontinued VCD because of serious peripheral neuropathy and 2 cases (3.65％) died of respiratory failure because of serious infection. Conclusions The VCD regimen is effective and safe in the treatment of newly diagnosed or relapsed/refractory MM patients in China. VCD is safe in patients with renal dysfunction.

Objective:To prepare water-soluble graphene-based itraconazole antifungal eye drops and evaluate its antifungal activity against Fusarium solani. Methods:By oxidative modification of graphene and modification of polymer materials, water-soluble graphene oxide-modified polyethylene glycol (GO-PEG) composites were prepared.The composites were characterized by scanning electron microscopy, zeta potential, and Raman spectroscopy.The antifungal drug itraconazole was loaded onto the GO-PEG vector by solvent evaporation method, and itraconazole eye drops were obtained.The drug loading of itraconazole eye drops was measured using a UV and visible spectrophotometer.The antifungal effect in vitro was assessed by the microdilution method and light microscopy. Results:Scanning electron microscopy showed that GO-PEG had a two-dimensional nanosheet structure and many wrinkles.The zeta potential of GO-PEG was -42.40 mV.Raman spectroscopy showed that the ID/ IG of GO-PEG was 1.003.Using the water-soluble GO-PEG vector, a maximum itraconazole concentration of 10 mg/ml was achieved with a 10 000-fold increase in apparent solubility (10 mg/ml vs 0.001 mg/ml). The antifungal results showed that the minimum inhibitory concentration of itraconazole eye drops against Fusarium solani was approximately 1.88 μg/ml, but the GO-PEG vector has no significant antifungal activity against Fusarium solani. Conclusions:GO-PEG achieves effective loading and solubilization of itraconazole, demonstrating an in vitro inhibitory effect on Fusarium solani.

Objective:To investigate the efficacy and safety of anlotinib in distant metastatic radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC).Methods:Retrospective analysis was performed on 17 patients with distant metastatic RAIR-DTC (6 males, 11 females, age: 57.0(45.5, 63.0) years) from Affiliated Hospital of Qingdao University between October 2018 and February 2023, including 13 patients receiving first-line treatment and 4 patients receiving second-line treatment with anlotinib. The changes of serum thyroglobulin (Tg) during the treatment of anlotinib, the changes of maximum diameter of the target lesion at the last follow-up compared with the diameter at baseline, the imaging efficacy, and treatment-related adverse events were analyzed. The serological and imaging effects of the first-line treatment group and the second-line treatment group were compared. The Fisher exact test was used to analyze the differences between groups.Results:The follow-up time of 17 patients was 17.3(9.5, 21.4) months, and the objective response rate (ORR) and disease control rate (DCR) were 7/17 and 16/17, respectively. There were no significant differences of ORR (6/13 vs 1/4; P=0.603) and DCR (13/13 vs 3/4; P=0.235) between the first-line and second-line treatment groups. The change rates of serum Tg at 3, 6 weeks and the last follow-up were -30.2%(-61.2%, -15.5%), -64.8%(-90.6%, -32.3%), and -85.8%(-96.1%, -50.7%), respectively. At the last follow-up, the change rate of maximum diameter of target lesions was -20.0%(-45.0%, -5.2%). The incidence of treatment-related adverse reactions was 14/17, and 2 patients (2/17) had grade 3 or above adverse reactions. Conclusion:Anlotinib shows superior efficacy with tolerable toxicity in the first-line treatment of distant metastatic RAIR-DTC, and hopefully plays an important role in second-line treatment for RAIR-DTC resistant to sorafenib.