Objective To analyzed distribution characteristics of gene mutation and gene carrying rate of thalassaemia in Shenzhen.Methods 2 500 cases with adult,neonatal umbilical cord blood of 2 500 cases for alpha thalassaemia,beta thalas-saemia,gene types and carry frequency were analyzed.Results 8 types of alpha thalassemia gene 128 cases,rate of detection was 5.12% (128/2 500),and the main genetic types were-SEA/αα(54 cases,42.19%),-SEA/-α3.7 (32 cases,25%)respec-tively.2 500 cases of adult samples were checked out 7 types of gene mutation 101 cases,and detection rate was 4.04%(101/2 500).Main gene mutation type were CD41-42 (39 cases,38.61%),IVS-2-654 (20,21 cases,79%),CD17 (18 cases, 17.82%)and-28 (13 cases,12.87%)respectively.Conclusion Shenzhen thalassaemia mutation type and frequency had ob-vious regional characteristics and times characteristics,health authorities should strengthen epidemiology study,formulate corresponding prevention and intervention measures.

Objective To compare the therapeutic effect of dark plum mixture on rats with radiation-induced xerostomia, given by gastric gavage and oral spray. Methods Rat model of radiation-induced xerostomia were developed by electron linear accelerator. Wistar rats were randomly divided into spray group and gastric gavage group, and normal group, positive control group and normal control group were set up within these two groups. The dark plum mixture was administered for 14 days. After treated for 7 days and 14 days, saliva was collected and submandibular gland samples were collected. The salivary secretion, Sorgan index, component analysis and pathological changes of submaxillary glands between the groups were assessed. Results On the 7thday after irradiation, the saliva secretion and gland coefficient of the dark plum spray group were significantly higher than the positive control group and normal control group (P＜ 0. 05). The saliva secretion, gland coefficient and saliva amylase activity of the dark plum mixture spray group were significantly higher than the dark plum mixture gastric gavage group (P＜ 0. 05). On the 14th day after irradiation, the saliva secretion and gland coefficient of the oral spray group were significantly higher than the gastric gavage group (P ＜ 0. 05 ). The pathological examination of submandibular gland tissues showed that 7 days after irradiation, there were less interglandular space and inflammatory cell infiltration in the oral spray group than the gastric gavage group. On the 14th day after irradiation, the ductal damage and cell nuclear pyknosis in the oral spray group were milder than the gastric gavage group. Vacuolated necrosis and nuclear pyknosis of some glandular cells were visible in the gastric gavage group 7 and 14 days after irradiation. Conclusions Compared with gastric gavage, the oral spray of dark plum mixture increases more saliva and salivary α-amylase secretion, effectively promote the repair of submandibular glandular cells after salivary gland irradiation, and indicates a better therapeutic effect on radiation-induced xerostomia.

Objective: To evaluate the efficacy and safety of high-dose fluconazole alone or combined with flucytosine as initial therapy for cryptococcal meningitis (CM) in non-human immunodeficiency virus (HIV)-related patients. Methods: Twenty-five non-HIV-infected patients with CM from June 2015 to September 2018 in Huashan Hospital, Fudan University, who were initially treated with high-dose fluconazole with or without flucytosine for at least seven days were retrospectively reviewed.Clinical features and antifungal (600-800 mg/d) regimens were recorded, clinical responses and drug-related adverse events were evaluated. Mann-Whitney test and Fisher′s exact probabilities test were applied to compare variables between groups. Results: Of the 25 patients enrolled in this study, 15 had predisposing factors. Headache (25 cases), fever (21 cases), vomiting (13 cases) and neck stiffness (13 cases) were common manifestations. Abnormalities of cranial computed tomography (CT) scan and/or magnetic resonance imaging (MRI) were found in 22 cases.Nineteen patients were treated with high-dose fluconazole plus flucytosine for initial therapy, and six patients were treated with high-dose fluconazole alone. The course of initial regimens with high-dose fluconazole was 42 (29, 120) days. At the end of initial therapy, partial response in 20 patients, stable response in three patients and death in two patients were observed, and the overall effective rate was 80%(20/25). In treatment failure group of initial treatment, the proportion of patients with baseline cerebrospinal fluid opening pressure over 300 mmH₂O (1 mmH₂O=0.009 8 kPa) and with altered mental status were both significantly higher compared with those in treatment success group. Fluconazole related adverse drug events were observed including elevated transaminases (one case), gastrointestinal symptoms combined with hypokalemia (two cases), and systemic rash (three cases). Except for three patients with rash reduced the dosage of fluconazole, no other patients were given dosage adjustment. Conclusion High-dose fluconazole alone or combined with flucytosine is effective and safe for the initial therapy of non-HIV-related CM patients.

This study was aimed to observe the clinical effect and quality of life (QOL) of Si-Zi (SZ) powder for hot compress to improve gastrointestinal functions of hemodialysis patients.A total of 60 hemodialysis patients were randomly divided into the treatment group and the control group.Gastrointestinal Symptom Rating Scale (GSRS) and QOL of both groups before and after the treatment of SZ powder were compared continuously.The results showed that after intervention,the total relieve rate was 96.7％ in treatment group,and 53.3％ in the control group.The effect of SZ powder group was to obviously improve the gastrointestinal symptoms and QOL (P ＜ 0.05).It was concluded that SZ powder for hot compress can improve gastrointestinal functions and increase QOL of hemodialysis patients.

Objective:To study the non-target metabolomics analysis and to analyze the metabolomic changesof cerebrospinal fluid (CSF) in patients with tuberculous meningitis.Methods:Case-control study. From July 2018 to July 2019, 20 cerebrospinal fluid specimens of diagnosed patients with tuberculous meningitis were collectedin the department of neurology from the first medical center of the PLA general hospital and the eighth medical center of the PLA general hospital and 20 CSF without tuberculous meningitis as the control. Among them, there were 12 males and 8 femalesin the tuberculous meningitis group, aged (37.9±16.1) years; there were 13 males and 7 femalesin the control group, aged (34.7±14.8) years. Using ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) technology with three different mode, namely reverse phase chromatography positive ion mode, reverse phase chromatography negative ion mode and hydrophilic chromatography positive ion mode,to detectthe metabolic fingerprints of patients′CSF and analyzed by SIMCA software for orthogonal partial least squares discriminant analysis (OPLS-DA). The variable importance projection value of OPLS-DA model (threshold value>1) plus the P value of t-test (P<0.05) was applied to find the differential metabolites in the cerebrospinal fluid of the two groups of patients.Results:Ten differential metabolites were found in CSF, including L-isoleucine, L-phenylalanine, L-kynurenine, L-methionine, L-tyrosine acid, dimethylglycine, L-alanine, L-threonine, L-histidine and L-lysine, and all of them were up-regulated in the tuberculous meningitis group.Conclusion:Changesof the amino acid metabolism found in the cerebrospinal fluid of tuberculous meningitis patients can provide basis for differential diagnosis and basic molecular research of tuberculous meningitis.

Objective Toinvestigatestatistically significant peptide peaks as biomarkersto diagnose osteoarticular tuberculosis, matrix-assisted laser desorption/ ionization time of flight mass spectrometry (MALDI-TOF MS) was applied to identify the characteristic fingerprint among the serum of patients with osteoarticular tuberculosis, rheumatoid arthritis and healthy adults.Methods Clinical Study. Serum samples of untreatedpatients with osteoarticular tuberculosis and rheumatoid arthritis were collected from August 2018 to December 2018, and serum samples of healthy adults from physical examination were collected as control. After analysis with MALDI-TOF MS, the serum peptide fingerprint datawas imported into software, and protein polypeptide peaks with obvious differences were screened to establish diagnostic models.Results Established the diagnostic model of osteoarticular tuberculosis and healthy adults with m/z 2943.9, 5929.6, 7615.4 and 9033.8 as differential protein polypeptides, the diagnostic model of osteoarticular tuberculosis and rheumatoid arthritis with m/z 4195.6, 5847.6, 5929.6 and 7748.6 as differential protein polypeptides. To these two models, the sensitivity were 95.00％ and 97.50％, respectively. The specificity were 85.71％ and 88.46％, respectively. The accuracy rates were 89.58％ and 92.39％, respectively. The AUC value of ROC curves were 0.8859 and 0.8709, respectively. Conclusions By mass spectrometry and software analysis, the serum protein polypeptides with statistical difference were found successfully. The related diagnostic modelsarealso established, which has certain reference value for auxiliary diagnosis of osteoarticular tuberculosis.

Objective To investigate the clinical efficacy and safety of high-dose caspofungin (70 mg/d)as initial or salvage treatment for invasive pulmonary aspergillosis.Methods Twenty-one patients with proven or probable invasive pulmonary aspergillosis from June 2014 to October 2017 in Huashan Hospital,Fudan University were retrospectively reviewed.According to the anti-fungal treatment before high-dose caspofungin application,patients were divided into initial treatment group and salvage treatment group.Patients' clinical data and laboratory data were collected.The characteristics,clinical efficacy,adverse reactions,one-year survival rate and the overall effective rate were evaluated.The prognosis of the two groups was compared by Kaplan-Meier analysis.Results Twenty of the 21 patients opportunistic acquired invasive pulmonary aspergillosis during the treatment of underlying diseases.Five patients were initially treated with high-dose caspofungin for 68 (62) days.At week 12,one patient achieved complete response,3 patients achieved partial response,and the overall effective rate was 80％ (4/5).Sixteen patients received caspofungin as salvage therapy for 66.50 (58) days,of which one patient got complete response at week 12,10 had partial response,and the overall effective rate was 68.75％ (11/16).One-year follow-up showed that no patient died in the initial treatment group,and the one-year survival rate was 100％ (5/5).In salvage treatment group,3 patients died of pulmonary bacterial infections and the one-year survival rate was 81.25％ (13/16).During treatment,one patient had elevated total bilirubin,which was possibly associated with high-dose caspofungin.Conclusions High-dose caspofungin regimen has good efficacy and safety,both for initial treatment and salvage therapy in patients with invasive pulmonary aspergillosis.

TAM(tumor-associated macrophage)is a kind of immune cell in tumor microenvironment,which mainly exists in tumor matrix to mediate inflammatory reaction.Generally,TAM can be stimulated by different cytokines to polarize into M1 macrophage or M2 macrophage with different phenotypes.In the early stage of tumor,M1 macrophages in TAM exhibit pro-inflammatory and anti-tumor activities,while as tumor progresses,TAMs tend to polarize into M2 macrophages to play anti-inflammatory and tumor-promoting roles.A large number of studies have shown that TAM is closely related to tumor growth,invasion,metastasis and poor prognosis.Therefore,targeting TAM has become the focus of anti-tumor immunotherapy.This paper has summarized the origin of TAM,and introduced the specific roles of TAM in promoting tumor proliferation,angiogenesis,migration and invasion and the formation of immunosuppressive environment.At the same time,the research progress of TAM-targeted anti-tumor immu-notherapy in recent years was discussed from 3 aspects:inhibiting monocyte recruitment,promoting TAM apoptosis and reshaping TAM phenotype.

Digestive tract diseases， especially digestive tract tumors， including liver cancer， pancreatic cancer， and colorectal cancer， have high incidence in China. Digestive tract tumor is one of the top 10 cancers in terms of the number of new cases and deaths in the world， and the incidence and mortality of tumor diseases have been increasing year by year. Therefore， the prevention and treatment of tumors is particularly important. With the application and promotion of traditional Chinese medicine in the medical field and the rapid development of molecular biology and pharmacology， more and more potential active components of Chinese medicinal materials have been extracted and studied. These active components can inhibit tumor cells in a multi-target and multi-pathway manner. Cinobufotalin is an effective component extracted from the skin of Bufo bufo gargarizans. It has been prepared into a variety of agents with anti-tumor， immunomodulatory， cardiac boosting， pain-easing， anti-inflammatory， and swelling-relieving activities. In clinical practice， cinobufotalin is mainly used to assist the treatment of liver cancer， lung cancer， colorectal cancer， gastric cancer and other malignant tumors， which can reduce the adverse reactions of patients in the middle and late stages and improve the quality of life and five-year survival rate of patients. The available studies of molecular mechanism have demonstrated that cinobufotalin can play a therapeutic role by inducing cell apoptosis， regulating cell cycle， inhibiting cell proliferation and angiogenesis， modulating immune response， reversing multidrug resistance， enhancing radiochemotherapy sensitivity， inhibiting tumor inflammation， invasion， and metastasis， etc. This review focuses on the clinical application and mechanism of cinobufotalin against digestive tract tumors in recent years， aiming to provide a theoretical basis for the anti-tumor research of cinobufotalin， promote the application of cinobufotalin in tumor treatment， and facilitate the further research and development of this compound.