Autoimmune disease(AID)is a disease in which the body loses tolerance to autoantigens and the immune system attacks its own tissues,resulting in organ and tissue damage and certain clinical manifestations.Studies have proved that pathogenic T cells can be selectively inhibited or killed by TCR vaccine in the treatment of AID,thus bringing broad application prospect.This pa-per briefly summarizes the research status of TCR vaccine in AID field,regarding action mechanism,related diseases and safety of TCR vaccine.

OBJECTIVE To explore the effects of posaconazole combined with proton pump inhibitors （PPI） on the blood concentration and the risk of invasive fungal disease （IFD） in patients with malignant hematological disorder. METHODS In accordance with the random number table method， 40 patients with malignant hematological disorders who were admitted to the hematology department of our hospital between December 2020 and December 2021 were chosen and divided into control group （20 cases） and observation group （20 cases）. The control group received Posaconazole oral suspension alone， while the observation group received Posaconazole oral suspension combined with PPI. The incidence of IFD， attainment rate of blood concentration， the time from the start of prophylaxis to IFD onset， the fatality associated with IFD， treatment of infected patients， and blood concentrations of posaconazole on 7th， 14th， 21st， and 28th day after posaconazole application were compared between 2 groups； the occurrence of adverse events during drug administration in the two groups was recorded. RESULTS The study was stopped because 2 patients in the observation group and 9 patients in the control group received hospital departures after taking posaconazole for fewer than 7 days. The incidence of IFD in the observation group was significantly higher than control group， and the attainment rate of blood concentration in the observation group was significantly lower than control group （P＜0.05）. There was no significant difference in the time from the start of prophylaxis to IFD onset， the fatality associated with IFD， treatment of infected patients and the incidence of adverse events （P＞ 0.05）. The blood concentration of posaconazole in the observation group was significantly lower than control group on 7th day of medication （P＜0.05）； there was no significant in blood concentration of posaconazole between 2 groups on the 14th day of medication （P＞0.05）. CONCLUSIONS Posaconazole combined with PPI can reduce the blood concentration of patients with malignant hematological disorders， increase the risk of IFD. Clinical practice should try to avoid the combination of the two or use them under the guidance of therapeutic drug monitoring.

OBJECTIVE To systematically evaluate the efficacy and safety of vonoprazan in the treatment of gastroesophageal reflux disease， and to provide evidence-based reference for clinical drug use. METHODS Randomized controlled trials （RCTs） about vonoprazan （trial group） versus placebo or proton pump inhibitor （control group） were searched in PubMed， the Cochrane Library， Web of Science， CNKI， Wanfang， VIP and CBM databases from the inception to June， 2022. After literature screening and data extraction， the qualities of included literature were evaluated with bias assessment tool recommended by Cochrane system evaluator manual 5.1.0. Meta-analysis， sensitivity analysis and publication bias analysis were conducted by using RevMan 5.4 software. RESULTS A total of 9 RCTs were included， involving 1 882 patients. The results of meta-analysis showed that： total response rate [OR＝1.94，95%CI（1.45，2.58），P＜0.000 01]， cure rate [OR＝2.27，95%CI（1.33，3.86），P＝0.003] and remission rate [OR＝1.81，95%CI（1.28， 2.55）， P＝0.000 7] of trial group were significantly higher than control group； there was no significant difference in the incidence of adverse drug events， diarrhea， nasopharyngitis， upper respiratory tract infection and alkaline phosphatase elevation between two groups （P＞0.05）. The results of subgroup analysis showed that cure rate of trial group was significantly higher than control group at 2 weeks of treatment （P＜0.05）； at 4 and 8 weeks of treatment， there was no significant difference in the cure rate between two groups （P＞0.05）. There was no statistically significant difference in the cure rate between two groups at 2， 4 and 8 weeks of treatment among the patients with Los Angeles grade A/B （P＞0.05）； among the patients with Los Angeles grade C/D， the cure rate of patients in the trial group was significantly higher than control group at 2， 4 and 8 weeks of treatment （P＜0.05）. The results of sensitivity analysis and publication bias analysis showed that the results of this study were robust and the possibility of publication bias was small. CONCLUSIONS Vonoprazan has a considerable effectiveness and safety in the treatment of gastroesophageal reflux disease.

Tacrolimus (FK506) is a 23-membered macrolide with immunosuppressant activity that is widely used clinically for treating the rejection after organ transplantation. The research on tacrolimus production was mainly focused on biosynthesis methods, within which there are still some bottlenecks. This review summarizes the progress made in tacrolimus biosynthesis via modification of metabolic pathways and control of fermentation process, with the hope to address the technical bottlenecks for tacrolimus biosynthesis and improve tacrolimus production by fermentation engineering and metabolic engineering.
Tacrolimus ; Immunosuppressive Agents ; Fermentation ; Macrolides ; Anti-Bacterial Agents

Objective:To analyze the clinical characteristics of necrotizing otitis externa(NOE) and to discuss its clinical staging and treatment.Methods:A retrospective case series study was conducted in the Otorhinolaryngology Head and Neck Surgery Center of Beijing Friendship Hospital. Patients hospitalized in our department with diagnosis of NOE between June 2015 to December 2021 were included. There were 23 patients (23 affected ears), with 19 males and 4 females, aged 32-85 years (the median age was 68 years old). We analyzed and summarized the main symptoms and signs, laboratory examinations, imaging examinations, treatments and prognosis of the patients, and established a database for data collection and sorting.Results:All the 23 patients had various complications. There were 19 cases of type 2 diabetes, 5 cases of anemia, 3 cases of hypoalbuminemia, 2 cases of chronic renal insufficiency, and 1 case of uremia. The main symptoms on admission were otalgia, otorrhea, hearing loss, angular deviation, limited mouth opening, dysphagia and hoarseness. Physical examination showed swelling of the external ear canal (EEC), granulation tissue of the EEC, thin purulent secretion of the EEC, facial paralysis, restricted mouth opening, and decreased vocal cord movement. Etiological results showed 15 cases of Pseudomonas aeruginosa, 5 cases of Staphylococci and 3 cases of Aspergillus fumigatus. Imaging mainly showed abnormal soft tissue shadows of the EEC and middle ear, and temporomandibular joint, parapharyngeal space, skull base, intracranial and other adjacent structures were involved according to the different invasion directions of the lesions. According to the characteristics of these patients, we summarized a diagnostic criteria and clinical staging. All patients received systematic anti-infection, surgery and symptomatic support treatment. Until January 30, 2022, 4 patients died, including 1 case of extensive intracranial infection caused by NOE, and 3 cases of other systemic diseases after the affected ears were recovered and discharged from hospital. The other 19 patients′ ears were cured, the symptoms of otalgia and otorrhea disappeared, and the epithelization of the surgical cavity was good. Conclusion:The clinical manifestations of NOE lack specificity, and the diagnosis should be made according to the medical history, physical examination and auxiliary examination. According to different clinical stages, corresponding treatment measures should be formulated. The treatment is based on multidisciplinary comprehensive treatment, mainly surgical treatment. Early intervention has a good prognosis, otherwise, multiple-group of cranial nerve injury or intracranial infection implies poor prognosis.

To investigate the mechanism of Shouwu Jiangzhi decoction in treatment of hyperlipidemia by suppress apoB-48 in small intestines, Golden Syrian hamsters were randomly devided into blank group, model group, fenobrate treatment group and Shouwu Jiangzhi decoction treatment group based on weight. The hyperlipidemia models of golden Syrian hamsters were induced by high fat diet(HFD)treatment for 4 weeks, then administered orally with drugs for 4 weeks. The serum indexes of HDL-C, LDL-C, TG and TC were determined by microplate methods, ELISA kits were used to evaluate the contents of serum TNF-α, apoB-48 and FFA. The protein expression levels of p38, ERK, JNK, SREBP, TNF-α and apoB-48 in small intestines were determined by Western blots. The results showed that Shouwu Jiangzhi decoction can effectively increase the serum HDL-C level and reduce the serum level of TG, LDL-C, TNF-α and apoB-48 in HFD-induced hamsters. Furthermore, Shouwu Jiangzhi decoction can significantly downregulate the protein expressions of p38, JNK, ERK, SREBP, TNF-α and apoB-48 in small intestines. Results above indicate that Shouwu Jiangzhi decoction may downregulate the protein expression of apoB-48 to treat hyperlipidemia via partially downregulating TNF-α/MAPK signal pathway.

By collecting relevant ancient literature, with retention of urine, umbilical therapy and Shenque (CV 8) as key words, various umbilical therapies for retention of urine from thedynasty todynasty were retrieved and summarized. The results indicated rich knowledge of umbilical therapy was recorded in ancient literature (thedynasty to thedynasty), including 9 kinds of therapies e.g. sticking umbilical method, ironing umbilical method, pasting umbilical method, smearing umbilical method, filling umbilical method, sealing umbilical method, covering umbilical method, dripping umbilical method and bundling umbilical method. Moreover, the detailed methods were briefly explained. It is hoped to provide reference for modern application of umbilical therapy for retention of urine.

BACKGROUND: Inert biomaterials such as metal usually hold poor biocompatibility and weak bonding force, which is against the effect of dental or bone implants. Therefore, how to improve their biocompatibility has become the research hotspot.OBJECTIVE: To prepare collagen-coated titanium alloy (Ti6Al4V), and to assess its biocompatibility.METHODS: Ti6Al4V served as the matrix, the 3-amino propyl triethoxy silane (KH550) as the crosslinking agent, and the three-dimensional printed titanium alloy coated by collagen type Ⅰ and Ⅱ was prepared,respectively. The coated materials were co-cultured with mouse preosteoblasts MC-3T3-E1 to evaluate its biocompatibility. The effect of different kinds of collagen on the cell differentiation was compared by differential recognition of surface proteins.RESULTS AND CONCLUSION: When the N content on the titanium alloy surface (Φ10 cm) was 8.41%, the cladding quantity of collagen type Ⅰ and Ⅱ was 0.81 and 0.77 mg, respectively. Compared with the bare titanium alloy, the cell adhered well and distributed extensively on the coated titanium alloy,which showed strong viability and fast proliferation.The cells cultured on collagen type Ⅰ coated materials expressed the proteins associated with matrix synthesis, and those on collagen type Ⅱ coated materials expressed the proteins associated with mineralization. These results clarify that the collagen coating can improve the biocompatibility of titanium alloy, and different types of collagens act on different functional proteins.

Objective: To investigate the relationship between serum levels of high sensitivity cardiac troponin T (hs-cTnT) and the severity of coronary lesions in patients with stable coronary artery disease (SCAD). Methods: A total of 450 SCAD patients with coronary angiography (CAG) conifrmed diagnosis in our hospital were studied, and serum levels of hs-cTnT were examined at 3 days prior CAG in all patients. Based on tertiles of Gensini score, the patients were divided into 3 groups: Low score group,n=153 patients with Gensini score<14, Intermediate score group, n=145 patients with Gensini score at 14-28 and High score group,n=152 patients with Gensini score>28. The relationships between Gensini score and hs-cTnT levels were analyzed among 3 groups. The optimal cut-off value of hs-cTnT for predicting high Gensini score and the need of revascularization were studied by ROC curve, the relationships between hs-cTnT and high Gensini score, the need of revascularization were further detected by Logistic regression analysis. Results: The median values (25%-75%) of hs-cTnT in Low score group, Intermediate score group and High score group were 6.72 (4.20, 8.93) pg/ml, 7.90 (5.74, 12.68) pg/ml and 14.99 (10.26, 24.30) pg/ml respectively, allP<0.01. ROC curve analysis indicated that the area under curve (AUC) of hs-cTnT for predicting high Gensini score was 0.837 (95% CI 0.803-0.874), for the need of revascularization was 0.772 (95% CI 0.728-0.817); the best cut-off value of hs-TnT for predicting high Gensini score was 10.04 pg/ml and for the need of revascularization was 8.56 pg/ml. Logistic regression analysis suggested that with adjusted age, gender, the history of hypertension, diabetes, smoking, blood levels of creatinine, LDL-C and hs-CRP, hs-cTnT was still an independent predictor for high Gensini score (OR=1.13, 95% CI 1.06-1.20,P<0.001) and for the need of revascularization (OR=1.19, 95% CI 1.14-1.24,P<0.001). Conclusion: Serum level of hs-cTnT has been related to severity of coronary lesions in SCAD patients, hs-cTnT might be used as one of the pre-operative predictor for severe coronary disease and for the need of revascularization.

A method for quantitation of collagen was established by detecting marker peptide with high performance liquid chromatography-mass spectrometry (HPLC-MS). Theoretical marker peptides were selected by sequence comparison. Bovine collagen type I was digested with trypsin. Marker peptides typical for collagen type I were identified with HPLC-MS. The relationship between the abundance of marker peptides and collagen concentration was established. The results show that GEAGPSGPAGPTGAR and the other 5 peptides showed high resolution during chromatographic separation and high signal intensity during MS analysis. Peptide signal intensity and collagen concentration showed a good linear relationship in the range from 0.1 to 3 mg/mL. Bovine tendon and collagen sponge were used as actual samples and collagen contents were determined as 90.2% and 93.4% respectively. Quantitation of marker peptides of collagen was a feasible method to identify and quantify collagens in medical device research and development.
Animals ; Cattle ; Chromatography, High Pressure Liquid ; Collagen Type I ; analysis ; Mass Spectrometry ; Peptides ; analysis