We reported a case of polyglandular syndrome induced by programmed death-1(PD-1) inhibitors. The patient was a 51-years-old male with non-small cell lung cancer, treated with PD-1 inhibitor nivolumab/pembrolizumab because of postoperative subcarinal lymph node metastasis indicated by PET-CT. During 14 cycles of PD-1 inhibitor treatment, the patient successively developed primary hypothyroidism, and type 1 diabetes mellitus(T1DM). More than five months after the withdrawal of pembrolizumab, the patient experienced recurrentce. Laboratory examinations showed mild hyponatremia and hypopituitarism including ACTH and growth hormone(GH)/insulin-like growth factor-1(IGF-1) insufficiency. This is the first report of a patient diagnosed as polyglandular syndrome caused by PD-1 inhibitor. In particularly, the hypothyroidism and T1DM did not improve after drug withdrawal, while hypopituitarism was further aggravated. This case reminds us that we should pay more attention to the changes of endocrine function during and after the treatment of PD-1 inhibitor, so that we can make the correct diagnosis and take proper medical measures timely, to avoide missed diagnosis, and improper treatment.

With the development of molecular biology, biomaterials and tissue engineering, regenerative treatment of pulpal and periradicular diseases is facing new opportunities. At present, a large number of studies on dental pulp regeneration reveal that cytokines are essential for promoting migration, proliferation and osteogenic differentiation of dental pulp stem cells. In this paper, we review several kinds of cytokines related to dental pulp regeneration, and analyze their roles and regulatory mechanisms in dental pulp regeneration.

BACKGROUND: There is no report on the treatment of suppurative discitis with posterior microendoscopic discectomy, antibiotic artificial bone implantation and one-stage percutaneous pedicle screw fixation. OBJECTIVE: To evaluate the clinical effectiveness of posterior microendoscopic debridement, antibiotic artificial bone implantation and one-stage percutaneous pedicle screw fixation for pyogenic spondylodiscitis. METHODS: Thirty-one patients with suppurative discitis admitted at the Department of Spinal Surgery, the First Affiliated Hospital of Guangzhou Medical University from January 2014 to December 2017, including 17 males and 14 females, aged 28-78 years, were included. All the patients underwent posterior microendoscopic lesion clearance and antibiotic artificial bone grafting and one-stage percutaneous pedicle screw fixation. The erythrocyte sedimentation rate and C-reactive protein levels were detected at postoperative follow-up. The Visual Analog Scale and the Japanese Orthopaedic Association scores were used for detection. RESULTS AND CONCLUSION: (1) All the surgical operations of the 31 patients were successfully completed and all patients had immediate relief of low back pain and lower extremity radiation pain. They were able to move ground wearing a waistband at 1-4 days postoperatively. (2) Thirty-one patients were followed up for 9-18 months. All patients had a significant decrease in C-reactive protein and erythrocyte sedimentation rate at 1 week after surgery, and C-reactive protein and erythrocyte sedimentation rate were in the normal range at 1, 3, and 6 months postoperatively. (3) The Visual Analog Scale scores of all patients at 1 week of follow-up were significantly lower than those before surgery (P < 0.05) , and the Japanese Orthopaedic Association scores were significantly higher than those before surgery (P < 0.05) . (4) In the follow-up examination of CT and MRI, there was no recurrence, pseudoarticular formation or internal fixation loosening. (5) These results suggest that posterior microendoscopic discectomy, antibiotic artificial bone implantation combined with one-stage percutaneous pedicle screw fixation for treating suppurative discitis can result in little trauma, few bleeding and rapid pain relief, and patients can move to the ground early. The operation method has a good clinical effect.

Objective:To study the medication rules of treating cervical spondylosis by National TCM master Liu Bailing based on data mining and network pharmacology, and explore the potential action mechanism of its core compounds.Methods:By collecting the prescriptions of National TCM master Liu Bailing treating cervical spondylosis in the past 8 years, this paper analyses the frequency, nature, flavor, meridian, hierarchical clustering and association rules of those prescriptions by RStudio to obtain the core prescription. Then, the effective components of the core prescription were collected by using TCMSP, and the network of "medicine-component-target" was constructed by using Cytoscape 3.8.0; by searching for databases like GEO, DisGeNET, TTD HPO and Genecards were retrieved to obtain the target data set of cervical spondylosis; by using STRING 11.0 platform to construct protein interaction network; by using DAVID platform to cary out gene ontology (GO) and KEGG pathway enrichment analysis; by using Auto Dock software for molecular docking.Results:In the 844 prescriptions, there are 199 Chinese medicines and the properties are mainly warm, plain and cold; the flavors were mainly sweet, pungent and bitter; mainly belong to the liver, spleen, and kidney meridians. The Association Rule shows that the core compound is made up of Salvia miltiorrhiza, Gastrodia elata, Rhizoma corydalis, Alisma rhizoma, centipede, Astragalus membranaceus and Rhizome of Pueraria. Besides, 140 effective constituents and 247 targets of the core prescription were screened, and the main constituents were quercetin, kamanol, luteolin, tanshinone ⅡA, β-sitosterol, etc. 13 core targets among the core prescription treating cervical spondylosis were obtained, which were enriched into 30 pathways including toll-like receptor signaling pathway, TNF signaling pathway and HIF-1 signaling pathway. Conclusion:National TCM master Liu Bailing treatment of cervical spondylosis mainly focuses on expelling wind and relieving pain, dredging meridians and soothing tendons, and the mechanism of action of the core prescription may focus on inhibiting inflammatory response and relieving oxidative stress, providing guidance and reference for the clinical treatment of cervical spondylosis.

Objective To report a case of Costello syndrome complicated by curis laxa,and to make a molecular genetic diagnosis.Methods Clinical data were collected from a case of Costello syndrome complicated by cutis laxa.Skin tissues were resected from the patient,and peripheral blood samples were obtained from the patient's parents and 150 unrelated healthy controls.Genomic DNA was extracted from these samples,and all the exons and their flanking sequences of the HRAS gene were analyzed by DNA sequencing.Results The 13-month-old female patient presented with growth retardation,severe malnutrition,coarse facial appearance,severely loose skin over the limbs,and decrease or disappearance of subcutaneous fat.A heterozygous mutation c.34G ＞ T (p.Gly12Cys) was detected in exon 2 of the HRAS gene in the patient,but not in her parents or 150 unrelated healthy controls.Conclusion The c.34G ＞ T (p.Gly12Cys) mutation in exon 2 of the HRAS gene may be responsible for Costello syndrome in the patient.

Objective To compare the efficacy and safety of the long-term intermittent maintenance treatment with tacrolimus 0.03％ ointment versus traditional treatment in reducing relapses and prolonging the recurrence interval in children with moderate to severe atopic dermatitis (AD).Methods A two-phase randomized,open-labelled,controlled clinical trial was conducted from September 2012 to November 2013.In the first phase,a total of 171 children aged 2-15 years with moderate to severe AD were enrolled from 7 hospitals in China,and received conventional treatment with tacrolimus 0.03％ ointment twice a day for 2-6 weeks.At the end of the treatment,the patients who achieved an investigator's global assessment (IGA) score ≤ 2 (n =125) were randomly classified into 2 groups to receive the second-phase treatment:test group (n =62) receiving intermittent maintenance treatment with tacrolimus 0.03％ ointment twice a week (Monday and Thursday),and control group (n =63) receiving no treatment.If the patients in the 2 groups experienced relapse,they received conventional treatment with tacrolimus 0.03％ ointment twice a day.The overall observation period was 6 months.The primary endpoint was the time to the first relapse,which was defined as the number of days from the end of the first-phase treatment to the first relapse.The secondary endpoints included the number of relapses at the second-phase trial,the disease severity at the time of relapse,the duration of relapse,the pruritus score at the time of relapse,the total amount of tacrolimus ointment used,the total response rate at the second-phase trial,and the incidence of adverse events.Results A total of 125 children with AD were enrolled into the second-phase trial,and 121 of them completed the follow-up.Among the 121 patients,the recurrence rate was significantly lower in the test group (25/60,41.7％) than in the control group (46/61,75.4％;x2 =14.20,P ＜ 0.001).The time to the first relapse was significantly longer in the test group (46.9 ± 37.7 d) than in the control group (28.8 ± 32.3 d;Z =1 093.50,P =0.020).The total number of recurrence was 31 and 86 in the test group and control group respectively,and the mean number of recurrence in each patient was significantly lower in the test group (0.52 ± 0.68) than in the control group (1.41 ± 1.23,t =4.96,P ＜ 0.001).There were no significant differences between the two groups regarding disease severity during relapse (eczema area and severity index:Z =971.50,P =0.39),duration of relapse (Z =747.00,P =0.07),and pruritus score during relapse (Z =894.00,P =0.95).The therapeutic drug was tolerated well in all the children,and no tacrolimus-related serious adverse events occurred.Conclusion The intermittent maintenance treatment with tacrolimus 0.03％ ointment twice a week for 6 months can effectively and safely prevent and reduce relapses,and prolong the recurrence interval in children with moderate to severe AD.

Objective:To compare the embedding anastomosis with the intermittent eversion anastomosis on the pancreatic fistula rates after laparoscopic pancreaticoduodenectomy (LPD).Methods:The clinical data of 116 patients who underwent LPD at the Center Hospital of Xianyang City affiliated to Xi' an Jiaotong University Health Science Center from March 2016 to March 2020 were retrospectively studied. According to the method of pancreaticojejunostomy used, these patients were divided into the following two groups: the embedding anastomosis group ( n=55) and the intermittent eversion anastomosis group ( n=61). The duration of pancreaticojejunostomy, bilioenterostomy and gastrointestinal anastomoses, and the amounts of intraoperative blood loss and postoperative complication rates were compared between the two groups. Results:Of 116 patients in this study, there were 67 males and 49 females, with a median age of 61.5 years. No perioperative death occurred in the 2 groups. The operation time, digestive tract reconstruction time and pancreaticojejunostomy time in the embedded anastomosis group were (260±20), (65±15) and (35±15) min, respectively, which were significantly lower than those in the intermittent eversion anastomosis group (305±25), (81±25) and (45±12) min, (all P<0.05). The grade A and B pancreatic fistula rates in the embedded anastomosis group were 27.3%(15/55) and 21.8%(12/55), respectively, which were significantly higher than those in the intermittent eversion anastomosis group [8.2%(5/61) and 6.6%(4/61)], (all P<0.05). The postoperative hospital stay in the intermittent eversion anastomosis group (10.3±1.1) d was significantly lower than that in the embedding anastomosis group [(15.2±3.2) d, P<0.05]. Conclusion:In LPD, when compared with embedded pancreaticojejunostomy, intermittent eversion pancreaticojejunostomy reduced the postoperative pancreatic fistula rate and shortened the postoperative hospital stay.

Objective:To study the influence of intensive magnet fields on radiation dose measurement, and to demonstrate the feasibility of measuring magnet field correction factor by a combination of medical linac with variable magnet fields in view of needing for accurate measurement of the doses from reference beam arising in MR image-guided radiotherapy.Methods:A photon radiation field and a variable field with 6 MV nominal high voltage were produced by using conventional medical electron linear accelerator equipped with a pair of electromagnets with magnetic field strength up to 1.5 T. Both PTW30013 and PTW31010 ionization chambers were used to test the responses of ionization chambers under different magnetic field strengths at four orientations in which the angles between ionization chamber axis and magnetic field direction were 0°, 180°, 90° and 270°, respectively. The magnetic factors, kB, M was calculated and compared with the reported values in literature. Results:The response of ionization chamber was proportional to the magnetic field strength before it reached to a peak around 1 T, and then fell down as the magnetic field continued to rise. When the magnetic field was 0.35 T, the magnetic factors of PTW31010 were 0.988 2±0.000 3 and 0.997 4±0.000 4 corresponding to 90° and 0° directions, the discrepancy between 0° scenario and literature was 0.05% ± 0.04%. When the magnetic field reached 1.5 T, the magnetic factor of PTW30013 was 0.958 9±0.000 5 at the situation of 90°, which was 0.60% ± 0.05% different from the literature value.Conclusions:Conventional 6 MV medical accelerator equipped with electromagnet can be used to measure the magnetic field factor of reference dosimetry for MRIgRT.

Objective:To evaluate the efficacy of total laparoscopic surgery vs. open surgery for hilar cholangiocarcinoma. Methods:The clinical data of 45 patients undergoing laparoscopic radical resection of hilar cholangiocarcinoma and 42 patients by open surgery from Mar 2017 to Mar 2021 were retrospectively analyzed.Results:There was no significant difference in demographics, Bismuth classification and excision extension between the two groups (all P>0.05). The laparoscopic surgery used longer time ( t=-1.366, P<0.05). The intraoperative blood loss, number of lymph node dissection and postoperative hospital stay favored laparoscopic method( t=0.043, t=0.026, t=-1.852, P<0.05). R 0 radical resection rate，postoperative complications were also in favor of laparoscopic surgery ( χ2=3.216, χ2=2.566, all P<0.05). There was no significant difference in postoperative pathology and in hospital expenses (all P>0.05). The 1- and 3-year survival rate of the laparoscopic group was superior (all P<0.05). Conclusions:In spite of longer operational time，patients in laparoscopic hilar cholangiocarcinoma radical resection group have shorter postoperative in hospital stay and longer postoperative survival time.

Child, Preschool ; Ethnic Groups ; Female ; Humans ; Male ; Pedigree ; beta-Thalassemia ; genetics