Objective:To investigate the diagnostic value of 99mTc-methylenediphosphonate(MDP) whole body bone scintigraphy in early brucellosis patients with bone and joint injuries. Methods:According to the Diagnosis for Brucellosis (WS 269-2019), combined with epidemiological history, clinical manifestations and serological tests, from November 2020 to April 2021, 15 early brucellosis patients (the course of disease was within 6 months) who had not received any drug treatment diagnosed at the Department for Brucellosis Prevention and Control, Qinghai Institute for Endemic Disease Prevention and Control were selected as the research subjects, and 99mTc-MDP whole body bone scintigraphy was performed on the patients to evaluate the images and analyze the pathological changes. Results:The 99mTc-MDP whole body bone scintigraphy of 15 patients with early brucellosis showed abnormalities, and the abnormal concentration of radionuclides mainly occurred in the 8th to 12th thoracic vertebrae (T8-12), the 1st to 2nd lumbar vertebrae (L1-2) and L4-5. Among them, the thoracic vertebrae abnormalities were T8, T9, T10, T11 and T12 in 1 case each; lumbar vertebrae abnormalities were 1 case of L1, 1 case of L2, 4 cases of L4, and 5 cases of L5. Conclusions:The 99mTc-MDP whole body bone scintigraphy is abnormal in patients with early brucellosis. Bone scintigraphy has certain value in the diagnosis of bone and joint injuries in patients with early brucellosis.

Objective:To observe multiple locus variable-number tandem repeat analysis (MLVA) typing of Brucella isolated from Himalayan marmot in Qinghai-Tibet Plateau of Qinghai Province, and to explore the relationship between the strains and strains previous isolated from Qinghai Province. Methods:Blood samples of Himalayan marmot were collected in Qinghai-Tibet Plateau of Qinghai Province from March 2019 to October 2020. Pathogens were isolated and cultured from Brucella antibody positive samples identified by using the rose bengal test (RBT). Conventional biological methods and molecular biological methods (BCSP31-PCR and AMOS-PCR) were used for strain identification. At the same time, MLVA method was used to genotype the isolated strains, and cluster analysis was used to analyze the genetic relationships between the strains based on the genotype of 70 Brucella isolated from different hosts in Qinghai Province. Results:A total of 1 466 blood samples of Himalayan marmot were collected from Qinghai-Tibet Plateau. Two strains of Brucella were isolated and cultured from 64 RBT-positive samples, named QH2013054 and QH2013062, respectively. They were identified as Brucella ovis biotype Ⅲ by conventional and molecular biological methods. The MLVA genotyping results showed that QH2013054 and QH2013062 were different at the Bru16 locus, indicating different MLVA genotypes. Cluster analysis showed that strain QH2013054 had the same MLVA genotype as 7 strains, among which 6 strains were from 3 farmers and 3 sheep from the same family in Gonghe County, and 1 strain was from a farmer in Menyuan Hui Autonomous County. The strain QH2013062 had the same MLVA genotype as 4 strains, including 3 strains from 3 farmers in Menyuan Hui Autonomous County and 1 strain from a farmer in Tu Autonomous County of Huzhu. Conclusions:The strains of Brucella isolated from Himalayan marmot in Qinghai-Tibet Plateau of Qinghai Province have the same MLVA genotype as some strains of Brucella isolated from humans and sheep in Qinghai Province. It is speculated that the host humans, sheep and Himalayan marmot in Qinghai-Tibet Plateau may have a common source of infection.

Objective:To master the epidemic trend of human brucellosis in Qinghai Province, so as to provide basis for scientific prevention and control of the disease.Methods:In 2019 and 2020, at the national and provincial brucellosis monitoring sites in Qinghai Province, a total of 18 counties (cities and districts, hereinafter referred to as counties), no less than 400 serum samples were sampled every year for brucellosis Rose-Bengal plate agglutination test (RBPT) and serum tube agglutination test (SAT), which would be tested and judged according to the criteria of "Diagnosis for Brucellosis" (WS 269-2019).Results:In 2019, a total of 1 612 people were monitored in national brucellosis monitoring sites, 93 were RBPT positive, 54 were SAT positive, 54 were diagnosed, and the prevalence rate was 3.35% (54/1 612). In 2020, 1 677 people were monitored in national brucellosis monitoring sites, 151 were RBPT positive, 80 were SAT positive, 80 were diagnosed, and the prevalence rate was 4.77% (80/1 677). There were significant differences in RBPT positive rate, SAT positive rate and prevalence rate among national monitoring sites between the two years (χ 2 = 12.52, 4.24, 4.24, P < 0.05). In 2019, a total of 6 043 people were monitored in provincial brucellosis monitoring sites, 128 were RBPT positive, 91 were SAT positive, 87 were diagnosed, and the prevalence rate was 1.44% (87/6 043). In 2020, 5 664 people were monitored, 108 were RBPT positive, 59 were SAT positive, 52 were diagnosed, and the prevalence rate was 0.92% (52/5 664). There was no significant difference in RBPT positive rate among provincial monitoring sites between the two years (χ 2 = 0.66, P = 0.416), and the differences in SAT positive rate and prevalence rate were statistically significant among provincial monitoring sites between the two years (χ 2 = 4.98, 14.57, P < 0.05). Conclusion:In 2019 and 2020, there are human brucellosis in national and provincial brucellosis monitoring sites in Qinghai Province.

Objective:To analyze the results of serum erythropoietin (EPO) in adults patients with Kaschin-Beck disease (KBD) in Qinghai Province.Methods:According to the "Diagnosis of Kaschin-Beck Disease" (WS/T 207-2010), by using clinical examination and X-ray, adults over 20 years old in KBD areas of Xinghai County and Guide County, Hainan Tibetan Autonomous Prefecture, Qinghai Province, were divided into KBD case group ( n = 109) and internal control group ( n = 95) in July 2019. At the same time, healthy people were selected as external control group ( n = 90) in Xunhua County. Then 2 ml fasting cubital venous blood was collected from the target population to separate serum. The serum EPO level was determined by enzyme-linked immunosorbent assay (ELISA). Results:There was no significant difference in age and sex ratio among the 3 groups ( F = 0.73, P = 0.484; χ 2 = 1.03, P = 0.611). There was significant difference in serum EPO levels among the 3 groups [KBD case, internal and external control groups: (30.74 ± 26.23), (19.73 ± 11.53) and (10.83 ± 4.48) U/L, F = 26.51, P < 0.001]. Multiple comparisons showed that there were statistically significant differences in serum EPO levels between KBD case group and the internal and external control groups ( P < 0.05), but there was no significant difference between the internal and external control groups ( P > 0.05). Conclusions:The serum EPO level in adult KBD patients in Qinghai Province is increased significantly.

Objective:Combined with the actual work requirements of brucellosis in Qinghai Province, to design a management information system for brucellosis patients, in order to realize the information of diagnosis and treatment of brucellosis patients.Methods:Based on the theory of management information system, according to the functional requirements of the actual work and performance parameters, the general framework of management information system was designed, the establishment of the management information system was gradually completed, and the system was improved through the system testing.Results:The system was easy to use and easy to operate, and patient's detailed information, diagnosis and treatment results and treatment plan could be obtained quickly. At the same time, follow-up, trace investigation, and brucellosis prevention and treatment propaganda could be carried out.Conclusions:The established brucellosis management information system can realize the electronic management of patient information, master the disease development and diagnosis and treatment results of brucellosis patients. Through follow-up investigation, the system can increase active screening and early warning of suspected cases, and provide health education to realize early diagnosis and early treatment of the patients.

Objective:To explore the efficacy and safety of intraoperative hyperthermic intraperitoneal chemotherapy combined with total laparoscopic D2 radical gastrectomy in the treatment of gastric cancer.Methods:The clinical data of 127 patients with gastric cancer who were admitted to the Central Hospital of Hanzhong in Shaanxi Province from August 2017 to July 2019 were retrospectively analyzed. All patients underwent total laparoscopic D2 radical gastrectomy, of which 58 patients underwent total laparoscopic D2 radical gastrectomy combined with intraoperative hyperthermic intraperitoneal chemotherapy (observation group), and 69 patients underwent total laparoscopic D2 radical gastrectomy (control group). Observation indicators included surgical and postoperative recovery situations and postoperative tumor-related indicators. Follow-up was performed by using outpatient examination and telephone interview, and the content of follow-up included patient's adjuvant chemotherapy, tumor recurrence and metastasis, and surgery-related complications.Results:In the observation group, the intraoperative blood loss was (199±48) ml, the number of lymph node dissection was 35±8, the total hospitalization cost was (53 261±4 316) yuan, alanine aminotransferase was (30±10) U/L, and creatinine was (124±26) μmol/L; in the control group, the intraoperative blood loss was (184±46) ml, the number of lymph node dissection was 34±13, the total hospitalization cost was (52 146±4 817) yuan, alanine aminotransferase was (31±10) U/L, and creatinine was (128±33) μmol/L; there were no significant differences between the two groups ( t values were 1.833, 0.618, 1.363, 0.721, and 0.856, all P > 0.05). In the observation group, the operating time was (352±44) min, carcinoembryonic antigen (CEA) at 1 month after operation was (3.9±2.1) ng/ml,CEA at 6 months after operation was (12.7±7.2) ng/ml, tumor abnormal protein (TAP) at 1 month after operation was (75±36) μm 2,TAP at 6 months after operation was (131±33) μm 2; in the control group, the operating time was (308±58) min,CEA at 1 month after operation was (8.3±4.5) ng/ml, CEA at 6 months after operation was (15.8±4.2) ng/ml, TAP at 1 month after the surgery was (88±24) μm 2, TAP at 6 months after operation was (149±37) μm 2; there were significant differences between the two groups ( t values were 4.792, 7.185, 2.832, 2.284, and 2.984, all P<0.05). One hundred and twenty seven patients were followed up for 12-24 months. Fifty-one and 58 patients in the observation group and control group received postoperative adjuvant chemotherapy, and there was no significant difference between the two groups ( χ2 = 0.389, P = 0.533). Tumor recurrence was respectively detected in 0 and 6 patients in the observation group and control group at 6 months after operation; tumor recurrence was respectively detected in 2 and 11 patients in the observation group and control group at 1 year after operation; the differences in the recurrence rates between the two groups were statistically significant (both P < 0.05). Conclusion:Intraoperative hyperthermic intraperitoneal chemotherapy combined with total laparoscopic surgery for gastric cancer does not increase the patient's perioperative risk and the incidence of postoperative complications, and it can reduce the risk of postoperative recurrence and improve the short-term efficacy.

Objective:To detect serum Col2-3/4 C-terminal cleavage product of type Ⅱ collagen (C2C) and pyridinoline (PYD) among brucellosis patients at early period, and to provide a better understanding of the changes of bone and joint collagen metabolism in the early stage of brucellosis.Methods:From 2013 to 2016, 61 cases of brucellosis patients at early period (within 6 months) from brucellosisout patient of Qinghai Institute for Endemic Disease Prevention and Control were selected as case group, and 67 cases of healthy volunteers were selected as control group. Serum C2C and PYD levels in all samples were measured simultaneously with enzyme linked immunosorbent assay (ELISA).Results:The median serum C2C of patients with early brucellosis was 83.45 ng/ml and that of the control group was 73.35 ng/ml. There was significant difference in serum C2C between the case group and the control group ( Z = 5.027, P < 0.05). The median serum PYD of patients with early brucellosis was 278.45 nmol/L and that of the control group was 212.75 nmol/L. There was significant difference in serum PYD between the case group and the control group ( Z = 6.967, P < 0.05). Conclusion:Serum C2C and PYD levels of brucellosis patients at early period are increased.

OBJECTIVE：To investigate th e stabilities of antitumor candid ate Gedatolisib in plasma in vitro and simulated gastric/intestinal fluids ，and to analyze the possible catabolites in plasma. METHODS ：HPLC method was adopted. Using indometacin as internal standard ，the contents of Gedatolisib incubated in plasma of SD rats （male）for 0，0.5，1.0，1.5，2.0，3.0 h and blank simulated gastric fluid （pH 1.3，no enzyme ），blank simulated intestinal fluid （pH 6.8，no enzyme ），simulated gastric fluid（pH 1.3，containing pepsin ）and simulated intestinal fluid （pH 6.8，containing trypsin ）for 0，0.5，1.0，2.0，3.0，4.0，6.0 h were determined. The remaining percentage of Gedatolisib was calculated. UPLC-Q-TOF/MS was used to analyze the TIC of blank plasma and incubated samples. The differential peaks were compared， and catabolites were inferred by MS 1Z073）.gzwjkj2019-1- chromatograms. RESULTS ： The remaining percentage in plasma of rats for 2.0 h was about 63％，and there was nosignificant change after continued incubation. The remaining percentage of Gedatolisib incubated in blank simulated intestinal fluid for different time ranged （99.18 ± 2.15）％ -（103.20 ± 3.41）％ . The remaining percentage in simulated com intestinal fluids for 2.0 h ranged （88.76 ± 1.53）％ . The remaining percentage in blank simulated gastric fluids for 2.0 h was ranged （85.63±1.55）％，and there was no significant change after continued incubation. The remaining percentage in simulated gastric fluid was from （94.94±3.52）％（0 h）to（16.19±1.17）％ （6.0 h）. TIC of UPLC-Q-TOF/MS showed that the differential peaks of incubated samples and blank plasma was 6.42 min under positive mode scanning ，molecular ion peak of m/z 616.335 1，simulated 632.327 7，630.317 0，602.278 6 [M+H]+ could be found in scanning channel. It was speculated that Gedatolisib could generate 1-（4-（3-（4，6-dimorpholino-1，3，5-triazin-2-yl）phenyl）urea） benzoyl）-N，N-dimethylpiperidin-4-amine oxide ，1-（4-（4-（dimethylamino）piperidine-1-carbonyl）phenyl）-3-（4-（4-morpholino-6- （3-oxomorpholino）-1，3，5-triazin-2-yl）phenyl）urea and 1-（4-（3-（4-（4，6-dimorpholino-1，3，5-triazin-2-yl）phenyl）urea） benzoyl）-N-methylpiperidine. CONCLUSIONS ：Gedatolisib is not stable in rat plasma ，and it may undergo terminal N oxidation， morpholine ring oxidation and terminal N demethylation. Gedatolisib is stable in artificial intestinal fluid and blank artificial gastric/ intestinal fluid ，and degrades obviously in the presence of pepsin.

OBJECTIVE： To design and synthesize N-aroyl substituted indoline-3-acetic acid derivatives and evaluate their in vitro hypoglycemic activity. METHODS： Using indoline derivative 2-[5-（benzyloxy）-1-（4-chlorobenzoyl）-2-methyl-1H-inclol-3-yl]acetic acid （GY3） as leading compound， 4-（benzyloxy）phenyl hydrazine hydrochloride and methyl 4-oxopentanoate as raw material， 8 kinds of N-aroyl （3-hydroxybenzoyl， 3-cyanobenzoyl， 4-nitrobenzoyl， 4-methylsulfonylbenzoyl， 4-acetamidobenzoyl， 3-acetylaminobenzoyl， isoniacyl and pyridine-2-formyl） substituted indoline-3-acetic acid derivatives were synthesized via 4 steps reactions： Fischer indole cyclization， reduction， amidation and hydrolyzation. The human hepatoma HepG2 cell lines were used to investigate the glucose consumption activity of the target compounds. RESULTS： Totally 8 various N-aroyl substituted indoline-3-acetic acids were synthesized and their structures were confirmed by mass spectrum（MS）， nuclear magnetic resonance 1H-NMR and 13C spectrum. Under the condition of 1.0 μmol/L， the percentage of glucose- promoting consumption of the synthesized compounds on HepG2 cells was 5.4％-9.1％. 2-[（2R， 3S）-5-benzyloxy-2-methyl-1-（4-methylsulfonyl benzoyl）-2，3-dihydro-indole-3-yl] acetic acid showed the best hypoglycemic activity. The percentage of glucose- promoting consumption was （9.1±1.81）％， which was close to that of positive control metformin [（10.58±1.68）％]， but less potent than that of leading compound GY3[（12.15±0.78）％]. CONCLUSIONS： Different electron-withdrawing substituents are introduced into N-aroyl aromatic rings of dihydroindole compounds， such as cyano， nitro， methyl sulfonyl； hypoglycemic activity decreases in varying degrees and is weaker than halogen substituents.