Xanthine oxidase (XO) is an important therapeutic target for the treatment of hyperuricemia and gout. Based on the previously identified potent XO inhibitor 1, seventeen oxadiazoles and their ring-opening analogues were designed and synthesized via the bioisostere replacement strategy. Among them, compounds 2l, 2n, and 3b showed obvious XO inhibitory activity at the concentration of 10 μmol·L^-1, and compound 3b exhibited an IC₅₀ value of 1.45 μmol·L^-1.

Objective To study the application value of different transbronchial biopsies in the diagnosis of central lung cancer in elderly patients.Methods The clinical data of 97 elderly patients with central lung cancer diagnosed by pathology from June 2020 to June 2023 in the 923rd Hospital of Chinese People's Liberation Army Joint Logistic Support Force were retrospectively analyzed.According to the different initial transbronchial biopsy methods,the patients were divided into the endobronchial biopsy(EBB)group(n=51)and the conventional transbronchial needle aspiration(cTBNA)group(n=46).The histopathological results were statistically analyzed,and the first biopsy positive rates of EBB and cTBNA in the diagnosis of senile central lung cancer were calculated and compared.At the same time,the differences of biopsy tolerance and complications between the two groups were evaluated.Results The squamous cell carcinoma proportions in both groups were over 50%.There was no significant difference in the first biopsy positive rate between the two groups(P>0.05).The incidence of temporary retreat of the scope due to subjective tolerance in the EBB group was higher than that in the cTBNA group,and the difference was statistically significant(P<0.05).There was a statistically significant difference in the incidence of intraoperative complications of different grades between the two groups(P<0.001).Among them,the incidence of grade 2 and above complications during surgery in the EBB group was significantly higher than that in the cTBNA group(P<0.001).Conclusion For elderly patients with central lung cancer,the success rate of the first biopsy of EBB and cTBNA is roughly equivalent,but the incidence of postoperative complications of the latter is significantly lower than that of the former.cTBNA can be used as the first biopsy method for this population.

OBJECTIVES: To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients. METHODS: A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed. RESULTS: An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048). CONCLUSIONS Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).
Administration, Inhalation ; Adult ; China ; Coronavirus Infections ; diagnosis ; drug therapy ; mortality ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Integrative Medicine ; Interferon-alpha ; administration & dosage ; Lopinavir ; administration & dosage ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; diagnosis ; drug therapy ; mortality ; Risk Assessment ; Severe Acute Respiratory Syndrome ; diagnosis ; drug therapy ; mortality ; Severity of Illness Index ; Survival Rate

Background: The effect of short-segment decompression/fusion versus long-segment decompression/fusion and osteotomy for Lenke-Silva type VI adult degenerative scoliosis (ADS) has not been clarified. This study aimed to compare the clinical and radiographic results of short-segment fusion vs. long-segment fusion and osteotomy for patients with Lenke-Silva type VI ADS. Methods: Data of 28 patients who underwent spinal surgery for ADS from January 2012 to January 2014 in the General Hospital of Northern Theater Command were reviewed. Of the 28 patients, 12 received long-segment fusion and osteotomy and 16 received short-segment fusion. Radiographic imaging parameters and clinical outcomes, including the sagittal vertical axis (SVA), lumbar lordosis (LL) angle, pelvic tilt (PT), sacral slope (SS), the visual analog scale (VAS), Japanese Orthopedic Association (JOA), Oswestry disability index (ODI), and lumbar stiffness disability index (LSDI) scores, were recorded. The difference between groups was compared using the dependent t test or Chi-squared test. Results: The Cobb and LL angles and SVA improved in both groups; however, PT and SS angles did not improve following short fusion. There were significant differences in the post-operative SVA (26.8 ± 5.4 mm vs. 47.5 ± 7.6 mm, t = -8.066, P < 0.001), PT (14.7 ± 1.8° vs. 29.1 ± 3.4°, t = -13.277, P < 0.001), and SS (39.8 ± 7.2° vs. 26.1 ± 3.3°, t = 6.175, P < 0.001) between the long and short fusion groups. All patients had improved ODI, JOA, and VAS scores post-operatively (all P < 0.001), with no significant difference between the groups (all P > 0.05). The post-operative LSDI score was 3.5 ± 0.5 in the long fusion group, which was significantly higher than that of the short fusion group (1.4 ± 0.7; P < 0.001). Conclusions The clinical outcomes of patients with Lenke-Silva type VI ADS who underwent short-segment decompression/fusion were comparable to those of patients who underwent long-segment decompression/fusion and osteotomy despite poor correction of sagittal imbalance. Moreover, short-segment decompression/fusion showed a short operation time and reduced surgical trauma.

Aim To investigate the effect of adenosine on the autophagy and proliferation of hepatocellular carcinoma cells, and improve the curative effect of a-denosine on hepatocellular carcinoma. Methods HepG2 cells were incubated with adenosine, CCK-8 method was used to study the changes of cell prolifera-tion,Western blot was used to study the expression of LC3-Ⅱ and LC3-Ⅰ, and MDC staining was used to observe the number of autophagosomes. Results HepG2 cells were incubated with adenosine(1.0~4.0 mmol·L-1) for 48 h,the proliferation of HepG2 cells were detected at the different time points (12,24,48 h),and the result showed the proliferation was signifi-cantly inhibited by adenosine (P < 0.01). HepG2 cells were incubated with adenosine (0.2,0.5,1.0, 2.0,4.0 mmol·L-1) for 24 h,the ratio of LC3-Ⅱ/LC3-Ⅰ decreased significantly in low concentration of adenosine group (0.2, 0.5 mmol·L-1, P <0.05;1.0 mmol·L-1,P<0.01),and the ratio of LC3-Ⅱ/LC3-Ⅰ increased significantly in higher concentration of adenosine group (4.0 mmol·L-1, P <0.05). HepG2 cells were incubated with adenosine(1.0 mmol·L-1) for 24 h, the ratio of LC3-Ⅱ/LC3-Ⅰ de-creased significantly at 6,12 and 24 h detecting point, the number of autophagosomes were reduced, the low-est ratio of LC3-Ⅱ/LC3-Ⅰ and autophagosomes were observed at 12 h detecting point(P<0.01). Conclu-sions Adenosine inhibits the proliferation of hepato-cellular carcinoma cells,the low concentration of aden-osine inhibits the autophagy,while the high concentra-tion of adenosine increases the autophagy, which is of great significance to reduce multi-drug resistance and improve the therapeutic effect of anti-hepatoma drugs.

Purpose To investigate the clinical manifesta-tions and morphologic features of placental site nodules (PSNs), and its clinical significance. Methods Twenty patients diag-nosed as PSNs were collected, then a retrospective analysis was conducted, and the characteristics of clinical data and follow-up results were analyzed,including of clinical manifestations, ultra-sonographic evaluation, morphologic and immunohistochemical features. Results The age of patients ranged from 25 to 41 years (32. 48 ± 4. 77 years in average). Three fifths of patients had pregnancy history for at least two times and the interval time to the last pregnancy ranged from 5 to 37 months (15. 33 ± 8. 05 months on average). 15 (75% ) patients went to the hospital because of abnormal vaginal bleeding. In our study, most of the samples showed a membrane-like structure without definite nod-ule. Microscopically, single or multiple, well-circumscribed and oval small nodules were found in endometrial tissue. In most ca- ses, the hyalinization was generally uniform in the center of the nodules, more or less intermediate trophoblasts appeared on the edge of the nodules. Immunohistochemically, the strong diffuse expressed CK (AE1/AE3), CAM5. 2, EMA, GATA-3, Cyclin E and p63 were detected in most of all cases, and PLAP showed strong focal expression, α-inhibin and hPL showed faint focal expression, Ki-67 staining for proliferative index was less than 4% . Conclusion PSN is a benign lesion of the intermediate trophoblast at the chorionic leave. Some diseases including hya-linized decidua, epithelioid trophoblastic tumor, and squamous cell carcinoma with hyalinization need to be identified. Some im-munohistochemical markers may be certain helpful in distinguis-hing as necessary.

Objective: To analyze clinical features and prognosis of hepatocellular carcinoma (cHCC) patients after liver resection, so as to clarify the prognostic risk factors. Methods: We retrospectively reviewed the data of patients who underwent mesohepatectomy for cHCC at Tianjin Medical University Cancer Hospital and Chinese Academy of Medical Sciences Cancer Hospital between October 2006 and December 2014. The patients were assigned into three subgroups according to disease-free survival (DFS): high risk (DFS≤1 year), middle risk (1 year3 years). Clinicopathological characteristics were compared and prognostic factors were evaluated using univariate and multivariate analyses. Results: In total, 173 patients were reviewed. The median overall survival (OS) in the high-risk group was 13.5 months compared with 24.0 months in the middle-risk group and 45.5 months in the low-risk group. Univariate analysis showed that liver capsule invasion (P=0.022), tumors adjacent to major vascular vessels (<1 cm) (P<0.01), HCC size>50 mm (P=0.012), presence of microvascular invasion (P<0.001), tumor invasive growth (P<0.001), and preoperative transarterial chemoembolization (TACE; P=0.028) were significant risk factors for recurrence. The main risk factors for OS were male gender (P=0.013), alpha-fetoprotein >200 ng/mL (P=0.005), tumor size >50 mm (P=0.013), adjacent to major vascular vessels (P<0.001), high Edmondson-Steiner differentiation grade (P=0.003), preoperative TACE (P=0.010), and tumor invasive growth (P=0.001). Cox multivariate analysis demonstrated that tumors adjacent (<1 cm) to major vascular trunks and tumor invasive growth were inde-pendent prognostic factors for both DFS and OS. In total, 40.5% patients in the high-risk group had both risk factors; this percentage was 13.4% in the middle-risk group and 3.1% in the low-risk group (P=0.001). A prognostic model including the above 9 factors were created based on Logistic regression to predict the percentage of patients belonging to the high-risk group. The results showed that the prediction accuracy continued to increase with the number of more factors added. When all the 9 factors were included, the pre-dictive percentage was 82.1%. Conclusions: cHCC patients in the high-risk group had more risk factors than those in the middle-and low-risk groups. A prognostic model containing these factors may provide accurate prediction of survival or risk stratification, and cHCC patients with these risk factors should be candidates for aggressive following-up and adjuvant therapy.

Objective:To evaluate the effects of individual extralevator abdominoperineal excision (ELAPE) of rectal neoplasms in the low posterior wall on the pelvic floor by finite element analysis. Methods:MIMICS 10.01, Geo Magic Studio 12, and ANSYS Workbench 14.0 were used to analyze the magnetic resonance data obtained from the pelvic region of 27 healthy nulliparous volunteers. Three types of finite element models (intact model, ELAPE model, and individual ELAPE model) were developed. The maximal stress on non levator ani tissues were analyzed using the three models, while the maximal stress on levator ani tissues were analyzed using the in-tact model and the individual ELAPE model. Their stress distributions under the same pressure were analyzed and compared. Results:The maximal stress on non levator ani tissues obtained using the intact model, ELAPE model, and individual ELAPE model were (1.963± 0.061), (5.127 ± 0.070), and (3.667 ± 0.126) MPa, respectively, with P<0.01. High-stress zones were obtained at the joints with pelvic walls on both sides using the three models, while the maximal stresses were obtained at the joints with pubis on both sides. The maxi-mal stress on levator ani tissues obtained using the intact model and individual ELAPE model were (0.812 ± 0.042) MPa and (1.437 ± 0.043) MPa, respectively. Thus, the individual ELAPE model yielded higher values of maximal stress compared to the intact model. Both models generated high-stress zones at the joints with tendinous arch of levator ani tissues on both sides, and maximum stresses at the joints with pubis on both sides. Conclusion:Individual ELAPE decreases the stress on non levator ani tissues. This suggests that the risk of postoperative pelvic floor hernia is relatively reduced.

Medical care on the battlefield is the core and basis of echelons of care.This review summarizes the background and characteristics of medical care units on the battlefield from the birth and growth of mobile army surgical hospitals before being replaced by forward surgical teams and combat support hospitals, since the United States Armed Forces began to lead the world military revolution during and after the World WarⅡ.Quick adaptation to the combat envi-ronment and the combat modes is the main reason that medical care units on the battlefield are adjusted continuously.This paper may provide some ideas for the development of our medical care units on the battlefield in the future.

OBJECTIVETo investigate the correlation between nurse job burnout and salivary lysozyme activity.

METHODSThe saliva samples of 131 subjects were collected at four time points for two consecutive days with saliva collection tubes. The acquisition time points were 8:00 (baseline concentration), 10:00 (morning), 15:30 (afternoon), and 17:30 (recovery period). At the same time every subjects completed the job burnout questionnaire to investigate their general demographic characteristics and job burnout level. The salivary lysozyme concentration was measured with ELISA. The data were analyzed by partial correlation analysis and multiple stepwise regression analysis.

RESULTSThere were significant differences in the salivary lysozyme activity between subjects with different ages, working years, and education levels. The work period vitality and the average energy of ≤ 30 age group were higher than other two groups and the recovery energy was higher than >35 age group. Working period vitality, the average energy of group >15 years were less than ≤ 10 years group. The work period energy and the average energy of university (college) and above group were lower than high school (secondary) and the following group. Job burnout and its three dimensions had a significant negative correlation with salivary lysozyme concentration (P < 0.01). Depersonalization and emotional exhaustion were the negative impact factors for salivary lysozyme activity at baseline. Emotional exhaustion and personal fulfillment were the negative impact factors for salivary lysozyme activity during the working period. Personal fulfillment was the negative factor for salivary lysozyme activity during the recovery period and the average salivary lysozyme activity.

CONCLUSIONSalivary lysozyme activity is sensitive for nurse job burnout, so it can be used as an objective evaluation index of job burnout.

Burnout, Professional ; epidemiology ; psychology ; Emotions ; Fatigue ; Humans ; Muramidase ; analysis ; Nurses ; psychology ; Occupational Diseases ; epidemiology ; psychology ; Regression Analysis ; Salivary Proteins and Peptides ; analysis ; Surveys and Questionnaires