Bone organoids can simulate the complex structure and function of the bone tissues, which makes them a frontier technology in organoid researches. Bone organoids show a tremendous potential of applications in bone disease modeling, bone injury repair, and medicine screening. Although advancements have been made so far in constructing bone organoids with functional structures like mineralization, bone marrow, trabecular bone, callus, woven bone, etc, the researches in this field are confronted with numerous challenges such as lack of standardized construction strategies and unified evaluation criteria, which limits their further promotion and application. To standardize researches in bone organoids, the Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, the Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, the Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and the Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine organized related experts to formulate Expert consensus on the construction, evaluation, and application of bone organoids ( version 2024) based on an evidence-based approach. A total of 17 recommendations were put forth, aiming to standardize researches and clinical applications of bone organoids and enhance their value in scientific research and clinical practice.

Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.

Objective To investigate the effect of Kunxian capsule combined with candesartan axetil on blood pressure, renal function, blood lipids and inflammatory factors in patients with chronic glomerulonephritis complicated with hypertension. Methods 101 patients with chronic glomerulonephritis who were admitted to our hospital from November 2017 to December 2019 were selected and randomly divided into observation group (51 cases) and control group (50 cases). The control group was treated with candesartan cilexetil on the basis of conventional treatment, and the observation group was treated with Kunxian capsule on the basis of the control group. The clinical efficacy and adverse reactions of the two groups were compared. Results The total effective rate of the observation group was significantly higher than that of the control group (P<0.05). After treatment, the blood pressure, renal function indexes (24 h Upro, BUN, Scr), blood lipid indexes (TG, TC, LDL-C), and inflammatory factors of the two groups (IL-6, hs-CRP) significantly decreased, and the observation group was significantly lower than the control group (P<0.05). After treatment, the blood lipid index HDL-C of the two groups increased significantly, and the blood lipid index HDL-C of the observation group was significantly higher than that of the control group (P<0.05). Conclusion Kunxian capsule combined with candesartan axetil can enhance the clinical efficacy, improve renal function, regulate blood lipids and reduce inflammation in patients with chronic glomerulonephritis complicated with hypertension.

As a non-physiological way of ventilation, mechanical ventilation has a great effect on the respiratory mechanics. The biggest problem of artificial airway is that it brings extra airway resistance to the respiratory tract. For different parts of the lung, positive pressure ventilation could cause different mechanic states. We can find the formation and influencing factors of transpulmonary pressure, transchest wall pressure, trans-lung-chest pressure, trans-diaphragmatic pressure, trans-pulmonary-diaphragmatic pressure, intrapleural pressure, plateau pressure and driving pressure, by analyzing the mechanic state in a unit area of the chest or diaphragm position in the way of basic mechanics. It is obviously different in the pulmonary pressure gradient caused by inspiratory driving between in spontaneous breathing and in mechanical ventilation. The pressure is transmitted from the periphery to the center in spontaneous breathing in physiological state, playing a traction role for lung tissue. The pressure is transmitted from the center to the periphery in positive pressure ventilation without spontaneous breathing, playing a pushing role for lung tissue. It can be divided into two stages in positive pressure ventilation with spontaneous breathing. The first stage is from inspiratory trigger effort to trigger sensitivity. It is similar to spontaneous inspiration in physiological state. The pressure gradient in this stage is from the peripheral to center. But the period is very short. The second stage is the positive pressure ventilation progress after the trigger sensitivity. The pressure gradient is caused by the pulling of the patient's spontaneous inhalation and the pushing of the positive pressure ventilation of the ventilator. There is a certain complementarity in the distribution and transmission of pressure, especially for non-physiological positive pressure ventilation. Therefore, through these basic mechanical analysis, clinical medical staff can better understand the impact of mechanical ventilation on respiratory mechanics.

Objective:To explore the application effect of global trigger tool (GTT) in detecting adverse events in ICU patients.Methods:According to contents of triggers in the GTT white paper, combined with the scope of domestic adverse event reporting and some ICU indexes, 16 triggers were established. A total of 1 683 medical records were collected from ICU of the Second People's Hospital of Liaocheng in Shandong Province from July 2018 to June 2019. According to the inclusion/exclusion criteria, 421 medical records of discharged patients were randomly selected according to the number of sampling intervals and 420 medical records were reviewed after eliminating repeated medical records. GTT method was used for retrospective analysis.Results:Of the 420 medical records actually used for review, 14 of the 16 triggers were positive, and the positive frequency of triggers was 128 cases, involving 62 patients. Adverse events were identified 51 times, involving 43 patients, with a detection rate of 10.24% (43/420) . Among the 51 cases of adverse events, 37 cases (72.55%) were Grade E, 13 cases (25.49%) were Grade F, and 1 case (1.96%) was Grade H. No Grade G or I was found. In the same year, 18 cases of adverse events were reported voluntarily in ICU, the reporting rate was 1.07% (18/1 683) .Conclusions:GTT can be effectively applied to the detection of adverse events in ICU patients, and a properly designed trigger can improve the detection rate.

TSCI have dyskinesia and sensory disturbance that can cause various life-threaten complications. The patients with traumatic spinal cord injury (TSCI), seriously affecting the quality of life of patients. Based on the epidemiology of TSCI and domestic and foreign literatures as well as expert investigations, this expert consensus reviews the definition, injury classification, rehabilitation assessment, rehabilitation strategies and rehabilitation measures of TSCI so as to provide early standardized rehabilitation treatment methods for TSCI.

To detect serum cAMP-responsive element-binding protein-regulated transcription coactivator 3 (CRTC3) level in subjects with type 2 diabetes mellitus and abdominal obesity and to investigate the relationship of serum CRTC3 level with glycolipid metabolism and insulin resistance. One hundred and seventy patients with type 2 diabetes (T2DM group) and 80 normal controls (NC group) were recruited in the study. They were divided into non-abdominal obesity (NAO) and abdominal obesity (AO) subgroup. Abdominal obesity was defined as waist circumference ≥90 cm in men and ≥85 cm in women. Body fat parameters were measured and body mass index, waist-to-hip ratio were determined. Fasting blood glucose (FBG), 2 h postload blood glucose (2hBG), lipids, HbA_1C, fasting insulin, fasting C-peptide, CRTC3, and adiponectin were also detected. Insulin resistance and pancreas β cell function were assessed by modified homeostasis model assessment for insulin resistance (HOMA-IR) and β cell function (HOMA-β). Bivariate correlation analysis showed that serum CRTC3 level was positively correlated with waist circumference, body mass index, waist-to-hip ratio, systolic blood pressure, diastolic blood pressure, FBG, 2hBG, HbA_1C, total cholesterol, triglyceride, fasting C-peptide, and HOMA-IR (P<0.05 or P<0.01), and was negatively correlated with high density lipoprotein-cholesterol, adiponectin, and HOMA-β (P<0.05). Multivariate linear regression analysis showed that waist-to-hip ratio, adiponectin, total cholesterol, FBG, and HOMA-IR were independently related to serum CRTC3 level (P<0.05 or P<0.01). Serum CRTC3 level was increased in patients with type 2 diabetes as well as in abdominal obesity, and was closely related with glycolipid metabolism, adiponectin, and insulin resistance.

Objective: To investigate the expression and clinical significance of programmed death-ligand 1 (PD-L1), programmed death-ligand 2 (PD-L2), and their receptor programmed cell death protein 1 (PD-1) in EBV-positive T/NK lymphoproliferative disease [Epstein-Barr virus-positive T/natural killer (NK)-cell lymphoproliferative disease, EBV(+)-T/NK-LPD]. Methods: The pathological paraffin-embedded tissues of 17 patients with EBV(+)-T/NK-LPD from the First Affiliated Hospital of Zhengzhou University from January 2013 to December 2017 were collected. These patients include 12 males and 5 females, aged 10-82 years old, the average age being 29 years, 4 people in gradeⅠ, 7 in gradeⅡ, 3 in gradeⅢ, and 3 people with hydroa vacciniforme-like lymphoproliferative disorders. Immunohistochemical SP method was used to detect the expression of PD-1, PD-L1, and PD-L2 in human EBV(+)-T/NK-LPD tissues. The relationship between PD-1, PD-L1, PD-L2 expression, and clinicopathological parameters, pathological grades and prognosis were analyzed by Fisher's exact probabilities and Spearman rank correlation. Result: After statistical analysis, the results showed that in 17 cases of tissue samples, there were 12 cases with positive PD-1 expression, 6 cases with positive PD-L1 expression and 5 cases with positive PD-L2 expression. There was no significant correlation between PD-1 and PD-L2 expression and prognosis (P>0.05). PD-L1 expression showed a positive correlation with prognosis (P<0.05). There was no significant correlation between the expression of PD-L1 and PD-L2 with age, sex, as well as LDH and Ki-67 levels (P>0.05). Moreover, there was no significant correlation of PD-1 and PD-L2 expression with pathological grade (r=0.141, r=-0.149, both P>0.05). However, there was a negative correlation between the PD-L1 expression and pathological grade (r=-0.563), and the correlation between the PD-L1 ex-pression and pathological grade was statistically significant (P<0.05). Conclusions: PD-1, PD-L1, and PD-L2 are abnormally expressed in the pathological tissues of EBV(+)-T/NK-LPD. Although there was no significant correlation between the expression of PD-1 and prognosis or pathological grade, it was significantly higher in EBV+T/NK-LPD. PD-1/PD-Ls associated signaling pathway is expected to be a potential new target for EBV(+)-T/NK-LPD immunotherapy.

A qualitative analytical method of liquid chromatography coupled with ion trap time-of-flight mass spectrometry (LC-IT-TOF/MS) was developed for identification of major constituents in propolis from China (Shandong).The LC-IT-TOF-MS was performed on a Shim-pack VP-ODS column (2.0 mm× 150 mm,5 μm) with the mobile phase consisting of acetonitrile and water containing 0.2％ formic acid in gradient mode,and the flow rate was set at 0.3 mL/min.Negative ion mode was used for IT-TOF-MS.According to the accurate molecular weight,MS fragment pathway,comparison with the retention time of reference compounds,total 31 compounds,including twenty-five phenolic acids and six flavonoids were identified.The LC-IT-TOF-MS qualitative analysis method can be used for analyzing major components of propolis quickly and accurately.

Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus demonstrated to be associated with human disease. Infection by the HTLV-1 can cause T-cell leukemia (ATL) in adults. HTLV-1 bZIP factor (HBZ) is a viral protein encoded by the minus strand of the HTLV-1 provirus. Among the regulatory and accessory genes of HTLV-1, HBZ is the only gene that remains intact and which is expressed consistently in all patients with ATL. Moreover, HBZ has a critical role in the leukemogenesis of ATL. Here, we review the function of HBZ in the oncogenesis of HTLV-1 and its molecular mechanism of action.
Animals ; Basic-Leucine Zipper Transcription Factors ; genetics ; metabolism ; Carcinogenesis ; HTLV-I Infections ; pathology ; virology ; Human T-lymphotropic virus 1 ; genetics ; metabolism ; Humans ; Leukemia, T-Cell ; pathology ; virology ; Retroviridae Proteins ; genetics ; metabolism