BACKGROUND:Overactive osteoclasts disrupt bone homeostasis and play a bad role in the pathological mechanisms of related skeletal diseases,such as osteoporosis,fragility fractures,and osteoarthritis.Studies have confirmed that ellagic acid and ellagtannin have the potential to inhibit osteoclast differentiation.As their natural metabolites,urolithin A has antioxidant,anti-inflammatory,anti-proliferative and anti-cancer effects,but its effect on osteoclast differentiation and its underlying molecular mechanisms remain unclear. OBJECTIVE:To explore the effect of urolithin A on osteoclast differentiation induced by receptor activator for nuclear factor-κB ligand and its mechanism. METHODS:Mouse mononuclear macrophage leukemia cells(RAW264.7)that grew stably were cultured in vitro.Toxicity of urolithin A(0,0.1,0.5,1.5,2.5 μmol/L)to RAW264.7 cells were detected by cytotoxic MTS assay to screen out the safe concentration.Different concentrations of urolithin A were used again to intervene with receptor activator for nuclear factor-κB ligand-induced differentiation of RAW264.7 cells in vitro.Then,tartrate-resistant acid phosphatase staining and F-actin ring and nucleus staining were performed to observe its effect on the formation and function of osteoclasts.Finally,the expressions of urolithin A on upstream and downstream genes and proteins in the MAPK signaling pathway were observed by western blot and RT-qPCR assays. RESULTS AND CONCLUSION:Urolithin A inhibited osteoclast differentiation and F-actin ring formation in a concentration-dependent manner and 2.5 μmol/L had the strongest inhibitory effect.Urolithin A inhibited the mRNA expression of Nfatc1,Ctsk,Mmp9 and Atp6v0d2 and the protein synthesis of Nfatc1 and Ctsk,related to osteoclast formation and bone resorption.Urolithin A inhibited the activity of osteoclasts by downregulating the phosphorylation of p38 protein to inhibit the mitogen-activated protein kinase signaling pathway.

Objective:To develop a deep transfer learning method for the differential diagnosis of osteonecrosis of the femoral head (ONFH) with other common hip diseases using anteroposterior hip radiographs.Methods:Patients suffering from ONFH, DDH, and other hip diseases including primary hip osteoarthritis, non-infectious inflammatory hip disease, and femoral neck fracture treated in the First Affiliated Hospital of Guangzhou University of Chinese Medicine from January 2018 to December 2020 were enrolled in the study. A clinical data set containing anteroposterior hip radiographs of the eligible patients was created. Data augmentation by rotating and flipping images was performed to enlarge the data set, then the data set was divided equally into a training data set and a testing data set. The ResNet-152, a deep neural network model, was used in the study, but the original Batch Normalization was replaced with Transferable Normalization to construct a novel deep transfer learning model. The model was trained to distinguish ONFH and DDH from other common hip diseases using anteroposterior hip radiographs on the training data set and its classification performance was evaluated on the testing data set.Results:The clinical data set was comprised of anteroposterior hip radiographs of 1024 hips, including 542 with ONFH, 296 with DDH, and 186 with other common hip diseases (56 hips with primary osteoarthritis, 85 hips with non-infectious inflammatory osteoarthritis, 45 hips with femoral neck fracture). After data augmentation, the size of the data set multiplied to 6144. The model was trained 100 050 times in each task. Accuracy was used as the representative parameter to evaluate the performance of the model. In the binary classification task to identify ONFH, the best accuracy was 95.80%. As for the multi-classification task for classification of ONFH and DDH from other hip diseases, the best accuracy was 91.40%. The plateau of the model was observed in each task after 50 000 times of training. The mean accuracy in plateaus was 95.35% (95% CI: 95.33%, 95.37%), and 90.85% (95% CI: 90.82%, 90.87%), respectively. Conclusion:The present study proves the encouraging performance of a deep transfer learning method for the first-visit classification of ONFH, DDH, and other hip diseases using the convenient and economical anteroposterior hip radiographs.

Objective:To analyze the changes in plasma endothelin-1 (ET-1) concentrations in the patients with acute respiratory distress syndrome (ARDS).Methods:Fourteen patients with ARDS induced by trauma, 8 males and 6 females, aged 19-80 yr, were studied. The severity of ARDS was graded according to the Berlin definition of ARDS after admission to intensive care unit (ICU). Venous blood samples were obtained on 1st, 3rd and 5th days after admission to ICU, the plasma ET-1 concentrations were measured by radioimmunoassay, the pulmonary vascular permeability index (PVPI) was determined by PiCCO technique, and multiple organ dysfunction (MOD) score and lung injury score (LIS) were assessed. Spearman correlation of plasma ET-1 concentrations with MOD score, LIS and PVPI was analyzed.Results:MOD score, LIS, PVPI and plasma ET-1 concentrations were significantly decreased in mild ARDS patients ( n=5) as compared with moderate ARDS patients ( n=9, P<0.05). The plasma ET-1 concentration was positively correlated with MOD score, LIS and PVPI ( r=0.69, 0.76, 0.62, P<0.001). Conclusions:Plasma ET-1 concentrations can reflect the pulmonary vascular permeability and even the severity of the disease in the early stage of ARDS, so it is necessary to carry out dynamic monitoring in the patients.

To investigate the effects of streptavidin and dimethylsilicone oil on the detection rate of microscopic lesions under gastroscopy, a total of 353 patients who underwent painless gastroscopy were categorized into the experimental group (given streptavidin combined with sodium bicarbonate, n=176) and the control group (given dimethylsilicone oil combined with sodium bicarbonate, n=177). Clinical indexes such as visual field clarity, examination duration, number of rinses, detection rate of micro lesions, early cancer detection rate and incidence of adverse reactions were recorded in the gastroscopy examination of the two groups. The experimental and control groups were compared in terms of visual field clarity (1.84±0.51 points VS 2.15±0.48 points, t=-5.900), fundus mucus properties (1.04±0.43 points VS 1.46±0.76 points, t=-6.347) and number of rinses (0.76±0.66 times VS 1.18±0.72 times, t=-5.628) with significant differences ( P<0.001). The examination time in the experimental group was slightly higher than that in the control group (10.01±4.40 min VS 8.98±4.22 min, t=2.239, P=0.026). The detection rate of microscopic lesions was significantly higher in the experimental group than that in the control group [97.73%(172/176) VS 91.53%(162/177), χ2=6.665, P=0.010]. There was no significant difference in the detection rate of inflammatory hyperplasia, polyps, precancerous lesions or cancer between the experimental group and the control group ( P>0.05). There was no preoperative drinking discomfort in either group, and 4 cases of intraoperative choking occurred in each of the experimental and the control group with no significant difference ( P>0.999). No postoperative adverse reaction occurred in either group. Taking streptavidin before operation could significantly improve visual field clarity and the detection rate of microscopic lesions, which helps to detect early lesions in stomach.

Objective:To evaluate the efficacy of Chaichuan Tongren Mixture supplemented with hysteroscopic recanalization in the treatment of tubal obstructive infertility of liver depression and qi stagnation type.Methods:A total of 60 patients with tubal obstructive infertility of liver depression and qi stagnation type who met the inclusion criteria were selected, between August 2018 and June 2020, and they were divided into the observation group with 31 cases and the control group with 29 cases, according to the random number table method. The control group was treated with hysteroscopic recanalization, while the observation group was given Chaichuan Tongren Mixture on the basis of the control group. Both groups were treated for 4 months and followed up for 12 months. TCM syndromes were scored before and after treatment, and prostaglandin E 2 (PGE 2) was detected by fully automatic biochemical analyzer and levels of TNF-α, CRP and IL-6 were measured by ELISA. The tubal patency of patients after treatment was observed, the pregnancy status was recorded after the end of follow-up and the clinical efficacy was evaluated. Results:The total effective rate was 96.77% in the observation group and that in the control group was 75.86% ( χ2=4.01, P<0.01). The scores of breast distending pain, irregular menstruation, dark purple menstrual flow and lumbosacral pain in the observation group after treatment were significantly lower than those in the control group ( t values were 17.69, 21.67, 20.89, 14.67, 18.20, respectively, all Ps<0.001). After treatment, the levels of serum PGE 2, TNF-α, CRP, and IL-6 were significantly lower in the observation group than those in the control group [(65.31±6.73) ng/L vs. (87.10±8.85) ng/L, t=10.78; (6.90±0.71) ng/L vs. (11.35±1.23) ng/L, t=17.30; (2.47±0.25) mg/L vs. (5.10±0.52) mg/L, t=25.23; (12.38±1.26) ng/L vs. (30.16±3.15) ng/L, t=29.05] ( P<0.01). After treatment, there was statistical significance in the total effective rate of tubal patency of 96.8% (30/31) in the observation group compared to 79.3% (23/29) in the control group ( χ2=4.43, P<0.01). At the end of follow-up, the pregnancy rate was 71.0% (22/31) in the observation group and 44.8% (13/29) in the control group, and the difference was statistically significant ( χ2=4.21, P<0.01). Conclusion:The Chaichuan Tongren Mixture supplemented with hysteroscopic recanalization can reduce the levels of inflammatory mediators and increase the pregnancy rate of patients with tubal obstructive infertility of liver depression and qi stagnation type.

Objective:To evaluate the effectiveness and safety of enhanced recovery after surgery(ERAS)in perioperative period of liver transplantation.Methods:The authors searched systematically domestic and foreign databases to collect researches on applying ERAS for liver transplantation. The retrieval period was from database inception to November 2020. Quality assessment and data extraction were performed by two researchers according to the inclusion criteria. Meta-analysis of postoperative indicators(length of ICU stay, total length of hospital stay, postoperative complications, admission rate & mortality rate)was performed by RevMan 5.3.5 software.Results:3 Three randomized controlled studies (RCTs) and 4 cohort studies were selected with a total of 1 016 patients, including 404 in ERAS group and 612 in conventional group(traditional perioperative management). The results of Meta-analysis revealed that, as compared with control group, length of ICU stay was significantly shorter in ERAS group [weighted mean difference(WMD)=-2.20, 95% CI: -2.43~-1.97, P<0.05]; Total length of hospital stay was significantly shorter in ERAS group [WMD=-5.85, 95% CI: -8.20~-3.49, P<0.05]; The incidence of postoperative complications was significantly shorter in ERAS group [OR=0.61, 95% CI: 0.42~0.88, P<0.05]. However, no inter-group statistically significant differences existed between admission rate or mortality rate( P>0.05). Conclusions:In perioperative period of liver transplantation, using ERAS protocol can shorten length of ICU stay and total length of hospital stay, lower the incidence of postoperative complications and accelerate patient recovery.

Objective:To investigate the expression and clinical significance of Golgi phosphoprotein 3 (GOLPH3) and NOD-like receptor protein 3 (NLRP3) in gallbladder carcinoma (GBC).Methods:Surgical specimens and clinical data were collected from 63 patients with GBC who underwent radical cholecystectomy in the 904th Hospital of Joint Logistic Support Force of PLA from January 2014 to January 2019. In the GBC group, there were 21 males and 42 females, with an average age of 62.5 years. For 30 patients with mild to moderate atypical hyperplasia of gallbladder during the same period were included in the precancerous lesion group, including 9 males and 21 females, with an average age of 62.4 years. Normal gallbladder specimens from 20 patients who underwent surgical resection due to liver trauma or giant hepatic hemangioma were collected and included in the normal group, including 7 males and 13 females, with an average age of 61.9 years. The expressions of GOLPH3, NLRP3, Ki-67 were detected by immunohistochemistry. Log-rank test and Cox regression were adopted to analyze the GOLPH3 and NLRP3 expression and survival prognosis of gallbladder cancer patients.Results:Expression of GOLPH3 and NLRP3 in the tumor group, precancerous lesion group and normal group was decreased separately. In GBC tissues, the level of GOLPH3 and NLRP3 was positively correlated with the Ki-67 expression ( r=0.972 and r=0.969, both P<0.05). Multivariate analysis showed that high level of GOLPH3 ( HR=4.891, 95% CI: 1.776-13.470) and NLRP3 ( HR=3.006, 95% CI: 1.273-7.099) was an independent risk factor for predicting the postoperative survival of patients with GBC (both P<0.05). Conclusion:GOLPH3 and NLRP3 are highly expressed in GBC tissues, and high expression of GOLPH3 and NLRP3 is an independent risk factor for postoperative survival in patients with GBC.

Objective:To investigate a cluster epidemic of COVID-19 after a mass gathering activity in Ningbo of Zhejiang province and analyze the transmission chain and status of infection cases of different generations.Methods:The tracking of all the close contacts of the first COVID-19 case and epidemiological investigation were conducted on January 29, 2020 after a cluster epidemic of COVID-19 related with a Buddhism rally on January 19 (the 1.19 rally) in Ningbo occurred. The swabs of nose/throat of the cases and close contacts were collected and tested for nucleic acids by real-time fluorescence quantitative RT-PCR.Results:From January 26 to February 20, 2020, a total of 67 COVID-19 cases and 15 asymptomatic infection cases related with the 1.19 rally were reported in Ningbo. The initial case was the infection source who infected 29 second generation cases and 4 asymptomatic infection cases, in whom 23 second generation cases and 3 asymptomatic infection cases once took bus with the initial case, the attack rate was 33.82% (23/68) and the infection rate was 38.24% (26/68). The risks of suffering from COVID-19 and being infected were 28.91 times and 26.01 times higher in rally participants taking bus with initial case compared with those taking no bus with initial case. In this epidemic, 37 third+generation cases and 11 related asymptomatic infection cases occurred, the attack rate was 2.88% (37/1 283) and the infection rate was 4.76% (48/1 008). The main transmission routes included vehicle sharing and family transmission.Conclusion:It was a cluster epidemic of COVID-19 caused by a super spreader in a massive rally. The epidemic has been under effective control.

Objective To investigate the expressions and the significance among the three markers TGF β1,Survivin and Caspase-3 in intrahepatic bile duct tissues in patients with intrahepatic bile duct stones.Method Total of 130 paraffin section of intrahepatic bile duct tissue were collected at Department of Pathology,The 904th Hospital of Joint Logistic Support Force of PLA from 2013 to 2018.Total of 50 patients with intrahepatic bile duct stones complicated with bile duct strictures (the stenosis group),40 patients with intrahepatic bile duct stones with chronic inflammation (the inflammation group),and 40 patients with normal liver tissues (the normal control group) were included in this study.The expressions of TGF β1,Survivin and Caspase-3 in liver tissues were detected by immunohistochemistry and compared among the 3 groups to find their correlations with the clinicopathological features of the disease of the patients.Results TGF β1 was expressed in 72.0％ of the patients in the stenosis group,37.5％ in the inflammatory group,and 15.0％ in the normal control group.The differences among the groups were significant (P ＜ 0.05);Survivin was expressed in 78.0％ of the patients in the stenosis group,47.5％ in the inflammatory group,and 25.0％ in the normal control group.The differences among the groups were significant (P ＜ 0.05);Caspase-3 was expressed in 10.0％ of the patients in the stenosis group,42.5％ in the inflammatory group,and 75.0％ in the normal control group.The differences among the groups were significant (P ＜ 0.05).Within the stenosis group,TGF β1 was negatively correlated with Caspase-3 (r =-0.882,P ＜ 0.05),and positively correlated with Survivin (r =0.889,P ＜ 0.05).Survivin and Caspase-3 were also negatively correlated (r=-0.923,P＜0.05).Conclusion Abnormal expressions of TGF β1,Survivin and Caspase-3 were involved in the formation of intrahepatic bile duct stones associated with bile duct strictures.

Objective To analyze the clinical characteristics and treatment strategy of phosphaturic mesenchymal tumors in hips.Methods From May 2017 to November 2017,five patients with phosphaturic mesenchymal tumors in hips,who treated in our hospital were retrospectively reviewed.The clinical manifestations,laboratory inspection,radiological examination,pathological examination and treatment were analyzed.Results Two male cases (40％) and 3 female (60％) were included.The overall age was 49～63 years old (average 54.40±5.37 years old).The course was 19～101 months (average 51.20±32.41months).Four cases of tumor were located in femoral head and 1 case was in femur intertrochanteric region.The maximum tumor diameter was 0.76～1.83 cm (average 1.28±0.39 cm).The early clinical manifestations of the patients were mainly non-specific bone pain or fatigue.The symptoms of the hip were not obvious.All patients had been misdiagnosed.After pathological frac-ture of the hip,the patient suffered from hip pain,thigh pain,fatigue,etc.,or limited hip function.The severe patients had a systemic multiple pathologic fractures.The serum phosphorus was lower than normal in preoperative period and recovered to normal level in 3-8 days after surgery.The postoperative ALP decreased significantly than preoperative in 4 patients and 1 case was slightly higher than preoperative.Preoperative 1,25-(OH)2-D3 and PTH were in normal range.99Tcm-octreotide (OCT) scan or 68Ga DOTA-TATE PET/CT can detect the disease.X-ray,CT and MRI can identify the lesions.The lesions of femoral head were basically under the joint surface,with a nodular change.Part of the tumor was infiltrating and close to the cortex.The pathology was mainly manifested as a large number of thin-walled vessels in the bone trabeculae.There were dense spindle cells or astrocytes between the blood vessels and the atypia is not obvious.Three patients were treated with total hip arthroplasty and two with segmental resection and bone graft.After surgical removal of the tumor,the patient's systemic pain or anemic symptoms were gradually relieved and the joint function was restored.Meanwhile,the bone density was increased.Conclusion The clinical features of the phosphaturic mesenchymal tumors in hips were not obvious.Comprehensive diagnosis should be carried out in combination with the clinical manifestations,laboratory examination,radiological examination and pathological examination.Total hip arthroplasty or segmental resection with bone graft can effectively remove the tumor and achieve good prognosis.