OBJECTIVES: To investigate the effect of Qianggu Kangshu Formula (QGKSF) for alleviating osteoclast differentiation in rheumatoid arthritis and the underlying mechanism. METHODS: RAW264.7 cells cultured under hypoxic conditions were treated with RANKL to induce osteoclast differentiation and incubated with normal rat serum or sera from rats medicated with methotrexate (MTX) or QGKSF at low and high doses. Cell viability, TRAP-positive multinucleated cells and F-actin ring formation in the treated cells were assessed with CCK-8 assay, TRAP staining and Phalloidin staining, respectively. Autophagy and autophagosomes in the cells were observed with MDC staining and transmission electron microscopy. ELISA was used to measure IL-6 and TNF-α levels in the culture supernatant, and the expressions of HIF-1α, BNIP3, Bcl-2, Beclin1, LC3-I, LC3-II, P62 and TRAP mRNAs and proteins were analyzed using RT-qPCR and Western blotting. RESULTS: In hypoxia- and RANKL-induced RAW264.7 cells treated with normal rat serum, significant increments of TRAP-positive cells and F-actin ring formation were observed with an enhanced autophagic fluorescence intensity and increased autophagosomes. Treatment of the induced cells with rat sera medicated with MTX and low- and high-dose QGKSF obviously reduced the TRAP-positive cells, F-actin rings and autophagosomes as well as the autophagic fluorescence intensity. RANKL treatment significantly increased IL-6 and TNF-α levels in RAW264.7 cells, which were obviously decreased by treatment with MTX- and QGKSF-medicated sera. RANKL also significantly increased the mRNA and protein expression levels of HIF-1α, BNIP3, Bcl-2, Beclin1, LC3 and TRAP and lowered P62 expressions, and these changes were effectively reversed by treatment with MTX- and QGKSF-medicated sera. CONCLUSIONS QGKSF attenuates RANKL-induced osteoclast differentiation in hypoxic RAW264.7 cells by inhibiting the HIF-1α/BNIP3 autophagy signaling pathway, suggesting its potential for treatment of bone destruction in rheumatoid arthritis.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Osteoclasts/drug effects* ; Autophagy/drug effects* ; Mice ; Signal Transduction/drug effects* ; Rats ; Cell Differentiation/drug effects* ; Arthritis, Rheumatoid/pathology* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; RAW 264.7 Cells ; Membrane Proteins/metabolism* ; Mitochondrial Proteins

This article summarized the clinical experience of MEI Guoqiang in treating lung cancer of phlegm-heat obstructed in the lung syndrome with modified Xiaoxianxiong Decoction （小陷胸汤）. It is believed that the key pathogenesis of lung cancer with phlegm-heat obstructed in the lung syndrome is the phlegm-heat toxin accumulation. According to the different pathogenic effects of qi stagnation， blood stasis， pathogenic toxin， phlegm-damp， qi deficiency， yin deficiency in the occurrence and development of the disease， it is advocated to clear heat and resolve phlegm， and additionally the methods of diffusing the lung and relieving cough， resolving toxins and dissipating masses， rectifying qi and activating blood， dispelling dampness， supplementing and boosting qi and yin are used if necessary. Multiple methods are used together and flexibly matched. In clinical practice， Xiaoxian-xiong Decoction with the function of clearing heat and relieving phlegm is recommended as the basic formula for further modification. For patients with mild lung symptoms， modified Xiaoxianxiong Decoction is commonly used， while for those with obvious symptoms， self-made Maxing Xianxiong Decoction（麻杏陷胸汤） in modifications is suggested. For patients with Shaoyang （少阳） diseases， modified Chaihu Xianxiong Decoction （柴胡陷胸汤） is often used.

Objective:To investigate the correlation of endoscopy findings with symptoms in patients undergoing gastroscopy.Methods:Patients who underwent gastroscopy for the first time in Renji Hospital of Shanghai Jiao Tong University School of Medicine from January to December 2017 were included in the questionnaire survey. The participants were asked to report their main symptoms of the digestive tract in details, and gastroscopy was completed within 2 weeks. Final gastroscopic diagnosis was made based on both gastroscopy and pathology, then patients were divided into the major-lesion (peptic ulcer and malignancy) group and the non-major-lesion (chronic gastritis, reflux esophagitis and others) group. The correlation of gastrointestinal symptoms with gastroscopic findings was analyzed. The risk for major gastroscopic lesions (peptic ulcer and malignant tumors) was assessed by multivariate Logistic regression analysis.Results:A total of 5 885 patients completed the questionnaire, 5 496 (93.4%) of whom completed gastroscopy. The detection rates of peptic ulcer were 12.3% (373/3 028), 12.6% (52/412), 17.9% (49/273), 9.5% (64/675) and 9.2% (102/1 108) in patients with dyspepsia, reflux, alarm, other symptoms and no symptoms, respectively, the detection rates of malignant tumors were 1.2% (36/3 028), 0.7% (3/412), 7.7% (21/273), 0.7% (5/675) and 0.4% (4/1 108), respectively in these patients. The most common symptoms was dyspepsia, accounted for 58.3% (373/640) and 52.2% (36/69) patients with peptic ulcer and malignant tumors, respectively. Alarm symptoms were found in 30.4% (21/69) patients with malignant tumors, and 15.9% (102/640) peptic ulcer patients and 5.8% (4/69) malignant tumor patients had no gastrointestinal symptoms. Compared to asymptomatic individuals, patients with dyspepsia ( P<0.001, OR=1.52, 95% CI: 1.21-1.92) and those with warning symptoms ( P<0.001, OR=2.87, 95% CI: 2.02-4.08) had significantly increased risk for major lesions (peptic ulcer and malignant tumors) detected by gastroscopy. Conclusion:Although dyspepsia and alarm symptoms are positively associated with upper gastrointestinal malignancy and peptic ulcer, they are of limited predictive value for upper gastrointestinal diseases.

Objective To summarize the preliminary clinical outcomes of combination therapy with molecular targeted agents/immunological agents and to explore the potential value of multidisciplinary therapy in the treatment of postoperative refractory recurrent hepatobiliary tumor.Methods 52 cases of postoperative refractory recurrent hepatobiliary tumor during June 2016 to January 2019 from outpatient and inpatient departments at the First Medical Center of PLA General Hospital were prospectively collected,including 37 males and 15 females,with a mean age of (56.2 ± 8.5) years.Referring to the results of next-generation sequencing (NGS) and other-omics,we designed individualized therapy options for each patient.Follow-ups were done regularly and tumor responses were assessed by modified response evaluation criteria in solid tumors (mRECIST).Results Of 52 patients,median follow-up was 10 months (range 3-31 months).14 (26.9％) patients achieved a complete response (CR).8 (15.3％) patients achieved a partial response (PR).14 (26.9％) patients had stable disease (SD).16 (30.8％,including 4 deaths) had progressive disease (PD).Objective response rate and disease control rate were 42.3％ (22/52) and 69.2％ (36/52),respectively.The median progression-free survival (PFS) was 7 months.6-and 12-month overall survival rates were 100％ (48/48),87.5％ (21/24),respectively.Conclusions Precision medicine has good guidance on the treatment of refractory recurrence of hepatobiliary tumors.The combination therapy of multi-target tyrosine kinase inhibitors and immune checkpoint inhibitors may achieve better disease control and deserve further promotion in clinical application.

Objective To investigate the MRI features of primary hepatic neuroendocrine tumor (PHNET). Methods Clinical information and MR imaging features of 13 histopathologically confirmed PHNET patients were retrospectively reviewed. All patients underwent routine MRI examination including T2WI and chemical shift imaging, diffusion weighted imaging (DWI) and dynamic contrast-enhanced imaging. All lesions were divided into two groups according to the maximum diameter (≥ 30 mm for large lesion group and<30 mm for small lesion group). The following MRI features of lesions were evaluated:location, size, growth pattern, signal intensity (T1WI, T2WI, DWI, in-and opposed-phase) and dynamic contrast-enhancement pattern. The pathologic features were also analyzed. Results The PHNET can be single lesion(n=7)or multiple lesions(n=6)in which 4 cases showed diffuse pattern.One hundred and six lesions in 13 patients were detected.The median diameter of all lesions was 20 mm(ranging from 3 to 200 mm).Fourteen lesions were found in≥30 mm group and 92 lesions in<30 mm group.(1)In≥30 mm group,all lesions had well-defined margin,heterogeneous hyperintensity on T2WI,heterogeneous hypointensity on T1WI and halo sign on DWI. All lesions showed cystic degeneration, necrosis and pseudo-capsule. Three lesions showed dilation of bile duct around the lesion, and three lesions hemorrhaged and three lesions signal dropped on out-of-phase.On arterial phase,7 lesions showed ring-like enhancement,and the other 7 lesions showed heterogeneous enhancement;then on portal venous phase and delayed phase, 8 lesions showed persistent enhancement and the other 6 lesions showed"wash-out"appearance.Three cases showed lymphadenopathy in the peritoneum and liver hilum. (2) In<30 mm group, 76 lesions showed well-circumscribed edge and the other 16 lesions had ill-defined margin. Eighty two lesions showed relatively homogeneous hyperintensity on T2WI and relatively homogeneous hypointensity on T1WI. One lesion showed heterogeneous hyperintensity on T2WI and heterogeneous hypointensity on T1WI.Nine lesions showed halo and nodular hyperintensity and the other 83 lesions nodular hyperintensity on DWI.Ten lesions demonstrated cystic degeneration and necrosis. Ten lesions showed pseudocapsule. All lesions showed no dilation of bile duct, hemorrhage and signal drop on out-of-phase. On arterial phase, 31 lesions showed ring-like enhancement, 3 lesions showed heterogeneous enhancement and 58 lesions showed homogeneous enhancement;on portal venous phase and delayed phase,62 lesions showed persistent enhancement and 30 lesions showed"wash-out"sign. No lymphadenopathy was found in this group. In the pathologic analysis, hemorrhage and central necrosis were detected in the gross specimens.And in the 13 cases of PHNET,1,3 and 9 cases were classified into G1, G2 and G3 grade, respectively. Conclusions The PHNET can be single or multiple with various sizes. The large lesions often show heterogeneous signal intensity on T2WI and T1WI with cystic degeneration, necrosis, hemorrhage, pseudo-capsule and dilated bile duct, peripheral hyperintensity on DWI, ring-enhancement or heterogeneous slight enhancement in arterial phase, while small lesions often show ring-enhancement or homogeneous obvious enhancement in arterial phase.

Objective To investigate the MRI features of renal oncocytoma(RO). Methods We retrospectively analyzed the data of 26 patients by histologically confirmed with RO in Chinese PLA General Hospital from September 2006 to May 2017 and performed pre-operative MRI and dynamic contrast-enhanced MRI.Lesions were divided into two groups based on the diameter:large group with large than 3 cm(16 cases,16 lesions)and small group with less than 3 cm(10 cases,11 lesions).Features of each lesion were analyzed, including location, pseudocapsules, lipids and other 11 indicators. Tumor imaging features were compared between two groups by univariate and multivariate logistic regression analysis. Results Of 27 RO lesions, 12 were located in the left kidney and 15 in the right kidney. Twenty five lesions appeared exophytic(92.6%,25/27),10 lesions showed exophytic angular interface(37.0%,10/27), 25 lesions showed pseudocapsule(92.6%,25/27),4 lesions appeared lipid(14.8%,4/27),2 lesions showed cystic degeneration or necrosis(7.4%,2/27),1 lesion showed hemorrhage(3.7%,1/27),13 lesions appeared fibrous scar(48.1%,13/27),19 lesions with moderate or intense enhancement in the corticomedullary phase (70.4%, 19/27), 9 lesions with wheel-spoke-like enhancement (33.3%, 9/27), and 2 lesions showed segmental enhancement inversion (7.4%, 2/27). Univariate logistic regression exhibited statistically significant correlation between exophytic angular interface with renal parenchyma,fibrous scar,moderate or intense enhancement in the corticomedullary phase,and wheel-spoke-like enhancement of the tumors both in small and large RO groups with OR value of 0.054, 9.898, 8.400 and 10.000, respectively. In the multivariate logistic regression analysis, exophytic angular interface with renal parenchyma and intense enhancement in the corticomedullary phase were found to be high risk factors with OR value of 0.033 and 15.381,respectively.Conclusions The main manifestation of RO on MRI is that both kidneys can occur, with many exogenesis, pseudocapsules, but less lipids, cystic degeneration, necrosis, hemorrhage and segmental enhanced reversal;smaller lesions(diameter<3 cm)tend to conical interface,while larger lesions (diameter≥3 cm)may have fibrous scars,spoke-shaped enhancement,moderate and significantly enhanced cortical phase characteristics.

Objective To explore the value of ultra?high b?value DWI in diagnosis of prostate cancer in central gland. Methods Seventy?one consecutive patients, who were scheduled for prostate biopsy, were prospectively screened. T2WI, conventional DWI with b?value of 1 000 s/mm2 and ultra?high b?value DWI with b?value of 2 000 s/mm2 and 3 000 s/mm2 were performed in each examination. Twelve?core ultrasound guided prostate systematic biopsy was operated within 3 weeks after MRI examination. Images were interpreted based on prostate MR guidelines (PI?RADS) and were corresponding to histological results conducted by ultrasound guided prostate systematic biopsy. Using biopsy as the gold standard, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for different imaging methods. Sensitivity and specificity differences between ultra?high b?value DWI and conventional DWI were analyzed using the McNemar test. The areas under the curves (AUCs) between ultra?high b?value DWI and other modalities were compared by using the Z test. Results Forty lesions were identified in the prostate central glands from the 33 sample patients in 71 examinees. Twenty two lesions were identified as prostate cancer in 15 patients and 18 lesions were identified as benign prostatic hyperplasia in 18 patients. MRI analysis of lesions in central gland, 27 (67.5%), 20 (50.0%), 32 (80.0%) and 35 (87.5%) were diagnosed accurately with the T2WI, conventional DWI and ultra?high b?value DWI (b=2 000, 3 000 s/mm2) respectively. The sensitivity and specificity for ultra?high b?value DWI was 90.9%and 83.3% with a b?value of 3 000 s/mm2 and was 86.4% and 72.2% for 2 000 s/mm2. These values were significantly higher than conventional DWI with a b?value of 1 000 s/mm2 (59.1%and 38.9%, P<0.05). The detection of lesions was comparable with ultra?high b?value DWI at 2 000 s/mm2 and 3 000 s/mm2 (P>0.05). The AUCs were 0.674, 0.510, 0.793 and 0.871 in T2WI, conventional DWI and ultra?high b?value DWI at 2 000 s/mm2 and 3 000 s/mm2 respectively. ROC analysis showed greater AUCs for the ultra?high b value DWI, than for the T2WI and conventional DWI (P<0.05). Conclusion The ultra?high b?value DWI is a valuable MRI modality in the diagnosis of prostate cancer in central gland.

Objective Maxillary canine palatal impaction is a common deformity in stomatology and its etiology remains dis-putable.The aim of this study is to investigate the crown-root morphology of the adjacent lateral incisors in patients with palatally impacted maxillary canines using cone-beam computed tomography ( CBCT) in order to explore its etiology. Methods Using CBCT scanning, we examined 94 maxillary canines in 84 patients, including 27 palatally impacted maxillary canines in 24 patients ( the experi- mental group) , 37 buccally impacted maxillary canines in 30 age-and sex-matched subjects ( control group A) , and 30 normal maxil-lary canines in 30 age-and sex-matched subjects ( control group B) .We selected some necessary reference planes, measured the ori-entation and position of the chosen canines, and studied the morphology of the adjacent lateral incisors by CS 3D imaging, followed by statistical analysis of 17 of the linear variables obtained. Results Compared with control group A, the experimental group showed significantly shorter tooth length ([22.930 ±1.849]mm vs [21.240 ±1.651]mm, P<0.05), crown length ([9.270 ±0.559]mm vs [8.150 ±0.889] mm, P<0.05), and mesiodistal width at 4 mm to the cementoenamel junction (CEJ) ([7.260 ±0.579]mm vs [5.900 ±0.581] mm, P<0.05) as well as shorter buccolingual width at the CEJ level, mesiodistal width at 4 mm to the CEJ, buc-colingual width at 4 mm apical to the CEJ, distance from the canine cusp to the coronal and occlusal planes, and coronal angulation of the canine (all P<0.05).There was a negative correlation between maxillary canine palatal impaction and age (P<0.05). Conclusion One of the main causes of maxillary canine palatal impaction is that the adjacent lateral incisor is too small to provide suf-ficient guidance to the canine.The severity of maxillary canine palatal impaction increases with the age of the patient.

Objective To explore the psychological characteristics of cancer long-term survivors.Methods One hundred and fifty one cancer long-term survivors(survival time ≥5 years) were chosen for participation from Guangzhou and Shenzhen by the coin method in this study.The qualitative data of the patients'psychological characteristics were collected by individual interviews,and the patients'behavioral and psychological characteristics were measured by the Tumor Psychological Scale(TPS),the Cancer Coping Modes Questionnaire(CCMQ) and the Psychological Adjustment Scale for Cancer Patients(PASCP).The psychological characteristics of the 151 cancer long-term survivors were compared with the average level of cancer patients (over 557 patients).Quantitive data were analyzed by two independent samples't-test.Results (1) Most cancer long-term survivors knew their diagnosis in two weeks after they were diagnosed.The cancer long-term survivors were better in mentality and got more social supports.Most long-time survivors attributed their success to good psychological well-being and positive treatments.(2) The TPS scores of cancer long-term survivors group(1.99 ± 0.45,1.68 ± 0.51,1.33 ± 0.32,1.87 ± 0.44,1.78 ± 0.41 respectively) were lower than the scores of the average level of cancer patients (3.06 ±2.12,3.08 ± 2.03,2.86 ± 2.08,3.02 ± 2.06,2.98 ± 1.75 respectively) in the dimensions of personality,emotion,unconscious,cognition and the total average score.The differences were significant statistically(P ＜ 0.01).The CCMQ scores of cancer long-term survivors group were higher than the scores of the average level of cancer patients in the dimension of confrontation and catharses.In the dimensions of avoidance and suppression,resignation and fantasy,the scores of cancer long-term survivors group were lower than the scores of the average level of cancer patients.All the differences were significant statistically (P ＜ 0.05).The PASCP scores of cancer long-term survivors group were higher than the scores of the average level of cancer patients in the dimension of emotion/self-esteem,subjective feeling,interpersonal relationship/social life,the daily life and the other.The differences was significant statistically(P＜ 0.001).Conclusion There are common characteristics of cancer long-term survivors such as good mental health state,lower tumor psychological level,positive coping styles,getting better psychological adjustment.

Objective To investigate the influence of atorvastatin on tumor necrosis factor - α (TNF- α) of sepsis rats.Methods Sepsis models were established using male SD rats by cecal ligation and puncture (CLP).A total of 100 healthy rats were divided into 4 groups ( n =25) randomly ( random number):sham- operation group,CLP group,low- dose atorvastatin group and high -dose Atorvastatin group.Blood samples of 5 rats in each group were collected at postoperative 0,3,6,12 and 24 hours,to detect tumor necrosis factor - α (TNF - α) levels in plasma.Observe and compare the mobility of rats in each group and specimens of small intestine were taken for histopathological examination by optical microscope.Results At 0 hour,plasmic TNF - α levels in 4 groups were statistically equal (P ＞ 0.05 ).In plasma of sham - operation group,changes of TNF - α levels were not obvious.Compared with CLP group,TNF - α levels in low - dose and high - dose Atorvastatin groups were both significantly lower ( P ＜0.01 ) at postoperative 3,6,12 and 24 hours.And TNF-α levels in high -dose Atorvastatin group were significantly lower than those in low - dose group ( P ＜ 0.01 ) at the 4 time points.The mortality of sepsis was higher in CLP model group than other groups,That of Atorvastatin group was significantly lower than CLP model group but higher than control group and high - dose group was lower than low - dose group.Conclusions Atorvastatin can inhibit the expression of TNF - α in blood plasma of sepsis rats and reduce inflammatory reaction.