BACKGROUND:Carnosic acid,a bioactive compound found in rosemary,has been shown to reduce inflammation and reactive oxygen species(ROS).However,its mechanism of action in osteoclast differentiation remains unclear. OBJECTIVE:To investigate the effects of carnosic acid on osteoclast activation,ROS production,and mitochondrial function. METHODS:Primary bone marrow-derived macrophages from mice were extracted and cultured in vitro.Different concentrations of carnosic acid(0,10,15,20,25 and 30 μmol/L)were tested for their effects on bone marrow-derived macrophage proliferation and toxicity using the cell counting kit-8 cell viability assay to determine a safe concentration.Bone marrow-derived macrophages were cultured in graded concentrations and induced by receptor activator of nuclear factor-κB ligand for osteoclast differentiation for 5-7 days.The effects of carnosic acid on osteoclast differentiation and function were then observed through tartrate-resistant acid phosphatase staining,F-actin staining,H2DCFDA probe and mitochondrial ROS,and Mito-Tracker fluorescence detection.Western blot and RT-PCR assays were subsequently conducted to examine the effects of carnosic acid on the upstream and downstream proteins of the receptor activator of nuclear factor-κB ligand-induced MAPK signaling pathway. RESULTS AND CONCLUSION:Tartrate-resistant acid phosphatase staining and F-actin staining showed that carnosic acid dose-dependently inhibited in vitro osteoclast differentiation and actin ring formation in the cell cytoskeleton,with the highest inhibitory effect observed in the high concentration group(30 μmol/L).Carnosic acid exhibited the most significant inhibitory effect during the early stages(days 1-3)of osteoclast differentiation compared to other intervention periods.Fluorescence imaging using the H2DCFDA probe,mitochondrial ROS,and Mito-Tracker demonstrated that carnosic acid inhibited cellular and mitochondrial ROS production while reducing mitochondrial membrane potential,thereby influencing mitochondrial function.The results of western blot and RT-PCR revealed that carnosic acid could suppress the expression of NFATc1,CTSK,MMP9,and C-fos proteins associated with osteoclast differentiation,and downregulate the expression of NFATc1,Atp6vod2,ACP5,CTSK,and C-fos genes related to osteoclast differentiation.Furthermore,carnosic acid enhanced the expression of antioxidant enzyme proteins and reduced the generation of ROS during the process of osteoclast differentiation.Overall,carnosic acid exerts its inhibitory effects on osteoclast differentiation by inhibiting the phosphorylation modification of the P38/ERK/JNK protein and activating the MAPK signaling pathway in bone marrow-derived macrophages.

Tongue diagnosis is an important method of TCM diagnosis and treatment.Tongue is the key link of auxiliary diagnosis of tongue feature extraction and processing,and also is the bottleneck of intelligent tongue diagnosis in traditional Chinese medicine.Using image processing,artificial intelligence technology to the tongue as a quantitative and identify characteristics of traditional Chinese medicine,looking for both conforms to the original thinking of TCM,and TCM tongue diagnosis method of accurately,has become a common concern of traditional Chinese medicine and computer field.From the mobile terminal tongue as auxiliary diagnostic system of traditional Chinese medicine tongue acquisition basic attribute,tongue diagnosis and image information building,tongue like features are required for accurate extraction and so on related key technology is analyzed,and build overall architecture,so as to provide technical reference for the tongue like intelligent diagnosis,promote the development of technology of tongue diagnosis in traditional Chinese medicine modernization.

Objective:To summarize the clinical characteristics and therapeutic efficacy of central nervous system (CNS) aspergillosis.Methods:The clinical manifestations, laboratory examination, neuroimaging features, treatment and prognosis of 37 cases of CNS aspergillosis diagnosed and treated in the First Medical Center of People′s Liberation Army General Hospital from January 2000 to January 2021 were retrospectively analyzed. According to the correlation between intracranial lesions and paranasal sinus lesions, they were divided into two groups: rhino-cerebral aspergillosis (RA, n=21) group and cerebral aspergillosis (CA, n=16) group. Results:Only 16.2% (6/37) of CNS aspergillosis patients had a clear background of immunosuppression, but 35.1% (13/37) were complicated with diabetes. The most common clinical manifestations were headache (73.0%, 27/37), cranial nerve involvement (59.5%, 22/37) and fever (37.8%, 14/37). Cerebrospinal fluid characteristics included increased pressure (53.8%, 14/26), increased white blood cell count (46.7%, 14/30), decreased glucose (30.0%, 9/30), increased protein (70.0%, 21/30), and high positive results of the metagenomic next-generation sequencing (mNGS) of pathogenic microorganism (7/10). Cranial magnetic resonance imaging showed that commonly involved sites were sinus, orbital apex, posterior orbit, cavernous sinus (43.2%, 16/37) and cerebral lobes (27.0%, 10/37). Treatment options included antifungal drugs alone (64.9%, 24/37), combination of drugs and surgery (27.0%, 10/37) and surgery alone (8.1%, 3/37). Compared with the CA group, RA group had fewer males [47.6% (10/21) vs 14/16, χ2=6.34, P=0.012] and older age [(54.2±19.4) years vs (38.4±18.4) years, t=2.50, P=0.017], and was more prone to headache [85.7% (18/21) vs 9/16, χ2=4.00, P=0.046) and cranial nerve involvement [81.0% (17/21) vs 5/16, χ 2=9.31, P=0.006]. The misdiagnosis rate of these patients in the early stage was 73.0% (27/37). A total of 29 patients (85.3%, 29/34) were treated with voriconazole successively, and the course of treatment was 3.0 (0.5, 10.4) months. Compared with salvage therapy, the mortality of primary therapy was lower (4/17 vs 9/12, χ2=7.54, P=0.006). All patients were followed up to December 2021, and 17 patients died, with a mortality rate of 45.9% (17/37). Conclusions:CNS aspergillosis may have no definite immunosuppressive background. Some of CNS aspergillosis patients are complicated with diabetes, and the clinical manifestations of the disease lack specificity, with high misdiagnosis rate in the early stage, no inflammatory changes in cerebrospinal fluid, and high positive rate of mNGS for pathogenic microorganism. Early and long-term application of voriconazole can significantly reduce the mortality rate.

Objective:To explore the effects of teaching with standardized patients and trauma simulators in surgical debridement training.Methods:Forty-two undergraduate medical students were randomly divided into research group ( n=21) and control group ( n=21) during surgical debridement training in clinical skills simulation training courses. The research group received training using standardized patients combined with trauma simulators, while the control group received training using the simulated teaching method. After training, an examination test and a questionnaire survey were conducted to investigate whether the teaching method under study improved students' doctor-patient communication skills, humanistic care skills, and clinical operational skills. SPSS 20.0 was used to perform the t test and chi-square test. Results:The research group had significantly higher scores in debridement procedures [(65.63±2.58) vs. (62.92±3.88)], communication [(18.62±0.67) vs. (12.71±1.89)], and humanistic care [(8.52±0.51) vs. (6.33±1.11)] than the control group (all P<0.05). The survey results showed that medical students were more satisfied with the teaching method with standardized patients and trauma simulators, believing that it could improve doctor-patient communication skills, humanistic care skills, and clinical practice levels ( P<0.05). Conclusion:The teaching method with standardized patients and trauma simulators can improve training effects, which is worth promotion.

OBJECTIVE To analyze the main components of Chelidonii Herba-Corydalis Rhizoma （CHCR）， and to predict pharmacodynamic substances against estrogen receptor （ER） -positive breast cancer and their potential targets and signaling pathways， followed by verifying experiments. METHODS The ethanol extract of CHCR was analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS/MS）. The network pharmacology analysis was performed for the screened components. The network diagram of CHCR “active components-target-pathway” was constructed， and the enrichment pathway in vitro was validated. RESULTS A total of 58 chemical components were identified， including 57 alkaloids and 1 organic acid. A total of 38 active ingredients were screened from the network pharmacology， and 38 core targets were found in the protein-protein interaction network of “component-disease” intersection targets； 258 gene ontology entries and 137 Kyoto encyclopedia of genes and genomics pathways were obtained， mainly including estrogen signal pathway， phosphatidylinositol-3-kinase/protein kinase B （PI3K/Akt） signal pathway， etc. The results of validation test showed that the median inhibitory concentration of CHCR to MCF-7 cells was 693 μg/mL； 150， 300， 600 μg/mL CHCR could significantly reduce the expressions of phosphorylated PI3K， phosphorylated Akt， ERα protein and ESR1 mRNA （P＜0.01）. CONCLUSIONS The anti-ER-positive breast cancer effect of CHCR may be related to the regulation of ER and PI3K/Akt pathways， which has the characteristics of multi-component and multi-target effects.

ObjectivesTo investigate characteristics and influencing factors of short-term variation of systolic blood pressure of community hypertension patients in Shanghai. MethodsBased on the standardized blood pressure measurement data of hypertensive patients in Shanghai （2018‒2021） and the noninfectious chronic disease management system database， coefficient of variation of systolic blood pressure （CV_S） was described and the influencing factors were analyzed. ResultsAmong 112 680 community hypertension patients， males accounted for 46.87% with a median age of 69 years. CV_S was 0.038 6 ± 0.035 0. Generalized linear model analysis showed the following influencing factors of CV_S： gender， females were higher than males， B=0.032， P<0.001； age group， 60‒69 years， 70‒79 years old group， and ≥80 years groups were all higher than <50 years group， B=0.042， 0.056， and 0.074 respectively with P values of 0.020， 0.002， and <0.001 respectively； smoking， smoking cessation and smoking everyday was lower than never smoking， B=-0.032 and-0.028 respectively with P values of 0.023 and 0.007 respectively； systolic blood pressure， 140‒159 mmHg group， 160‒179 mmHg group， and ≥180 mmHg group were lower then <140 mmHg group， B=-0.039， -0.091， and -0.175 respectively with P values all <0.001； and measurement season， autumn was lower than spring， （B=-0.056， P<0.001）. The paired test showed that CV_S calculated from the three measurements was 1.04% higher than that calculated from the two measurements （P<0.001）. ConclusionThe coefficient of variation of systolic blood pressure of community hypertension patients in Shanghai has large variation， and was influenced by many factors.

Objective:To investigate whether the necroptosis pathway receptor interacting protein 1-receptor interacting protein 3-mixed lineage kinase domain-like protein (RIP1-RIP3-MLKL) is involved in fluoride-induced osteoblastic death.Methods:Human osteosarcoma cell line (Saos-2 cells) were cultured in vitro and divided into NC group, sodium fluoride (NaF) groups (5.0, 10.0, 20.0 and 40.0 mg/L NaF), necroptosis inhibitor Necrostatin-1 (Nec-1) group (50.0 μmol/L Nec-1) and NaF + Nec-1 groups (5.0, 10.0, 20.0 and 40.0 mg/L NaF + 50.0 μmol/L Nec-1). After cultured for 24 and 48 h, respectively, cell proliferation was determined via the CCK-8 method, and the activity of lactate dehydrogenase (LDH) was determined by chemical colorimetry. To further analyze the influence of NaF on RIP1-RIP3-MLKL pathway, Saos-2 cells were divided into NCⅡgroup and NaFⅡgroups (2.5, 5.0, 10.0, 20.0 and 40.0 mg/L NaF). After cultured for 24 and 48 h, respectively, the protein expression levels of RIP1, RIP3 and MLKL were determined by Western blotting. Results:The cell proliferation rates (%: 100.00 ± 0.59, 104.90 ± 0.44, 104.16 ± 0.41, 82.45 ± 1.91, 64.59 ± 1.83, 103.56 ± 0.41, 107.18 ± 0.87, 105.35 ± 1.28, 89.63 ± 1.20, 77.51 ± 1.30; 100.00 ± 0.33, 107.92 ± 0.44, 101.78 ± 1.06, 75.45 ± 0.39, 57.94 ± 1.17, 106.74 ± 0.21, 111.85 ± 0.21, 107.82 ± 0.68, 82.34 ± 0.56, 70.19 ± 0.99) among all groups were significantly different at both 24 and 48 h ( F = 77.13, 2 313.43, P < 0.05). Except the cell proliferation rate of the 10.0 mg/L NaF + Nec-1 group that was not significantly different with that of the 10.0 mg/L NaF group at 24 h ( P > 0.05), the cell proliferation rates of other NaF + Nec-1 groups were significantly higher than those of corresponding NaF groups at both 24 and 48 h ( P < 0.05). The proliferation rate was negatively correlated with fluoride concentration ( r24 h = - 0.976, r48 h = - 0.969, P < 0.001). The LDH activity in all concentrations of NaF groups was significantly higher than that in NC group and corresponding NaF + Nec-1 groups at both 24 and 48 h ( P < 0.05). The LDH activity was positively correlated with fluoride concentration ( r24 h = 0.985, r48 h = 0.988, P < 0.001). The protein expression levels of RIP1, RIP3 and MLKL of 5.0 mg/L NaFⅡ group at 24 h, RIP3 of 5.0 mg/L NaFⅡ group at 48 h, and RIP1, RIP3 and MLKL of 10.0, 20.0 and 40.0 mg/L NaFⅡ groups at both 24 and 48 h were higher than that in NCⅡ group ( P < 0.05). The protein expression levels of RIP1, RIP3 and MLKL were positively correlated with fluoride concentration ( r24 h-RIP1 = 0.881, r48 h-RIP1 = 0.952, r24 h-RIP3 = 0.867, r48 h-RIP3 = 0.938, r24 h-MLKL = 0.758, r48 h-MLKL = 0.907, P < 0.001). Conclusion:Fluoride can directly cause necroptosis of osteoblasts through the RIP1-RIP3-MLKL pathway, and the severity of cell damage is closely related to fluoride concentration, Nec-1 has partially reversed the effects of fluoride.

Objective:To investigate the effect of methoxyamine combined with target guided fluid in elderly patients undergoing pancreaticoduodenectomy.Methods:90 elderly patients undergoing pancreaticoduodenectomy were randomly divided into methoxyamine group and control group, with 45 cases in each group. The patients in both groups were treated with intravenous inhalation combined anesthesia. The stroke volume variation (SVV) was maintained at 7%-10% and the central venous pressure (CVP) was 4-8 cmH 2O. In methoxyamine group, 3 μg/(kg·min) methoxyamine was continuously pumped, while the control group was pumped with the same amount of normal saline at the same speed. The intraoperative infusion volume, urine volume, bleeding volume, blood transfusion cases, intraoperative mean arterial pressure, heart rate, blood gas analysis results, B-type natriuretic peptide (BNP), creatinine, urea nitrogen level and postoperative exhaust time were compared between the two groups. Results:Compared with the control group, the patients in methoxyamine group had less infusion volume, urine volume, lower postoperative BNP level and heart rate, shorter postoperative exhaust time (all P<0.05), and higher mean arterial pressure ( P<0.05). There was no significant difference in blood loss, blood transfusion cases, PaO 2, PaCO 2, pH, creatinine and urea nitrogen between the two groups (all P>0.05). In addition, the number of patients in the methoxyamine group who used pressor drugs was less than that in the control group ( P<0.05), and the frequency of bradycardia was more than that in the control group ( P<0.05). The proportion of tachycardia and urapidil was similar in the two groups (all P>0.05). Conclusions:Methoxyamine combined with target guided fluid therapy can reduce the intraoperative infusion volume of pancreaticoduodenectomy in elderly patients, stabilize circulation, shorten postoperative exhaust time, and contribute to the recovery of gastrointestinal function.

Objective:To analyze the influenza vaccination status of chronic disease management patients in Qingpu district of Shanghai and the vaccination characteristics of different characteristic populations, so as to provide scientific basis for improving the influenza vaccination rate of chronic disease patients in the community.Methods:By comparing the data of Shanghai chronic disease management information system, immunization planning information system and medical association platform, 89 453 subjects who met the inclusion and exclusion criteria in Qingpu district were selected as the research objects. The vaccination coverage rate of the study subjects was calculated according to gender, age group, urban and rural distribution, occupation, chronic disease type and quantity, and the vaccination coverage rate of different subgroups was compared to analyze the influencing factors of vaccination coverage rate.Results:Most of the 89 453 patients with chronic diseases were 60 years old and above (71.93%). Patients with hypertension, diabetes, chronic obstructive pulmoriary disease (COPD) and three chronic diseases accounted for 87.12%, 28.67%, 8.71% and 1.83%, respectively. Influenza vaccination coverage in the 2016/2017 flu season was low, at 0.32%. Influenza vaccination coverage rate of women (0.37%) was higher than that of men (0.27%), which was 1.41 times respectively(95% CI: 1.16, 1.72) that of men patients. The coverage rate of influenza vaccination for the 70-79 year-old group was the highest (0.74%), which was 1.74 times respectively(95% CI: 1.39, 2.19) that of 60-69 year-old patients. The vaccination coverage rate of government departments and institutions was the highest (1.14%), which was 12.58 times respectively(95% CI: 4.52, 34.99) that of retirees. The vaccination rate of COPD patients (3.68%) was 2.50 times (95% CI: 1.66, 3.77) higher than that of patients without COPD.Conclusions:Influenza vaccination rate for chronic disease management patients in Qingpu district of Shanghai is low. Gender, occupation, age and types of chronic diseases are the influencing factors. Patients with chronic disease management should be included in the priority vaccination targets for influenza vaccines, and vaccination intervention for occupational chronic diseases such as non-retired agriculture and forestry patients, especially male patients, should be strengthened to improve influenza vaccination coverage rate.

Objective:To analyze the effect of influenza vaccination intervention among key populations of chronic disease management in communities of Shanghai.Methods:A total of 50 787 patients aged ≥60 with diabetes, hypertension and chronic obstructive pulmonary disease (COPD) in Huangpu, Yangpu, Baoshan and Qingpu districts of Shanghai from January 2013 to August 2017 were selected as the intervention group, and 52 268 people from key populations with chronic disease management in Xuhui, Hongkou, Jiading and Fengxian districts were selected as the control group according to the geographical location and economic level. The intervention group accepted follow-up and health education of influenza vaccination via chronic disease outpatient based on information system. The implementation time of the intervention was from September 2017 to January 2018. The basic information and diagnosis information of two groups, and intervention completion of the intervention group were obtained from Shanghai chronic disease management information system and hospital record system.Results:The age of the intervention group and the control group were (76.76±8.33) and (77.97±8.51) years old, respectively ( P<0.001); and there were statistical differences in gender, occupational and influenza vaccination rate between the two groups ( P<0.001). A total of 28 644 (56.40%) subjects of the intervention group received intervention. There was no significant difference in age composition between finished and unfinished intervention groups ( P=0.095), and there was significant difference in gender composition ( P=0.044). Before the intervention, the vaccination rate of the intervention group was 0.75% (382 subjects) which was lower than that of the control group with 1.02% (533 subjects) (χ 2=20.96, P<0.001). After the intervention, the vaccination rate of the intervention group was 1.73% (496 subjects) which was higher than that of the control group with 1.42% (744 subjects) (χ 2=11.65, P=0.001). Subjects that were male, younger, uptake of influenza vaccine before the intervention, received intervention and professional and technical personnel were more likely to take influenza vaccine, with OR (95 %CI) 1.29 (1.13-1.47), 0.97 (0.96-0.98), 260.30 (215.21-314.83), 1.85 (1.61-2.11) and 1.48 (1.10-1.99), respectively. Conclusion:Influenza vaccination intervetion raised the vaccination rate of key population of chronic disease management. Male, younger, those who had been vaccinated before the intervention, who received the intervention, and professional and technical personnel were more likely to be vaccinated.