BACKGROUND:Mechanical stimulation has been confirmed to promote osteogenic differentiation of bone marrow stromal stem cells,but the mechanism is unknown.Primary cilia are important mechanoreceptors and regulate various signaling pathways such as TGF-β1/BMP-2/SMAD.They are likely to be important targets for mechanical regulation of bone marrow stromal stem cells. OBJECTIVE:To investigate the effect and mechanism of fluid shear stress on osteogenic differentiation of bone marrow stromal stem cells. METHODS:Rat bone marrow stromal stem cells were divided into control group,mechanical stimulation group(fluid shear mechanics intervention by shaking table),mechanical stimulation + IFT88 silencing group(mechanical stimulation + silencing IFT88 expression with siRNA).After 24 hours of intervention,qRT-PCR was utilized to determine the expression of transforming growth factor β1 and bone morphogenetic protein 2.Western blot assay was used to detect the expression of phosphorylated SMAD2/3 protein.Immunofluorescent staining of primary cilia was conducted and morphology was analyzed. RESULTS AND CONCLUSION:Shear stress stimulation could promote the transcriptional activity of transforming growth factor β1 and bone morphogenetic protein 2 genes,and increase the expression of phosphorylated SMAD2/3 protein.After siRNA interfered with primary cilia,this mechanical response effect was significantly reduced.There was a Spearman correlation between the change ratio of the primary cilium area of bone marrow stromal stem cells and the increased ratio of transforming growth factor β1 and bone morphogenetic protein 2 gene transcription.These findings indicate that primary cilia/intraflagellar transport mediates the activation of fluid shear stress-responsive transforming growth factor β1/bone morphogenetic protein 2/SMAD signaling pathway and promotes osteogenic differentiation of bone marrow stromal stem cells.

Objective In order to explore the influence and effect of case teaching method based on real patients in oto-rhinolaryngology on clinical practice ability of general practice.Methods 96 trainees of general practice in otolaryngology de-partment from January 2018 to January 2021 were randomly divided into two groups:a CBL group and a control group.In the CBL group,CBL teaching method was adopted based on real patients in Otorhinolaryngology.Conventional teaching method was used in the control group.Results The theoretical scores of written test and the examination of clinical skill operation scores of the CBL group and the control group were analyzed.There was significant difference between the two groups(P＜0.05).The students in CBL group were more satisfied with clinical thinking ability,analysis and problem solving ability,active learning abil-ity,learning efficiency,teacher-student interaction,doctor-patient communication ability and consultation skills than the control group.There was significant difference between the two groups(P＜0.05).Conclusion The CBL teaching method can obvi-ously improve the learning enthusiasm and clinical practice ability of general resident training doctors.The teaching quality has been significantly improved.It is of great value to cultivate excellent general practitioners.

Objective:To investigate and compare the clinical outcomes of the arterial pre-occlusion technique(APOT) and the traditional technique in the surgery of locally advanced pancreatic cancer with arterial involvement after conversion therapy.Methods:This is a retrospective cohort study. The clinical data of 145 patients with locally advanced pancreatic cancer with arterial involvement admitted to the Department of Hepato-Biliary-Pancreatic Surgery of the First Hospital Affiliated to Naval Medical University,from January 2020 to December 2022 were retrospectively analyzed. All patients completed neoadjuvant therapy for tumors, and the feasibility of radical surgical treatment was determined by a multidisciplinary collaborative team evaluation before surgery. According to whether the intraoperative artery was pre-occluded, 145 patients were divided into two groups, including 28 cases in the APOT group(16 males, 12 females, aged (59.0±9.4) years), and 117 cases in the routine surgery group(76 males, 41 females, aged (55.1±8.2) years). To ensure comparability of baseline data between the APOT group and the routine surgery group, a 1∶2 match was performed using the propensity score matching method, and the caliper value was 0.006 45. The t-test,the Mann-Whitney U test, χ2 test or Fisher′s exact test were used to compare the data between the two groups,respectively. Results:After matching the propensity score,there were 28 cases in the APOT group and 56 cases in the routine surgery group. There were no significant differences in gender,age,preoperative comorbidities,preoperative body mass index,surgical approaches,chemotherapy regimen,stereotactic body radiation therapy ratio,tumor markers,and type of invaded artery between the two groups (all P>0.05).The arterial occlusion time M(IQR) in the APOT group was 7.0(3.8)minutes(range:3 to 15 minutes),and no ischemic manifestations were observed in the distal target organs that blocked blood vessels after surgery. The operation time was (170.3±57.7)minutes in the APOT group and (235.0±80.2)minutes in the routine surgery group,and the difference was statistically significant ( t=-3.800, P<0.01). The APOT group also experienced less intraoperative blood loss(650(588)ml vs. 800(600)ml; U=1 026.500, P=0.021). No significant differences were found between the groups in combined vein resection and reconstruction,celiac trunk resection,early postoperative complications, readmission rates at 30 days,and postoperative length of stay(all P>0.05). Extra-arterial dissection was performed in all patients,with arterial resection and reconstruction in 3 cases: 2 cases in the APOT group(1 case involving the superior mesenteric artery and 1 case involving the common hepatic artery) and 1 case in the routine group(involving the common hepatic artery). Postoperative abdominal bleeding occurred in 4 cases,with 3 cases in the routine group,1 case in the routine group. The R0 resection rate was 85.7%(24/28) in the APOT group and 80.4%(45/56) in the routine group,without significant differences between the groups( P=0.763). The median overall survival time was 27.6 months for the APOT group and 22.5 months for the routine group,while the median disease-free survival was 11.7 months and 16.8 months,respectively,with no significant differences between the two groups( P=0.532, P=0.927). Conclusion:The arterial pre-occlusion technique can be used for extra-arterial dissection in patients with locally advanced pancreatic cancer involving the arteries,reducing surgery time and intraoperative blood loss.

Objective:To investigate and compare the clinical outcomes of the arterial pre-occlusion technique(APOT) and the traditional technique in the surgery of locally advanced pancreatic cancer with arterial involvement after conversion therapy.Methods:This is a retrospective cohort study. The clinical data of 145 patients with locally advanced pancreatic cancer with arterial involvement admitted to the Department of Hepato-Biliary-Pancreatic Surgery of the First Hospital Affiliated to Naval Medical University,from January 2020 to December 2022 were retrospectively analyzed. All patients completed neoadjuvant therapy for tumors, and the feasibility of radical surgical treatment was determined by a multidisciplinary collaborative team evaluation before surgery. According to whether the intraoperative artery was pre-occluded, 145 patients were divided into two groups, including 28 cases in the APOT group(16 males, 12 females, aged (59.0±9.4) years), and 117 cases in the routine surgery group(76 males, 41 females, aged (55.1±8.2) years). To ensure comparability of baseline data between the APOT group and the routine surgery group, a 1∶2 match was performed using the propensity score matching method, and the caliper value was 0.006 45. The t-test,the Mann-Whitney U test, χ2 test or Fisher′s exact test were used to compare the data between the two groups,respectively. Results:After matching the propensity score,there were 28 cases in the APOT group and 56 cases in the routine surgery group. There were no significant differences in gender,age,preoperative comorbidities,preoperative body mass index,surgical approaches,chemotherapy regimen,stereotactic body radiation therapy ratio,tumor markers,and type of invaded artery between the two groups (all P>0.05).The arterial occlusion time M(IQR) in the APOT group was 7.0(3.8)minutes(range:3 to 15 minutes),and no ischemic manifestations were observed in the distal target organs that blocked blood vessels after surgery. The operation time was (170.3±57.7)minutes in the APOT group and (235.0±80.2)minutes in the routine surgery group,and the difference was statistically significant ( t=-3.800, P<0.01). The APOT group also experienced less intraoperative blood loss(650(588)ml vs. 800(600)ml; U=1 026.500, P=0.021). No significant differences were found between the groups in combined vein resection and reconstruction,celiac trunk resection,early postoperative complications, readmission rates at 30 days,and postoperative length of stay(all P>0.05). Extra-arterial dissection was performed in all patients,with arterial resection and reconstruction in 3 cases: 2 cases in the APOT group(1 case involving the superior mesenteric artery and 1 case involving the common hepatic artery) and 1 case in the routine group(involving the common hepatic artery). Postoperative abdominal bleeding occurred in 4 cases,with 3 cases in the routine group,1 case in the routine group. The R0 resection rate was 85.7%(24/28) in the APOT group and 80.4%(45/56) in the routine group,without significant differences between the groups( P=0.763). The median overall survival time was 27.6 months for the APOT group and 22.5 months for the routine group,while the median disease-free survival was 11.7 months and 16.8 months,respectively,with no significant differences between the two groups( P=0.532, P=0.927). Conclusion:The arterial pre-occlusion technique can be used for extra-arterial dissection in patients with locally advanced pancreatic cancer involving the arteries,reducing surgery time and intraoperative blood loss.

Objective:To observe the effects of ointment and massage on inflammation, oxidative stress and angiogenesis after skeletal muscle trauma, and to explore their mechanisms.Methods:Forty-two adult male Sprague-Dawley rats were randomly divided into a blank group ( n=6), an ointment and massage (O&M) group ( n=18) and a model group ( n=18). The blunt contusion model of gastrocnemius malformation was established in both the O&M and model groups using self-made percussion instruments. Two hours after successful modeling, the anti-inflammatory pain-relieving cream was applied to the injured area, and massaged evenly and gently for 5 minutes. That was repeated with an interval of 12 hours. No treatment was given to the model and blank groups. On the 1st, 3rd and 7th days after modeling, injured gastrocnemius muscles were resected after collecting abdominal blood. Hematoxylin-eosin (HE) staining and immunofluorescent (CD34) staining were applied, and serum superoxide dismutase (SOD) and malondialdehyde (MDA) contents were detected. Results:HE staining showed that at each time point the gastrocnemius muscle fibers of the model group were significantly more swollen and deformed, collapsed and dissolved than those of the blank group, with a large number of inflamed cells. The O&M group had better recovery, with more newly-generated muscle cells, less inflammatory infiltration and more normal cell shapes than the model group. Fluorescence was stronger in the O&M and model groups than in the blank group at each time point, with that of the O&M group significantly stronger than in the model group. The average SOD and MDA levels in the model and O&M groups were significantly higher than in the blank group, and on the 1st and 3rd days the O&M group′s average SOD level was significantly higher than the model group′s average, though by the 7th day there was no significant difference. The average MDA content of the O&M group was significantly lower than the model group′s average at each time point.Conclusion:Ointment and massage can effectively reduce the local inflammatory response and oxidative stress after a skeletal muscle injury. They can accelerate local angiogenesis, promoting the repair of damaged tissues.

Objective:To retrospectively construct competency-based portfolios for medical students to analyze the factors influencing competency self-assessment, and to explore an approach to efficient portfolio construction.Methods:The participants were randomly selected among medical graduates of 2015 in Shantou University Medical College. Through records collection and an online questionnaire survey, portfolios were built for the participants based on their development data during eight years from college entrance, college education, to post-graduation medical education. The correlation between variables was determined using Kendall's tau-b correlation coefficients. The inter-group differences were analyzed using the Mann-Whitney U test. Results:A total of 126 usable questionnaires for effective developmental portfolios were collected. There were a total of 208 indicators collected, including 79 questionnaire indicators (including 36 for competency self-assessment). The reliability coefficient (Cronbach's α) of the questionnaire was 0.984. The factors related to competency self-assessment were identified. Conclusion:This study provides a basis for the implementation of portfolio assessment, which can promote students' self-assessment and competency development. Optimizing the indicator system, building an online platform, increasing participants' participation motivation, and emphasizing self-reflection and feedback will help improve the efficiency of developmental portfolio construction and its performance.

Objective:To analyze the risk factors of clinically significant bleeding in patients with severe acute pancreatitis (SAP).Methods:The clinical data of SAP patients who were managed at Changhai Hospital affiliated to Naval Medical University from January 1, 2014 to October 31, 2022 were retrospectively analyzed. Twenty-nine SAP patients with clinically significant bleeding were classified to form the bleeding group. There were 23 males and 6 females, aged (56.25±14.01) years old. Another 116 SAP patients with similar general data but with no clinically significant bleeding during the same hospitalization period were included to form the non-bleeding group based on a ratio of 1∶4. There were 94 males and 22 females, aged (56.14±13.96) years old in this non-bleeding group. The general data, modified CT severity index (MCTSI), bedside index for severity of acute pancreatitis (BISAP) and other clinical data of the two groups were collected to determine the risk factors of bleeding in SAP patients.Results:Of the 29 patients with bleeding, 6 had gastrointestinal bleeding, 14 had intra-abdominal bleeding, and 9 had mixed bleeding sites, 15 were cured and discharged, and 14 died. All the 29 SAP patients with bleeding received treatment using drugs. In addition, 8 patients underwent successful hemostasis using digital subtraction angiography, 3 underwent successful endoscopic hemostasis, 2 underwent successful surgical hemostasis, and 2 underwent successful conservative drug hemostasis. Multivariate logistic regression analysis showed that SAP patients with higher MCTSI ( OR=1.824, 95% CI: 1.187-2.802), longer prothrombin time (PT) ( OR=3.431, 95% CI: 1.470-8.007) and higher BISAP ( OR=2.286, 95% CI: 1.054-4.957) had an increased risk of bleeding (all P<0.05). Conclusion:The prognosis of SAP patients was compromised with bleeding. High MCTSI, prolonged PT, and high BISAP were independent risk factors for bleeding in SAP patients.

Objective:To investigate the cause of misdiagnosis of neck, shoulder, waist, and leg pain caused by bone metastases and to improve the outpatient diagnosis rate.Methods:Five misdiagnosed cases of bone metastases who were admitted to the Traditional Chinese Medicine Department of Orthopedics and Traumatology, School of Traditional Chinese Medicine, Southern Medical University from January 2019 to July 2020 were included in this study. Their clinical manifestations, diagnosis results (outside hospital diagnosis and outpatient diagnosis), and imaging manifestations were retrospectively analyzed.Results:Five cases of bone metastases were misdiagnosed to have cervical spondylosis, lumbar disc herniation, femoral head necrosis, femoral shaft fracture, and ankle sprain. Accelerated red blood cell sedimentation rate and increased C-reactive protein level were found in all five cases. Bone metastases were confirmed by X-ray, CT, and MRI examination results. All of them had warning signs for bone metastasis: age > 50 years, history of a tumor, unexplained weight loss, general malaise, neck, shoulder, waist, and leg pain without an obvious cause, sudden worsening of pain, night pain, resting pain, pain on direct palpation, no obvious improvements in these symptoms after symptomatic treatment for 1 month, disease development not conforming to the general law of cervical spondylosis, lumbar disc herniation, femoral head necrosis, femoral shaft fracture, and ankle sprain, increases in red blood cell sedimentation rate, C-reactive protein, and alkaline phosphatase levels, which are not consistent with the symptoms of cervical spondylosis, lumbar disc herniation, femoral head necrosis, femoral shaft fracture, and ankle sprain, and slight external force leading to fractures.Conclusion:Further tests and imaging examinations should be performed according to warning signs. Clinical schemes of malignant bone tumors suitable for general practitioners can easily, economically, and effectively identify malignant bone tumors.

Objective To assess the efficacy of tenofovir disoproxil fumarate (TDF) in chronic hepatitis B (CHB) patients receiving antiviral therapy for three years. Methods A total of 157 CHB patients treated with TDF alone for ≥3 years from January 2015 to August 2020 in the Second Affiliated Hospital of Xi'an Jiaotong University were retrospectively studied. The patients were divided into HBeAg-positive and HBeAg-negative groups based on their baseline HBeAg levels. The data of serum HBV DNA and HBsAg levels at baseline, the first, second and third year of treatment were collected to analyze the dynamic changes. The t -test was used to compare continuous variables with normal distributions between two groups, while the Mann-Whitney U test was used to compare continuous variables with non-normal distribution between two groups. Repeated measurement data with non-normal distribution were first transformed into logarithms and the intra- or between-group comparison was performed using repeated measures analysis of variance. The chi-square test or Fisher exact test was used to compare categorical variables between groups. Results HBV DNA clearance rate in HBeAg-positive patients was significantly lower than that in HBeAg-negative patients during the first and second years of TDF treatment (1st year: 65.8% vs 81.0%, χ 2 =4.676, P < 0.05; 2nd year: 87.7% vs 98.8%, Fisher exact test, P < 0.05). When TDF treatment was given for three years, there was no significant difference in HBV DNA clearance rates (97.3% vs 100%, Fisher exact test, P > 0.05). The baseline HBsAg levels in HBeAg-positive and HBeAg-negative patients were 10 633.6 (2 084.8-24 005.7) IU/mL and 1 402.8 (311.0-2 863.5) IU/mL, respectively, and decreased to 1 534.9 (912.7-5 885.9) IU/mL and 677.8 (119.4-1 974.8) IU/mL after 3 years of TDF treatment, with a significant difference between two groups ( F =25.456, P < 0.001). In HBeAg-positive patients, the median decline value of HBsAg level was significantly higher in the first year [1 856.5 (158.4-12 103.1) IU/mL] than in the second year [879.8 (130.5-2 382.5) IU/mL] or the third year [479.9 (95.0-1 662.4) IU/mL] ( F =10.972, P < 0.001), while there was no significant difference in HBeAg-negative patients ( F =0.513, P > 0.05). In addition, after 3 years of TDF treatment, 59.2% of patients achieved HBsAg < 1500 IU/mL, with a HBsAg negative rate of 1.3%. Conclusion After 3 years of TDF treatment, all HBeAg-negative CHB patients can achieve HBV DNA negative conversion; for HBeAg-positive CHB patients, 97.3% of them achieved HBV DNA negative conversion, while 2.7% of them were still HBV DNA detectable. The HBsAg level declined over treatment time, and the decline rate of HBsAg level in HBeAg positive patients showed a trend of "first fast and then slow". After 3 years of TDF treatment, 59.2% of patients achieved HBsAg < 1500 IU/mL.

Objective: To investigate the image quality of ultralow-dose CT (ULDCT) of the chest reconstructed using a cycle-consistent generative adversarial network (CycleGAN)-based deep learning method in the evaluation of pulmonary tuberculosis. Materials and Methods: Between June 2019 and November 2019, 103 patients (mean age, 40.8 ± 13.6 years; 61 men and 42 women) with pulmonary tuberculosis were prospectively enrolled to undergo standard-dose CT (120 kVp with automated exposure control), followed immediately by ULDCT (80 kVp and 10 mAs). The images of the two successive scans were used to train the CycleGAN framework for image-to-image translation. The denoising efficacy of the CycleGAN algorithm was compared with that of hybrid and model-based iterative reconstruction. Repeated-measures analysis of variance and Wilcoxon signedrank test were performed to compare the objective measurements and the subjective image quality scores, respectively. Results: With the optimized CycleGAN denoising model, using the ULDCT images as input, the peak signal-to-noise ratio and structural similarity index improved by 2.0 dB and 0.21, respectively. The CycleGAN-generated denoised ULDCT images typically provided satisfactory image quality for optimal visibility of anatomic structures and pathological findings, with a lower level of image noise (mean ± standard deviation [SD], 19.5 ± 3.0 Hounsfield unit [HU]) than that of the hybrid (66.3 ± 10.5 HU, p < 0.001) and a similar noise level to model-based iterative reconstruction (19.6 ± 2.6 HU, p > 0.908). The CycleGAN-generated images showed the highest contrast-to-noise ratios for the pulmonary lesions, followed by the model-based and hybrid iterative reconstruction. The mean effective radiation dose of ULDCT was 0.12 mSv with a mean 93.9% reduction compared to standard-dose CT. Conclusion The optimized CycleGAN technique may allow the synthesis of diagnostically acceptable images from ULDCT of the chest for the evaluation of pulmonary tuberculosis.