[Objective]To simulate the biomechanics mechanism and environment of humeral fracture caused by indirect impact force for the purpose of biomechanics understanding and treatment of such fracture.[Method]Based on the data source, which was high-resolution anatomic slice images from approximal clavicle to distal humerus, 1 mm thickness and totally 380 layers, the geometric model of total shoulder joint was established according to the order:point, line,area, and further meshed to set up the three dimension finite element model of shoulder, fracture sites and instantaneous stress and strain of humerus were simulated and analyzed under the condition which longitudinal impact force was loaded on the humerus based on the 12 functional positions of shoulder(abduction 30?、 45?、 60?、 90?, and simultaneous neutrality, internal rotation 45?,external rotation 45?).[Result]According to the humeral shaft load-strain curve in different functional positions of shoulder, linear relation was found when load changed from 0 N to 250 N, after which non-linear come out, and even load was removed , bone was deformed eternally. With the rise in load amount, the increase in stress was detected. When abduction degree changed from 90? to 30?, the strain of humerus, both the lateral and the medial increased gradually,and increase in internal rotation 45?and external rotation 45? was more significant than that in neutrality. Meanwhile, stress difference could be seen between the lateral and the medial , and medial was larger than the lateral. Increase in stress in rotation positions was quicker and more than that in other functional positions.[Conclusion]Based on 4 abduction degrees (30?, 45?, 60?, 90?) and 3 rotation degrees(neutrality, internal rotation 45?,external rotation 45?) ,the three dimensional finite element shoulder could simulate precisely stress, strain, general trend of fracture line, three dimension images of bone failure. Three dimension finite element simulation and analysis of shoulder is a valuable mechanical method for research on biomechanics theory related to humerus fracture.

BACKGROUND: It has been reported tbat there are rich expressions of serotonin transporter (5-HTT) in the cortical and limbic regions related to emotion and behavior in cerebrum. Regulation of the intensity and persistence of serotonergic nerve response can change the serotonergic neurotransmission, meanwhile, 5-HTT is also an important target for selective serotonin reuptake inhibitors (SSRIs).OBJECTIVE: To observe whether there is a correlation of 5-HTT gene polymorphism with plasma level of 5-HT and the clinical response of SSRIs in the population of Nanjing area.DESIGN: A case-control observation.SETTING: Department of Psychiatry, Brain Hospital of Nanjing Medical University.PARTICIPANTS: Totally 132 inpatients with depression in the Department of Psychiatry, Brain Hospital of Nanjing Medical University and 100 volunteer healthy blood donors were taken as the observational subjects between January 2001 and December 2003.METHODS: The genotype was analyzed with polymerase chain reaction (PCR) polymorphism analysis in the patients with depression and healthy subjects; plasma level of 5-HT was analyzed with high performance liquid chromatography-electrical chemistry detector (HPLC-ECD); and the clinical response to the antidepressants were assessed with Hamilton depression rating scale (HAMD).MAIN OUTCOME MEASURES: The analytical results of 5-HTT genotype frequency and allele frequency in both groups, and the relationship between 5-HTT genotype and plasma level of 5-HT before and after SSRIs treatment were observed.RESULTS: Blood samples were collected from all the 132 patients with depression and 100 normal healthy subjects, and they all finished the scale test and entered the analysis of results. ① There were no significant differences between the depression group and normal control group in the 5-HTT gene genotype frequencies (LL: 24.2%, LS: 44.7%, SS31.1%; LL:29.0%, LS: 47.0%, SS: 24.0%, x2=1.405 8, P ＞ 0.05) and allelefrequencies (L:46.59%, S: 53.41%; L: 52.5%, S: 47.5%, x2=0.696 2, P ＞ 0.05). ② The total score of HAMD had significant differences before treatment among the depressive patients of different genotypes (F=6.48, P=0.002 1). After 4-week treatment of SSRIs antidepressants, the total score of HAMD was significantly decreased, and there was significant difference in the decrease of score (F=3.38, P= 0.037). ③ The plasma level of 5-HT had significant differences before treatment among the depressive patients of different genotypes (F=5.38,P= 0.005 7). After 4-week treatment of SSRIs antidepressants, the plasma level of 5-HT was increased, and the increased level was significantly different among different genotypes (F=23.55, P ＜ 0.01).CONCLUSION: The 5-HTT polymorphism may be not associated with the attack of depression, but with the severity of depression and the clinical responses of SSRIs in the population of Nanjing area, and the genotype in this area may become a reference index for the realization of individualized treatment in patients with depression.

BACKGROUND: Monoamine hypothesis has been demonstrated by researches. However, the correlation between the metabolite of plasma monoamine neurotransmitter and anti-depression treatment in patients with depression has less been reported.OBJECTIVE: To study the effect of different drugs on metabolite of plaama monoamine neurotransmitter, and the correlation between the metabolite of plasma monoamine neurotransmitter and anti-depression treatment in patients with depression.DESIGN: Case controlled study.SETTING: Neurological Department and Brain Institute of Nanjing Medical University.PARTICIPANTS: Forty patients with depression hospitalized in Nanjing Brain Hospital (depression group) were diagnosed with the second revised edition of China classification of mental diseases(CCMD-2) and the tenth edition of International classification of diseases. And the total score of Hanmilton rating scale for depression(HAMD) was more than 17. Healthy voluntary blood donators in the control group were from Nanjing Municipal Central Blood Station( n = 20).INTERVENTIONS: Antidepressant was used in the depression for 4 weeks: fluoxetine 20 mg per day; 5-serotonin selective reuptake inhibitor (SSRI) paroxetine 20 mg per day; venlafaxime 50- 100 mg per day;5-serotonin and morepinephrine selective reuptake inhibitor(SNRI) fluvoxamine 50-100 mg per day. High performance liquid chromatograpy(HPLC)was used to measure the level of metabolite of plasma monoamine neurotransmitter in patients with depression before and 42 week after treatment, and the HAMD was used to evaluate clinical effect of the patients.MAIN OUTCOME MEASURES: The levels of metabolites of plasma monoamine neurotransmitters in patients with depression: 5-hydroxyindoleace tic acid(5-HIAA), 3-methoxy-4-hydroxyphenylglycol(MHPG) and homovani llic acid(HVA) were measured before and 4th week after treatment.RESULTS: The levels of 5-HIAA, MHPG and HVA of the metabolites of plasma monoamine neurotransmitters in patients with depression before treatment [ (20.3±14.6), (124.8±103.6), (54.7±32.1) μg/L] were all lower than those in the normal control group[ (39.5±28.4), (334.5 ±107.3), (88.5±37.2) μg/L], with statistically significant differences (P＜0.05). After SSRI treatment, the 5-HIAA content[ (37.1±21.9)μg/L]was significantly increased as compared with that before treatment, whose difference indicated significant meaning ( P＜0.05), but the differences in MHPG and HVA had no significant meaning as compared with those before treatment(P＞0.05) . After SNRI treatment, 5-HIAA and MHPG contents [(35.4±25.2 ), (291.2±120.4) μg/L] both were significantly increased, which indicated significant difference as compared with those before treatment( P＜0.05); but HVA level had no significant changes.CONCLUSION:'The peripheral neurotransmitter metabolites in plasma can reflect their states in brain. The change of neurotransmitter metabolite in plasma can be regarded as an important reference index for the evaluation of depression.

BACKGROUND:In recent decades, total knee arthroplasty is widely used in the treatment of terminal knee joint diseases, such as osteoarthritis, rheumatoid arthritis, traumatic arthritis and other bone diseases. The methods of osteotomy, soft tissue balance and prosthesis rotation positioning have always been debated and discussed in total knee arthroplasty. OBJECTIVE:To explore the repair effect of total knee arthroplasty for terminal knee disease. METHODS:Total knee arthroplasty was performed for treating terminal knee disease in 31 cases (31 knees), including 26 cases of osteoarthritis (26 knees) and 5 cases of rheumatoid arthritis (5 knees). Al cases accompanied flexion contracture deformity to different degrees. The maximum angle of flexion deformity was < 25°. Al patients were scored by hospital for special surgery knee score before and after replacement. Al 31 knees were treated with fixed platform posterior-stabilized prostheses. RESULTS AND CONCLUSION:No complications, such as early infection and prosthesis dislocation, were found after surgery. Joint pain apparently lessened, flexion and varus deformity obviously improved after replacement. Postoperative X-ray films showed good prosthesis position and low limb alignment. Al cases were folowed up for 6-12 months. The hospital for special surgery knee score improved significantly from preoperatively 46.4±5.3 to postoperatively 84.6±10.5 after 6 months of folow-up. Excelent and good rate was 84%. Results indicate that total knee arthroplasty for treating terminal knee disease has a good clinical effect. However, the operation is complex and precise technique is required.

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment landscape for chronic myeloid leukemia (CML). However, TKI resistance poses a significant challenge, leading to treatment failure and disease progression. Resistance mechanisms include both BCR::ABL1-dependent and BCR::ABL1-independent pathways. The mechanisms underlying BCR::ABL1 independence remain incompletely understood, with CML cells potentially activating alternative signaling pathways, including the AKT/mTOR and JAK2/STAT5 pathways, to compensate for the loss of BCR::ABL1 kinase activity. This study explored tumoral VISTA (encoded by VSIR) as a contributing factor to TKI resistance in CML patients and identified elevated tumoral VISTA levels as a marker of resistance and poor survival. Through in vitro and in vivo analyses, we demonstrated that VSIR knockdown and the application of NSC-622608, a novel VISTA inhibitor, significantly impeded CML cell proliferation and induced apoptosis by attenuating the AKT/ mTOR and JAK2/STAT5 pathways, which are crucial for CML cell survival independent of BCR::ABL1 kinase activity. Moreover, VSIR overexpression promoted TKI resistance in CML cells. Importantly, the synergistic effect of NSC-622608 with TKIs offers a potent therapeutic avenue against both imatinib-sensitive and imatinib-resistant CML cells, including those harboring the challenging T315I mutation. Our findings highlight the role of tumoral VISTA in mediating TKI resistance in CML, suggesting that inhibition of VISTA, particularly in combination with TKIs, is an innovative approach to enhancing treatment outcomes in CML patients, irrespective of BCR::ABL1 mutation status. This study not only identified a new pathway contributing to TKI resistance but also revealed the possibility of targeting tumoral VISTA as a means of overcoming this significant clinical challenge.

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment landscape for chronic myeloid leukemia (CML). However, TKI resistance poses a significant challenge, leading to treatment failure and disease progression. Resistance mechanisms include both BCR::ABL1-dependent and BCR::ABL1-independent pathways. The mechanisms underlying BCR::ABL1 independence remain incompletely understood, with CML cells potentially activating alternative signaling pathways, including the AKT/mTOR and JAK2/STAT5 pathways, to compensate for the loss of BCR::ABL1 kinase activity. This study explored tumoral VISTA (encoded by VSIR) as a contributing factor to TKI resistance in CML patients and identified elevated tumoral VISTA levels as a marker of resistance and poor survival. Through in vitro and in vivo analyses, we demonstrated that VSIR knockdown and the application of NSC-622608, a novel VISTA inhibitor, significantly impeded CML cell proliferation and induced apoptosis by attenuating the AKT/ mTOR and JAK2/STAT5 pathways, which are crucial for CML cell survival independent of BCR::ABL1 kinase activity. Moreover, VSIR overexpression promoted TKI resistance in CML cells. Importantly, the synergistic effect of NSC-622608 with TKIs offers a potent therapeutic avenue against both imatinib-sensitive and imatinib-resistant CML cells, including those harboring the challenging T315I mutation. Our findings highlight the role of tumoral VISTA in mediating TKI resistance in CML, suggesting that inhibition of VISTA, particularly in combination with TKIs, is an innovative approach to enhancing treatment outcomes in CML patients, irrespective of BCR::ABL1 mutation status. This study not only identified a new pathway contributing to TKI resistance but also revealed the possibility of targeting tumoral VISTA as a means of overcoming this significant clinical challenge.

Objective:To compare the efficacy and safety of bi-level positive airway pressure (BiPAP) ventilation and heated humidified high flow nasal cannula (HHHFNC) ventilation as initial respiratory support for premature infants with respiratory distress syndrome (RDS).Methods:From January 2019 to June 2021, premature infants [gestational age (GA) 28~35 weeks)] with grade Ⅰ to Ⅲ RDS admitted to Suining County People's Hospital were prospectively enrolled. The infants were randomly assigned into BiPAP group and HHHFNC group. The clinical characteristics, ventilation efficacy and complications were analyzed.Results:A total of 33 infants were in BiPAP group and 32 in HHHFNC group. No significant differences existed between the two groups in the following items: the frequency of apnea within 24 h of ventilation, FiO 2 and PaCO 2 at 24 h, the use of pulmonary surfactant (PS), the incidence of non-invasive ventilation failure within 72 h, non-invasive ventilation duration and the age achieving total enteral nutrition. HHHFNC group had lower score in premature infants pain profile (PIPP) than BiPAP group at 24 h of non-invasive ventilation [4 (3, 6) vs. 8 (6, 11), P<0.001]. No significant differences existed in nasal injury, pneumothorax, intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia and mortality rate between the two groups ( P>0.05). Conclusions:As the initial treatment for premature infants with grade Ⅰ to Ⅲ RDS, BiPAP and HHHFNC has similar rates of non-invasive ventilation failure within 72 h,non-invasive ventilation duration and adverse events. HHHFNC may ease the pain of the infants.

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment landscape for chronic myeloid leukemia (CML). However, TKI resistance poses a significant challenge, leading to treatment failure and disease progression. Resistance mechanisms include both BCR::ABL1-dependent and BCR::ABL1-independent pathways. The mechanisms underlying BCR::ABL1 independence remain incompletely understood, with CML cells potentially activating alternative signaling pathways, including the AKT/mTOR and JAK2/STAT5 pathways, to compensate for the loss of BCR::ABL1 kinase activity. This study explored tumoral VISTA (encoded by VSIR) as a contributing factor to TKI resistance in CML patients and identified elevated tumoral VISTA levels as a marker of resistance and poor survival. Through in vitro and in vivo analyses, we demonstrated that VSIR knockdown and the application of NSC-622608, a novel VISTA inhibitor, significantly impeded CML cell proliferation and induced apoptosis by attenuating the AKT/ mTOR and JAK2/STAT5 pathways, which are crucial for CML cell survival independent of BCR::ABL1 kinase activity. Moreover, VSIR overexpression promoted TKI resistance in CML cells. Importantly, the synergistic effect of NSC-622608 with TKIs offers a potent therapeutic avenue against both imatinib-sensitive and imatinib-resistant CML cells, including those harboring the challenging T315I mutation. Our findings highlight the role of tumoral VISTA in mediating TKI resistance in CML, suggesting that inhibition of VISTA, particularly in combination with TKIs, is an innovative approach to enhancing treatment outcomes in CML patients, irrespective of BCR::ABL1 mutation status. This study not only identified a new pathway contributing to TKI resistance but also revealed the possibility of targeting tumoral VISTA as a means of overcoming this significant clinical challenge.

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment landscape for chronic myeloid leukemia (CML). However, TKI resistance poses a significant challenge, leading to treatment failure and disease progression. Resistance mechanisms include both BCR::ABL1-dependent and BCR::ABL1-independent pathways. The mechanisms underlying BCR::ABL1 independence remain incompletely understood, with CML cells potentially activating alternative signaling pathways, including the AKT/mTOR and JAK2/STAT5 pathways, to compensate for the loss of BCR::ABL1 kinase activity. This study explored tumoral VISTA (encoded by VSIR) as a contributing factor to TKI resistance in CML patients and identified elevated tumoral VISTA levels as a marker of resistance and poor survival. Through in vitro and in vivo analyses, we demonstrated that VSIR knockdown and the application of NSC-622608, a novel VISTA inhibitor, significantly impeded CML cell proliferation and induced apoptosis by attenuating the AKT/ mTOR and JAK2/STAT5 pathways, which are crucial for CML cell survival independent of BCR::ABL1 kinase activity. Moreover, VSIR overexpression promoted TKI resistance in CML cells. Importantly, the synergistic effect of NSC-622608 with TKIs offers a potent therapeutic avenue against both imatinib-sensitive and imatinib-resistant CML cells, including those harboring the challenging T315I mutation. Our findings highlight the role of tumoral VISTA in mediating TKI resistance in CML, suggesting that inhibition of VISTA, particularly in combination with TKIs, is an innovative approach to enhancing treatment outcomes in CML patients, irrespective of BCR::ABL1 mutation status. This study not only identified a new pathway contributing to TKI resistance but also revealed the possibility of targeting tumoral VISTA as a means of overcoming this significant clinical challenge.

Objective:To explore the effects of pelvic-abdominal mechanics exercises during pregnancy on improving pelvic floor function in primiparous women during the perinatal period.Methods:A single-center prospective study selected 200 primipara of singleton pregnancies with prenatal care and delivery established at Shanghai Tongren hospital from June 2022 to June 2023 as the study subjects. Participants were divided into two groups: the exercise group (100 cases) and the control group (100 cases) by using a random number table method, five participants dropped out of the study due to reasons such as follow-up failure. Ultimately, the exercise group consisted of 97 cases, while the control group consisted of 98 cases. Participants who engaged in pelvic-abdominal mechanics exercises for at least 3 months, exercising once a week, were included in the exercise group. Those who did not engage in exercise were included in control group. Comparing the two groups in terms of pregnancy discomfort symptoms, delivery outcomes, postpartum pelvic floor electromyography results, postpartum quality of life, and pelvic floor disease incidence. The statistical methods utilized included independent t-test, Pearson chi-square test, Fisher′s exact test, and Mann-Whitney U test. Results:In the late stage of pregnancy, the VAS score for low back pain was 5.05±1.22 in the exercise group and 5.47±1.55 in the control group, with a statistically significant difference ( t=2.090, P<0.05). The PFDI-20 score was 23.33±8.41 in the exercise group and 25.76±8.34 in the control group, with a statistically significant difference ( t=2.026, P<0.05). The PFIQ-7 score was 19.21±7.69 in the exercise group and 26.66±6.19 in the control group, with a statistically significant difference ( t=6.851, P<0.05). There was no statistically significant difference in sleep quality and incidence of urinary incontinence between the two groups in late pregnancy ( t=1.252, P=0.396, P>0.05). In terms of childbirth outcomes, the exercise group had a vaginal delivery rate of 81.44% (79 cases), while the control group had a rate of 64.28% (63 cases), with a statistically significant difference (χ 2=9.022, P<0.05). The duration of the second stage of labor was (42.68±21.38) minutes in the exercise group and (50.54±21.33) minutes in the control group, with a statistically significant difference ( t=2.178, P<0.05). At 42 days postpartum, the evaluation of pelvic floor function showed that the vaginal pressure in the exercise group was 62.19±10.04, while in the control group it was 52.68±15.55, with a statistically significant difference ( t=-5.074, P<0.05). The MOS grading in the exercise group was 3.82±1.26, whereas in the control group it was 2.34±1.55, with a statistically significant difference ( t=-7.355, P<0.05). In terms of the incidence of postpartum pelvic floor disorders, the occurrence of pelvic organ prolapse was 7.22% in the exercise group and 12.24% in the control group, with no statistically significant difference (χ 2=1.402, P>0.05). The occurrence rate of stress urinary incontinence was 13.4% in the exercise group and 30.61% in the control group, with a statistically significant difference ( P=0.015, P<0.05). Conclusion:Pelvic-abdominal mechanics exercises may have some advantages in reducing symptoms related to perinatal pelvic floor dysfunction, enhancing pelvic floor function, and preventing the occurrence of pelvic floor disease.