Objective:To analyze the effects of Mulligan technique combined with isokinetic exercise training (IET) on isokinetic muscle strength and neuromuscular control ability in patients with knee osteoarthritis (KOA).Methods:A retrospective case-control study was conducted. A total of 49 patients with KOA who underwent IET at Honghui Hospital Affiliated to Xi'an Jiaotong University from January 2021 to January 2022 were included in the control group. An additional 49 patients with KOA who received Mulligan technique and IET at the same hospital from June 2022 to June 2023 were included in the observation group. Both groups were treated for 8 successive weeks. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, Lysholm score, proprioception metrics [including average track error (ATE) and test time execution (TTE)], isokinetic muscle strength [peak torque (PT) and average power (AP) for flexors and extensors at 60°/s, 90°/s, and 120°/s)]were compared between the two groups before and after 4 and 8 weeks of intervention. Additionally, Visual Analog Scale score was compared between the two groups at baseline and after 8 weeks of intervention.Results:There was no statistically significant difference in WOMAC score, Lysholm score, or PT and AP levels for flexor and extensor muscles at 60°/s, 120°/s, and 180°/s between the two groups before intervention (all P > 0.05). After 4 and 8 weeks of intervention, the levels of PT and AP for both flexors and extensors at 60°/s, 120°/s, and 180°/s, as well as the Lysholm scores, were significantly higher in the observation group compared with the control group [PT level: t = -0.10, -3.03, -3.85, -0.35, -3.62, -3.95, -0.27, -5.51, -6.52, -1.13, -2.74, -3.68, -0.09, -2.91, -5.79, -0.13, -4.66, -6.05; AP level: t = -0.23, -4.77, -6.15, 0.01, -3.10, -3.75, -0.13, -3.73, -3.44, 0.16, -2.09, -4.05, -0.17, -3.71, -3.51, -0.27, -3.26, -3.69; Lysholm score: t = -7.17, -6.44; all P < 0.05]. After 4 and 8 weeks of intervention, the WOMAC score, ATE, and TTE in the observation group were significantly lower than those in the control group [WOMAC score: t = 3.68, 0.64; ATE level: t = 3.88, 4.13; TTE level: t = 4.86, 4.60; all P < 0.05]. After 8 weeks of intervention, both groups had lower Visual Analog Scale scores compared with their scores before the intervention (U control group = -8.75, U observation group = -8.63), with the observation group showing significantly lower scores than the control group ( U = -5.95, P < 0.001). Conclusions:The Mulligan technique combined with IET can effectively alleviate knee joint pain in patients with KOA, promote the recovery of knee joint function, enhance proprioceptive recovery, and improve neuromuscular control abilities.

Objective:To analyze the effects of Mulligan technique combined with isokinetic exercise training (IET) on isokinetic muscle strength and neuromuscular control ability in patients with knee osteoarthritis (KOA).Methods:A retrospective case-control study was conducted. A total of 49 patients with KOA who underwent IET at Honghui Hospital Affiliated to Xi'an Jiaotong University from January 2021 to January 2022 were included in the control group. An additional 49 patients with KOA who received Mulligan technique and IET at the same hospital from June 2022 to June 2023 were included in the observation group. Both groups were treated for 8 successive weeks. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, Lysholm score, proprioception metrics [including average track error (ATE) and test time execution (TTE)], isokinetic muscle strength [peak torque (PT) and average power (AP) for flexors and extensors at 60°/s, 90°/s, and 120°/s)]were compared between the two groups before and after 4 and 8 weeks of intervention. Additionally, Visual Analog Scale score was compared between the two groups at baseline and after 8 weeks of intervention.Results:There was no statistically significant difference in WOMAC score, Lysholm score, or PT and AP levels for flexor and extensor muscles at 60°/s, 120°/s, and 180°/s between the two groups before intervention (all P > 0.05). After 4 and 8 weeks of intervention, the levels of PT and AP for both flexors and extensors at 60°/s, 120°/s, and 180°/s, as well as the Lysholm scores, were significantly higher in the observation group compared with the control group [PT level: t = -0.10, -3.03, -3.85, -0.35, -3.62, -3.95, -0.27, -5.51, -6.52, -1.13, -2.74, -3.68, -0.09, -2.91, -5.79, -0.13, -4.66, -6.05; AP level: t = -0.23, -4.77, -6.15, 0.01, -3.10, -3.75, -0.13, -3.73, -3.44, 0.16, -2.09, -4.05, -0.17, -3.71, -3.51, -0.27, -3.26, -3.69; Lysholm score: t = -7.17, -6.44; all P < 0.05]. After 4 and 8 weeks of intervention, the WOMAC score, ATE, and TTE in the observation group were significantly lower than those in the control group [WOMAC score: t = 3.68, 0.64; ATE level: t = 3.88, 4.13; TTE level: t = 4.86, 4.60; all P < 0.05]. After 8 weeks of intervention, both groups had lower Visual Analog Scale scores compared with their scores before the intervention (U control group = -8.75, U observation group = -8.63), with the observation group showing significantly lower scores than the control group ( U = -5.95, P < 0.001). Conclusions:The Mulligan technique combined with IET can effectively alleviate knee joint pain in patients with KOA, promote the recovery of knee joint function, enhance proprioceptive recovery, and improve neuromuscular control abilities.

Objective:To understand the clinical characteristics of rivaroxban-related adverse events (AE) in perioperative patients.Methods:The relevant databases at home and abroad (as of April 20, 2020) were searched and the case reports of AE associated with rivaroxban used during perioperative period were collected. Relevant information in patients (nationality, gender, age, medical history, application of rivaroxaban, combined drugs, and the occurrence, treatment, and outcome of AE, etc.) was extracted and analyzed descriptively.Results:A total of 42 case reports of AE caused by rivaroxban during perioperative period were collected, involving 46 patients from 11 countries. Of the 46 patients, 25 (54.3%) were male and 21 (45.7%) were female with an age of 16-96 years. In terms of the reasons for medication, 34 patients used rivaroxban before operation for prevention of postoperative venous thrombosis, 7 used rivaroxban after operation for prevention atrial fibrillation, stroke, or systemic thrombosis after operation, 4 discontinued rivaroxban during perioperative period, and 1 did not explain the reason for using rivaroxban. Past medical history were described in 21 patients, including hypertension, hyperlipidemia, and diabetes, etc. Combined medication was described in 22 patients, including antibiotics, non-steroidal anti-inflammatory drugs, analgesics, cardiovascular and cerebrovascular drugs, etc. The onset time of AE was recorded in 31 patients, which was 2 hours to 2 months after medication and most within 1 month. AE associated with rivaroxban were bleeding in 29 patients, liver injury in 7 patients, anaphylaxis in 6 patients, kidney injury in 3 patients, thrombosis in 3 patients, thrombocythemia in 2 patients, thrombocytopenia, pulmonary embolism, acute attack of coronary atherosclerotic heart disease, and visual loss in 1 patient each. After the occurrence of AE, 31 patients were improved after rivaroxban withdrawn, switching to other anticoagulants, and receiving symptomatic treatment; 1 patient improved after changing concomitant medications as well as reducing the dose of rivaroxban; 2 patients did not stop the drug in time and developed new allergic reaction; 2 patients were improved after using rivaroxban again; 1 patient died of hemorrhagic shock due to gastrointestinal bleeding; 9 patients′ outcome were unknown. Among the 46 patients, 18 had medication errors, of which 16 had dose error and 2 had compatibility errors.Conclusions:Hemorrhage is the most common AE related to rivaroxban in the perioperative use of rivaroxban, which mainly occurs within 1 month after medication. The overall prognosis is good after rivaroxban withdrawal, switching to other anticoagulants, and symptomatic treatment. Medication error is one of the causes of AE related to rivaroxban in perioperative period.

Objective:To understand the clinical characteristics of rivaroxban-related adverse events (AE) in perioperative patients.Methods:The relevant databases at home and abroad (as of April 20, 2020) were searched and the case reports of AE associated with rivaroxban used during perioperative period were collected. Relevant information in patients (nationality, gender, age, medical history, application of rivaroxaban, combined drugs, and the occurrence, treatment, and outcome of AE, etc.) was extracted and analyzed descriptively.Results:A total of 42 case reports of AE caused by rivaroxban during perioperative period were collected, involving 46 patients from 11 countries. Of the 46 patients, 25 (54.3%) were male and 21 (45.7%) were female with an age of 16-96 years. In terms of the reasons for medication, 34 patients used rivaroxban before operation for prevention of postoperative venous thrombosis, 7 used rivaroxban after operation for prevention atrial fibrillation, stroke, or systemic thrombosis after operation, 4 discontinued rivaroxban during perioperative period, and 1 did not explain the reason for using rivaroxban. Past medical history were described in 21 patients, including hypertension, hyperlipidemia, and diabetes, etc. Combined medication was described in 22 patients, including antibiotics, non-steroidal anti-inflammatory drugs, analgesics, cardiovascular and cerebrovascular drugs, etc. The onset time of AE was recorded in 31 patients, which was 2 hours to 2 months after medication and most within 1 month. AE associated with rivaroxban were bleeding in 29 patients, liver injury in 7 patients, anaphylaxis in 6 patients, kidney injury in 3 patients, thrombosis in 3 patients, thrombocythemia in 2 patients, thrombocytopenia, pulmonary embolism, acute attack of coronary atherosclerotic heart disease, and visual loss in 1 patient each. After the occurrence of AE, 31 patients were improved after rivaroxban withdrawn, switching to other anticoagulants, and receiving symptomatic treatment; 1 patient improved after changing concomitant medications as well as reducing the dose of rivaroxban; 2 patients did not stop the drug in time and developed new allergic reaction; 2 patients were improved after using rivaroxban again; 1 patient died of hemorrhagic shock due to gastrointestinal bleeding; 9 patients′ outcome were unknown. Among the 46 patients, 18 had medication errors, of which 16 had dose error and 2 had compatibility errors.Conclusions:Hemorrhage is the most common AE related to rivaroxban in the perioperative use of rivaroxban, which mainly occurs within 1 month after medication. The overall prognosis is good after rivaroxban withdrawal, switching to other anticoagulants, and symptomatic treatment. Medication error is one of the causes of AE related to rivaroxban in perioperative period.

Objective To explore the influencing factors of the onset of autism spectrum disorder in male children.Methods Totally 151 male children with autism spectrum disorder were selected as case group and 119 healthy male children matched with the age of the case group in the same administrative region were taken as the control group.All children were assessed with the questionnaire for children's autism etiology and risk factors.Results (1) The differences in children having anorexia and partial eclipse (x2 =50.763,P＜0.01),father's age during pregnancy (x2 =11.441,P=0.043),place of pregnancy (x2 =50.763,P＜0.01),hypertension of pregnancy (x2 =5.693,P=0.026),intrauterine hypoxia (x2 =9.332,P=0.002),umbilical cord around the neck(x2 =18.483,P＜0.01),parents smoking and drinking history during pregnancy (x2 =13.660,P=0.008),parental smoking (x2 =12.901,P=0.005) and alcohol consumption (x2 =8.386,P=0.039) during pregnancy,birth height of child (x2 =8.870,P=0.031),amniotic fluid pollution (x2 =4.561,P=0.043),participation time of artificial feeding,major caregivers,delayed development indicators in infants and young children and whether or not the harmonious parent-child relationship were statistically significant(P＜0.05).(2) Children with anorexia and partial diet (OR =12.284,95％ CI =2.768-54.507),living in rural areas during pregnancy (OR =17.251,95％ CI =1.899-1 56.745),parents' history of smoking and drinking (OR =6.191,95％ CI =1.678-22.838),and intrauterine hypoxia during pregnancy (OR=38.859,95％CI=2.944-512.930) may be risk factors for male autism spectrum disorder.Conclusion To correct children's anorexia bias,improve the living environment in pregnancy,reduce pregnancy complications and avoid exposure to tobacco and alcohol pollution during maternal pregnancy can be an effective entry point for the prevention and control of autism spectrum disorders in male children.

Objective To study the expression of hypoxia inducible factor-1 (HIF-1 ) and Notch signaling pathway downstream gene HES 1 in the hippocampus of pubertal rats with status epilepsy (SE), and to explore the regulation site of HIF-1αin Notch signaling pathway. Methods One hundred and seventy-six 21-day-old SD rats were randomly divided into control group (NS group), pentetrazole (PTZ)-induced SE group (PTZ group), and Notch signaling pathway speciifc inhibitor (DAPT) intervention group (DAPT group). In PTZ group PTZ was intraperitoneally injected to build SE model and in NS group normal saline was injected as control. The intraperitoneal injection of diazepam was used to terminate SE seizures. After successful modeling, the bilateral hippocampuses were isolated after the rats were sacriifced at 0.5, 1, 2, 4 and 8 h, respectively, and RT-PCR was performed to detect the mRNA expression of HES 1 and HIF-1α. The Western Blot was performed to detect protein expression in hippocampuses which were collected at 2 , 4 , 8 , 12 , and 24 h after successful modeling. DAPT group received intraperitoneal injection of DAPT 30 min before the start of molding, then the hippocampuses were isolated at 2 and 8 h after successful modeling. RT-PCR was performed to detect the mRNA expression of HES 1 and HIF-1αat 2 h, and Western blot was performed to detect protein expression at 8 h. Results At each time point after SE, the expression of mRNA of HES 1 and HIF-1αand the expression of protein were higher than the same time point of NS group (P

Objective To explore the effects of Ginkgolide B on the expression of hypoxia inducible factor 1 α (HIF-1α) and P I3K/Akt pathway in the hippocampus of developing rats after pentylenetetrazol(PTZ)-induced status epilepticus,and to investigate the correlation between HIF-1α expression and PI3K/Akt pathway.Methods Ninety-six SD rats aged 21 days were randomly divided into normal saline group(group NS),status epilepticus group (group P),GKB treatment groups (group G+P),GKB +wortmannin treated group (group G+P+W),wortmannin treated group(group P+W).The brain tissue were harvested from the rats at 4 and 8 hours after the inducement,but in the group G+P at 1 h,4 h,8 h,24 h.Immunohistochemistry and Western blot were used respectively to detect HIF-1α and p-Akt protein expression.Results (1) For the group G+P,there were statistical differences in the expression levels of p-Akt protein between 1 h,4 h,8 h and 24 h(P＜0.01),The p-Akt protein reached the peak level at 4 hours (0.85±0.03),there were statistical differences in the expression levels of HIF-1α protein between 1 h,4 h,8 h and 24 h(P＜0.01),the HIF-1α expression reached the peak level at 8 hours(1.00±0.13).(2) The expression of HIF-1α in all the groups at 8 hours time point:the expression levels of HIF-1α in the group P and group G+P were significantly higher than those in the group NS (P＜0.01) and the expression levels of HIF1α in the group G+P were higher than those in the group P(P＜0.01).Using wortmannin,the PI3K/Akt specific inhibitor,HIF-1α protein expression in the group G+P+W and P+W was significantly decreased when compared with the group G+P and P (P＜0.01).(3)The expression of p-Akt in all the groups at 4 hours time point:the expression levels of p-Akt in the group P and group G+P were significantly higher than those in the group NS (P＜0.01) and the expression levels of p-Akt in the group G+P were higher than those in the group P (P＜ 0.01).Using wortmannin,p-Akt protein expression in the group G+P+W and P+W was significantly decreased when compared with the group G+P and P (P＜0.01).Conclusion GKB can activate PI3K/Akt signaling pathway,and the pathway is involved in regulating the expression of HIF-1α.

Objective To investigate the correlation between hypoxia-inducible factor-1α (HIF-1α) expression and activation of phosphatidyl inositol 3-kinase and serine/threonine kinase signal pathway in the hippocampus of developing rats after status epilepticus (SE).Methods Fifty-four SD rats aged 21 days were randomly divided into control group (n=24),SE group (n=24),wortmannin treatment group (n=6); SE rat models of the SE group were induced by intraperitoneal injection of 1％ 1,5-Pentamethylenetetrazole (PTZ); rats of the control group received injection of normal saline (NS); for wortmannin treatmnet group,the rats received intraperitoneal injection ofwortmannin 30 minutes before the inducement; the brain tissues were harvested from the rats at 1,4,8 and 24 h after the inducement,but only at 4 h in the wortmannin treatment group.The HIF-1α and Akt positive cells were detected with irnmunohistochemistry method.HIF-1α,Akt and p-Akt protein expressions were measured by Western blotting.Results In SE group,the HIF-1α expression began to occur at 1 h,significantly increased at 4 h after inducement,reached the peak level at 8 h,and began to decrease at 24 h; Akt protein positive cells showed no significant difference between each two time points; the p-Akt protein was significantly increased at 1 h,reached the peak level at 4 h and began to decrease at 8 h.However,the expression levels of HIF-1α and p-Akt protein in the control group were extremely low at each time point.So,the HIF-1α expression level in the SE vehicle group was significantly higher than that in the control group (P＜0.05); the p-Akt protein expression in SE group at 1,4 and 8 h was significantly higher than that in the control group (P＜0.05).The changes of Akt protein in the SE group were not time-dependent,and no significant difference was evident when it was compared with that of the control group (P＞0.05).Using wortmannin,the PI3K/Akt specific inhibitor,HIF-lα protein expression was significantly decreased when it was compared with the SE vehicle group (P＜0.05).Conclusion After status epilepticus in the developing rats,the PI3K/Akt signaling pathway is activated and the pathway involves in regulating the HIF-1α expression.

Combined with the practice of curriculum reform in Xuzhou Medical College for for-eign clinical medical students, this paper discussed its experiences in compiling the teaching syllabus, programming rational courses, increasing practical class hours, establishing corresponding elective courses, taking various teaching methods and using flexible testing mode.

Objective To study the distribution and expression of Semaphorins-3A protein in brain of postnatal rats.Methods Semaphorins-3A positive cells were observed by immunohistochemistry in the cerebral cortex,hippocampus,dentate gyms and entorhinal cortex in postnatal 0d,7d,14d,21 d and 28d of Sprague Dawley rats.Results Semaphorins-3A positive cells widely distributed in the granule cell layer ( Ⅱ ),external pyramidal cell layer ( Ⅲ ),internal granular cell layer ( Ⅳ ),pyramidal cell layer ( Ⅴ ) and layer of polymorphous cells ( Ⅵ ),in addition to the molecular layer ( Ⅰ ) of the parietal,occipital,frontal,temporal,insular,cingulate cortex,piriform cortex and entorhinal cortex with postnatal 0d,7d,14d,21d and 28d rats.The amount of semaphorins-3A positive cells(IOD) in the entorhinal cortex was 84916.23 ± 3266.34 in P0d,77711.41 ± 2634.26 in P7d,74124.25 ± 3989.09 in P14d,65887.63 ± 3406.57 in P21d and 57705.96 ± 3136.35 in P28d,meanwhile the region of semaphorins-3A positive cells narrowed in the part level with Ⅱ -Ⅵ levels of cortex.Similarly semaphorins-3A positive cells distributed mainly in granule cell layer of dentate gyrus,CA1,CA3 region and only a few of semaphorins-3A positive cells scattered in the multi-line layer in hippocampus.The expression level of semaphorins-3Awas significant difference among postnatal 0d,7d,14d,21d and 28d rats (P＜0.01).Conclusion Semaphorins-3A positive cells widely distribute in the various cortex and hippocampus in developing rat brain,and the region of semaphorins-3A is reduced with age growth of rats.