Objective:To investigate the effects of ubiquitin-specific protease (USP) 7/47 inhibitor (Cat. No. 1247825-37-1) on the proliferation and apoptosis of acute myeloid leukemia (AML) cells with or without internal tandem duplications of the Flt3 gene (Flt3-ITD). Methods:ATP assay was used to detect the effects of 1247825-37-1 on the cell viability of two AML cell lines (MOLM13 and MV4-11) harboring Flt3-ITD mutation and one AML cell line (THP-1) without Flt3-ITD mutation as well as the primary Flt3-ITD-mutant and non-mutant AML cells from patient samples. Flow cytometry was used to detect the apoptosis of AML cell lines treated by different concentrations of 1247825-37-1.Results:Compared with the control group, 1247825-37-1 was able to significantly inhibit the proliferation of MOLM13, MV4-11 and THP-1 cells ( P<0.000 1). Besides, the cell viability of primary AML cells was also inhibited by 1247825-37-1, and a stronger inhibitory effect on non-mutant AML cells was observed. The USP7/USP47 inhibitor 1247825-37-1 could inhibit the proliferation of AML cells in a dose-dependent manner and a low dose (2 or 4 μmol/L) of 1247825-37-1 would be effective. Moreover, 1247825-37-1 was also able to efficiently induce the apoptosis of above AML cell lines in a dose-dependent manner. Conclusions:The USP7/USP47 inhibitor 1247825-37-1 significantly inhibits the proliferation of AML cells with or without Flt3-ITD mutation.

BACKGROUND:After the treatment of femoral shaft fracture with the intramedullary nail,the third fracture open reduction indications are controversial.Some scholars believe that limited open reduction can achieve anatomical reduction,conducive to fracture healing;but some scholars believe that no open reduction of the third fracture still has a high fracture healing rate. OBJECTIVE:To investigate the effect of the circumference and displacement of the third fragment on fracture healing after intramedullary nailing of femoral shaft fractures with the third fragment. METHODS:A retrospective cohort study was conducted to analyze the clinical data of 142 patients suffered a femoral shaft fracture with a third fragment admitted to the Affiliated Lianyungang Hospital of Xuzhou Medical University from February 2016 to December 2021.The fracture were classified into three types according to the circumference of the third fracture with reference to the diaphyseal circumference at the fracture site:type 1 in 71 cases,type 2 in 52 cases,and type 3 in 19 cases.Referring to the diaphyseal diameter,the fractures were classified into three degrees according to the degree of the third fragment displacement:degree I in 95 cases,degree II in 31 cases,and degree III in 16 cases.All patients were treated with femoral interlocking intramedullary nails,and no intervention was performed for the displaced third fragment during the operation.Postoperative follow-up was performed to compare the fracture healing rate,healing time,and the modified Radiographic Union Scale for Tibia at month 9 after surgery in each group.The effect of third fracture fragment circumference and degree of displacement on fracture healing was assessed. RESULTS AND CONCLUSION:(1)All 142 patients were followed up for at least 12 months,with a mean of(14.7±4.1)months,and the overall healing rate was 73.4%.(2)When the third fragment was displaced by degree I,the healing rate,healing time,and modified Radiographic Union Scale for Tibia score at month 9 were not statistically significant among the three sub-groups of circumference classification.(3)When the third fragments were displaced by degree II or III,the healing rate and healing time were not statistically significant among the three subgroups of circumference classification;the modified Radiographic Union Scale for Tibia score at month 9 in the type 1 group was higher than that in the type 2 and 3 groups(P = 0.017).(4)Logistic regression analysis showed that a greater third fragment displacement and circumference were associated with lower fracture healing rates(P<0.05).(5)These findings indicate that in the treatment of femoral shaft fractures with third fragment by intramedullary nails,when the fracture fragment is displaced to degree I,the circumference size has little effect on fracture healing,and no intervention is required during surgery.When the third fragment is displaced to degree II or III and the circumference of which is type 1,a higher modified Radiographic Union Scale for Tibia score can still be obtained with no intervention of the third fragment.However,when the circumference is of type 2 or type 3,it significantly affects the fracture healing.Consequently,intraoperative intervention to reduce the distance of displacement of the fragment is required to lower the incidence of nonunion.The displacement of the third fracture fragments has a greater impact on fracture healing than their circumference.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Objective:To observe the effects of Mongolian medicine warm acupuncture treatment on the behavior and NLRP3, ASC, Caspase-1, GSDMD, and inflammatory factors in hippocampus of the depression model rats; To explore the mechanism.Methods:Totally 40 male SD rats were divided into control group, model group, warm acupuncture group, and fluoxetine group using a random number table method, with 10 rats in each group. Except for the control group, chronic unpredictable stress models were established in all other groups. After 1 hour of daily stress stimulation, the warm acupuncture group received Mongolian medicine warm acupuncture intervention. The fluoxetine group was orally administered with 2.1 mg/kg fluoxetine hydrochloride, while the control group and model group were orally administered with equal volumes of distilled water once a day for 21 days. The body weight of rats was measured, and their behavior was evaluated by sugar water consumption test, open field test, and Morris water maze test. ELISA was used to measure the levels of IL-1 β, IL-18, IL-6, and TNF-α in the serum. Western blot and PCR were used to detect the protein and mRNA levels of NLRP3, ASC, Caspase-1, GSDMD, and IL-1 in the hippocampus.Results:Compared with the model group, the warm acupuncture group and fluoxetine group showed an increase in body weight ( P<0.05), sugar water consumption ( P<0.05), vertical movement frequency and horizontal crossing grid number ( P<0.05), shortened escape latency ( P<0.05), and increased crossing platform frequency ( P<0.05); the levels of serum IL-1β, IL-18, TNF-α, and IL-6 decreased ( P<0.05); the protein and mRNA expressions of NLRP3, Caspase-1, ASC, GSDMD, IL-1β in the hippocampus of rats decreased ( P<0.05). Conclusion:Mongolian medicine warm acupuncture can prevent depressive behaviors in rats by reducing NLRP3-mediated cell death and inflammation.

Objective:To investigate the alterations of brain resting-state functional connectivity in patients with leukoaraiosis(LA), and to explore its neuropathological mechanism of cognitive dysfunction.Methods:From August 2022 to February 2023, 28 patients with LA(LA group) and 30 gender, age and education level matched normal controls(NC group) in Jiangsu Shengze Hospital affiliated to Nanjing Medical University were prospectively recruited.Mini mental state examination, trail-making test, and Stroop color-word test were used to evaluate the cognitive function of participants, rs-fMRI images were processed by DPABI V6.1 based on MATLAB R2022a.Voxel-mirrored homotopic connectivity(VMHC) values were calculated and two-sample t test were performed to compare the differences in local brain activity between the two groups.The brain regions with significant differences were selected as the seeds to calculate the functional connectivity(FC) values of the whole brain, and Pearson correlation analyses were performed to evaluate the correlation between the FC values and neuropsychological scores. Results:The VMHC values of the calcarine fissure and surrounding cortex(CAL) (x=±18, y=-63, z=15), postcentral gyrus(PoCG) (x=±39, y=-27, z=48), lingual gyrus(LING) (x=±12, y=-51, z=-6), middle occipital gyrus(x=±27, y=-75, z=24) and insula(x=±36, y=6, z=3) in the LA group were lower than those in the NC group( P<0.05). The seed points FC results showed, FC values between right CAL(CAL.R) and bilateral precuneus(PCUN), right dorsolateral prefrontal cortex(DLPFC.R) and right temporal_mid were reduced in the LA group( P<0.05); FC values between PoCG.R and left CAL, left temporal_mid and right LING were reduced too( P<0.05). Additionally, the FC value in the LA group between CAL.R and DLPFC.R was negatively correlated with the Stroop C score( r=-0.39, P<0.05). The FC value in LA group and NC group between CAL.R and DLPFC.R was negatively correlated with the Stroop C score( r=-0.48, P<0.001)and also negatively correlated with the trail making test B(TMT-B) score( r=-0.40, P<0.01), and the FC value between CAL.R and PCUN.L was negatively correlated with the TMT-B score( r=-0.45, P<0.001). Conclusion:Desynchronized interhemispheric functional connectivity and abnormal cortical circuit functional connectivity were probably associated with the underlying neural mechanisms of cognitive impairment in LA.

Objective:To evaluate the influence of manual digitorum sensory stimulation (MDSS) of hemiplegic fingers in median nerve F-wave in stroke patients.Methods:Thirty patients with hemiplegia after stroke, admitted to Department of Rehabilitation Medicine, Second Affiliated Hospital of Anhui Medical University from June 2019 to October 2022 were selected; all patients had thumb flexor modified Ashworth scale (MAS) grading≥1. Hemiplegic MDSS was given; bilateral median nerve F-wave before MDSS and median nerve F-wave at the hemiplegic side immediately after MDSS were recorded.Results:Compared with that at the healthy side before MDSS, amplitude of median nerve F-wave at the hemiplegic side was significantly increased ( P<0.05). Compared with that before MDSS, amplitude of F-wave at the hemiplegic side after MDSS in patients with thumb flexor MAS grading≤2 were significantly decreased ( P<0.05), while that in patients with thumb flexor MAS grading≥3 was significantly increased ( P<0.05). Conclusion:Amplitudes of median nerve F-wave at the hemiplegic side in patients with different thumb flexor MAS grading show that MDSS can not only inhibit the excitability of tonic motor unit related to muscle spasm, but also enhance the excitability of kinetic-motor unit mainly related to explosive power in severe muscle spasm.

Liver cirrhosis is the final stage of various chronic liver diseases, and the common etiologies of liver cirrhosis include chronic viral hepatitis, nonalcoholic fatty liver disease, autoimmune liver diseases, and inherited metabolic liver disease. An accurate etiological diagnosis is an important prerequisite for etiological treatment. Unexplained liver cirrhosis refers to liver cirrhosis without a definite etiology after medical history inquiry, physical examination, and auxiliary examination. At present, liver histopathological examination is a gold standard for the diagnosis of liver cirrhosis and an important basis for exploring the etiology of liver cirrhosis. It may help with the etiological diagnosis of unexplained liver cirrhosis to evaluate the pattern of liver fibrosis, the type of inflammatory injury, and related pathological changes with reference to a comprehensive analysis of related medical history, signs, laboratory examination, and radiological examination. This article reviews the pathological features and diagnostic thinking of unexplained liver cirrhosis.

ObjectiveTo investigate the changes of surface electromyography (sEMG) of the flexors and extensors of the affected fingers after manual digitorum sensory stimulation (MDSS) in the hemiplegic patients after stroke. MethodsFrom April to August, 2020, 50 stroke patients in Department of Rehabilitation Medicine, the Second Hospital of Anhui Medical University accepted MDSS on the nail beds and the third knuckles of affected fingers, until the fingers extended actively. The tension of affected flexor pollicis brevis, flexor digitorum superficialis and extensor digitorum were assessed with modified Ashworth Scale (MAS) before and immediately after stimulation; while the root mean square (RMS) of sEMG of bilateral flexor pollicis brevis, flexor digitorum superficialis and extensor digitorum were recorded. ResultsThe MAS score of all the muscles decreased after stimulation (|Z| > 2.699, P < 0.01), while the RMS of affected extensor digitorum increased (t = -2.069, P < 0.05). Compared with the unaffected ones, RMS of affected flexor pollicis brevis and extensor digitorum decreased before and after stimulation (t > 2.450, P < 0.05). ConclusionMDSS may immediately relieve the spasm of flexors of hemiplegic fingers after stroke, which associates with the promoting muscle strength of the extensors.

Objective:To investigate the clinical outcome of transposition of the medial gastrocnemius muscle flap in repairing the middle and upper tibial soft tissue defects.Methods:The clinical data of patients with mid-upper tibial tissue defects admitted to the Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine from September 2016 to June 2020 were retrospectively analyzed. Doppler ultrasound was used to detect and mark the blood vessels and branches of the lower limbs before surgery, the medial gastrocnemius muscle flap was designed according to the wound condition of the patient, the soft tissue defects in the middle and upper part of the tibia were repaired by transposition, and the appearance, color, feel, texture, gait and plantar flexion strength of the affected foot, as well as the recovery of the donor site were followed up after surgery. For patients with chronic osteomyelitis, the efficacy is evaluated with reference to McKee and other osteomyelitis treatment standards, including three levels: cure, improvement and recurrence.Results:A total of 11 patients were enrolled, including 9 males and 2 females, aged 48 to 69 years. The area of soft tissue defect ranged 3.8 cm×5.7 cm-14.2 cm×7.6 cm, and the flap size ranged 13.0 cm×6.0 cm-21.0 cm×13.0 cm. After surgery, one case had blisters at the distal end, which were cured after conservative measures. Other flaps and donor wounds presented good blood circulation, the shape and function recovered satisfactorily, and the incision healed uneventfully. 11 cases were followed up for 7-18 months after surgery, with an average of 13.2 months, and the appearance, color and texture of the flap were basically satisfactory. The two-point distance perception of the flap was 13-20 mm 9 months after surgery, with an average of 15 mm. At the last follow-up visit, the plantar flexion strength of the affected side was weaker than that of the healthy side, but the gait was basically normal. All 4 patients with chronic osteomyelitis met the clinical cure criteria, and there was no rash, swelling, overheat and pain, rupture, exudation and sinus tract formation at the primary lesion during the follow-up period (average 14 months), and no osteosclerosis and dead bone formation were found on X-ray examination. There was no deformity and dysfunction at the donor site. There was one case presented pigmentation at the donor site of the thigh. Some cases presented superficial scarring.Conclusions:The transposition of the medial gastrocnemius muscle flap repairs the middle and upper tibial tissue defects without sacrificing the major blood vessels, and the flap survival rate is high, the complications are minimal, and the function and morphological recovery of the receiving area are good.

Objective:To investigate the clinical outcome of transposition of the medial gastrocnemius muscle flap in repairing the middle and upper tibial soft tissue defects.Methods:The clinical data of patients with mid-upper tibial tissue defects admitted to the Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine from September 2016 to June 2020 were retrospectively analyzed. Doppler ultrasound was used to detect and mark the blood vessels and branches of the lower limbs before surgery, the medial gastrocnemius muscle flap was designed according to the wound condition of the patient, the soft tissue defects in the middle and upper part of the tibia were repaired by transposition, and the appearance, color, feel, texture, gait and plantar flexion strength of the affected foot, as well as the recovery of the donor site were followed up after surgery. For patients with chronic osteomyelitis, the efficacy is evaluated with reference to McKee and other osteomyelitis treatment standards, including three levels: cure, improvement and recurrence.Results:A total of 11 patients were enrolled, including 9 males and 2 females, aged 48 to 69 years. The area of soft tissue defect ranged 3.8 cm×5.7 cm-14.2 cm×7.6 cm, and the flap size ranged 13.0 cm×6.0 cm-21.0 cm×13.0 cm. After surgery, one case had blisters at the distal end, which were cured after conservative measures. Other flaps and donor wounds presented good blood circulation, the shape and function recovered satisfactorily, and the incision healed uneventfully. 11 cases were followed up for 7-18 months after surgery, with an average of 13.2 months, and the appearance, color and texture of the flap were basically satisfactory. The two-point distance perception of the flap was 13-20 mm 9 months after surgery, with an average of 15 mm. At the last follow-up visit, the plantar flexion strength of the affected side was weaker than that of the healthy side, but the gait was basically normal. All 4 patients with chronic osteomyelitis met the clinical cure criteria, and there was no rash, swelling, overheat and pain, rupture, exudation and sinus tract formation at the primary lesion during the follow-up period (average 14 months), and no osteosclerosis and dead bone formation were found on X-ray examination. There was no deformity and dysfunction at the donor site. There was one case presented pigmentation at the donor site of the thigh. Some cases presented superficial scarring.Conclusions:The transposition of the medial gastrocnemius muscle flap repairs the middle and upper tibial tissue defects without sacrificing the major blood vessels, and the flap survival rate is high, the complications are minimal, and the function and morphological recovery of the receiving area are good.