Circular RNA(circRNA)is an emerging class of endogenous non-coding RNA,which is widely expressed in the brain and plays an important role in a variety of biological processes.Research has shown that circRNA plays a key role in physiological and pathological processes of the brain,such as neurodevelopment,synaptic plasticity and neurodegenerative diseases through a variety of mecha-nisms such as adsorption of microRNA,binding to proteins and translation of peptides.In the field of drug addiction,the expression of circRNA is significantly changed in animal models and brains of addicts,and the regulation involves neural adaptation in brain regions that form the reward circuit such as the nucleus accumbens and prefrontal cortex.Additionally,addiction-related circRNAs are closely associated with neurotransmitter systems,signaling pathways,and neuroinflammatory responses,and they influ-ence the formation and maintenance of drug addiction by modulating gene expression networks related to drug addiction.Here,the biogenesis and regulatory mechanism of circRNA as well as its important role in brain function and drug addiction are reviewed in order to provide a new perspective for explora-tions of the pathological mechanism of drug addiction.

Objective To evaluate and compare the maturity of autografts and allografts as well as the postoperative clinical outcomes 10 years after anterior cruciate ligament reconstruction(ACLR).Methods A retrospective analysis was conducted on 64 patients who underwent anterior cruciate liga-ment reconstruction,with an average follow-up period of about 10 years.Autografts were used in 36 cases(56.2%),and allografts in 28 cases(43.8%).Both groups were recorded the knee Lysholm scores,IKDC subjective scores,and stability tests results(KT-1000 side-to-side difference and Lach-man test).Moreover,graft maturity was assessed using the knee magnetic resonance imaging(MRI),and the Signal-to-Noise Quotient(SNQ)for both types of grafts was measured.Results No significant differences were observed between the autograft and allograft groups in the average follow-up time(10.1±2.1 and 10.5±1.8 years)(P=0.376),the SNQ value(24.1±8.8 and 23.2±8.7)(P= 0.652),the Lysholm score(90±10.3 and 89.4±8.9)(P=0.805)and the anterior joint stability dur-ing follow-up(P=0.923).Moreover,the average IKDC score and incidence of abnormal tension of the ligament measured by KT1000 of the autograft group were higher than the allograft group[(84.5±8.3)vs.(80.4±7.8),P=0.075;14.3%vs.8.3%,P=0.724].Meanwhile,ACL re-tear occurred to two cas-es in the autograft group(5.6%)and the allograft group(7.1%),respectively,showing no significant dif-ference(P=0.795).Conclusion Ten years after ACLR,no significant differences are found in graft ma-turity,clinical outcomes,or joint stability between patients using autografts and allografts.Moreover,the rate of graft re-tear is comparable between the two groups.

Objective:To compare the clinical efficacy between fusion with anterior plate and cross screw (APCS) via the anterolateral approach and that with posterior plate (PP) via the posterior approach in ankle arthrodesis.Methods:A retrospective study was conducted to analyze the 64 patients (64 feet) with end-stage ankle arthritis who had been admitted to Department of Foot and Ankle Surgery, Honghui Hospital of Xi'an Jiaotong University from January 2017 to March 2021. They were 24 males and 40 females with an age of (57.7±5.5) years; by the Kellgren-Lawrence staging, 25 cases were in grade Ⅲ and 39 ones in grade Ⅳ. According to the different surgical approaches and internal fixation methods, the patients were divided into a APCS group of 31 cases subjected to the fusion with APCS via the anterolateral approach and a PP group of 33 cases subjected to the fusion with PP via the posterior approach. The clinical efficacy was compared between the 2 groups and between preoperatoion and postoperation in terms of talus center migration (TCM), sagittal talar migration (STM), foot and ankle ability measure (FAAM), and visual analog scale (VAS).Results:There was no statistically significant difference in the preoperative baseline data between the 2 groups of patients, indicating comparability ( P>0.05). In the PP group, the postoperative STM [(4.45±2.21)] mm was significantly smaller than the postoperative one [(7.22±4.22)] mm ( P<0.001). There were no statistically significant differences in the postoperative comparisons of TCM and STM between the 2 groups, in the comparison between postoperative TCM and preoperative TCM in the PP group, or in the comparisons between postoperative and preoperative TCM and STM in the APCS group ( P>0.05). All patients were followed up for (28.1±6.8) months. At the last follow-up, there was no statistically significant difference between the 2 groups in the FAAM life score, FAAM exercise score, or VAS pain score ( P>0.05). The FAAM life score, FAAM motor score, and VAS pain score at the last follow-up were significantly improved in all the patients compared with the preoperative values ( P<0.05). Fusion failure was found in only 1 patient in the APCS group. Conclusion:Both PP and APCS fusion techniques can lead to similarly fine clinical outcomes in ankle arthrodesis, but PP may lead to a significant correction of sagittal talar migration.

OBJECTIVE: To assess the effectiveness of supramalleolar osteotomy (SMOT) as a therapeutic intervention for varus-type ankle arthritis, while also examining the associated risk factors that may contribute to treatment failure. METHODS: The clinical data of 82 patients (89 feet) diagnosed with varus-type ankle arthritis and treated with SMOT between January 2016 and December 2020 were retrospectively analyzed. The patient cohort consisted of 34 males with 38 feet and 48 females with 51 feet, with the mean age of 54.3 years (range, 43-72 years). The average body mass index was 24.43 kg/m ² (range, 20.43-30.15 kg/m ²). The preoperative tibial anterior surface angle (TAS) ranged from 77.6° to 88.4°, with a mean of 84.4°. The modified Takakura stage was used to classify the severity of the condition, with 9 feet in stage Ⅱ, 41 feet in stage Ⅲa, and 39 feet in stage Ⅲb. Clinical functional assessment was conducted using the Maryland sore, visual analogue scale (VAS) score, and psychological and physical scores in Health Survey 12-item Short From (SF-12). Radiology evaluations include TAS, talar tilt (TT), tibiocrural angle (TC), tibial medial malleolars (TMM), tibiocrural distance (TCD), tibial lateral surface angle (TLS), and hindfoot alignment angle (HAA). The results of clinical failure, functional failure, and radiology failure were statistically analyzed, and the related risk factors were analyzed. RESULTS: The operation time ranged from 45 to 88 minutes, with an average of 62.2 minutes. No complication such as fractures and neurovascular injuries was found during operation. There were 7 feet of poor healing of the medial incision; 9 pin tract infections occurred in 6 feet using external fixator; there were 20 cases of allograft and 3 cases of autograft with radiographic bone resorption. Except for 1 foot of severe infection treated with bone cement, the remaining 88 feet were primary healing, and the healing area was more than 80%. All patients were followed up 24-82 months, with an average of 50.2 months. Maryland score, VAS score, SF-12 psychological and physiological scores, and TAS, TC, TLS, TCD, TT, TMM, HAA, and Takakura stage were significantly improved at last follow-up ( P<0.05). Postoperative clinical failure occurred in 13 feet, functional failure in 15 feet, and radiology failure in 23 feet. Univariate analysis showed that obesity, TT>10°, and Takakura stage Ⅲb were risk factors for clinical failure, HAA≥15° and Takakura stage Ⅲb were risk factors for functional failure, and TT>10° was risk factor for radiographic failure ( P<0.05). Further logistic regression analysis showed that TT>10°, HAA≥15°, and TT>10° were risk factors for clinical failure, functional failure, and radiographic failure, respectively ( P<0.05). CONCLUSION SMOT is effective in the mid- and long-term in the treatment of varus-type ankle arthritis, but it should be used with caution in patients with obesity, severe hindfoot varus, severe talus tilt, and preoperative Takakura stage Ⅲb.
Male ; Female ; Humans ; Middle Aged ; Ankle ; Ankle Joint/surgery* ; Retrospective Studies ; Osteoarthritis/surgery* ; Osteotomy/methods* ; Risk Factors

OBJECTIVE: To summarize the progress of clinical diagnosis and treatment of diabetic Charcot neuroarthropathy (CNO) of foot and ankle to provide reference for clinical treatment. METHODS: The research literature on diabetic CNO of foot and ankle at home and abroad was widely reviewed, and the stages and classification criteria of CNO were summarized, and the treatment methods at different stages of the disease course were summarized. RESULTS: CNO is a rapidly destructive disease of bone and joint caused by peripheral neuropathy, which leads to the formation of local deformities and stress ulcers due to bone and joint destruction and protective sensory loss, which eventually leads to disability and even life-threatening. At present, the modified Eichenholtz stage is a commonly used staging criteria for CNO of foot and ankle, which is divided into 4 stages by clinical and imaging manifestations. The classification mainly adopts the modified Brodsky classification, which is divided into 6 types according to the anatomical structure. The treatment of diabetic CNO of foot and ankle needs to be considered in combination with disease stage, blood glucose, comorbidities, local soft tissue conditions, degree of bone and joint destruction, and whether ulcers and infections are present. Conservative treatment is mainly used in the active phase and surgery in the stable phase. CONCLUSION The formulation of individualized and stepped treatment regimens can help improve the effectiveness of diabetic CNO of foot and ankle. However, there is still a lack of definitive clinical evidence to guide the treatment of active and stable phases, and further research is needed.
Humans ; Ankle ; Ulcer/complications* ; Arthropathy, Neurogenic/therapy* ; Ankle Joint ; Diabetes Mellitus ; Diabetic Foot/therapy*

The cisplatin-based concurrent chemoradiotherapy (CCRT) has been accepted as a standard treatment for most locally advanced cervical cancer. Compared with radiation therapy alone, CCRT can increase tumor control and survival rates, whereas it also can increase the incidence of acute hematological toxicity, which results in the treatment interruption or delay, and may even affect clinical efficacy and prognosis of patients. Therefore, how to reduce the incidence and severity of acute hematological toxicity induced by CCRT is a hot spot of clinical research. Previous studies have demonstrated that the occurrence of hematological toxicity is associated with the volume and dose of irradiated pelvic bone marrow. With the development of modern radiotherapy technology, precise radiotherapy technologies, such as intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT), not only guaranteed the enough dose for tumor, but also realized the protection of normal tissues. This article will focus on the feasibility of bone marrow sparing during CCRT for cervical cancer, and summarize the research progress in recent years.

Objective:To explore the safety and efficacy of immune checkpoint inhibitors(ICI)for patients with tumor recurrence after liver transplantation(LT).Methods:A single-center retrospective study was conducted for 6 recipients of tumor recurrence after LT on a therapy of ICI admitted into Shulan(Hang Zhou)Hospital from September 2015 to June 2018.The authors examined the occurrences of graft rejection and clinical outcomes of overall response rate, progression-free survival and overall survival after dosing of PD-1/PD-L1 inhibitors.Results:Six patients enrolled with tumor recurrence on a therapy of ICI undergoing LT due to hepatocellular carcinoma (HCC). Nivolumab (n=4) and duvalizumab (n=2) were administrated.The median session of treatment was 8.3(2-31) cycles.The disease outcomes were stable (3/6, 50%) and progressive (3/6, 50%), The progression-free survival time of 3 disease-controlled patients was 1.5, 16.2 and 18 months and the median survival time after recurrence was 19.75(10.8-37.8) months.Rejection occurred in 1 patients (1/6, 16.7%) and the occurring time of rejection was 28 days after PD-1 inhibitor dosing.After acute rejection, high-dose corticosteroids and immunoglobulin were ineffective and the patient died from acute rejection related liver failure.Conclusions:ICI may be employed as a salvage treatment for tumor recurrence after LT for HCC.Due to a possibility of severe acute rejection, usage should be cautious under close monitoring of liver function.

Objective:To explore the risk factors of sarcopenia in liver cirrhosis and construct a diagnosis model for sarcopenia in cirrhosis.Methods:73 patients with liver cirrhosis hospitalized in Department of Gastroenterology of Shanxi Provincial People's Hospital between June 2021 and June 2022 were included. Common measurements in liver cirrhosis and abdominal CT scans of all patients were collected. The cross-sectional area of skeletal muscle at L3 level was calculated by sliceomatic and the skeletal muscle index (SMI) was subsequently obtained by height standardization. The patients were divided into sarcopenia group and non-sarcopenia group using Asian cut-off per European Working Group on Sarcopenia in Older People-2nd meeting (EWGSOP2) criteria. Risk factors related to sarcopenia in cirrhosis were analyzed and a subsequent diagnosis model was established.Results:among the cirrhotic patients included in the study, the prevalence of sarcopenia was 65.75% (48/73), 47.73% (21/44) in males and 93.10% (27/29) in females, respectively. There were significant differences in age, sex, BMI, liver function grade per Child Pugh classification, etiology, ferritin level, prothrombin time and hemoglobin level between sarcopenia and non-sarcopenia groups (P < 0.05). Age, liver function, sex and ferritin level were closely related to the occurrence of sarcopenia in cirrhosis. A diagnostic model was developed based on these 4 indexes and the area under curve reached up to 95.7%.Conclusion:≥ 60 years old, female, Child-Pugh C grade and ferritin < 29.60 μg/L are independent risk factors for sarcopenia in cirrhosis and the model with these indexes shows good diagnostic value for sarcopenia in cirrhosis.

Objective:To evaluate the efficacy and safety of anti-human T lymphocyte porcine immunoglobulin (P-ATG) with recombinant human tumor necrosis factor-α receptor Ⅱ:IgG Fc fusion protein (rhTNFR∶Fc, Etanercept) on grade Ⅲ/Ⅳ acute graft-versus-host disease (aGVHD) after allogenic hematopoietic stem cell transplantation (allo-HSCT) .Methods:Thirty-five patients with Grade Ⅲ/Ⅳ aGVHD who received P-ATG with etanercept therapy after allo-HSCT were retrospectively analyzed. P-ATGs (5 mg·kg -1·d -1) were administrated for 3 to 5 days, and then 5mg/kg was sequentially administrated, QOD to BIW. Etanercepts were administrated 25 mg, twice a week (12.5 mg, BIW for pediatric patients) . Results:Among the 35 patients with grade Ⅲ/Ⅳ aGVHD, 21 were males and 14 females, with a median age of 10 (3-54) years. A total of 19 cases of acute myeloid leukemia, 13 of acute lymphoblastic leukemia, 1 of severe aplastic anemia, 1 of myelodysplastic syndrome, and 1 of mixed phenotypic acute leukemia were noted. The overall response (OR) rate of P-ATG with etanercept was 85.7% (30/35) , with complete response (CR) and partial response (PR) rates of 34.3% (12/35) and 51.4% (18/35) , respectively, on day 28. The OR rate of grade Ⅲ aGVHD group was higher than of grade IV aGVHD group [100% (19/19) vs. 68.8% (11/16) , P=0.004]. On day 56, the OR rate became 77.2% (27/35) , with CR and PR rates of 62.9% (22/35) and 14.3% (5/35) , respectively. The OR rate of grade Ⅲ aGVHD group was also higher than of grade Ⅳ aGVHD group [89.5% (17/19) vs. 62.5% (10/16) , P=0.009]. Thirty-five patients had no adverse effects such as fever, chills, and rash during the P-ATG infusion, and no obvious liver and kidney function damage was observed after treatment. The main treatment-related complication was infection. The reactivation rates of CMV and EBV were 77.1% (27/35) and 22.9% (8/35) , respectively, and the bacterial infection rate was 48.6% (17/35) . With a median follow-up time of 13 (1-55) months after HSCT, the 1-year and 2-year OS rates were (68.1±8.0) % and (64.3±8.4) % , respectively. The 1-year OS rate of grade Ⅲ aGVHD group was superior to grade Ⅳ aGVHD group [ (84.2±8.4) % vs. (47.6±13.1) % , χ2=3.38, P=0.05]. Conclusion:This study demonstrated that P-ATG with etanercept was effective and safe in treating grade Ⅲ-Ⅳ aGVHD after allo-HSCT.

Objective To investigate the changes of serum corticosterone and inflammatory factors in rats with different burn degrees. Methods One hundred and fifty male healthy Wistar rats were randomly divided into normal control group, moderate and severe burn hormone treatment groups, and moderate and severe burn physiological saline treatment groups, each group with 30 rats. After anesthesia, the rat models with burn Ⅱ,Ⅲ degrees of 30% back surface area were replicated; the burn, fluid infusion and steroid therapy were not carried out in the normal control group. After modeling, the moderate and severe burn hormone treatment groups were given intra-abdominal cavity injection of hydrocortisone 200 mg/d; while in the moderate and severe burn normal saline treatment groups, normal saline 4 mL·kg-1·d-1 was injected into the abdominal cavity. The dynamic changes of serum corticosterone, tumor necrosis factor-α(TNF-α), and interleukin-6 (IL-6) levels were detected at 1, 4, 12 hours and 1, 3 and 7 days after burn injury in each group. Results The levels of serum corticosterone at different time points after moderate and severe burn injury treatment were higher than those in normal control group, the degree of increase at 4 hours after injury in severe burn saline treatment group was more significant than that in moderate and severe burn hormone treatment groups and moderate burn saline treatment group (ng/L: 200.45±2.63 vs. 110.56±9.23, 146.02±3.28, 160.02±8.22). Except the level at 1 hour after injury in the moderate and severe burn hormone treatment groups, the TNF-αlevels in all the other groups at different time points were significantly higher than those in the normal control group (all P < 0.05); the IL-6 levels in various treatment groups were all higher than the IL-6 level in the normal control group, moreover, the increase degree on 1 day after injury in the severe burn saline treatment group was more obvious than the degrees in the moderate and severe burn hormone treatment groups and the moderate burn saline treatment group [TNF-α(ng/L): 39.78±4.30 vs. 15.99±1.40, 20.58±2.10, 25.98±1.60, IL-6(ng/L): 210.20±6.70 vs. 125.45±3.10, 149.81±4.20, 161.40±3.80, all P < 0.05]. Conclusion The burn stress may lead to the significant increase of serum corticosterone level in rats, and the stress dose of hydrocortisone has a certain regulatory effect on serum corticosterone and inflammatory factors in rats after different degrees of burn.