OBJECTIVE: To compare the effects of piriformis muscle release versus preservation in total hip arthroplasty (THA) via supercapsular percutaneously-assisted total hip (SuperPATH) approach on muscle injury. METHODS: Forty-nine patients undergoing initial THA via SuperPATH approach between June 2022 and June 2023 were randomly divided into two groups, with 24 patients in trial group and 25 patients in control group. The trial group received piriformis muscle release intraoperatively, whereas the control group underwent muscle preservation. There was no significant difference in baseline data such as gender, age, body mass index, disease type, American Society of Anesthesiologists (ASA) grading, and preoperative muscle infiltration, muscle atrophy, muscle injury serological indicators, Harris score, etc. ( P>0.05). The incision length, operation time, intraoperative blood loss, total blood loss, hospital stay, preoperative and postoperative 1-day muscle injury serological indicators [including creatine kinase (CK) and lactic dehydrogenase (LDH)], and incidence of complications between two groups were recorded. Harris score was used to evaluate the recovery of hip joint function. MRI was used to evaluate the extent of hip muscle injuries (gluteus minimus, gluteus medius, piriformis, obturator internus, quadratus femoris), including tendon integrity, degree of muscle fat infiltration, and degree of muscle atrophy preoperative and 1 year postoperatively. RESULTS: The operation time, intraoperative blood loss, and total blood loss in the trial group were significantly shorter than those in the control group ( P<0.05). There was no significant difference in the incision length and length of hospital stay between the two groups ( P>0.05). Both groups showed a significant increase in serum CK and LDH levels on postoperative day 1 compared to preoperative levels ( P<0.05), but there was no significant difference between the two groups ( P>0.05). All patients were followed up, the follow-up time for the trial group and the control group was (14.8±2.8) and (15.1±3.0) months, respectively, with no significant difference ( t=-0.400, P=0.691). Incisions healed by first intention in both groups, with 1 case in the trial group and 2 cases in the control group experiencing venous thrombosis in the calf muscle space. There was no complication such as deep vein thrombosis, pulmonary embolism, hip dislocation, prosthesis loosening, or periprosthetic infection in the lower limbs. There was no significant difference in the incidence of complications between the two groups ( P>0.05). At 1 year after operation, both groups of patients showed a significant increase in Harris scores compared to preoperative levels ( P<0.05), but there was no significant difference between the two groups ( P>0.05). Compared with preoperative results, both groups showed significant fat infiltration in the piriformis and obturator muscles at 1 year after operation ( P<0.05), while there was no significant fat infiltration in the gluteus minimus, gluteus medius, and quadratus femoris muscles ( P>0.05). At 1 year after operation, except for the higher incidence of piriformis muscle fat infiltration in the control group compared to the trial group ( P<0.05), there was no significant difference in the incidence of other muscle infiltrations between the two groups ( P>0.05). At 1 year after operation, both groups of piriformis and obturator muscles showed significant muscle atrophy compared to preoperative levels ( P<0.05). The gluteus minimus and gluteus medius showed mild atrophy compared to preoperative levels, while the maximum transverse diameter of the quadriceps muscle slightly increased, but the differences were not significant ( P>0.05). There was no significant difference in the maximum cross-sectional diameter or cross-sectional area changes of each muscle between the two groups ( P>0.05). At 1 year after operation, the continuity of the gluteus medius and quadratus femoris muscles in both groups was intact. Both groups had some patients with incomplete continuity of the piriformis muscle, obturator internus, and gluteus minimus, but the difference was not significant ( P>0.05). CONCLUSION The SuperPATH approach THA may cause injury to the piriformis, gluteus minimus, and obturator internus. The piriformis muscle release does not increase muscle injury, but it can shorten the operation time and reduce bleeding.
Humans ; Arthroplasty, Replacement, Hip/adverse effects* ; Male ; Female ; Muscle, Skeletal/surgery* ; Middle Aged ; Aged ; Postoperative Complications/epidemiology* ; Adult ; Operative Time ; Muscular Atrophy ; Creatine Kinase/blood* ; Length of Stay ; Treatment Outcome

Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Objective:To investigate the risk factor of hepatocellular carcinoma (HCC) with vessels encapsulating tumor clusters (VETC) and the application value of its risk scoring model.Methods:The retrospective cross-sectional study was conducted. The clinicopathological data of 149 patients with HCC who were admitted to two medical centers, including 97 cases in the Jiangnan University Medical Center and 52 cases in the Affiliated Xingtai People′s Hospital of Hebei Medical University, from January 2017 to April 2020 were collected. There were 116 males and 33 females, aged (58±12)years. There were 74 cases with VETC and 75 cases without VETC. Observation indica-tors: (1) clinical characteristics of patients with and without VETC; (2) imaging features of patients with and without VETC; (3) multivariable analysis of HCC patients with VETC; (4) construction of VETC related risk scoring model and its performance evaluation; (5) postoperative early tumor recurrence of patients with and without VETC who were confirmed by risk scoring model and histopathological examination. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Count data were described as absolutes, and comparison between groups was conducted using the chi-square test and continuous correction chi-square test. Variables of clinical and imaging characteristics with statistically signifi-cant were included in the multivariate analysis. Multivariate analysis was conducted using the Logistic regression model of backward stepwise selection. VETC related risk scoring model was constructed based on the results of Logistic regression model. The receiver operating characteristic (ROC) curve was drawn, and the area under curve (AUC), the sensitivity, specificity, accuracy and their 95% confidence interval ( CI) were calculated. The maximizing Youden index was the optimal cutoff value for VETC prediction. The Hosmer Lemeshow goodness of fit test was used to assess the consistency between VETC risk scoring model predicted VTEC status and the true VETC status. The Kaplan-Meier method was used to calculate survival rates and draw survival curves. The Log-rank test was used for survival analysis. Results:(1) Clinical characteristics of patients with and without VETC. Cases with postoperative albumin <36 g/L were 57 in patients with VETC, versus 68 in patients without VETC, respectively, showing a significant difference between them ( χ2=5.13, P<0.05). (2) Imaging features of patients with and without VETC. Cases with lesion imaging presence as nonperipheral washout, cases with lesion imaging presence as mosaic architecture, cases with lesion imaging presence as intratumoral hemorrhage, cases with lesion imaging presence as corona enhancement, cases with lesion imaging presence as non-smooth tumor margin, cases with lesion imaging presence as peritumoral enhancement in arterial phase, cases with lesion imaging presence as intratumoral arteries, cases with lesion imaging presence as peritumoral hypointensity in hepatobiliary phase, cases with lesion imaging enhancement type as uniform low enhancement, uniform high enhance-ment, heterogeneous enhancement with septations and heterogeneous enhancement with irregular ring-like structures, cases with intratumoral necrosis or ischemic, cases with tumor diameter >5 cm were 73, 35, 33, 15, 39, 28, 42, 27, 4, 5, 27, 38, 45, 46 in patients with VETC, versus 64, 16, 13, 3, 19, 15, 9, 13, 9, 35, 5, 26, 10, 10 in patients without VETC, respectively, showing significant differences in the above indicators between them ( χ2=8.92, 11.15, 12.97, 9.28, 11.74, 5.77, 33.14, 6.96, 41.79, 36.05, 37.86, P<0.05). (3) Multivariable analysis of patients with VETC. Results of multivariable analysis showed that lesion imaging enhancement as heterogeneous enhancement with septations, lesion imaging enhancement as heterogeneous enhancement with irregular ring-like structures, intratumoral necrosis or ischemia and tumor diameter >5 cm were independent risk factors influen-cing patients with VETC ( odds ratio=4.18, 7.62, 4.23, 4.08, 95% CI as 1.60?11.60, 2.00?31.70, 1.71?10.90, 1.60?10.80), P<0.05). (4) Construction of VETC related risk scoring model and its performance evaluation. The VETC related risk scoring model was constructed as (heterogeneous enhancement with septations, presence: 1.0, absence: 0)+(heterogeneous enhancement with irregular ring-like structures, presence: 1.5, absence: 0)+(intratumoral necrosis or ischemia, presence: 1.0, absence: 0)+(main tumor diameter >5 cm, presence: 1.0, absence: 0). The AUC, sensitivity, specificity, and accuracy of VETC related risk scoring model were 0.86 (95% CI as 0.80?0.92), 79.7% (95% CI as 69.2%?87.3%), 80.0% (95% CI as 69.6%?87.5%) and 79.9% (95% CI as 72.7%?85.5%), respectively. Results of Hosmer-Lemeshow goodness of fit test showed a good consistency between VETC risk scoring model predicted VETC status and true VETC status ( P>0.05). (5) Postoperative early tumor recurrence of patients with and without VETC who were confirmed by risk scoring model and histopathological examination. All 149 patients were followed up for 29(range, 26?35)months. The time to tumor recurrence and 2-year cumulative tumor recurrence rate of 149 patients were 29(range, 24?33)months and 43.0%, respectively. The 2-year tumor cumulative recurrence rate of patients with and without VETC predicted by risk scoring model was 47.8% and 37.9%, respectively, showing a significant difference between ( χ2=3.90, P<0.05). The 2-year cumulative tumor recurrence rate of patients with and without VETC confirmed by postoperative histopathological examination was 47.4% and 38.1%, respectively, showing a significant difference between ( χ2=4.20, P<0.05). Conclusions:Lesion imaging enhancement as heterogeneous enhancement with septations or irregular ring-like structures, intratumoral necrosis or ischemia and tumor diameter >5 cm are independent risk factors influen-cing HCC patients with VETC. The proposed risk scoring model based on those three risk factors achieves an optimal preoperative diagnostic performance.

Objective:To investigate the effect of Notch on periprosthetic fracture (PPF) of the femoral prosthesis after primary total knee arthroplasty.Methods:A total of 34 patients diagnosed with femoral PPF at Xi'an Honghui Hospital were retrospectively collected from January 2013 to December 2020. There were 4 males and 30 females with a mean age of 69.2±7.2 years (range, 55-84 years). A total of 102 patients without PPF were matched by gender and age as the control group in a ratio of 1∶3. There were 12 males and 90 females with a mean age of 69.2±7.2 years (range, 55-84 years). The main observation indexes included patients' general information and factors such as coronal alignment, prosthesis design and Notch conditions. Then, subgroup analysis was performed with the depth and Tayside classification of Notch to analyze their effects on PPF.Results:The PPF and control groups were comparable in terms of baseline information such as gender, age, body mass index (BMI), and surgical side. There was no significant difference between the two groups in coronal alignment (χ 2=1.019, P=0.601) and prosthesis design (χ 2=1.545, P=0.214). There was no statistical difference in Notch between the PPF and control groups (χ 2=3.548, P=0.060). The mean length of Notch in the PPF group was 4.5±2.7 mm, compared with 4.9±2.8 mm in the control group, with no significant difference between the two groups ( t=0.732, P=0.465). Further subgroup analysis using a Notch depth of 3 mm as a cut-off and Tayside classification revealed a statistical difference between the two groups (χ 2=11.262, P=0.004; χ 2=14.601, P=0.003). Compared with patients without Notch, the risk of PPF was higher when the depth of Notch exceeded 3 mm, with an odds ratio ( OR) of 4.88 (95% CI: 1.76, 13.51). The incidence of PPF was higher when Notch depth reached Tayside grade 3 or 4. Compared with patients without Notch, the risk of PPF would be 6.99-fold (95% CI: 1.85, 26.32) higher when Notch depth reached grade 3. In female patients, there was a significant difference in Notch status between the PPF and control groups (χ 2=3.956, P=0.047), with a higher risk of PPF in female patients with Notch, OR 2.33 (95% CI: 1.01, 5.43). In patients who underwent right-sided TKA, the risk of PPF was higher in patients with Notch compared to those without Notch (χ 2=5.502, P=0.019), with an OR of 3.58 (95% CI: 1.19, 10.75). Conclusion:The Notch has no significant effect on the femoral PPF after primary total knee arthroplasty. However, the risk of PPF will increase significantly when the Notch depth exceeds 3 mm or is above Tayside grade 3.

Objective To compare the difference in the effects on liver function between transjugular intrahepatic portosystemic shunt (TIPS) alone and the combination of TIPS and left gastric vein embolization (LGVE) in patients with liver cirrhosis.Methods This research was a retrospective study.From September 2014 to September 2015,31 patients with liver cirrhosis underwent TIPS (TIPS group) and 29 patients with liver cirrhosis underwent TIPS combined with LGVE (TIPS+LGVE group) were enrolled.The data of the liver function of patients before and after operation were collected and the Child-Pugh score and model for end-stage liver disease (MELD) were also calculated.Student's t test and chi-squared test were performed for statistical analysis.Results The preoperative portal vein pressures of TIPS group and TIPS+LGVE group were (28.48±2.77) mmHg (1 mmHg=0.133 kPa) and (28.38± 2.92) mmHg,respectively.And after operation,the portal vein pressures decreased to (17.81 ± 1.47) mmHg and (17.97 ± 2.04) mmHg,respectively,and the differences were both statistically significant (t=18.908 and 11.648,both P＜0.01).At 12 months after operation,Child-Pugh score of TIPS+ LGVE group was 5.69 ± 1.19,which was significantly lower than that before operation (7.03±1.76),and the difference was statistically significant (t=3.398,P=0.001),which was also lower than that of TIPS group at the same time point (6.52 ± 1.54),and the difference was statistically significant (t =2.303,P=0.025).At 12 months after operation,the component ratio of patients with Child-Pugh grade A of TIPS±LGVE group was 89.7％ (26/29),which was higher than that before operation (44.8％,13/29),and the difference was statistically significant (x2=13.228,P＜0.01).The component ratio of patients with Child-Pugh grade B was 6.9 ％ (2/29),which was lower than that before operation (41.4 ％,12/29),and the difference was statistically significant (x2 =9.416,P＜ 0.01).Conclusions TIPS significantly reduces portal vein pressure in patients with liver cirrhosis and it does not deteriorate liver function of patients in the long term.The combination of TIPS and LGVE is better than TIPS alone in improving liver function in patients with liver cirrhosis,especially in improvig long-term liver function in patients of Child-Pugh A and B grade.

BACKGROUND:Stromal cellderived factor 1 in chemotactic migration of endogenous neural stem cells plays a very important role, but the specific migration mechanism is unclear
OBJECTIVE:To observe the effects of exogenous stromal cellderived factor 1 on chemotactic migration and proliferation of neural stem cells in the rat hippocampus
METHODS:Exogenous stromal cellderived factor 1 (5μL, 500μ/L) was injected into the hippocampus of Sprague-Dawley rats to establish animal models. Brain tissues were taken after days 3, 7, 14 and 21 of perfusion to prepare paraffin sections. Thereafter, nestin expression in the injection region and hippocampus was detected using immunohistochemical method. Experimental control and blank control groups were set.
RESULTS AND CONCLUSION:Paraffin section immunohistochemical results displayed the number of nestin-positive cells in the injection and the hippocampus was gradual y increased. At 3 and 7 days, nestin expression was a little and increased at 14 days, forming a migration tendency to the injection region. At 21 days, there were more nestin-positive cells in the injection area and hippocampus. However, there were no changes as above in the experimental control and blank control groups. The results showed that exogenous stromal cellderived factor 1 may induce the proliferation of neural stem cells in the hippocampus and may be involved in chemotactic migration of endogenous neural stem cells.

Objective To apply the exogenous monocyte chemoattractant protein-1 (MCP-1) to induce the neural stem cells in vivo.Methods 64 adult male Sprague-Dawley rats were randomly divided into blank (n=4), control (n=30) and experimental (n=30) groups. The experimental group was injected with MCP-1 into the cerebra, and the control group with PBS, and the blank group with no intervention.The number of nestin positive cells in brain was observed with immunohistochemistry 3, 5, 7, 14, 21 days after injection. Results The number of nestin positive cells increased with time in the cortex and hippocampus in the experimental group (P<0.001). There was no significant difference between the control group and the blank group (P>0.05). Conclusion Exogenous MCP-1 may induce the increase of neural stem cells in vivo.

Objective To explore the relationship among expression of peroxisome proliferators-activated receptors γ (PPARγ) in human glioma, malignancy and outcome. Methods The level of PPARγ was detected with immunohistochemistry in the glioma from 48 cases with glioma. The progression-free survival and overall survival were compared with Kaplan-Meier survival curve between the patients with more expression of PPARγ and less ones. Results The expression of PPARγ decreased (P<0.01) with the the tumor malignancy increasing from grade I to IV, which was negatively correlated (r=-0.770, P<0.01). Both the progression-free and overall survival time were significant difference between the patients with more expression of PPARγ and less ones (P<0.01). Conclusion PPARγ expression correlates with the malignancy of human glioma, which may predict the outcome of the patients.