Objective:To explore and compare the effect and prognosis of small bone window surgery at different timings in the treatment of hypertensive intracerebral hemorrhage (HICH).Methods:Using a retrospective analysis, HICH patients admitted to department of neurosurgery of Guihang Guiyang Hospital were selected from May 2021 to May 2023. According to the different surgical timings, the patients were divided into ultra-early group (time from onset to surgery <6 h) and early group (onset to surgery time ≥6~<24 h). Propensity score was used to match 51 cases in each group. The perioperative indicators (surgical time, intraoperative blood loss, hospital stay, hematoma clearance rate), incidence rates of complications, neurological function (National Institute of Health Stroke Scale (NIHSS), Barthel index), endothelin and arginine vasopressin (AVP) before surgery and after 7 days of surgery, clinical efficacy (Glasgow Outcome Scale (GOS)) at 1 month after surgery, rebleeding rate and mortality rate within 1 year after surgery were compared between both groups. Chi-square test was used for between-group comparison of enumeration data, t test was adopted for between-group comparison of measurement data with normal distribution, and non-parametric rank sum test was adopted for comparison of ranked data between groups.Results:The intraoperative blood loss and hospital stay in ultra-early group with (186.54±20.15) mL and (14.45±2.04) d were significantly less or shorter than (220.10±24.61) mL and (16.79±2.52) d in early group, the difference was statistically significant ( t values were 7.54 and 5.15; both P<0.001). At 7 days after surgery, the NIHSS ((14.55±1.57) and (16.14±2.13) points), endothelin ((69.14±6.37) and (73.48±6.83) mg/L) and AVP ((12.81±2.02) and (14.35±2.23) μg/L) in ultra-early group and early group were significantly lower than before ((32.67±3.81) and (32.38±3.53) points, (89.67±7.25) and (88.24±6.38) mg/L, (18.47±2.41) and (18.04±2.37) μg/L) while the Barthel index ((72.35±10.14) and (67.45±9.78) points) was significantly higher than before ((49.45±7.41) and (47.87±7.37) points),and the difference was statistically significant ( t values were 31.40, 28.13, 15.19, 11.28, 12.85, 8.10, 13.02, and 11.42, respectively; all P<0.001) and the NIHSS, endothelin and AVP in ultra-early group were significantly lower than in early group, while the Barthel index was significantly higher than early group, the difference was statistically significant ( t values were 4.29, 3.32, 3.66, and 2.48 respectively; P values were <0.001, 0.001, <0.001, and 0.015, respectively ). GOS grading (grade I-grade V: 1, 3, 9, 22, 16 cases) in ultra-early group at 1 month after surgery was significantly better than that in early group (grade I-V: 3, 5, 10, 26, 7 cases) ( Z=1.97, P=0.049). Conclusion:Both ultra-early and early small bone window surgery have good results in the treatment of HICH, but ultra-early surgery is more beneficial to the recovery of patients' neurological function and has better prognosis, which can be used as a reference.

Objective:To investigate the correlation between multifidus muscle cross-sectional area (CSA), fat infiltration index (FI), and the grading of lumbar facet joint degeneration (FJD).Methods:A retrospective analysis was conducted on the clinical data of 105 patients with lumbar FJD treated at Sichuan Orthopaedic Hospital between January 2015 and December 2020. Patients were divided into three groups according to the Weishaupt grading system: 37 cases with Weishaupt grade 1 (Mild Group), 44 cases with Weishaupt grade 2 (Moderate Group), and 24 cases with Weishaupt grade 3 (Severe Group). Baseline characteristics [sex, age, body mass index (BMI), treatment duration], pathological features at initial diagnosis [segmental distribution, bone mineral density (BMD) T-score, facet joint asymmetry, endplate morphology, Modic classification, Oswestry Disability Index (ODI), Japanese Orthopaedic Association (JOA) score], and multifidus muscle MRI findings [multifidus cross-sectional area (CSA) and fat infiltration index (FI)] were compared among the three groups. The correlation between lumbar multifidus CSA, FI, and FJD grade was analyzed. Normally distributed measurement data were expressed as xˉ± s; comparisons among multiple groups were performed by one-way ANOVA, pairwise comparisons were performed by LSD- t tests. Counting data were expressed as case (%) and compared by χ2 test. Spearman correlation analysis was used to analyze the correlation between lumbar multifidus MRI parameters and FJD grade. Results:There were no statistically significant differences among the three FJD groups in sex, age, BMI, treatment duration, segmental distribution, BMD T-score, proportion of facet joint asymmetry, endplate morphology, Modic classification, ODI, or JOA score (all P>0.05). At the L4-5 level, the multifidus CSA on the affected side in the severe group was significantly smaller than in the moderate group and mild group [(6.2±1.2) cm2 vs. (7.0±1.1) cm2 vs. (7.8±1.2) cm2], and the CSA in the moderate group was smaller than in the mild group (all P<0.05). At both the L4-5 and L5-S1 levels, the FI on the affected side in the severe group was significantly greater than in the moderate group and mild group [(0.48±0.12) vs. (0.39±0.15) vs. (0.29±0.10) at L4-5; (0.49±0.12) vs. (0.41±0.10) vs. (0.30±0.13) at L5-S1], and the FI in the moderate group was greater than in the mild group (all P<0.05). Spearman correlation analysis showed that at the L4-5 level, multifidus CSA on the affected side was negatively correlated with FJD grade ( r=-0.41, P=0.004). At the L5-S1 level, FI on the affected side was positively correlated with FJD grade ( r=0.58, P<0.001). Conclusion:The CSA and FI of the multifidus muscle on the affected side in the lumbar spine exhibit significant correlations with the severity of FJD grading. Clinically, early functional exercises can be implemented based on the degree of multifidus muscle degeneration observed in patients.

Objective:To explore and compare the effect and prognosis of small bone window surgery at different timings in the treatment of hypertensive intracerebral hemorrhage (HICH).Methods:Using a retrospective analysis, HICH patients admitted to department of neurosurgery of Guihang Guiyang Hospital were selected from May 2021 to May 2023. According to the different surgical timings, the patients were divided into ultra-early group (time from onset to surgery <6 h) and early group (onset to surgery time ≥6~<24 h). Propensity score was used to match 51 cases in each group. The perioperative indicators (surgical time, intraoperative blood loss, hospital stay, hematoma clearance rate), incidence rates of complications, neurological function (National Institute of Health Stroke Scale (NIHSS), Barthel index), endothelin and arginine vasopressin (AVP) before surgery and after 7 days of surgery, clinical efficacy (Glasgow Outcome Scale (GOS)) at 1 month after surgery, rebleeding rate and mortality rate within 1 year after surgery were compared between both groups. Chi-square test was used for between-group comparison of enumeration data, t test was adopted for between-group comparison of measurement data with normal distribution, and non-parametric rank sum test was adopted for comparison of ranked data between groups.Results:The intraoperative blood loss and hospital stay in ultra-early group with (186.54±20.15) mL and (14.45±2.04) d were significantly less or shorter than (220.10±24.61) mL and (16.79±2.52) d in early group, the difference was statistically significant ( t values were 7.54 and 5.15; both P<0.001). At 7 days after surgery, the NIHSS ((14.55±1.57) and (16.14±2.13) points), endothelin ((69.14±6.37) and (73.48±6.83) mg/L) and AVP ((12.81±2.02) and (14.35±2.23) μg/L) in ultra-early group and early group were significantly lower than before ((32.67±3.81) and (32.38±3.53) points, (89.67±7.25) and (88.24±6.38) mg/L, (18.47±2.41) and (18.04±2.37) μg/L) while the Barthel index ((72.35±10.14) and (67.45±9.78) points) was significantly higher than before ((49.45±7.41) and (47.87±7.37) points),and the difference was statistically significant ( t values were 31.40, 28.13, 15.19, 11.28, 12.85, 8.10, 13.02, and 11.42, respectively; all P<0.001) and the NIHSS, endothelin and AVP in ultra-early group were significantly lower than in early group, while the Barthel index was significantly higher than early group, the difference was statistically significant ( t values were 4.29, 3.32, 3.66, and 2.48 respectively; P values were <0.001, 0.001, <0.001, and 0.015, respectively ). GOS grading (grade I-grade V: 1, 3, 9, 22, 16 cases) in ultra-early group at 1 month after surgery was significantly better than that in early group (grade I-V: 3, 5, 10, 26, 7 cases) ( Z=1.97, P=0.049). Conclusion:Both ultra-early and early small bone window surgery have good results in the treatment of HICH, but ultra-early surgery is more beneficial to the recovery of patients' neurological function and has better prognosis, which can be used as a reference.

Objective:To investigate the correlation between multifidus muscle cross-sectional area (CSA), fat infiltration index (FI), and the grading of lumbar facet joint degeneration (FJD).Methods:A retrospective analysis was conducted on the clinical data of 105 patients with lumbar FJD treated at Sichuan Orthopaedic Hospital between January 2015 and December 2020. Patients were divided into three groups according to the Weishaupt grading system: 37 cases with Weishaupt grade 1 (Mild Group), 44 cases with Weishaupt grade 2 (Moderate Group), and 24 cases with Weishaupt grade 3 (Severe Group). Baseline characteristics [sex, age, body mass index (BMI), treatment duration], pathological features at initial diagnosis [segmental distribution, bone mineral density (BMD) T-score, facet joint asymmetry, endplate morphology, Modic classification, Oswestry Disability Index (ODI), Japanese Orthopaedic Association (JOA) score], and multifidus muscle MRI findings [multifidus cross-sectional area (CSA) and fat infiltration index (FI)] were compared among the three groups. The correlation between lumbar multifidus CSA, FI, and FJD grade was analyzed. Normally distributed measurement data were expressed as xˉ± s; comparisons among multiple groups were performed by one-way ANOVA, pairwise comparisons were performed by LSD- t tests. Counting data were expressed as case (%) and compared by χ2 test. Spearman correlation analysis was used to analyze the correlation between lumbar multifidus MRI parameters and FJD grade. Results:There were no statistically significant differences among the three FJD groups in sex, age, BMI, treatment duration, segmental distribution, BMD T-score, proportion of facet joint asymmetry, endplate morphology, Modic classification, ODI, or JOA score (all P>0.05). At the L4-5 level, the multifidus CSA on the affected side in the severe group was significantly smaller than in the moderate group and mild group [(6.2±1.2) cm2 vs. (7.0±1.1) cm2 vs. (7.8±1.2) cm2], and the CSA in the moderate group was smaller than in the mild group (all P<0.05). At both the L4-5 and L5-S1 levels, the FI on the affected side in the severe group was significantly greater than in the moderate group and mild group [(0.48±0.12) vs. (0.39±0.15) vs. (0.29±0.10) at L4-5; (0.49±0.12) vs. (0.41±0.10) vs. (0.30±0.13) at L5-S1], and the FI in the moderate group was greater than in the mild group (all P<0.05). Spearman correlation analysis showed that at the L4-5 level, multifidus CSA on the affected side was negatively correlated with FJD grade ( r=-0.41, P=0.004). At the L5-S1 level, FI on the affected side was positively correlated with FJD grade ( r=0.58, P<0.001). Conclusion:The CSA and FI of the multifidus muscle on the affected side in the lumbar spine exhibit significant correlations with the severity of FJD grading. Clinically, early functional exercises can be implemented based on the degree of multifidus muscle degeneration observed in patients.

ObjectiveThis study aimed to evaluate the clinical efficacy of Ruyi Zhenbaowan（RYZBW）in the treatment of initial and early knee osteoarthritis （KOA） through a prospective multicenter，randomized，double-blind，and placebo-parallel controlled trial. MethodFrom October 13^th， 2021 to December 25^th， 2021， 240 KOA subjects meeting the acceptance criteria were enrolled in 15 sub-centers including Wangjing Hospital， Chinese Academy of Chinese Medical Sciences， and they were randomly divided into observation group and control group， with 120 cases in each group. The intervention measures for the observation group were RYZBW + health education， and the intervention measures for the control group were RYZBW placebo + health education. The intervention period in both groups was four weeks， and they were followed up for four weeks after the intervention. The primary outcome measure was the total score of Western Ontario and McMaster University Osteoarthritis Index score （WOMAC score）， and the secondary outcome measures were the response rate of visual scale （VAS） pain score， WOMAC sub item scores （joint pain， joint stiffness， and joint function）， quality of life （SF-12） score， and traditional Chinese medicine （TCM） syndrome score. Result（1） Efficacy evaluation. The marginal model results showed that the observation group was better than the control group in improving the WOMAC total score and WOMAC pain score in the treatment of KOA with RYZBW， and the difference was statistically significant （P<0.05）. There was no significant difference between the two groups in improving VAS score response rate， WOMAC function score， WOMAC stiffness score， SF12-PCS （quality of life-physical health） score， SF12-MCS （quality of life-mental health） score， and TCM syndrome score. （2） Subgroup analysis. ① In terms of VAS score response rate， the response rate of the observation group was higher than that of the control group for subjects with baseline VAS score of （4， 5］， and the difference was statistically significant （P<0.05）. ② In terms of TCM syndrome score， for subjects aged ［56， 60］ and ［61， 65］， the decrease in total TCM syndrome score in the observation group was better than that in the control group， and the difference was statistically significant （P<0.05）. ConclusionTibetan medicine RYZBW has good clinical efficacy in improving WOMAC total score， VAS score response rate， WOMAC pain score， WOMAC function score， and TCM syndrome score for patients with initial and early KOA， which can fill the lack of Tibetan medicine RYZBW in the treatment of KOA and make a demonstration study for the inheritance and development of ethnic medicine.

Objective:To observe and determine the gene mutation site and clinical phenotype of a NDP gene mutant family, and provide a basis for the prenatal diagnosis of offspring. Methods:A pedigree investigation study. Two patients and 6 family members of a third-generation Han family with NDP gene mutation who were admitted to the Maternal and Child Health Hospital of Gansu Province from July 2019 to December 2021 were included in the study. The patients and their parents underwent the examination of pupil light reflex, strip light imaging, visual acuity evaluation, fundus color photography, and wide-field fluorescein fundus angiography (FFA). Peripheral blood of all the subjects was collected, the pathogenic genes were screened by whole exome sequencing, and NDP genes were detected by amplification of multiple ligated probes. DNA prenatal diagnosis was performed by amniocentesis at 19th weeks of the mother's third gestation. Results:Proband (Ⅲ1), male, 4 years old, full term natural delivery. At about 40 days after birth, B-mode ultrasonography indicated total retinal detachment in both eyes. Normal hearing and intelligence. Fundus examination was not performed. First sibling of proband (Ⅲ2, big younger brother), ophthalmologic examination 30 days after birth, retinal detachment in both eyes. Proband's mother (Ⅱ2) had unvascularized peripheral temporal retina in both eyes. Wide-angle FFA examination showed no vascularization of the peripheral temporal retina in both eyes, and slight leakage of peripheral vascular fluorescein. The proband's second sibling (Ⅲ3, little younger brother) was screened for neonatal eye disease 1 day after birth. No abnormalities were observed outside both eyes. Cornea and lens transparent. No abnormalities were observed in the optic disc and macula in both eyes. No vascular curvature was observed in the peripheral retina. The results of gene detection showed that there was hemizygote deletion in exon 2 of NDP gene of the proband (Ⅲ1) and its big younger brother (Ⅲ2). His mother (Ⅱ2) had heterozygosity deletion in exon 2 of NDP gene. The phenotype and genetic test results of the proband's father (Ⅱ1), uncle (Ⅱ3), maternal grandfather (Ⅰ1) and maternal grandmother (Ⅰ2) were not abnormal. Conclusions:The hemizygote deletion in exon 2 of NDP gene is a pathogenic variation in the native family. The clinical phenotypes of different genders are different. Prenatal diagnosis is an effective way to block hereditary diseases in families.

Enzalutamide (ENZ) is a second-generation androgen receptor (AR) antagonist used for the treatment of castration-resistant prostate cancer (CRPC) and reportedly prolongs survival time within a year of starting therapy. However, CRPC patients can develop ENZ resistance (ENZR), mainly driven by abnormal reactivation of AR signaling, involving increased expression of the full-length AR (ARfl) or dominantly active androgen receptor splice variant 7 (ARv7) and ARfl/ARv7 heterodimers. There is currently no efficient treatment for ENZR in CRPC. Herein, a small molecule LLU-206 was rationally designed based on the ENZ structure and exhibited potent inhibition of both ARfl and constitutively active ARv7 to inhibit PCa proliferation and suppress ENZR in CRPC. Mechanically, LLU-206 promoted ARfl/ARv7 protein degradation and decreased ARfl/ARv7 heterodimers through mouse double minute 2-mediated ubiquitination. Finally, LLU-206 exhibited favorable pharmacokinetic properties with poor permeability across the blood-brain barrier, leading to a lower prevalence of adverse effects, including seizure and neurotoxicity, than ENZ-based therapies. In a nutshell, our findings demonstrated that LLU-206 could effectively inhibit ARfl/ARv7-driven CRPC by dual-targeting of ARfl/ARv7 heterodimers and protein degradation, providing new insights for the design of new-generation AR inhibitors to overcome ARfl/ARv7-driven CRPC.

Objective: To compare the effectiveness and clinical safety between the two through the observation of Orthokeratology lens and multifocal soft lens. Methods: By using prospective longitudinal design, sixty patients (120 eyes) with orthokeratology lens and multifocal soft lens were selected. After 1, 3, 6 and 12 months, our tests were conducted, including ocular surface disease index (OSDI) questionnaire, tear break up time(BUT), corneal fluerescein staining (CSF) and meibomian gland function assessment, before and after wearing glasses, ocular axis and refraction in 6,12 and 18 months after were evaluated to assess the effect of myopia control. Results: But in the orthokeratology lens group was lower than the soft lens group after two months. The difference was statistically significant( t=4.35, P <0.05). After 1 month of wearing glasses, BUT in the orthokeratologylens group was shorter than before( F=305.83, P <0.05). In the group of soft lens, there was no statistically significance before and after wearing glasses( F= 0.38, P >0.05). There was no difference in corneal fluorescence staining (CSF) and meibomian gland function between the two groups before and after wearing glasses.( F time=1.55, 1.38, 10.15, 1.50, P >0.05, F group=2.31, 0.02， P >0.05). After 18 months of wearing orthokeratology lens, the average degree of spherical lens increased by -0.53 D, which was different from that before wearing( F=6.54, P <0.05). After wearing soft lens 18 month, the average degree of spherical lens increase by -0.34 D, which was different from that before wearing( F=2.88, P <0.05). After 18 months of wearing glasses, there were differences in the growth of ocular axis between the two groups( F =2.73, 2.83, P <0.05). Conclusion Orthokeratology lens and multifocal soft lens are both safe and effective measures to control myopia.

Objective To explore the predictive value of the expression of CD44v6 and EGFR on the efficacy of neoadjuvant chemotherapy (NACT) in stageⅡ-Ⅲ cervical cancer. Methods A total of 53 patients with stageⅡ-Ⅲ cervical cancer diagnosed by pathology were selected. All patients received two cycles of paclitaxel+platinum NACT. The pathological tissue samples of cervical tumors before NACT treatment were collected. The expression of CD44v6 and EGFR were detected by the immunohistochemical SP method, and we analyzed their predictive value of NACT in stageⅡ-Ⅲ cervical cancer. Results Among the 53 patients, 38 were in the NACT effective group (CR+PR), and 15 were in the NACT ineffective group (SD+PD). The expression of CD44v6 in the ineffective group was significantly higher than that in the effective group (P < 0.05). The expression of CD44v6 was significantly different in patients with CR, PR, and SD (P < 0.05). The AUC of CD44v6 to NACT effect on stage Ⅱ-Ⅲ cervical cancer was 0.74 (P < 0.05). The patients in the high expression group of CD44v6 had worse efficacy in NACT than those in the low expression group of CD44v6 (P < 0.05). Pearson test showed that CD44v6 and EGFR expression were correlated (R=0.34, P < 0.05). Conclusion High expression of CD44v6 may reduce the efficacy of NACT in stageⅡ-Ⅲ cervical cancer, suggesting that the expression of CD44v6 has a certain predictive value and clinical significance in the efficacy of paclitaxel+platinum NACT on cervical cancer. Moreover, CD44v6 is positively correlated with EGFR expression.

Objective To collect the serum samples of patients with nonalcoholic fatty liver disease (NAFLD), and to investigate the changes in serum metabolic biomarkers before and after lifestyle intervention. Methods A total of 23 patients who were diagnosed with NAFLD in Department of Gastroenterology and Inpatient Department, Putuo District Central Hospital of Shanghai, from January 2019 to January 2020 were enrolled, and all patients received the intervention with aerobic exercise and equicaloric low-carbohydrate high-protein diet. A total of 13 healthy volunteers who underwent physical examination in Physical Examination Center were enrolled as control group. For the patients with NAFLD, basic information was collected before and after intervention, blood samples were collected twice to measure liver function, blood glucose, and blood lipids, and part of serum was used for serum metabolomics analysis. The serum samples were analyzed by ultra-performance liquid chromatography/tandem high-resolution mass spectrometry. The data collected were processed in Compound Discover, and then principal component analysis (PCA) and orthogonal partial least squares discriminant analysis were used to establish the profile of differentially expressed blood metabolites between patients and healthy people and perform the enrichment analysis of differentially expressed metabolic pathways. The independent samples t -test was used for comparison of normally distributed continuous data between two groups, and the Wilcoxon non-parametric test was used for comparison of non-normally distributed continuous data between two groups. Results After lifestyle intervention, the patients had significant reductions in body mass index ( P < 0.01), body weight ( P < 0.01), and serum biochemical parameters alkaline phosphatase, albumin, gamma-glutamyl transpeptidase, and alanine aminotransferase (all P < 0.05), as well as a significant reduction in total protein ( P < 0.01), while there were no significant improvements in cholinesterase, aspartate aminotransferase, and glucose. As for the four items for blood lipids, there was a significant reduction in triglyceride ( P < 0.01), while there were no significant improvements in high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total cholesterol. The metabolomics analysis showed that 33 serum metabolites changed significantly after lifestyle intervention. In addition, PCA results showed that after intervention, the level of metabolites in patients tended to be normal. The signaling pathway analysis showed that exercise and diet mainly affected the pathways of bile acid, unsaturated fatty acid synthesis, and phenylalanine metabolism. Conclusion Lifestyle intervention can achieve varying degrees of reduction in the body weight of patients with NAFLD, improve serum biochemical parameters, and regulate the abnormal metabolic pathway in patients with NAFLD, which has important clinical value and significance for guiding clinicians to formulate reasonable diet and exercise strategies for patients with NAFLD and prevent the progression of NAFLD.