Objective:To evaluate the outcomes of short-segment pedicle screw fixation after vertebroplasty augmentation using polymethylmethacrylate (PMMA) and laminectomy for stage Ⅲ Kümmell's disease with neurological symptoms.Methods:A retrospective study was conducted to analyze the clinical data of the 23 patients who had been treated at Department of Spinal Surgery, Beijing Jishuitan Hospital from January 2016 to August 2022 for single level stage Ⅲ Kümmell's disease with neurological symptoms by short-segment pedicle screw fixation after vertebroplasty augmentation using PMMA and laminectomy. There were 9 males and 14 females, with an age of (69.7±3.8) years. The visual analogue scale (VAS) for low back pain, Oswestry disability index (ODI) for low back pain, kyphotic Cobb angle of the fixed segment, and loss of the anterior vertebral body height were compared between preoperation, 2 weeks after operation, 2 years after operation, and the last follow-up. The improvements in American Spinal Injury Association (ASIA) impairment grading at the last follow-up compared to the preoperative levels, bone graft fusion rates at the last follow-up and complications were recorded.Results:All patients were followed up for (57.4±17.7) months after operation. The VAS pain scores [(2.2±0.3) points, (1.8±0.6) points and (1.6±0.5) points], ODIs (23.9%±4.5%, 21.6%±4.5% and 19.1%±3.8%), kyphotic Cobb angles of the fixed segments (12.2°±2.7°, 12.5°±2.6° and 12.8°±2.8°) and losses of the anterior vertebral body height (20.0%±3.4%, 20.2%±3.5% and 20.3%±3.5%) at 2 weeks after operation, 2 years after operation, and the last follow-up were significantly improved compared to the pre-operative values [(7.8±0.5) points, 79.7%±5.1%, 40.2°±6.2°, and 60.4%±14.2%, respectively] ( P<0.05). However, there were no significantly differences in the above values between 2 weeks after operation, 2 years after operation and the last follow-up ( P>0.05). Of the 2 patients with grade C, the ASIA grading at the last follow-up improved to grade D in one and to grade E in the other; of the 12 patients with grade D, the ASIA grading at the last follow-up improved to grade E in 11. The complications included 2 asymptomatic cases of bone cement leakage from the upper endplate of the affected vertebra, 1 asymptomatic case of bone cement leakage from the lower endplate of the affected vertebra, 1 asymptomatic case of bone cement leakage from the spinal canal, and 1 case of distant vertebral compression fracture. The last follow-up showed good bone graft fusion in all patients. Conclusion:In the treatment of stage Ⅲ Kümmell's disease with neurological symptoms, short-segment pedicle screw fixation after vertebroplasty augmentation using PMMA is a relatively minimally invasive, safe, and effective treatment, because it can alleviate back pain, improve neurological function and daily function, correct thoracolumbar kyphosis, restore vertebral height and reconstruct spinal stability without significant complications.

Objective:To evaluate the outcomes of short-segment pedicle screw fixation after vertebroplasty augmentation using polymethylmethacrylate (PMMA) and laminectomy for stage Ⅲ Kümmell's disease with neurological symptoms.Methods:A retrospective study was conducted to analyze the clinical data of the 23 patients who had been treated at Department of Spinal Surgery, Beijing Jishuitan Hospital from January 2016 to August 2022 for single level stage Ⅲ Kümmell's disease with neurological symptoms by short-segment pedicle screw fixation after vertebroplasty augmentation using PMMA and laminectomy. There were 9 males and 14 females, with an age of (69.7±3.8) years. The visual analogue scale (VAS) for low back pain, Oswestry disability index (ODI) for low back pain, kyphotic Cobb angle of the fixed segment, and loss of the anterior vertebral body height were compared between preoperation, 2 weeks after operation, 2 years after operation, and the last follow-up. The improvements in American Spinal Injury Association (ASIA) impairment grading at the last follow-up compared to the preoperative levels, bone graft fusion rates at the last follow-up and complications were recorded.Results:All patients were followed up for (57.4±17.7) months after operation. The VAS pain scores [(2.2±0.3) points, (1.8±0.6) points and (1.6±0.5) points], ODIs (23.9%±4.5%, 21.6%±4.5% and 19.1%±3.8%), kyphotic Cobb angles of the fixed segments (12.2°±2.7°, 12.5°±2.6° and 12.8°±2.8°) and losses of the anterior vertebral body height (20.0%±3.4%, 20.2%±3.5% and 20.3%±3.5%) at 2 weeks after operation, 2 years after operation, and the last follow-up were significantly improved compared to the pre-operative values [(7.8±0.5) points, 79.7%±5.1%, 40.2°±6.2°, and 60.4%±14.2%, respectively] ( P<0.05). However, there were no significantly differences in the above values between 2 weeks after operation, 2 years after operation and the last follow-up ( P>0.05). Of the 2 patients with grade C, the ASIA grading at the last follow-up improved to grade D in one and to grade E in the other; of the 12 patients with grade D, the ASIA grading at the last follow-up improved to grade E in 11. The complications included 2 asymptomatic cases of bone cement leakage from the upper endplate of the affected vertebra, 1 asymptomatic case of bone cement leakage from the lower endplate of the affected vertebra, 1 asymptomatic case of bone cement leakage from the spinal canal, and 1 case of distant vertebral compression fracture. The last follow-up showed good bone graft fusion in all patients. Conclusion:In the treatment of stage Ⅲ Kümmell's disease with neurological symptoms, short-segment pedicle screw fixation after vertebroplasty augmentation using PMMA is a relatively minimally invasive, safe, and effective treatment, because it can alleviate back pain, improve neurological function and daily function, correct thoracolumbar kyphosis, restore vertebral height and reconstruct spinal stability without significant complications.

Objective:To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT).Methods:This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups.Results:Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P>0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P<0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P<0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion:Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.

Objective:To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT).Methods:This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups.Results:Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P>0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P<0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P<0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion:Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.

Humans ; Parkinson Disease/diagnosis* ; Machine Learning

Abstract: Objective To analyze the accuracy and feasibility of GeneXpert MTB/RIF (GeneXpert) detection in the detection of Mycobacterium tuberculosis and the characteristics of rifampicin-resistant rpoB gene mutations. Methods A total of 4 234 sputum samples from suspected tuberculosis patients diagnosed in Sanya tuberculosis designated hospitals from 2015 to 2021 were selected and subjected to sputum smear, solid culture, drug sensitivity test by solid proportion method and GeneXpert detection. Results The positive detection rates of sputum smear, solid culture and GeneXpert of 4 234 sputum samples were 29.24% (1 238/4 234), 32.17% (1 362/4 234) and 35.40% (1 499/4 234), respectively. The positive detection rate of GeneXpert was higher than that of sputum smear, and the difference was statistically significant (χ2=36.775, P<0.01). It was slightly higher than solid culture, and the difference was not statistically significant (χ2=9.908, P=0.02). Taking solid culture results as the gold standard, the sensitivity and specificity of GeneXpert for detecting MTB were 91.04% (1 240/1 362) and 90.98% (2 613/2 872), respectively. According to the proportional drug susceptibility test results as the gold standard, the sensitivity and specificity of GeneXpert in detecting rifampicin resistance were 96.96% (96/99) and 98.86% (1 128/1 141), respectively, with the consensus rate of 98.71%. The accuracy of rifampicin resistance in GeneXpert group without probe mutation was significantly lower than that in group with probe mutation. There was a statistical difference in probe mutation frequency between newly treated and retreated cases. The analysis of rpoB gene mutation frequency characteristics showed: Probe E (50.00%) > Probe A (22.12%) > Probe D (14.42%) > Probe B (6.73%) > combined probe (5.77%) > Probe C (0.96%). Conclusions GeneXpert detection can quickly and effectively diagnose rifampicin-resistant tuberculosis, which is helpful for early clinical diagnosis and treatment. In this region, the rpoB gene mutation probes of rifampicin-resistant tuberculosis mainly occurr in Probe E and Probe A, with the least mutations in Probe C.

Congenital hydrocephalus is a major neurological disorder with high rates of morbidity and mortality; however, the underlying cellular and molecular mechanisms remain largely unknown. Reproducible animal models mirroring both embryonic and postnatal hydrocephalus are also limited. Here, we describe a new mouse model of congenital hydrocephalus through knockout of β-catenin in Nkx2.1-expressing regional neural progenitors. Progressive ventriculomegaly and an enlarged brain were consistently observed in knockout mice from embryonic day 12.5 through to adulthood. Transcriptome profiling revealed severe dysfunctions in progenitor maintenance in the ventricular zone and therefore in cilium biogenesis after β-catenin knockout. Histological analyses also revealed an aberrant neuronal layout in both the ventral and dorsal telencephalon in hydrocephalic mice at both embryonic and postnatal stages. Thus, knockout of β-catenin in regional neural progenitors leads to congenital hydrocephalus and provides a reproducible animal model for studying pathological changes and developing therapeutic interventions for this devastating disease.
Animals ; Disease Models, Animal ; Hydrocephalus/genetics* ; Mice ; Mice, Knockout ; Neurons ; beta Catenin/genetics*

Objective This retrospective study compared the detection rates of prostate cancer between freehand transperineal biopsy (FTPB) and template-guided transperineal biopsy (TYPB) in the patients with PSA levels ＜ 20 ng/ml.Methods From April 2017 to April 2019,768 patients with PSA levels ＜ 20 ng/ml were included into this study.Of these patients,406 underwent FTPB procedures and 362 underwent TTPB procedures.There were no significant differences of median age [66.00(61.00,70.00)vs.66.00 (61.00,71.25) years],height [170.00 (165.00,172.00) vs.170 (165.00,173.00) cm],weight [70.00 (63.88,75.00) vs.70.00 (63.75,75.00) kg],BMI [24.22 (22.22,25.95) vs.24.22 (22.49,25.82) kg/m2],PSA [8.75 (6.49,12.40) vs.8.69 (6.49,11.96) ng/ml],fPSA [1.18 (0.33,2.15) vs.1.15(0.76,1.88)ng/ml],prostate volume [39.79(25.55,53.94)vs.39.88(24.46,55.11)ml] between two groups.Patients' biopsy results were recorded,the differences of prostate cancer detection rates between these two groups were analyzed,specifically including the cancer with Gleason score ≥ 7 and the anterior zone cancer.Results The total prostate cancer detection rates were 33.7％ (137/406) and 39.0％ (141/362,P =0.134) in FTPB group and TTPB group respectively,and the detection rates of cancer with Gleason score≥7 were 23.9％ (97/406) and 32.0％ (116/362,P =0.012) respectively.The detection rates of anterior zone prostate cancer were 15.5％ (63/406) and 27.3％ (99/362,P ＜0.001).Moreover,in thepatients with PSA ＜ 10 ng/ml,the prostate cancer detection rates were 29.8％ (74/248) and 36.2％ (81/224,P =0.144) respectively,while the detection rates of cancer with Gleason score ≥7 were 19.4％ (48/248) and 29.9％ (67/224,P =0.008) respectively.Conclusions There was no significant difference in the total prostate cancer detection rates between 12-core TTPB group and 20-core FTPB group in the patients with PSA ＜ 20 ng/ml,but for the detection rate of cancer with Gleason score ≥ 7,TTPB group was significantly higher than FTPB group,especially in the patients with PSA ＜ 10 ng/ml.In addition,for anterior zone prostate cancer,the detection rate of TrPB group was also higher than FTPB group.

Objective: To explore the effect of natural hirudin on proliferation of human microvascular endothelial cells (HMVECs) and its preliminary mechanism of promoting angiogenesis. Methods: Three-dimensional culture models of HMVECs were established in vitro and observed by inverted phase contrast microscopy after 24 hours of culturing. Then, the three-dimensional culture models of HMVECs were treated with different concentrations (1, 4, and 7 ATU/mL) of the natural hirudin, respectively, and Dulbecco's modified Eagle's medium containing 10% fetal bovine serum as control. The cell proliferations of 4 groups were detected by cell counting kit 8 (CCK-8) method at 24, 48, and 72 hours; the angiogenesis of 4 groups were observed by tube formation assay at 24 hours; the expressions of vascular endothelial growth factor (VEGF) and Notch1 of HMVECs in 4 groups were observed by immunofluorescence staining at 24 hours. Results: The observation of cells in three-dimensional culture models showed that HMVECs attached to Matrigel well, and the cells formed tube structure completely after 24 hours. The results of CCK-8 test showed that the absorbance ( A) value of 1 and 4 ATU/mL groups were higher than that of control group at each time point ( P<0.05), and A value of 4 ATU/mL group was the highest. The A value of 7 ATU/mL group was significantly lower than those of 1 and 4 ATU/mL groups and control group ( P<0.05). The tube formation assay showed that the tube structure was more in 1 and 4 ATU/mL groups than in 7 ATU/mL group and control group, and in 4 ATU/mL group than in 1 ATU/mL group, showing significant differences ( P<0.05). There was no significant difference between 7 ATU/mL group and control group ( P>0.05). The results of immunofluorescence staining showed that compared with control group, the Notch1 expression was higher in 1 and 4 ATU/mL groups and lower in 7 ATU/mL group; and there was significant difference between 4 and 7 ATU/mL groups and control group ( P<0.05). The VEGF expression was higher in 1, 4, and 7 ATU/mL groups than in control group, in 4 ATU/mL group than in 1 and 7 ATU/mL groups, showing significant differences ( P<0.05). Conclusion: Natural hirudin can promote angiogenesis at low and medium concentrations, but suppress angiogenesis at high concentrations. Its mechanism may be related to the VEGF-Notch signal pathway.

Objective To investigate the influences of anterior thalamic nucleus (ANT) stimulation on neurogenesis in hippocampus of epileptic rats. Methods Thirty-two male SD rats were randomly alloca-ted to normal-control group ( n＝8),control-stimulation group ( n＝8),sham-stimulation group ( n＝8) and model-stimulation group(n＝8).Eqileptic SD rat model was established by using microinjection of kainic acid in hippocampal CA3 area,and administered 48 h continuous ANT stimulation in the chronic stage.Epileptic seizures were monitored and counted.The levels of Ki-67,a neurogenesis protein in hippocampus was deter-mined by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). Results The epi-lepsy seizure rate was (5.9±2.2) per week in the sham-stimulation group and (2.9±1.1) per week in model-stimulation group.Compared with sham-stimulated rats, ANT stimulation reduced seizures by 50.8%(P＜0.05).Western blot analysis revealed that the relative levels of Ki-67 in the hippocampus of model-stimula-tion group significantly higher than that of the sham-stimulation group((0.44±0.15) vs (0.19±0.73),P＜0.05).qRT-PCR analysis showed that relative levels of Ki-67 mRNA in the hippocampus of model-stimula-tion group were significantly higher than that of the sham-stimulation group((0.45±0.10) vs (0.15±0.06), P＜0.05). Conclusion Chronic ANT stimulation can promote neurogenesis in epileptic rats,which may be a principle mechanism of the beneficial effect of ANT stimulation on epilepsy.