Objective To investigate the neuroprotective effect of Tibetan medicine 70 Wei Pearl Pill(RNSP)on 6-hydroxydopamine(6-OHDA)induced Parkinson's disease model rats and its related mechanism.Methods Totally 48 male SD rats were randomly divided into control group,model group,model plus low-dose RNSP group(90 mg/kg),model plus medium-dose RNSP group(180 mg/kg),model plus high-dose RNSP group(360 mg/kg),and model plus madopar group(50 mg/kg),with 8 rats in per group.Except for the control group,the other rats were treated with 6-OHDA single injection into the striatum to establish the PD model.Each group was given intragastric administration after modeling and the control group and model group were given an equal volume of saline once a day for 4 weeks.The rats were subjected to apomorphine-induced rotation,experiments at the 2nd and 4th week after the completion of modeling,and the open field experiment was conducted the next day after the last rotation experiment to observe the animal behavior.After the behavioral experiment,the rats were stained with tyrosine hydroxylase(TH)in the substantia nigra pars compacta by immunohistochemical method and the positive neurons were counted.The protein levels of Bcl-2,BAX,Caspase-3 in substantia nigra and P38,P-P38,ERK,P-ERK,JNK,P-JNK in the striatum were detected by Western blotting.Results Compared with the control group,the rotation frequency and percentage of rotating rats in the model group increased significantly at the 2nd and 4th weeks after modeling;the open field active distance,average speed and times of crossing the grid were significantly decreased;and the rest time was significantly increased.While the number of TH positive neurons in the substantia nigra was significantly decreased,the BAX and Caspase-3 protein levels were increased significantly,Bcl-2 was decreased significantly,the ratios of P-P38/P38,P-JNK/JNK and P-ERK/ERK in the striatum were significantly increased in PD group.Compared with the model group,the rotation frequency and percentage of rotating rats in the low-,medium-and high-dose groups of RNSP had no significant changes after 2 weeks of administration,the rotation frequency in the high-dose group and percentage of rotating rats in the low-and medium-dose RNSP groups significantly decreased after 4 weeks of administration.The open field active distance,average speed,and times of crossing the grid were significantly increased;the rest time was significantly decreased.The number of TH positive neurons in the substantia nigra was significantly increased,the Bax and Caspase-3 protein levels were decreased significantly while the Bcl-2 was significantly increased.The ratios of P-P38/P38,P-JNK/JNK and P-ERK/ERK in the striatum were significantly decreased.Conclusion Tibetan medicine RNSP can improve the motor ability and reduce the loss of DA neurons in PD rats,and its mechanism may be related to inhibiting P38/JNK/ERK signaling pathway and reducing the apoptosis of midbrain neurons.

BACKGROUND: The achievement of an optimal return to sport (RTS) has remained a key goal after sports-related injuries, with the ongoing debate on the effectiveness of different surgical approaches for anterior cruciate ligament (ACL) rupture. This study aims to assess clinical outcomes and RTS across various surgical methods, such as anatomical single-bundle reconstruction (ASBR), central-axial single-bundle reconstruction (CASBR), and double-bundle reconstruction (DBR). METHODS: A randomized clinical trial was conducted, comprising 191 patients who underwent ACL rupture. These patients were divided into three groups based on the ACL reconstruction techniques they received (ASBR, CASBR, DBR). Over the 2-year follow-up period, the study assessed RTS through four single-hop tests, isokinetic extension tests, and limb asymmetry indices. Postoperative graft status was determined using the signal-to-noise quotient (SNQ), while knee function was evaluated using the International Knee Documentation Committee 2000 (IKDC-2000) score, Lysholm score, Tegner score, and degree of knee laxity. A binary logistic regression model was developed to forecast the factors influencing ideal RTS. RESULTS: DBR (67.63%) and CASBR (58.00%) exhibited higher RTS passing rates compared to ASBR (30.39%; χ2 = 19.57, P <0.05). Quadriceps strength symmetry in the lower limbs was identified as the key determinant of RTS ( χ2 = 17.08, P <0.05). The RTS rate was influenced by SNQs of the graft's tibial site (odds ratio: 0.544) and quadriceps strength of the reconstructed knee joint at 60°/s (odds ratio: 6.346). Notably, the DBR group showed enhanced knee stability, evidenced by superior results in the Lachman test ( χ2 = 13.49, P <0.01), objective IKDC-2000 ( χ2 = 27.02, P = 0.002), and anterior instability test ( χ2 = 9.46, P <0.01). Furthermore, DBR demonstrated superior clinical outcomes based on the Lysholm score (DBR: 89.57 ± 7.72, CASBR: 83.00 ± 12.71, ASBR: 83.21 ± 11.95; F = 10.452, P <0.01) and IKDC-2000 score (DBR: 90.95 ± 7.00, CASBR: 84.64 ± 12.68, ASBR: 83.63 ± 11.41; F = 11.78, P <0.01). CONCLUSION: For patients with ACL rupture, more ideal RTS rate and clinical outcomes were shown in the DBR group than in the ASBR and CASBR groups. Autograft status and quadriceps strength are postively related to RTS. TRIAL REGISTRATION ClinicalTrials.gov (NCT05400460).
Humans ; Anterior Cruciate Ligament Reconstruction/methods* ; Male ; Female ; Adult ; Anterior Cruciate Ligament Injuries/surgery* ; Young Adult ; Return to Sport ; Adolescent ; Anterior Cruciate Ligament/surgery* ; Treatment Outcome

Objective To investigate the neuroprotective effect of Tibetan medicine 70 Wei Pearl Pill(RNSP)on 6-hydroxydopamine(6-OHDA)induced Parkinson's disease model rats and its related mechanism.Methods Totally 48 male SD rats were randomly divided into control group,model group,model plus low-dose RNSP group(90 mg/kg),model plus medium-dose RNSP group(180 mg/kg),model plus high-dose RNSP group(360 mg/kg),and model plus madopar group(50 mg/kg),with 8 rats in per group.Except for the control group,the other rats were treated with 6-OHDA single injection into the striatum to establish the PD model.Each group was given intragastric administration after modeling and the control group and model group were given an equal volume of saline once a day for 4 weeks.The rats were subjected to apomorphine-induced rotation,experiments at the 2nd and 4th week after the completion of modeling,and the open field experiment was conducted the next day after the last rotation experiment to observe the animal behavior.After the behavioral experiment,the rats were stained with tyrosine hydroxylase(TH)in the substantia nigra pars compacta by immunohistochemical method and the positive neurons were counted.The protein levels of Bcl-2,BAX,Caspase-3 in substantia nigra and P38,P-P38,ERK,P-ERK,JNK,P-JNK in the striatum were detected by Western blotting.Results Compared with the control group,the rotation frequency and percentage of rotating rats in the model group increased significantly at the 2nd and 4th weeks after modeling;the open field active distance,average speed and times of crossing the grid were significantly decreased;and the rest time was significantly increased.While the number of TH positive neurons in the substantia nigra was significantly decreased,the BAX and Caspase-3 protein levels were increased significantly,Bcl-2 was decreased significantly,the ratios of P-P38/P38,P-JNK/JNK and P-ERK/ERK in the striatum were significantly increased in PD group.Compared with the model group,the rotation frequency and percentage of rotating rats in the low-,medium-and high-dose groups of RNSP had no significant changes after 2 weeks of administration,the rotation frequency in the high-dose group and percentage of rotating rats in the low-and medium-dose RNSP groups significantly decreased after 4 weeks of administration.The open field active distance,average speed,and times of crossing the grid were significantly increased;the rest time was significantly decreased.The number of TH positive neurons in the substantia nigra was significantly increased,the Bax and Caspase-3 protein levels were decreased significantly while the Bcl-2 was significantly increased.The ratios of P-P38/P38,P-JNK/JNK and P-ERK/ERK in the striatum were significantly decreased.Conclusion Tibetan medicine RNSP can improve the motor ability and reduce the loss of DA neurons in PD rats,and its mechanism may be related to inhibiting P38/JNK/ERK signaling pathway and reducing the apoptosis of midbrain neurons.

Astrocytes are the largest glial population in the mammalian brain. However, we have a minimal understanding of astrocyte development, especially fate specification in different regions of the brain. Through lineage tracing of the progenitors of the third ventricle (3V) wall via in-utero electroporation in the embryonic mouse brain, we show the fate specification and migration pattern of astrocytes derived from radial glia along the 3V wall. Unexpectedly, radial glia located in different regions along the 3V wall of the diencephalon produce distinct cell types: radial glia in the upper region produce astrocytes and those in the lower region produce neurons in the diencephalon. With genetic fate mapping analysis, we reveal that the first population of astrocytes appears along the zona incerta in the diencephalon. Astrogenesis occurs at an early time point in the dorsal region relative to that in the ventral region of the developing diencephalon. With transcriptomic analysis of the region-specific 3V wall and lateral ventricle (LV) wall, we identified cohorts of differentially-expressed genes in the dorsal 3V wall compared to the ventral 3V wall and LV wall that may regulate astrogenesis in the dorsal diencephalon. Together, these results demonstrate that the generation of astrocytes shows a spatiotemporal pattern in the developing mouse diencephalon.
Mice ; Animals ; Astrocytes ; Neuroglia/physiology* ; Diencephalon ; Brain ; Neurons ; Mammals

Objective:To investigate the characteristics of blood glucose fluctuation and risk factors in type 2 diabetic patients with asymptomatic hypoglycemia.Methods:From September 2018 to July 2021, 342 patients with type 2 diabete mellitus who were hospitalized in the Department of Endocrinology of Hefei Hospital Affilitated to Anhui Medical University were enrolled for a retrospective study. The mean amplitude of glycemic excursions(MAGE), coefficient of variation (CV), 24 hour mean blood glucose level (MG), and time in range (TIR) were obtained by continuous glucose monitoring (CGM). According to the results of CGM and whether the patients have hypoglycemia symptoms, they were divided into three groups: no hypoglycemia group, symptomatic hypoglycemia group, and asymptomatic hypoglycemia group. The differences in blood glucose fluctuations were compared among the three groups. Multivariate logistic regression analysis was used to evaluate the risk factors in type 2 diabete mellitus patients with asymptomatic hypoglycemia. The predictive value of MAGE for asymptomatic hypoglycemia was analyzed by receiver operating characteristic (ROC) curve.Results:Compared with the non-hypoglycemia group, the TIR in asymptomatic hypoglycemia group was higher ( Z=-2.042, P=0.041). The asymptomatic hypoglycemia group had lower MG, higher MAGE and CV compared with the other two groups(all P<0.05). Multivariate logistic regression analysis showed that urinary albumin/creatinine ratio (UACR), MAGE, and CV were the risk factors for asymptomatic hypoglycemia, while MG was the protective factor. After adjustment for other risk factors, MAGE was still associated with asymptomatic hypoglycemia ( OR=1.111, 95% CI 0.999-1.235, P=0.049). The sensitivity and specificity of MAGE in predicting asymptomatic hypoglycemia were 0.769 and 0.776, respectively. Conclusions:Patients with asymptomatic hypoglycemia present with larger TIR and MAGE. MAGE, UACR, and CV were risk factors for asymptomatic hypoglycemia. Moreover, MAGE has some predictive value for the occurrence of asymptomatic hypoglycemia.

Gene editing tools with nucleases as the main component have now implemented programmable targeted mutagenesis or insertion or deletion of mammalian genomes.From zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), CRISPR/Cas system to safer and more accurate Cas9 fusion protein gene editing tools and other nuclease gene editing tools, this paper systematically describes the development and evolution of gene editing, with detailed introduction to the development and optimization of next-generation gene editing tools, and a prospect of the clinical application of and challenges for gene editing tools.

Objective:To examine the safety and effectiveness of a novel stent assisted intestinal bypass for preventing anastomotic leakage in laparoscopic assisted radical resection of rectal cancer.Methods:The clinical data of 9 patients with rectal cancer who underwent laparoscopic radical resection and stent assisted intestinal bypass from September 2019 to June 2020 at the Department of Anus & Intestine Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University were retrospectively analyzed. There were 6 males and 3 females, aged (62.1±6.8) years (range: 53 to 75 years), underwent laparoscopic assisted radical resection of rectal cancer and stent assisted intestinal bypass. A degradable diverting stent was placed at the end of the ileum, and a drainage tube was placed at the proximal end of the stent to bypass the intestinal contents. After operation, the patients were given a diet with less residue. From the 14 th day after operation, abdomen X-ray films were taken every 5 to 7 days to observe the destination of the stent dynamically. When the stent was observed to be disintegrated into pieces, the drainage tube was clamped for 3 days to observe any side effects before the tube was removed. The operation time, the time of removing the bypass tube and the total hospital stay were recorded. Results:Laparoscopic assisted radical resection of rectal cancer and stent assisted intestinal bypass were successfully performed in all patients. The operation time was (230.4±48.0) minutes (range: 150 to 318 minutes), and the time of removing shunt tube was (28.8±4.6) days (range: 22 to 34 days). The duration of hospitalization was (21.0±8.6) days (range: 9 to 34 days). Postoperative pathological examination showed 7 cases of moderately differentiated adenocarcinoma, 1 case of moderately well differentiated adenocarcinoma and 1 case of mucinous adenocarcinoma. There were 2 cases of T1, 4 cases of T2 and 3 cases of T3. The number of lymph node dissection was 13.4±3.5 (range: 6 to 18), 3 cases were positive and 6 cases were negative. The post-operation follow-up time was 6 to 16 months, no anastomotic leakage or stenosis was found.Conclusion:Stent assisted intestinal bypass for the prevention of anastomotic leakage in laparoscopic assisted radical resection of rectal cancer is safe and feasible, and shows good short-term effect.

Objective:To examine the safety and effectiveness of a novel stent assisted intestinal bypass for preventing anastomotic leakage in laparoscopic assisted radical resection of rectal cancer.Methods:The clinical data of 9 patients with rectal cancer who underwent laparoscopic radical resection and stent assisted intestinal bypass from September 2019 to June 2020 at the Department of Anus & Intestine Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University were retrospectively analyzed. There were 6 males and 3 females, aged (62.1±6.8) years (range: 53 to 75 years), underwent laparoscopic assisted radical resection of rectal cancer and stent assisted intestinal bypass. A degradable diverting stent was placed at the end of the ileum, and a drainage tube was placed at the proximal end of the stent to bypass the intestinal contents. After operation, the patients were given a diet with less residue. From the 14 th day after operation, abdomen X-ray films were taken every 5 to 7 days to observe the destination of the stent dynamically. When the stent was observed to be disintegrated into pieces, the drainage tube was clamped for 3 days to observe any side effects before the tube was removed. The operation time, the time of removing the bypass tube and the total hospital stay were recorded. Results:Laparoscopic assisted radical resection of rectal cancer and stent assisted intestinal bypass were successfully performed in all patients. The operation time was (230.4±48.0) minutes (range: 150 to 318 minutes), and the time of removing shunt tube was (28.8±4.6) days (range: 22 to 34 days). The duration of hospitalization was (21.0±8.6) days (range: 9 to 34 days). Postoperative pathological examination showed 7 cases of moderately differentiated adenocarcinoma, 1 case of moderately well differentiated adenocarcinoma and 1 case of mucinous adenocarcinoma. There were 2 cases of T1, 4 cases of T2 and 3 cases of T3. The number of lymph node dissection was 13.4±3.5 (range: 6 to 18), 3 cases were positive and 6 cases were negative. The post-operation follow-up time was 6 to 16 months, no anastomotic leakage or stenosis was found.Conclusion:Stent assisted intestinal bypass for the prevention of anastomotic leakage in laparoscopic assisted radical resection of rectal cancer is safe and feasible, and shows good short-term effect.

Purpose: Seroma formation is a common complication in breast cancer patients undergoing mastectomy, and it negatively affects patient recovery after surgery. The present study aimed to evaluate a simple method using fascia suture technique to fix the flap and reduce the incidence of seroma. Methods: A single-center, prospective, randomized controlled trial was carried out among 160 patients who had undergone mastectomy from May 2018 to September 2019. All patients were randomly divided into the fascia suture group (n = 80) or control group (n = 80) and were followed up for at least 3 months for the assessment of immediate and late complications after surgery. Results: No significant differences were observed between the 2 groups with regard to the basic characteristics. Duration of surgery in the fascia suture group was longer by about 6 minutes compared with that in the control group (114.93 ± 13.67 minutes vs. 108.81 ± 15.20 minutes, p = 0.008). The fascia suture group had a shorter duration of drain placement (10.99 ± 3.26 days vs. 13.85 ± 5.37 days, p < 0.001), a smaller volume of the total drainage (460.95 ± 242.92 mL vs. 574.83 ± 285.23 mL, p = 0.007), and the first 3-day drainage (224.96 ± 101.01 mL vs. 272.3 ± 115.47 mL, p = 0.006), compared with the control group. The incidence of seroma formation (G2 or G3) was significantly lower in the fascia suture group compared with the control group (28.8% vs. 12.5%, p = 0.033). Besides, there was no statistical difference between the 2 groups in the assessment of other complications, including postoperative pain, hematoma, surgical site infections, flap necrosis, and skin dimpling (all p > 0.050). Conclusion The fascia suture technique is a simple and effective method for reducing seroma formation and should be used to prevent seroma formation after mastectomy.

Objective To evaluate the value of whole genome amplification (WGA) combined with array comparative genomic hybridization (aCGH) in prenatal diagnosis. Methods Array CGH were performed by the DNA of 18 prenatal specimens , which were amplified by WGA because of the low DNA yield. Result 3 of the 18 fetuses were 45, X0 and 9 of 15 fetuses with normal aCGH results showed healthy outcome. Conclusion It’ s feasible for prenatal diagnosis using WGA combined with aCGH which not only can shorten the reporting time but also keep the sensitivity and accuracy of detection.