Objective:To investigate the effects of repetitive transcranial magnetic stimulation(rTMS) on learning memory and abnormal Aβ deposition in cerebral amyloid angiopathy(CAA) model mice, and further to investigate whether the mechanism involves the transport function of glymphatic system.Methods:Eight-month-old SPF grade Tg-SWDI mice were randomly divided into the CAA group and the rTMS group according to the random number table method with 7 in each group.Seven wild-type mice of the same genetic background and age served as the control group. The mice in rTMS group received two weeks of high-frequency rTMS intervention, and the mice in CAA group and control group were only restrained without rTMS intervention.Learning and memory functions were evaluated using the Morris water maze test.Amyloid-beta deposition, glymphatic system clearance, and aquaporin-4(AQP4) polarization were assessed using immunofluorescence, and AQP4 expression levels were measured by Western blot.Statistical analysis of the data was conducted using SPSS 25.0 and GraphPad Prism 9.5 softwares.Repeated-measures ANOVA was used for data on escape latency, and one-way ANOVA was used for comparisons between multiple groups for other data.Results:(1)In the novel object recognition test, there were statistically significant differences in recognition indices among the three groups of mice ( F=22.59, P<0.05). Compared with the control group, the mice in the CAA group showed a significant decrease in the new object recognition index ( P<0.05).Compared with the CAA group, the mice in the rTMS group showed a significant increase in the new object recognition index ( P<0.05).(2)In the Y-maze, there were statistical differences in the spontaneous alternation rates among the three groups ( F=5.00, P<0.05). Compared with the control group, the spontaneous alternation rate in the CAA group was significantly lower ( P<0.05).And compared with the CAA group, the spontaneous alternation rate in the rTMS group was significantly higher ( P<0.05).(3)In the Morris water maze test, there were significant interactions in escape latency among the three groups ( F=4.05, P=0.02), significant main effects of time ( F=713.22, P<0.01), and significant main effects of group ( F=421.55, P<0.01). There was no significant statistical difference in swimming speed among the three groups ( F=0.19, P>0.05), while the difference of the number of entries into the inner zone and the proportion of time spent were statistically significant( F=71.67, 294.14, both P<0.05).Compared with the control group, the CAA group mice significantly decreased in the number of entries into the inner zone and the proportion of time spent in the middle zone (both P<0.01).(4)Compared with the CAA group, the rTMS group significantly increased in the number of entries into the inner zone and the proportion of time spent in the middle zone (both P<0.01).The result of immunofluorescence test showed that there was a statistically significant difference in the levels of Aβ in the cerebral vessels among the three groups( F=385.76, P<0.01).The levels of Aβ in the cerebral vessels of the CAA group (62.00±2.65) were significantly higher than those in the control group (9.00±1.00, P<0.01).The levels in the rTMS group (51.33±3.21) were significantly lower than those in the CAA group (62.00±2.65, P<0.01). Using the residual fluorescence tracer levels of the control group as a baseline, there were statistically significant differences in the tracer intensities in the corpus callosum and cerebral cortex( F=258.97, 46.44, both P<0.05), the tracer intensities in the corpus callosum (3.57±0.21) and cerebral cortex (4.96±0.79) of the CAA group mice were significantly higher than those in the rTMS group (1.45±0.14, 1.78±0.47, P<0.01). The polarization of AQP4 in the cerebral cortex of rTMS group (0.51±0.07) was significantly higher than that in the CAA group (0.30±0.02, P<0.01). Conclusion:rTMS can alleviate learning memory and abnormal Aβ deposition in CAA model mice by modulating AQP4 polarisation and promoting transport function of glymphatic system.

Chronic pain impairs functions across multiple dimensions,including physical,psychological,and social well-being.The neuro-immune mechanisms involve complex interactions between the immune system and nerve fibers at one or multiple levels of the peripheral or central nervous system.In recent years,research on the neuro-immune circuit mechanisms underlying the generation,transmission,modulation,and integration of chronic pain has advanced rapidly.However,the overall interactive dynamics of neuro-immune mechanisms remain unclear.This article systematically reviews recent advances in the neuro-immune mechanisms of chronic pain,elucidating the cascading transformation from peripheral to central sensitization.These findings provide a theoretical basis for a deeper understanding of the overall pathophysiological basis of pain chronicity and the exploration of effective clinical strategies.

Objective:To investigate the effects of repetitive transcranial magnetic stimulation(rTMS) on learning memory and abnormal Aβ deposition in cerebral amyloid angiopathy(CAA) model mice, and further to investigate whether the mechanism involves the transport function of glymphatic system.Methods:Eight-month-old SPF grade Tg-SWDI mice were randomly divided into the CAA group and the rTMS group according to the random number table method with 7 in each group.Seven wild-type mice of the same genetic background and age served as the control group. The mice in rTMS group received two weeks of high-frequency rTMS intervention, and the mice in CAA group and control group were only restrained without rTMS intervention.Learning and memory functions were evaluated using the Morris water maze test.Amyloid-beta deposition, glymphatic system clearance, and aquaporin-4(AQP4) polarization were assessed using immunofluorescence, and AQP4 expression levels were measured by Western blot.Statistical analysis of the data was conducted using SPSS 25.0 and GraphPad Prism 9.5 softwares.Repeated-measures ANOVA was used for data on escape latency, and one-way ANOVA was used for comparisons between multiple groups for other data.Results:(1)In the novel object recognition test, there were statistically significant differences in recognition indices among the three groups of mice ( F=22.59, P<0.05). Compared with the control group, the mice in the CAA group showed a significant decrease in the new object recognition index ( P<0.05).Compared with the CAA group, the mice in the rTMS group showed a significant increase in the new object recognition index ( P<0.05).(2)In the Y-maze, there were statistical differences in the spontaneous alternation rates among the three groups ( F=5.00, P<0.05). Compared with the control group, the spontaneous alternation rate in the CAA group was significantly lower ( P<0.05).And compared with the CAA group, the spontaneous alternation rate in the rTMS group was significantly higher ( P<0.05).(3)In the Morris water maze test, there were significant interactions in escape latency among the three groups ( F=4.05, P=0.02), significant main effects of time ( F=713.22, P<0.01), and significant main effects of group ( F=421.55, P<0.01). There was no significant statistical difference in swimming speed among the three groups ( F=0.19, P>0.05), while the difference of the number of entries into the inner zone and the proportion of time spent were statistically significant( F=71.67, 294.14, both P<0.05).Compared with the control group, the CAA group mice significantly decreased in the number of entries into the inner zone and the proportion of time spent in the middle zone (both P<0.01).(4)Compared with the CAA group, the rTMS group significantly increased in the number of entries into the inner zone and the proportion of time spent in the middle zone (both P<0.01).The result of immunofluorescence test showed that there was a statistically significant difference in the levels of Aβ in the cerebral vessels among the three groups( F=385.76, P<0.01).The levels of Aβ in the cerebral vessels of the CAA group (62.00±2.65) were significantly higher than those in the control group (9.00±1.00, P<0.01).The levels in the rTMS group (51.33±3.21) were significantly lower than those in the CAA group (62.00±2.65, P<0.01). Using the residual fluorescence tracer levels of the control group as a baseline, there were statistically significant differences in the tracer intensities in the corpus callosum and cerebral cortex( F=258.97, 46.44, both P<0.05), the tracer intensities in the corpus callosum (3.57±0.21) and cerebral cortex (4.96±0.79) of the CAA group mice were significantly higher than those in the rTMS group (1.45±0.14, 1.78±0.47, P<0.01). The polarization of AQP4 in the cerebral cortex of rTMS group (0.51±0.07) was significantly higher than that in the CAA group (0.30±0.02, P<0.01). Conclusion:rTMS can alleviate learning memory and abnormal Aβ deposition in CAA model mice by modulating AQP4 polarisation and promoting transport function of glymphatic system.

Chronic pain impairs functions across multiple dimensions,including physical,psychological,and social well-being.The neuro-immune mechanisms involve complex interactions between the immune system and nerve fibers at one or multiple levels of the peripheral or central nervous system.In recent years,research on the neuro-immune circuit mechanisms underlying the generation,transmission,modulation,and integration of chronic pain has advanced rapidly.However,the overall interactive dynamics of neuro-immune mechanisms remain unclear.This article systematically reviews recent advances in the neuro-immune mechanisms of chronic pain,elucidating the cascading transformation from peripheral to central sensitization.These findings provide a theoretical basis for a deeper understanding of the overall pathophysiological basis of pain chronicity and the exploration of effective clinical strategies.

Objective:To explore the effect of low-molecular-weight heparin calcium in preventing lower limb deep vein thrombosis after rectal cancer surgery.Methods:A retrospective case-control study was conducted. The clinical data of 30 rectal cancer patients with postoperative subcutaneous injection of low-molecular-weight heparin calcium in Beijing Hepingli Hospital from February 2018 to February 2022 were retrospectively analyzed, and 30 patients wearing antithrombotic elastic socks during the same period were selected as controls. In the antithrombotic elastic socks group, the appropriate thrombotic elastic socks were selected according to the actual situation of the patients after operation. Low-molecular-weight heparin calcium group was given subcutaneous injection of low-molecular-weight heparin calcium on the 2nd day after operation. The indexes of coagulation function, situation of postoperative lower limb deep vein thrombosis and perioperative indexes were analyzed.Results:The age of patients in the low-molecular-weight heparin calcium group was (62±12) years old, with 17 women and 13 men. The age of patients in the antithrombotic elastic socks group was (63±1) years old, with 18 women and 12 men. Before prevention, there were no significant differences in platelet count (Plt), activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT), fibrinogen (FIB), D-dimer (D-D) levels between the two groups (all P > 0.05). After prevention, the FIB and D-D levels of patients in the low-molecular-weight heparin calcium group [(3.3±0.7) g/L and (341±30) μg/L] were lower than those in the antithrombotic elastic socks group [(4.9±0.6) g/L and (428±40) μg/L] ( t values were 9.51 and 9.61, both P < 0.05), but there were no significant differences in Plt, APTT, TT and PT between the two groups (all P > 0.05). The rate of lower limb deep vein thrombosis in the low-molecular-weight heparin calcium group was lower than that in the antithrombotic elastic socks group [6.67% (2/30) vs. 26.67% (8/30), χ2 = 4.32, P < 0.05]. The drainage flow of anterior sacral drainage tube in the two groups decreased gradually on the 1st, 2nd, 3rd and 4th day after surgery, but there were no significant differences between the two groups (all P > 0.05). The thrombosis time of patients in the low-molecular-weight heparin calcium group was longer than that in the antithrombotic elastic socks group [(84±9) h vs. (73±10) h, t = 4.81, P < 0.05], but there were no significant differences between the two groups in the intraoperative bleeding amount, operation time and postoperative hospital stay (all P > 0.05). Conclusions:Compared with antithrombotic elastic socks, low-molecular-weight heparin calcium is more effective and safer in the prevention of lower limb deep vein thrombosis after rectal cancer surgery.

ObjectiveThis study conducted a "6 + 1" clinical comprehensive evaluation of the existing research on Zhichuanling oral liquid （ZOL） in the treatment of asthma，so as to clarify the clinical advantages and precise clinical positioning of ZOL in the treatment of asthma， lay a foundation for further research and academic promotion of ZOL， and provide new directions for patent cultivation. MethodAn evaluation method featuring a qualitative and quantitative combination was used， which considered the dimensions of safety，effectiveness，economy，innovation，suitability，accessibility， and traditional Chinese medicine （TCM） characteristics. According to Expert Meeting Law， relevant weights were obtained through voting. CSC_v2.0 software was used to calculate each dimension and convert it into the corresponding grade score. ResultBased on the existing materials，① ZOL instruction indicates the adverse reactions，taboo， and notes. Multiple data of clinical research before and after marketing and spontaneous reporting system shows that ZOL has controllable risk and good safety. Safety is rated as B grade. ② Multiple data of clinical research before marketing， systematic evaluation of clinical effectiveness， and Meta-analysis shows that ZOL has good effectiveness and clinical significance. Effectiveness is rated as a B grade. ③ Analysis of the cost-effectiveness of ZOL combined with conventional treatment shows that the economy of the drug is good and rated as a B grade. ④ ZOL has better innovation， which is rated as an A grade. ⑤ ZOL can basically meet the clinical drug needs based on the result of the questionnaire survey and has good suitability， which is rated as a B grade. ⑥ ZOL has better accessibility， and accessibility is rated as A grade. ⑦ ZOL involves a rich theory of TCM but insufficient experience of human usage. It is thus rated as a C grade in terms of TCM characteristics. Based on the results of "6 + 1" dimension，the clinical comprehensive evaluation of ZOL in the treatment of asthma （cold syndrome and heat syndrome）is rated as B category. ConclusionZOL has good clinical value and outstanding innovation and accessibility in the treatment of asthma （cold syndrome and heat syndrome）. It is recommended that ZOL be transformed into the relevant policy results of basic clinical drug management procedurally. At the same time，it is recommended to actively cultivate patents with TCM characteristics.

Objective:To explore the clinicopathological features and prognosis of renal mucinous tubular spindle cell carcinoma (MTSCC).Methods:The clinical data of 16 patients with MTSCC admitted to the First Affiliated Hospital of Zhengzhou University from July 2013 to July 2022 were retrospectively analyzed. There were six male cases and ten female cases. The mean age was (56.4±11.4) years old. Among them, 10 cases were asymptomatic, two complained of hematuria, three complained of lumbar pain, and one complained of lower limb pain. Twelve cases underwent preoperative enhanced CT examination, 6 cases of ultrasound examination, 3 cases of MRI examination, and 1 case of bone scan. Imaging manifestations showed that the masses were round or round-like with clear borders. Two cases combined with hemorrhage and three cases combined with calcification. Five cases showed exophytic growth, 10 cases partially exophytic, and 1 case completely endophytic. The maximum diameter of the tumor was (65.7±27.4) mm. The tumors were located in the left kidney in 11 cases and in the right kidney in 5 cases. The tumors were mildly delayed-enhancing under enhanced CT, long/short T1 signal mixed with long/short T2 signal under MRI, and diffusion-limited high signal under DWI. The tumors were hypoechoic masses without obvious blood flow signals under ultrasound. Twelve cases were diagnosed as renal occupying neoplasms, 2 cases were suggested as lack of blood supply renal tumor, and one was considered renal tumor rupture and bleeding. In one case, a bone scan suggested metastasis to the thoracic spine and pelvis. The metastatic renal tumor was diagnosed, and a renal puncture was performed to clarify the pathology. Eleven patients underwent laparoscopic radical nephrectomy, and 4 patients underwent partial nephrectomy. One case was metastasized without surgery and treated with apatinib mesylate and zoledronic acid.Results:The postoperative pathological specimens showed grayish, grayish-yellow, or grayish-red masses with a soft or medium texture. No perinephric, ureteral, or adrenal invasion was seen in all tumors. Microscopically, the tumor cells were round and ovoid. The tumor cells were arranged in tubular and striated shapes, and mucus pools were locally visible. No sarcomatous component was seen in all tumors. There were 9 patients with pT 1N 0M 0, 6 patients with pT 2N 0M 0, and 1 patient with pT 1N 0M 1. After operation, 2 patients with pT 2N 0M 0, who underwent laparoscopic radical nephrectomy were treated with pazopanib and sunitinib, respectively. All patients were followed up for a median of 50.7(25.8, 75.0)months, 15 patients were free of recurrent metastases, and 1 patient with pre-puncture metastasis died due to tumor progression of multiple pulmonary and bone metastases, with a survival of 16.9 months. Conclusions:Renal MTSCC is rare, mostly found on physical examination, with female patients predominantly, and imaging shows a lack of blood supply tumor. Surgery is the primary treatment method. Partial nephrectomy or radical nephrectomy could be chosen according to the tumor stage, kidney function, and patient's underlying condition, and patients have a good prognosis.

Objective:To compare the clinical effects of reverse shoulder arthroplasty and hemiarthroplasty in the treatment of three- or four-part proximal humeral fractures in the elderly.Methods:The clinical data of 58 elderly patients with three- or four-part proximal humeral fractures treated with hemiarthroplasty or reverse shoulder arthroplasty from June 2014 to June 2020 were retrospectively analyzed. Among them, 46 cases were from Sichuan Provincial Orthopaedic Hospital (22 cases of hemiarthroplasty and 24 cases of reverse shoulder arthroplasty), and 12 cases were from Tianjin Hospital (5 cases of hemiarthroplasty and 7 cases of reverse shoulder arthroplasty). In the hemiarthroplasty group, there were 27 patients, including 7 males and 20 females, with an average age of 70.29±6.81 years (range, 61-87 years), and there were 10 cases of 3-part fractures and 17 cases of 4-part fractures. In the reverse shoulder arthroplasty group, including 9 males and 22 females, with an average age of 75.06 ±4.25 years (range, 67-86 years), and there were 9 cases of 3-part fractures and 22 cases of 4-part fractures. The postoperative efficacy evaluation indexes included visual analogue scale (VAS), range of motion (ROM), prosthesis upward displacement, healing of greater tuberosity, scapular glenoid notch, American Shoulder and Elbow Surgeons (ASES) and Constant-Murley score.Results:The average follow-up was 50.63±16.02 months (range, 24-75 months) in the hemiarthroplasty group and 28.32±11.93 months (range, 14-56 months) in the reverse shoulder arthroplasty group. The anterior elevation in the reverse shoulder arthroplasty group was 118.22°±27.22°, and those in the hemiarthroplasty group was 102.77°±25.88°, which was significant difference ( t=2.21, P=0.032); the results of external rotation (ER) and internal rotation (IR) in two groups were similar, and no significant difference (ER: t=0.57, P=0.616; IR: χ 2=2.61, P=0.273); the average Constant-Murley and ASES in the reverse shoulder arthroplasty group were significantly better than those in the hemiarthroplasty group ( P=0.019 and 0.018); the complication rates of hemiarthroplasty group and reverse shoulder arthroplasty group were 37% (10/27) and 13% (4/31), respectively (χ 2=4.59, P=0.032). In the hemiarthroplasty group, 6 patients had upward movements of the prosthesis and 2 patients had wear of the glenoid side; notching (sirveaux grade 1) was noted in 1 patient in the reverse shoulder arthroplasty group. Conclusion:In the treatment of three- or four-part proximal humeral fractures in the elderly, reverse shoulder arthroplasty achieves significantly better functional results compared to hemiarthroplasty.

With the development of nuclear energy technology and the use of depleted uranium weapons, the uranium exposed population is gradually expanding and the health effects of uranium exposure are of increasing concern. The toxicity of uranium to kidney, a sensitive organ for uranium to enter the body to produce effects, cannot be ignored. As of now, the effects of uranium exposure on the kidney are still not well understood, the threshold of uranium-induced kidney injury has been controversial, and there is a lack of sensitive and specific biomarkers for the diagnosis of early kindey damage, especially in the context of chronic uranium exposure. For these reasons, this paper reviewed the results of research on dose-effect relationships and biomarkers of uranium-induced kidney injury and provided an outlook on future research directions, with the aim of providing a basis for subsequent study on animal experiments and population health effects related to uranium exposure.

Objective:To synthesize a 68Ga-labeled oxalyldiaminopropionic acid (ODAP)-urea based prostate specific membrane antigen (PSMA) targeting probe, and evaluate its properties in vitro and in vivo. Methods:Ligand P151 was synthesized by solid-phase synthesis and its Ki value was determined. The ligand P151 was added into the mixture of 68GaCl 3 and NaOAc solution and was reacted at 95 ℃ for 10 min. The labeling yield and in vitro stability of 68Ga-P151 were determined by high performance liquid chromatography (HPLC). The lipid-water partition coefficient (log P) and cell binding ability were determined. The biodistribution of 68Ga-P151 in normal KM mice was determined. MicroPET imaging of 68Ga-P151 was carried out in prostate cancer 22Rv1 tumor-bearing mice and compared with 68Ga-PSMA 617. Independent sample t test was used to analyze the data. Results:P151 was successfully synthesized with the Ki of 0.58 nmol/L, the labeling yield more than 95% and the radiochemical purity more than 95%. After placement in saline or human serum albumin (HSA) solution at 37 ℃ for 2 h, the radiochemical purity of 68Ga-P151 was still more than 95%, indicating a good stability in vitro. The lipid-water partition coefficient (log P) of 68Ga-P151 was -2.65±0.17, indicating a good hydrophilicity. 68Ga-P151 specifically bound to PSMA in prostate cancer LNCaP cells with the uptake value of (0.83±0.04) percentage injection activity (%IA)/10 5 cells. Biodistribution of normal mice showed that 68Ga-P151 was mainly excreted through kidneys and other organs showed low uptake. MicroPET imaging of tumor-bearing mice showed the maximum standardized uptake value (SUV max: 0.79±0.23 vs 0.54±0.05; t=2.12), tumor/kidney ratio (2.04±0.65 vs 1.88±0.33; t=0.44) and tumor/muscle ratio (12.83±5.18 vs 6.95±1.63; t=2.17) between 68Ga-P151 and 68Ga-PSMA 617 were not significantly different (all P>0.05). Conclusions:68Ga-P151 can be prepared simply and labeled in high yield and show improved pharmacokinetic properties in vivo. The imaging of 68Ga-P151 on PSMA positive tumor is comparable to that of 68Ga-PSMA 617, making it a potential radiopharmaceutical for the diagnosis of prostate cancer.