ObjectiveTo observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy （DR）. MethodsFourteen research centers participated in this study， which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group （120 cases） and a control group （120 cases）. The observation group was treated with Tangning Tongluo tablets， and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision， DR progression rate， retinal microhemangioma， hemorrhage area， exudation area， glycosylated hemoglobin （HbA1c） level， and TCM syndrome score were assessed before and after treatment， and the safety was observed. ResultsThe vision changed in both groups after treatment （P<0.05）， and the observation group showed higher best corrected visual acuity （BCVA） than the control group （P<0.05）. The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups， while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment， the number of microhemangiomas decreased in both the observation group （Z=-1.437， P<0.05） and the control group （Z=-2.238， P<0.05）， and it showed no significant difference between the two groups. As the treatment time prolonged， the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment， the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment， neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time， both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR， being capable of improving vision and reducing hemorrhage and exudation in the fundus.

BACKGROUND:Previous studies have confirmed that Wen-Shen-Tong-Du Decoction can promote the recovery of spinal cord injury by inhibiting pyroptosis of splenic B cells,promoting the phagocytosis of myelin debris by microvascular endothelial cells,affecting the migration and infiltration of microglia,promoting the recovery of damaged neurons,and decreasing neuronal apoptosis after spinal cord injury,but the mechanism of this is still not clear. OBJECTIVE:To investigate the effect of Wen-Shen-Tong-Du Decoction on the triggering receptor expressed on myeloid cells 2(TREM2)and PI3K/Akt signaling pathways in mice following spinal cord injury. METHODS:Thirty-six C57BL/6 mice were selected and randomly divided into a sham-operation group,a model group and a Wen-Shen-Tong-Du Decoction group,with 12 mice in each group.In the model and Wen-Shen-Tong-Du Decoction groups,mouse models of T10 spinal cord injury were prepared by the modified Allen's method.On the 1st day after modeling,the Wen-Shen-Tong-Du Decoction group was given Wen-Shen-Tong-Du Decoction by gavage,and the sham-operation group and the model group were given saline by gavage once a day for 28 days.During the drug administration period,mouse motor function was evaluated by Basso Mouse Scale score and inclined plane test.On the 7th and 28th days after modeling,hematoxylin-eosin staining was used to observe the histopathological changes in the spinal cord tissue of the mice;immunofluorescence double staining was used to detect the protein expression of ionized calcium binding adaptor molecule 1(IBA1)and TREM2;and western blot assay was used to detect the expression of TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2,Bax and Caspase3 in spinal cord tissue. RESULTS AND CONCLUSION:Basso Mouse Scale scores and inclined plane test results indicated that the motor function of the mouse hindlimbs was declined after spinal cord injury,and Wen-Shen-Tong-Du Decoction significantly improved motor function in mice with spinal cord injury.Hematoxylin-eosin staining results revealed that Wen-Shen-Tong-Du Decoction significantly ameliorated the pathological structure of spinal cord tissue compared with the model group,manifesting as reduced degrees of dorsal white matter and neuronal atrophy,decreased cytoplasmic vacuolization,and reduced inflammatory cell infiltration.Immunofluorescence double staining results showed that on the 7th day after modeling,the protein expression of IBA1 and TREM2 in the model group was lower than that in the sham-operation group(P＜0.05),and the protein expression of IBA1 and TREM2 in the Wen-Shen-Tong-Du Decoction group was higher than that in the model group(P＜0.05);on the 28th day after modeling,the protein expression of TREM2 in the model group was lower than that in the sham-operation group(P＜0.05),and the protein expression of TREM2 in the spinal cord tissue of the mice in the Wen-Shen-Tong-Du Decoction group was higher than that in the model group(P＜0.05).Western blot results analysis demonstrated that on the 7th day after modeling,compared with the sham-operation group,the model group exhibited a significant reduction in TREM2,PI3K,and Bcl2/Bax(P＜0.05),as well as a significant increase in p-Akt,Bax and p-Akt/Aktp-PI3K(P＜0.05);compared with the model group,the Wen-Shen-Tong-Du Decoction group showed a significant increase in TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2,p-PI3K/PI3K,p-Akt/Ak,and Bcl2/Bax(P＜0.05),as well as a significant decrease in Bax and Caspase3 protein expression(P＜0.05).On the 28th day after modeling,compared with the sham-operation group,the model group exhibited a significant reduction in TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2 and Bcl2/Bax(P＜0.05),as well as a significant increase in Bax protein expression(P＜0.05);compared with the model group,the Wen-Shen-Tong-Du Decoction group showed a significant increase in TREM2,PI3K,Akt,p-Akt,Bcl2,and Bcl2/Bax(P＜0.05),as well as a significant decrease in Bax protein expression(P＜0.05).To conclude,Wen-Shen-Tong-Du Decoction may activate the PI3K/Akt signaling pathway by up-regulating the expression of TREM2 protein in microglia,and then inhibit neuronal apoptosis,thus exerting neuroprotective effects and promoting the repair of spinal cord injury.

BACKGROUND:Neuregulin 1 has been shown to be characterized in cell proliferation,differentiation,and vascular growth.Human amniotic mesenchymal stem cells are important seed cells in the field of tissue engineering,and have been shown to be involved in tissue repair and regeneration. OBJECTIVE:To construct human amniotic mesenchymal stem cells overexpressing neuregulin 1 and investigate their proliferation and migration abilities,as well as their effects on wound healing. METHODS:(1)Human amniotic mesenchymal stem cells were in vitro isolated and cultured and identified.(2)A lentivirus overexpressing neuregulin 1 was constructed.Human amniotic mesenchymal stem cells were divided into empty group,neuregulin 1 group,and control group,and transfected with empty lentivirus and lentivirus overexpressing neuregulin 1,or not transfected,respectively.(3)Edu assay was used to detect the proliferation ability of the cells of each group,and Transwell assay was used to detect the migration ability of the cells.(4)The C57 BL/6 mouse trauma models were constructed and randomly divided into control group,empty group,neuregulin 1 group,with 8 mice in each group.Human amniotic mesenchymal stem cells transfected with empty lentivirus or lentivirus overexpressing neuregulin-1 were uniformly injected with 1 mL at multiple local wound sites.The control group was injected with an equal amount of saline.(5)The healing of the trauma was observed at 1,7,and 14 days after model establishment.Histological changes of the healing of the trauma were observed by hematoxylin-eosin staining.The expression of CD31 on the trauma was observed by immunohistochemistry. RESULTS AND CONCLUSION:(1)Human amniotic mesenchymal stem cells overexpressing neuregulin-1 were successfully constructed.The mRNA and protein expression of intracellular neuregulin 1 was significantly up-regulated compared with the empty group(P<0.05).(2)The overexpression of neuregulin 1 promoted the migratory ability(P<0.01)and proliferative ability of human amniotic mesenchymal stem cells(P<0.05).(3)Human amniotic mesenchymal stem cells overexpressing neuregulin 1 promoted wound healing in mice(P<0.05)and wound angiogenesis(P<0.05).The results showed that overexpression of neuregulin 1 resulted in an increase in the proliferative and migratory capacities of human amniotic mesenchymal stem cells,significantly promoting wound healing and angiogenesis.

BACKGROUND:The use of 3D-printed patient-specific instruments in opening wedge high tibial osteotomy has advantages such as shorter operative time,fewer fluoroscopic exposures,and higher correction accuracy.However,previous studies have reported issues such as significant damage to surrounding soft tissues and improper fixation of the plates. OBJECTIVE:To investigate the clinical efficacy of using 3D-printed patient-specific instruments combined with customized locking plate in opening wedge high tibial osteotomy for the treatment of knee osteoarthritis. METHODS:A total of 20 patients diagnosed with knee osteoarthritis were divided into the 3D group(n=10)and the conventional group(n=10)according to surgical methods.The 3D group underwent opening wedge high tibial osteotomy using 3D-printed patient-specific instruments combined with customized locking plate,while the conventional group underwent opening wedge high tibial osteotomy using conventional methods.The operative time,fluoroscopic exposures,incision length,pre-and postoperative hip-knee-ankle angle,medial proximal tibial angle,posterior tibial slope,the difference between the planned and actual correction angle,preoperative and 1,3,6 months postoperative knee range of motion and Lysholm score,and incidence of complications were analyzed and compared between the two groups. RESULTS AND CONCLUSION:(1)The operative time and fluoroscopic exposures were significantly shorter in the 3D group compared to the conventional group,with a statistically significant difference(P<0.001).(2)Both groups showed a significant improvement in postoperative hip-knee-ankle angle and medial proximal tibial angle compared to preoperative values,with a statistically significant difference(P<0.001),while there was no significant change in posterior tibial slope.In the 3D group,the postoperative hip-knee-ankle angle,medial proximal tibial angle,and posterior tibial slope differed from their respective preoperative planned values by(-0.22±0.72)°,(-0.20±0.73)°,and(0.23±0.37)°,but the differences were not statistically significant.The difference between the planned and actual correction angle of 3D group was significantly smaller than that of conventional group(P<0.05).(3)Both groups showed a gradual increase in knee range of motion and Lysholm scores after surgery(P<0.001).Compared to the conventional group,the 3D group had superior knee range of motion at 1 and 3 months postoperatively,as well as a higher Lysholm score at 1 month postoperatively,with statistically significant differences(P<0.05).There were no statistically significant differences in Lysholm score at 3 months and knee range of motion and Lysholm score at 6 months between the two groups(P>0.05).(4)Complications occurred in neither groups.(5)The above results indicate that both 3D-printed patient-specific instruments combined with customized locking plate and conventional methods have good clinical efficacy.However,the former has a shorter operative time,fewer fluoroscopic exposures,and faster postoperative recovery of knee joint function.Additionally,3D-printed patient-specific instruments can achieve preoperative planning accurately.

BACKGROUND:Black phosphorus has a high degree of homology with human bone,so it has been extensively studied in the field of bone tissue engineering in recent years.Since 2014,two-dimensional black phosphorus materials have garned significant attention in the field of biomedicine due to their excellent exceptional physical,chemical,and biological properties. OBJECTIVE:To summarize the advancements made in black phosphorus-based nanomaterials for bone tissue engineering,focus on the synthesis methods,osteogenic characteristics,and applications in biomaterials pertaining to two-dimensional black phosphorus nanomaterials. METHODS:Chinese and English key words were"black phosphorus,bone tissue engineering,bone defect,bone regeneration,osteogenesis."Relevant articles in PubMed and CNKI databases from January 2014 to December 2023 were searched.After exclusion and screening,96 articles were analyzed. RESULTS AND CONCLUSION:Black phosphorus nanomaterials play an important role in bone tissue engineering due to their good biocompatibility,biodegradability,photothermal action,antibacterial ability,drug loading performance,and special osteogenic effect,and are ideal candidate materials for promoting bone regeneration.The preparation of black phosphorus nanomaterials is mainly a top-down top-layer stripping method.The main principle is to weaken the van der Waals force between the black phosphorus layers by physical or chemical means to obtain a single or less layer of phosphanse,that is,black phosphorus nanosheets or quantum dots.Black phosphate-based nanocomposites are mainly divided into hydrogels,3D printing scaffolds,composite scaffolds,electrospinning,bionic periosteum,microspheres,and bionic coatings.The research of nano-black phosphorus in bone tissue engineering is in its infancy,and still faces many challenges:the behavior of black phosphorus in vivo and the interaction mechanism with various biomolecules need to be further studied.The long-term potential toxicity of black phosphorus is unknown.The manufacturing process for black phosphorus is difficult to control.Therefore,how to develop uniform size,safe,reliable,and efficient nano black phosphorus and transform it into clinical application requires interdisciplinary research on modern biomedical technology,physicochemical technology,and precision manufacturing technology.

Objective:To evaluate the clinical outcomes of combined complete preservation of chordal structure mitral valve replacement (C-MVR) with total anatomical arterial myocardial revascularization (TACR) in coronary patients with moderate-to-severe or severe ischemic mitral regurgitation (IMR).Methods:This is a retrospective multi-center case series study. Data were retrospectively collected from 127 patients with coronary artery disease with moderate to severe or severe IMR who received TACR with C-MVR from July 2015 to April 2024 in 13 hospitals in China. There were 90 males and 37 females, aged (56.5±10.7) years (range: 33 to 74 years). Perioperative data and follow-up data including left ventricular ejection fraction, left ventricular end-diastolic diameter, and patency rate of arterial grafts of patients were collected. Comparisons were made using paired sample t-test or χ2 test. Results:In this cohort of 127 patients, 67 underwent concurrent tricuspid valve repair. During surgery, 113 grafts of the left internal mammary artery (LIMA), 127 grafts of the left radial artery, 80 grafts of the right radial artery, and 110 grafts of the right internal mammary artery (RIMA) were harvested. The number of the distal anastomosis was 4.2±0.4 (range: 3 to 5). The aortic cross-clamp time and cardiopulmonary bypass time were (97.5±23.4) minutes (range: 90 to 161 minutes) and (145.4±19.2) minutes (range: 101 to 210 minutes), respectively. There was one operative death. Intraoperative placement of an intra-aortic balloon pump was performed in 21 patients to improve the left ventricular ejection. No sternal ischemic occurred. All patients completed follow-up, with a mean follow-up period of (64.3±7.5) months (range: 4 to 110 months). No major cerebrovascular events occurred during the follow-up period, and all patients survived. Left ventricular ejection fraction improved postoperatively (55.0%±5.3% vs. 41.0%±15.3%, t=17.23, P<0.01). The proportion of patients with New York Heart Association functional class ≤2 increased postoperatively (23.6% (30/127) vs. 87.3% (110/126), χ2=103.77, P<0.01). The proportion of patients with Canadian Cardiovascular Society Angina Classification ≤3 decreased postoperatively (4.8% (6/126) vs. 78.7% (100/127), χ2=142.19, P<0.01). The left ventricular end-diastolic diameter decreased postoperatively ((5.70±4.50) cm vs. (6.10±0.23) cm, t=12.15, P<0.01). Coronary multi-detector computed tomography angiography (MDCTA) follow-up was conducted for (60.5±11.7) months (range: 6 to 109 months) postoperatively. MDCTA confirmed the patency rates of the grafts: 96.4% (108/112) for the LIMA grafts, 88.9% (112/126) for the left radial artery grafts, 93.7% (74/79) for the right radial artery grafts, and 90.9% (100/110) for the free RIMA grafts. No significant differences in graft patency rates were observed between the arterial grafts ( χ2=5.24, P=0.155). Conclusion:The results of this multi-centre study demonstrate satisfactory mid-term results of C-MVR with TACR for the treatment of coronary artery disease with moderate to severe or severe IMR.

Objective: To analyze the trends in incidence and mortality of prostate cancer in Ningbo City, Zhejiang Province, so as to provide insights into the prevention and control of prostate cancer. Methods: Data of the incidence and mortality of prostate cancer in Ningbo City from 2011 to 2023 were collected through Ningbo Chronic Disease Collaborative Management System. The incidence and mortality of prostate cancer were calculated and standardized by the data from the sixth national population census in 2010 and the Segi's world standard population in 1960. The trends in incidence and mortality of prostate cancer were evaluated using average annual percent change (AAPC). Results: A total of 15 411 cases of prostate cancer were reported in Ningbo City from 2011 to 2023, and the crude incidence, Chinese-standardized incidence and world-standardized incidence were 39.62/105, 22.18/105 and 16.49/105, respectively, showing upward trends (AAPC=14.782%, 10.390% and 10.608%, all P<0.05). The Chinese-standardized incidence of prostate cancer was higher in urban areas than in rural areas, and both showed upward trends (25.14/105 vs. 19.44/105; AAPC=9.057% and 14.272%, both P<0.05). The crude incidence of prostate cancer in the groups aged 50-<60 years, 60-<70 years, 70-<80 years and ≥80 years showed upward trends (AAPC=11.657%, 14.031%, 10.734% and 5.300%, all P<0.05). A total of 3 739 deaths were reported, and the crude mortality, Chinese-standardized mortality and world-standardized mortality were 9.66/105, 5.23/105 and 3.71/105, respectively, showing upward trends (AAPC=8.458%, 3.620% and 3.602%, all P<0.05). The Chinese-standardized mortality of prostate cancer was higher in urban areas than in rural areas, and both showed upward trends (5.35/105 vs. 5.13/105; AAPC=3.183% and 3.962%, both P<0.05). The crude mortality of prostate cancer the groups ageds ≥80 years showed an upward trend (AAPC=7.482%, P<0.05). Conclusions From 2011 to 2023, the incidence and mortality of prostate cancer in Ningbo City showed upward trends. Special attention should be paid to urban residents, and prostate cancer screening should be strengthened among males aged 50 years and older.

Objective:To evaluate the clinical outcomes of combined complete preservation of chordal structure mitral valve replacement (C-MVR) with total anatomical arterial myocardial revascularization (TACR) in coronary patients with moderate-to-severe or severe ischemic mitral regurgitation (IMR).Methods:This is a retrospective multi-center case series study. Data were retrospectively collected from 127 patients with coronary artery disease with moderate to severe or severe IMR who received TACR with C-MVR from July 2015 to April 2024 in 13 hospitals in China. There were 90 males and 37 females, aged (56.5±10.7) years (range: 33 to 74 years). Perioperative data and follow-up data including left ventricular ejection fraction, left ventricular end-diastolic diameter, and patency rate of arterial grafts of patients were collected. Comparisons were made using paired sample t-test or χ2 test. Results:In this cohort of 127 patients, 67 underwent concurrent tricuspid valve repair. During surgery, 113 grafts of the left internal mammary artery (LIMA), 127 grafts of the left radial artery, 80 grafts of the right radial artery, and 110 grafts of the right internal mammary artery (RIMA) were harvested. The number of the distal anastomosis was 4.2±0.4 (range: 3 to 5). The aortic cross-clamp time and cardiopulmonary bypass time were (97.5±23.4) minutes (range: 90 to 161 minutes) and (145.4±19.2) minutes (range: 101 to 210 minutes), respectively. There was one operative death. Intraoperative placement of an intra-aortic balloon pump was performed in 21 patients to improve the left ventricular ejection. No sternal ischemic occurred. All patients completed follow-up, with a mean follow-up period of (64.3±7.5) months (range: 4 to 110 months). No major cerebrovascular events occurred during the follow-up period, and all patients survived. Left ventricular ejection fraction improved postoperatively (55.0%±5.3% vs. 41.0%±15.3%, t=17.23, P<0.01). The proportion of patients with New York Heart Association functional class ≤2 increased postoperatively (23.6% (30/127) vs. 87.3% (110/126), χ2=103.77, P<0.01). The proportion of patients with Canadian Cardiovascular Society Angina Classification ≤3 decreased postoperatively (4.8% (6/126) vs. 78.7% (100/127), χ2=142.19, P<0.01). The left ventricular end-diastolic diameter decreased postoperatively ((5.70±4.50) cm vs. (6.10±0.23) cm, t=12.15, P<0.01). Coronary multi-detector computed tomography angiography (MDCTA) follow-up was conducted for (60.5±11.7) months (range: 6 to 109 months) postoperatively. MDCTA confirmed the patency rates of the grafts: 96.4% (108/112) for the LIMA grafts, 88.9% (112/126) for the left radial artery grafts, 93.7% (74/79) for the right radial artery grafts, and 90.9% (100/110) for the free RIMA grafts. No significant differences in graft patency rates were observed between the arterial grafts ( χ2=5.24, P=0.155). Conclusion:The results of this multi-centre study demonstrate satisfactory mid-term results of C-MVR with TACR for the treatment of coronary artery disease with moderate to severe or severe IMR.

Neoadjuvant therapy has become the standard treatment for locally advanced resectable esophageal cancer, significantly improving long-term survival compared to surgery alone. Neoadjuvant therapy has evolved to include various strategies, such as concurrent chemoradiotherapy, chemotherapy, immunotherapy, or targeted combination therapy. This enriches clinical treatment options and provides a more personalized and scientific treatment approach for patients. This article aims to comprehensively summarize current academic research hot topics, review the rationale and evaluation measures of neoadjuvant therapy, discuss challenges in restaging methods after neoadjuvant therapy, and identify the advantages and disadvantages of various neoadjuvant therapeutic strategies.

A 71-year-old male presented with esophageal cancer and severe aortic valve regurgitation. Treatment strategies for such patients are controversial. Considering the risks of cardiopulmonary bypass and potential esophageal cancer metastasis, we successfully performed transcatheter aortic valve implantation and minimally invasive three-incision thoracolaparoscopy combined with radical resection of esophageal cancer (McKeown) simultaneously in the elderly patient who did not require neoadjuvant treatment. This dual minimally invasive procedure took 6 hours and the patient recovered smoothly without any surgical complications.