Objective:To prepare the anti-programmed death-ligand 1 (PD-L1) nanoantibody P3C8-C3Fab by ligating with C3Fab and to investigate its role in plasma half-life.Methods:The C3Fab peptide derived from protein G was molecularly fused with the nanobody P3C8 by DNA recombination technology. The nanoantibody P3C8-C3Fab was inducibly expressed and purified in the E. coli BL21 strain, and the binding of it to PD-L1 protein, mouse IgG, and PD-L1-expressing tumor cells was detected by enzyme-linked immunosorbent assay (ELISA). The residual P3C8-C3Fab was detected in mouse serum at different times using double-antibody sandwich ELISA to assess the prolongation of the plasma half-life of PD-L1 nanobodies by C3Fab. Results:The nanoantibody P3C8-C3Fab was successfully constructed, and it could efficiently express itself in soluble form in BL21. The purified NbP3C8-C3Fab protein was obtained with a mass fraction of about 90% at a yield of 7.18 mg/L. The affinity of P3C8-C3Fab for PD-L1 protein and mouse IgG gradually increased with increasing mass concentration and showed a concentration correlation. The binding of P3C8-C3Fab to lung cancer A549 cells showed a concentration correlation. The concentration standard curve of P3C8-C3Fab in mouse serum showed a typical S-shape with a concentration correlation. The plasma half-life of P3C8 was only 0.44 h, while the plasma half-life of P3C8-C3Fab was 21.27-fold higher, up to 9.36 h.Conclusions:The linkage of C3Fab to the nanobodies of P3C8 can significantly prolong the plasma half-life of P3C8, which is valuable for the improvement of in vivo nanobody effects.

Objective:To compare and discuss the mid-to-long-term outcomes of mitral valve repair (MVP) versus biological mitral valve replacement (bMVR) in patients aged 60 years and above with rheumatic mitral valve disease.Methods:This is a retrospective cohort study. A total of 765 patients aged 60 years and older, diagnosed with rheumatic mitral valve disease and who underwent MVP or bMVR at Beijing Anzhen Hospital from January 2010 to January 2023, were retrospectively included. Among them, 186 were male and 579 were female, with an age of (66.1±4.5) years (range: 60 to 82 years). Patients were divided into two groups based on the surgical method: the mitral valve repair group (MVP group, n=256) and the bioprosthetic mitral valve replacement group (bMVR group, n=509). A 1∶1 propensity score matching was performed using a caliper value of 0.2 based on preoperative data. Paired sample t-tests, χ2 tests, or Fisher′s exact tests were used for intergroup comparisons. Kaplan-Meier method was employed to plot survival curves and valve-related reoperation rate curves for both groups before and after matching, and Log-rank tests were used to compare the mid-to long-term survival rates and valve-related reoperation rates between the two groups. Results:A total of 765 patients who completed follow-up were ultimately included, with a follow-up period ( M(IQR)) of 5.1(5.0) years (range: 1.0 to 12.9 years). After matching, each group consisted of 256 patients. The incidence of early postoperative atrial fibrillation (39.1% vs. 49.2%, χ2=4.95, P=0.026) and early mortality rates (2.0% vs. 6.2%, χ2=4.97, P=0.026) were lower in the MVP group. Unadjusted Kaplan-Meier analysis showed significantly higher 5-year and 10-year survival rates for the MVP group (92.54% vs. 83.02%, 86.22% vs. 70.19%, Log-rank: P=0.001). After adjustment with propensity scores, the Kaplan-Meier analysis still indicated higher 5-year and 10-year survival rates in the MVP group compared to the bMVR group (92.54% vs. 85.89%, 86.22% vs. 74.83%, Log-rank: P=0.024). There were no significant differences in the rates of valve-related reoperation between the two groups before and after matching (5-year and 10-year reoperation rates pre-matching: 1.75% vs. 0.57%, 5.39% vs. 7.54%, Log-rank: P=0.207; post-matching: 1.75% vs. 0, 5.39% vs. 9.27%, Log-rank: P=0.157). Conclusion:For patients aged 60 years and above with rheumatic mitral valve disease, mitral valve repair offers better mid-to-long-term survival compared to biological valve replacement.

Objective:To compare and discuss the mid-to-long-term outcomes of mitral valve repair (MVP) versus biological mitral valve replacement (bMVR) in patients aged 60 years and above with rheumatic mitral valve disease.Methods:This is a retrospective cohort study. A total of 765 patients aged 60 years and older, diagnosed with rheumatic mitral valve disease and who underwent MVP or bMVR at Beijing Anzhen Hospital from January 2010 to January 2023, were retrospectively included. Among them, 186 were male and 579 were female, with an age of (66.1±4.5) years (range: 60 to 82 years). Patients were divided into two groups based on the surgical method: the mitral valve repair group (MVP group, n=256) and the bioprosthetic mitral valve replacement group (bMVR group, n=509). A 1∶1 propensity score matching was performed using a caliper value of 0.2 based on preoperative data. Paired sample t-tests, χ2 tests, or Fisher′s exact tests were used for intergroup comparisons. Kaplan-Meier method was employed to plot survival curves and valve-related reoperation rate curves for both groups before and after matching, and Log-rank tests were used to compare the mid-to long-term survival rates and valve-related reoperation rates between the two groups. Results:A total of 765 patients who completed follow-up were ultimately included, with a follow-up period ( M(IQR)) of 5.1(5.0) years (range: 1.0 to 12.9 years). After matching, each group consisted of 256 patients. The incidence of early postoperative atrial fibrillation (39.1% vs. 49.2%, χ2=4.95, P=0.026) and early mortality rates (2.0% vs. 6.2%, χ2=4.97, P=0.026) were lower in the MVP group. Unadjusted Kaplan-Meier analysis showed significantly higher 5-year and 10-year survival rates for the MVP group (92.54% vs. 83.02%, 86.22% vs. 70.19%, Log-rank: P=0.001). After adjustment with propensity scores, the Kaplan-Meier analysis still indicated higher 5-year and 10-year survival rates in the MVP group compared to the bMVR group (92.54% vs. 85.89%, 86.22% vs. 74.83%, Log-rank: P=0.024). There were no significant differences in the rates of valve-related reoperation between the two groups before and after matching (5-year and 10-year reoperation rates pre-matching: 1.75% vs. 0.57%, 5.39% vs. 7.54%, Log-rank: P=0.207; post-matching: 1.75% vs. 0, 5.39% vs. 9.27%, Log-rank: P=0.157). Conclusion:For patients aged 60 years and above with rheumatic mitral valve disease, mitral valve repair offers better mid-to-long-term survival compared to biological valve replacement.

FLASH radiotherapy (FLASH-RT) has garnered considerable attention globally in recent years. Compared to conventional radiotherapy, FLASH-RT can deliver the total radiation dose to the target volume in an extremely short time, reducing the radiation-induced damage to normal tissue while maintaining similar anti-tumor effects. FLASH-RT has been in the clinical trial stage, with several clinical research result being reported. Based on the collected global clinical research result of FLASH-RT in recent years, this study systematically reviewed FLASH-RT′s safety, radiation-related side effects, treatment efficacy, opportunities, and challenges in clinical trials.

Mitochondrial dysfunction after spinal cord injury (SCI) is recognized as a crucial pathological mechanism for secondary SCI. Studies have indicated that mitochondrial transfer plays a significant role in the process of neural regeneration following injury. After mitochondria migrating to injured neurons, they mainly function via enhancing the energy metabolism level of damaged neurons and reducing oxidative stress. In this article, we present an exhaustive overview on mechanism of mitochondrial transfer, and impact on neural regeneration after mitochondrial transfer so as to provide valuable insights for further exploring the role of mitochondrial transfer in SCI progression and offer innovative perspective on potential therapeutic strategies for SCI.

Objective:To explore the safety and effectiveness of axillary-coronary artery bypass (ACAB) of anterolateral incision multi-vessel coronary artery bypass surgery (MICS-CABG).Methods:Patients who underwent coronary artery bypass surgery in Peking University Third Hospital from May 2020 to December 2022 were included. 48 and 158 patients were included in MICS-ACAB and OPCABG group respectively. The mean age of the OPCABG group was (64.72±8.27) years old, and the male proportion was 77.2%(122 cases). The mean age of the MICS-ACAB group was (71.42±7.77) years old, and the male proportion was 79.2%(38 cases). Major adverse cardiovascular and cerebrovascular events (MACCE, including stroke, death, myocardial infarction and revascularization) and postoperative PCS scores of SF-36 were selected as the primary endpoint. The surgical complications and angiography patency rate of grafts were recorded to evaluate the clinical effects of MICS-ACAB.Results:The median number of bypass graft in two groups was 3. There were no significant differences in perioperative MACCE, re-operation rate, renal failure and lenth of postoperative hospital stay between two groups( P>0.05). 85.4% of patients reveived angiography assessment before discharge. There was no significant difference in graft patency between the MICS-ACAB group and OPCABG group (95.2% vs 88.8%, P=0.368). The results of propensity score matching analysis were consistent with the above conclusions. Both univariate analysis and multiple linear regression showed that MICS-ACAB could improve the PCS score of SF-36 at 7 days after surgery[(31.77±5.97) scores vs. (29.45±6.31) scores, P=0.025]. Conclusion:The safety of MICS-ACAB is satisfactory, which can achieve the completely revascularization and the patency rate of grafts is desirable. This procedure can significantly improve quality of life of patients in early postoperative period.

Objective:To screen and analyze the prognostic protein biomarkers of DLBCL, and to explore their value in the prognostic evaluation.Methods:163 cases of confirmed DLBCLs from January 2011 to December 2016 were collected with their clinical, pathological and follow-up data, which were all from our hospital. The expression of protein markers were tested using immunohistochemical staining (IHC) . The immune phenotypes independent of the International Prognostic Index (IPI) that affect overall survival (OS) and progression-free survival (PFS) of DLBCL were explored by COX regression model, and the effect of their co-expression on the prognosis were also analyzed.Result:BCL6 negative (PFS: HR=1.652, 95% CI 1.030-2.649, P=0.037) , P53 positive (OS: HR=1.842, 95% CI 1.008-3.367, P=0.047) , and BCL2 strong positive expressions (S+) (OS: HR=2.102, 95% CI 1.249-3.537, P=0.005; PFS: HR=2.126, 95% CI 1.312-3.443, P=0.002) are adverse prognostic factors of DLBCL that are independent of IPI. BCL6 - (PFS: HR=2.042, 95% CI 1.021-4.081, P=0.043) , P53 + (OS: HR=3.069, 95% CI 1.244-7.569, P=0.015) and BCL2 S+ (OS: HR=2.433, 95% CI 1.165-5.082, P=0.018; PFS: HR=3.209, 95% CI 1.606-6.410, P=0.001) are adverse prognostic factors in the group of age≤60-year-old; in the group of IPI score 0-2, cases with BCL6 - (OS: HR=2.467, 95% CI 1.322-4.604, P=0.005; PFS: HR=2.248, 95% CI 1.275-3.965, P=0.005) and BCL2 S+ (PFS: HR=2.045, 95% CI 1.119-3.735, P=0.020) have worse prognosis. The co-expression of BCL6 - and BCL2 S+ has significant influence on prognosis of DLBCL ( P=0.005 and P<0.001) , in which BCL6 +/non-BCL2 S+ ( n=86) has the best prognosis[3-year-OS (71.6±4.9) %, 3-year-PFS (67.0±5.1) %], and BCL6 -/BCL2 S+ ( n=10) has the worst prognosis[3-year-OS (20.0±12.6) %, 3-year-PFS (10.0±9.5) %]; the co-expression of BCL6 - and P53 + has no significant influence on prognosis ( P=0.061 and P=0.089) , however, those cases with BCL6 +/P53 - ( n=98) often get better prognosis[3-year-OS (70.6±4.7) %, 3-year-PFS (64.6±4.9) %] than others; the co-expression of P53 + and BCL2 S+ has significant influence on prognosis of DLBCL ( P<0.001 and P<0.001) , and P53 +/BCL2 S+ ( n=5) has the worst prognosis (3-year-OS and 3-year-PFS are both 0) ; BCL2 S+ cases get shorter OS and PFS, regardless of the expression of BCL6 and P53. Conclusion:The expression and co-expression of BCL6 negative, P53 positive and BCL2 S+ have certain value in the prognostic evaluation of DLBCL, especially in the group of age≤60-year-old and IPI score 0-2.

Objective:To summarize the clinical and pathological features of intravascular NK and T cell lymphoma for better understanding of such disease to reduce misdiagnosis and miss-diagnosis.Methods:Clinical and pathological features were analyzed retrospectively in one case of intravascular peripheral T-cell lymphoma, not otherwise specified (IVPTCL, NOS) , with literatures review.Results:The case presented in this study was a 66-year-old man. PET/CT scan showed multiple lymph nodes enlargement throughout the body. Normal lymph node structure could not be observed by tissue biopsy, while lymph follicles were partially disrupted. High-power light microscope revealed a large number of blood vessels with diffuse proliferation and dilation, where atypical lymphoid cell mass was restricted in the lumen and partially infiltrated the large blood vessel wall. These tumor cells were medium to large with moderate cytoplasm. The nucleus was irregular, single or multiple nucleoli could be seen, chromatin was condensed, some were empty and bright, and mitotic figures could be seen. Immunohistochemical staining showed that the neoplastic cells were positive for expression of CD3, CD43, CD8, GrB, TIA-1 and perforin. EBER in situ hybridization result was negative. Polymerase chain reaction test identified a clonal gene rearrangement of T-cell receptor γ. The patient was treated with CHOP in combination with chidamide, but died of infection and cardiopulmonary failure within 2 months. 56 cases of intravascular NK/T cell lymphoma with definite classification were collected from relevant literatures, including 47 cases with nasal type of extranodal NK/T cell lymphoma (27 were male and 20 were female) , 8 cases with anaplastic large cell lymphoma (3 males and 5 females) , and only one case with de nova IVPTCL, NOS in brain. We report the second case of IVPTCL,NOS, and notably originated from lymph node for the first time.Conclusions:Intravascular NK/T cell lymphoma is a highly aggressive disease with no effective treatment at present. Involvement of Lymph node has rarely been reported, and further studies on more cases are necessary.

Objective:To evaluate the clinical efficacy and safety of modified chitosan eye drops on rabbit Candida albicans keratitis model.Methods:Ten healthy female New Zealand rabbits were used to establish the superficial Candida albicans keratitis model by the corneal surface lens method in the right eye.Slit lamp microscopy and corneal scraping and microscopic examination were performed to preliminarily determine whether the keratitis model has been successfully established, the rabbits were then randomly divided into a model group and a modified chitosan group by the random number table method.The successfully established rabbit models which were determined by fungal culture results were retained.Five normal rabbits receiving no intervention served as a normal control group.The experimental eyes in the normal control and modified chitosan groups were treated with modified chitosan eye drops, Six times a day for one week, and subsequently four times a day for one week.No treatment was administered to the model group.The changes of corneal lesions and ocular surfaces were examined by slit lamp microscopy every day.At 1, 7, 14, 21 and 28 days after modeling, the eye condition and corneal clinical scores was assessed by slit lamp microscopy.The corneal conditions in each group was observed for two weeks after drug withdrawal.Results:The corneal scraping and microscopic examination results of eight rabbits models showed that the fungal hyphae and spores were positive.The fungal culture results showed that the separated pathogen was Candida albicans.The success rate of modeling was 80%(8/10). The clinical scores in the model group at 7, 14 and 21 days after modeling were 14.50±0.58, 6.25±0.50 and 2.50±0.58, respectively, and were significantly higher than 7.25±1.26, 2.75±0.50 and 1.25±0.50 in the modified chitosan group (all at P<0.05). In the model group, corneal edema was significantly aggravated, and the central white ulcer area was enlarged within seven days after modeling.Between 7 and 28 days after modeling, the corneal ulcer was gradually healed, while the central corneal scar and neovascularization were remained.The average healing time was (24.5±2.6)days.In the modified chitosan group, the corneal infiltration was significantly alleviated within seven days after modeling, and the fungal hyphae and spores of corneal scraping were negative on the 14th day after modeling.The average healing time in the modified chitosan group was (13.5±1.3)days, which was significantly shorter than that in the the model group (P<0.01). No recurrence of keratitis was observed in the modified chitosan group after two weeks of drug withdrawal.The cure rate was 100%.In the normal control group, the conjunctival hyperemia, corneal edema, and lesions were not observed during topical administration.Conclusion:The treatment with modified chitosan eye drop is effective in a rabbit superficial Candida albicans keratitis model, and have no obvious toxic effects on ocular tissues.

Objective:To explore the effect of high-frequency and low-frequency transcranial magnetic stimulation (rTMS) on the unaffected pharyngeal motor cortex of dysphagic stroke survivors.Methods:Forty-two stroke survivors with dysphagia were enrolled and randomly divided into a high-frequency stimulation group ( n=14), a low-frequency stimulation group ( n=13), and a sham group ( n=15). All received conventional swallowing training. The high- and low-frequency stimulation groups additionally received 250 pulses of 5Hz or 1Hz rTMS over the cortical representation of the mylohyoid muscle on the unaffected side daily for 2 consecutive weeks. In the sham group, sham rTMS was applied with identical protocols. Before and after the intervention, all subjects were subjected to a videofluoroscopic swallowing study and surface electromyography (sEMG). They were also evaluated using the fuctional dysphagia scale (FDS) and the penetration aspiration scale (PAS). Results:After the intervention, a significant improvement was observed in the average PAS, FDS and sEMG results in both rTMS groups compared with the sham control group. The average FDS score of the high-frequency stimulation group had improved significantly more than that of the low-frequency group.Conclusions:rTMS of the contra-lesional cortical representation of the mylohyoid muscle at either 5Hz or 1Hz can effectively improve dysphagia post-stroke. The higher frequency gives superior results.