Objective:Chimeric antigen receptor T-cell(CAR-T)immunotherapy has made major breakthroughs in the treatment of blood tu-mors.However,current CAR-T therapies face several limitations:they require autologous cells,involve a lengthy and costly production pro-cess,and use lentiviral transduction that carry risk of insertional carcinogenesis due to random integration.Therefore,there is an urgent need to develop a universal cost-effective cancer immunotherapy method generating CAR-T cells for in vivo cancer immunotherapy.Meth-ods:This study successfully established an exosome-mediated,T-cell targeted delivery system,demonstrating both precise design and func-tional efficacy for biomedical applications.To optimize CAR-T cell generation the transfection dose was adjusted,and the kinetics of CAR-T cell percentage were recorded.The cytotoxicity of the resulting CAR-T cells was evaluated in vitro by calcein-AM release.To test the tumor-killing in vivo of engineered exosomes,human PBMCs were injected into NPG mice via the tail vein to establish humanized mice,followed by intravenous injection of tumor cells to induce cancer.Results:To overcome the limitations of conditional autologous CAR-T cells,we de-veloped a T cell-targeted exosome system capable of specifically targeting human CD3+,CD4+,and CD8+T cells.CAR-T production was dose-dependent,with transfection efficiency reaching upto 97.8%at 106 particles/cell.Both in vitro cytotoxicity assays and in vivo animal experi-ments demonstrated that exosome-incubated CAR-T cells effectively eliminated CD19-positive Raji cells,highlighting their specificity and therapeutic potential in antigen-directed applications.Conclusions:We successfully established a CD8-targeting exosome delivery system for CAR-T cell production capable of transforming CD8+T cells into functional CAR-T cells,which showed significant tumor-killing ability in vitro and in mice.Compared with the traditional lentiviral vector for the preparation of CAR-T cells in vitro,in vivo-reprogrammed CAR-T cells us-ing our CD8-targeted exosome delivery system,with higher transfection efficiency,shorter production period,lower cost,and eliminated the risk of insertion carcinogenesis.This strategy promises to bring a new era of universal CAR-T medicine,which can improve cancer immuno-therapy and may hold promise as a therapeutic platform to treat various diseases.

Osteoporotic vertebral compression fractures(OVCFs)are common orthopedic conditions that can lead to spinal pain and deformity,which greatly affects the quality of life of patients.Currently,there are various treatment methods for OVCFs,but there is still a lack of standards for optimal treatment modalities.Therefore,this article introduces the current treatment methods and character-istics of epidemiology for OVCFs,in order to improve the awareness of this disease among clinicians and provide a reference for select-ing more appropriate treatment regimens.Conservative treatment measures,such as bracing and analgesia,are the basic treatment mea-sures for OVCFs,and anti-osteoporosis drugs play a crucial role in management.Minimally invasive procedures,including percutane-ous vertebroplasty and percutaneous balloon kyphoplasty,remain the primary surgical interventions,and traditional open surgeries are also an important part of treatment,such as anterior spinal fusion,combined anterior and posterior spinal fusion,posterior spinal fusion with three-column osteotomy,and posterior spinal fusion with vertebroplasty.Furthermore,surgeons should focus on the accumulation of related surgical techniques and skills during surgery to effectively address the challenges and complications associated with surgical interventions.Finally,scientific and appropriate treatment methods should be selected for patients,in order to improve long-term treat-ment outcomes and increase the degree of satisfaction among pa-tients.

Objective To report the diagnosis of a canine distemper virus outbreak among a colony of cynomolgus monkeys at an experimental monkey farm in 2019. MethodsA total of 46 samples were collected from 21 diseased cynomolgus monkeys (exhibiting symptoms such as facial rash, skin scurf, runny nose, and diarrhea) and from one deceased monkey at an experimental monkey breeding farm in South China in late 2019, including serum, skin rash swabs, and anticoagulated whole blood, liver, lung, and skin tissues were submitted for testing. All submitted samples were tested for canine distemper virus gene fragments using real-time quantitative PCR, while immunohistochemical staining was performed to detect canine distemper virus nucleoprotein in lung tissues. The skin tissue of the deceased monkey was ground and sieved. The filtrate was inoculated into a monolayer MDCK cell line for virus isolation. Then, whole-genome sequencing was performed to identify the isolated virus. The Clustal Omega tool was used to align and analyze the homology of different Asian canine distemper virus isolates. A phylogenetic tree was constructed, followed by genetic evolutionary analysis. ResultsClinical retrospective analysis revealed that the diseased cynomolgus monkeys exhibited symptoms similar to those observed in cynomolgus monkeys infected with measles virus. Necropsy findings showed red lesions in the lungs and significant hemorrhage in the colonic mucosa. Real-time quantitative PCR detected canine distemper virus nucleic acid in the serum, skin rash swabs of the infected monkeys, and various tissue samples of the deceased monkey, all of which tested positive. Calculation based on the standard curve formula indicated the viral load was highest in the skin tissue. Immunohistochemical staining of the deceased monkey's lung tissue demonstrated aggregation of CDV nucleoprotein in alveolar epithelial cells, bronchi, and bronchioles. A CDV strain was isolated from the skin tissue of the deceased monkey. Phylogenetic analysis indicated that this strain shares the closest relationship (98.86%) with the Asian-1 type canine distemper virus strain CDV/dog/HCM/33/140816, previously identified in dogs in Vietnam. ConclusionBased on comprehensive analysis of clinical symptoms, nucleic acid detection, viral protein immunohistochemistry, and whole-genome sequencing results, the diagnosis confirms that the cynomolgus monkeys in this facility are infected with canine distemper virus. It is recommended to include canine distemper virus as a routine surveillance target in captive monkey populations. Additionally, this study provides a foundation for further research on the molecular biological characteristics of canine distemper virus.

Objective To report the diagnosis of a canine distemper virus outbreak among a colony of cynomolgus monkeys at an experimental monkey farm in 2019. MethodsA total of 46 samples were collected from 21 diseased cynomolgus monkeys (exhibiting symptoms such as facial rash, skin scurf, runny nose, and diarrhea) and from one deceased monkey at an experimental monkey breeding farm in South China in late 2019, including serum, skin rash swabs, and anticoagulated whole blood, liver, lung, and skin tissues were submitted for testing. All submitted samples were tested for canine distemper virus gene fragments using real-time quantitative PCR, while immunohistochemical staining was performed to detect canine distemper virus nucleoprotein in lung tissues. The skin tissue of the deceased monkey was ground and sieved. The filtrate was inoculated into a monolayer MDCK cell line for virus isolation. Then, whole-genome sequencing was performed to identify the isolated virus. The Clustal Omega tool was used to align and analyze the homology of different Asian canine distemper virus isolates. A phylogenetic tree was constructed, followed by genetic evolutionary analysis. ResultsClinical retrospective analysis revealed that the diseased cynomolgus monkeys exhibited symptoms similar to those observed in cynomolgus monkeys infected with measles virus. Necropsy findings showed red lesions in the lungs and significant hemorrhage in the colonic mucosa. Real-time quantitative PCR detected canine distemper virus nucleic acid in the serum, skin rash swabs of the infected monkeys, and various tissue samples of the deceased monkey, all of which tested positive. Calculation based on the standard curve formula indicated the viral load was highest in the skin tissue. Immunohistochemical staining of the deceased monkey's lung tissue demonstrated aggregation of CDV nucleoprotein in alveolar epithelial cells, bronchi, and bronchioles. A CDV strain was isolated from the skin tissue of the deceased monkey. Phylogenetic analysis indicated that this strain shares the closest relationship (98.86%) with the Asian-1 type canine distemper virus strain CDV/dog/HCM/33/140816, previously identified in dogs in Vietnam. ConclusionBased on comprehensive analysis of clinical symptoms, nucleic acid detection, viral protein immunohistochemistry, and whole-genome sequencing results, the diagnosis confirms that the cynomolgus monkeys in this facility are infected with canine distemper virus. It is recommended to include canine distemper virus as a routine surveillance target in captive monkey populations. Additionally, this study provides a foundation for further research on the molecular biological characteristics of canine distemper virus.

Objective:To clarify the effects of simple subtalar fusion on distribution of plantar pressures.Methods:A retrospective study was conducted to analyze the 19 patients who had undergone simple subtalar fusion between January 2006 and December 2020 at Department of Orthopedics, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine. There were 13 males and 6 females with an age of (42.1±11.8) years and a duration of disease of 1.7 (1.0, 2.0) years. Another 14 normal subjects were recruited as normal controls [7 males and 7 females, with an age of (25.0±1.9) years]. The data of plantar pressure distribution were detected and analyzed by a Belgian Footscan? plantar pressure tester. The affected and healthy sides of the patients were compared with those of the normal group to analyze the peak pressures on different foot regions.Results:There was no significant difference in height or weight between the patients and the normal subjects ( P>0.05). The peak pressures on the first to the third metatarsal region of the forefoot and the medial region of the hindfoot of the affected foot were significantly lower than those of the normal foot in the patients ( P<0.05). The peak pressure on the forefoot region of a normal foot appeared in the third metatarsal region. In the patients, the peak pressure on the forefoot region of a healthy side shifted inward and appeared in the second metatarsal region, but the peak pressure on the forefoot region of an affected side shifted laterally and appeared in the fourth metatarsal region. The peak pressure on the midfoot of an affected side [(4.38±2.17) N/cm 2] was significantly higher than that on a healthy side [(3.04±1.80) N/cm 2] in the patients ( P=0.035). The peak pressures on the medial and lateral hindfoot regions of a healthy side were (7.12±1.91) N/cm 2 and (7.98±2.03) N/cm 2, respectively, showing no significant difference ( P=0.086). The peak pressure on the lateral hindfoot region of an affected side [(10.77±4.21) N/cm 2] was significantly higher than that on the medial hindfoot region [(8.71±2.89) N/cm 2] ( P=0.009). The peak plantar pressures on the affected side shifted to the lateral side in the patients. Conclusions:Subtalar fusion can exert significant effects on the distribution of plantar pressures. Specifically, the plantar pressures shift to the lateral side of an affected foot during all the gait stages while the plantar pressures on the healthy forefoot may compensate by transferring to the medial side in the patients.

Objective:To sinicize the English version of the rapid eye movement sleep behavior disorder symptom severity scale (RBDSSS) and to evaluate the reliability and validity of the Chinese version of RBDSSS (RBDSSS-C) among Chinese patients with rapid eye movement sleep behavior disorder (RBD).Methods:RBDSSS-C was ultimately formed through translation, back translation and revision according to the Brislin's translation model, including patient version (RBDSSS-PT) and bedpartner version (RBDSSS-BP). A questionnaire survey was conducted among 120 RBD patients to test the reliability and validity of the RBDSSS-C, using Cronbach’s α coefficient, Spearman-Brown coefficient, Spearman correlation analysis, content validity index and factor analysis. The correlation between RBDSSS-C and RBDQ-HK was examined.Results:For the Chinese version of RBDSSS-PT, the Cronbach’s α was 0.795, the split-half reliability was 0.756, and the test-retest reliability was 0.940. Item-level content validity indices (I-CVI) ranged from 0.833 to 1.000, and the scale-level CVI (S-CVI) was 0.937.For the Chinese version of RBDSSS-BP, the Cronbach’s α was 0.712, the split-half reliability was 0.813, and test-retest reliability was 0.950, with both I-CVI and S-CVI at 1.000.The scores of Chinese version of RBDSSS-PT and RBDSSS-BP were both significantly correlated with RBDQ-HK scores ( r=0.638, P<0.001 for RBDSSS-PT; r=0.639, P<0.001 for RBDSSS-BP). Factor analysis confirmed both single-factor structure for RBDSSS-PT and RBDSSS-BP.RBDSSS-PT showed χ2/ df=3.930, CFI=0.954, TLI=0.937, and RMSEA=0.093; RBDSSS-BP showed χ2/ df=8.300, CFI=0.975, TLI=0.966, and RMSEA=0.079. These results indicated adequate model fit. Conclusion:RBDSSS-C has good reliability and validity, and can be used as a reliable and effective tool to evaluate the severity of symptoms in Chinese RBD patients.

Objective:To sinicize the English version of the rapid eye movement sleep behavior disorder symptom severity scale (RBDSSS) and to evaluate the reliability and validity of the Chinese version of RBDSSS (RBDSSS-C) among Chinese patients with rapid eye movement sleep behavior disorder (RBD).Methods:RBDSSS-C was ultimately formed through translation, back translation and revision according to the Brislin's translation model, including patient version (RBDSSS-PT) and bedpartner version (RBDSSS-BP). A questionnaire survey was conducted among 120 RBD patients to test the reliability and validity of the RBDSSS-C, using Cronbach’s α coefficient, Spearman-Brown coefficient, Spearman correlation analysis, content validity index and factor analysis. The correlation between RBDSSS-C and RBDQ-HK was examined.Results:For the Chinese version of RBDSSS-PT, the Cronbach’s α was 0.795, the split-half reliability was 0.756, and the test-retest reliability was 0.940. Item-level content validity indices (I-CVI) ranged from 0.833 to 1.000, and the scale-level CVI (S-CVI) was 0.937.For the Chinese version of RBDSSS-BP, the Cronbach’s α was 0.712, the split-half reliability was 0.813, and test-retest reliability was 0.950, with both I-CVI and S-CVI at 1.000.The scores of Chinese version of RBDSSS-PT and RBDSSS-BP were both significantly correlated with RBDQ-HK scores ( r=0.638, P<0.001 for RBDSSS-PT; r=0.639, P<0.001 for RBDSSS-BP). Factor analysis confirmed both single-factor structure for RBDSSS-PT and RBDSSS-BP.RBDSSS-PT showed χ2/ df=3.930, CFI=0.954, TLI=0.937, and RMSEA=0.093; RBDSSS-BP showed χ2/ df=8.300, CFI=0.975, TLI=0.966, and RMSEA=0.079. These results indicated adequate model fit. Conclusion:RBDSSS-C has good reliability and validity, and can be used as a reliable and effective tool to evaluate the severity of symptoms in Chinese RBD patients.

Objective:Chimeric antigen receptor T-cell(CAR-T)immunotherapy has made major breakthroughs in the treatment of blood tu-mors.However,current CAR-T therapies face several limitations:they require autologous cells,involve a lengthy and costly production pro-cess,and use lentiviral transduction that carry risk of insertional carcinogenesis due to random integration.Therefore,there is an urgent need to develop a universal cost-effective cancer immunotherapy method generating CAR-T cells for in vivo cancer immunotherapy.Meth-ods:This study successfully established an exosome-mediated,T-cell targeted delivery system,demonstrating both precise design and func-tional efficacy for biomedical applications.To optimize CAR-T cell generation the transfection dose was adjusted,and the kinetics of CAR-T cell percentage were recorded.The cytotoxicity of the resulting CAR-T cells was evaluated in vitro by calcein-AM release.To test the tumor-killing in vivo of engineered exosomes,human PBMCs were injected into NPG mice via the tail vein to establish humanized mice,followed by intravenous injection of tumor cells to induce cancer.Results:To overcome the limitations of conditional autologous CAR-T cells,we de-veloped a T cell-targeted exosome system capable of specifically targeting human CD3+,CD4+,and CD8+T cells.CAR-T production was dose-dependent,with transfection efficiency reaching upto 97.8%at 106 particles/cell.Both in vitro cytotoxicity assays and in vivo animal experi-ments demonstrated that exosome-incubated CAR-T cells effectively eliminated CD19-positive Raji cells,highlighting their specificity and therapeutic potential in antigen-directed applications.Conclusions:We successfully established a CD8-targeting exosome delivery system for CAR-T cell production capable of transforming CD8+T cells into functional CAR-T cells,which showed significant tumor-killing ability in vitro and in mice.Compared with the traditional lentiviral vector for the preparation of CAR-T cells in vitro,in vivo-reprogrammed CAR-T cells us-ing our CD8-targeted exosome delivery system,with higher transfection efficiency,shorter production period,lower cost,and eliminated the risk of insertion carcinogenesis.This strategy promises to bring a new era of universal CAR-T medicine,which can improve cancer immuno-therapy and may hold promise as a therapeutic platform to treat various diseases.

Objective:To clarify the effects of simple subtalar fusion on distribution of plantar pressures.Methods:A retrospective study was conducted to analyze the 19 patients who had undergone simple subtalar fusion between January 2006 and December 2020 at Department of Orthopedics, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine. There were 13 males and 6 females with an age of (42.1±11.8) years and a duration of disease of 1.7 (1.0, 2.0) years. Another 14 normal subjects were recruited as normal controls [7 males and 7 females, with an age of (25.0±1.9) years]. The data of plantar pressure distribution were detected and analyzed by a Belgian Footscan? plantar pressure tester. The affected and healthy sides of the patients were compared with those of the normal group to analyze the peak pressures on different foot regions.Results:There was no significant difference in height or weight between the patients and the normal subjects ( P>0.05). The peak pressures on the first to the third metatarsal region of the forefoot and the medial region of the hindfoot of the affected foot were significantly lower than those of the normal foot in the patients ( P<0.05). The peak pressure on the forefoot region of a normal foot appeared in the third metatarsal region. In the patients, the peak pressure on the forefoot region of a healthy side shifted inward and appeared in the second metatarsal region, but the peak pressure on the forefoot region of an affected side shifted laterally and appeared in the fourth metatarsal region. The peak pressure on the midfoot of an affected side [(4.38±2.17) N/cm 2] was significantly higher than that on a healthy side [(3.04±1.80) N/cm 2] in the patients ( P=0.035). The peak pressures on the medial and lateral hindfoot regions of a healthy side were (7.12±1.91) N/cm 2 and (7.98±2.03) N/cm 2, respectively, showing no significant difference ( P=0.086). The peak pressure on the lateral hindfoot region of an affected side [(10.77±4.21) N/cm 2] was significantly higher than that on the medial hindfoot region [(8.71±2.89) N/cm 2] ( P=0.009). The peak plantar pressures on the affected side shifted to the lateral side in the patients. Conclusions:Subtalar fusion can exert significant effects on the distribution of plantar pressures. Specifically, the plantar pressures shift to the lateral side of an affected foot during all the gait stages while the plantar pressures on the healthy forefoot may compensate by transferring to the medial side in the patients.

Clinicians need to focus on various points in the diagnosis and treatment of insomnia.This article prescribed the treatment protocol based on the unique features,such as insomnia in the elderly,women experiencing specific physiologi-cal periods,children insomnia,insomnia in sleep-breathing disorder patients,insomnia in patients with chronic liver and kidney dysfunction.It pro-vides some reference for clinicians while they make decision on diagnosis,differentiation and treat-ment methods.