Methods: The clinical data of 26 patients diagnosed with irreducible atlantoaxial dislocation complicated by atlantodental bony obstruction were analyzed retrospectively. All patients underwent anterior retropharyngeal atlantodentoplasty, followed by posterior occipitocervical fusion. Details including surgical duration and blood loss volume were recorded. Radiographic data such as the anterior atlantodental interval, O–C2 angle, space available for the cord, clivus–canal angle, and cervical medullary angle, and clinical data including the Japanese Orthopedic Association (JOA) score were assessed. The fusion time of the grafted bone and the development of complications were examined. Results: In patients undergoing anterior retropharyngeal atlantodentoplasty, the surgical duration and blood loss volume were 120.1±16.4 minutes and 100.6±33.5 mL, respectively. The anterior atlantodental interval decreased significantly after the surgery (p <0.001). The O–C2 angle, space available for the cord, clivus–canal angle, and cervical medullary angle increased significantly after the surgery (p <0.001). The JOA score during the latest follow-up significantly increased compared with that before the surgery (p <0.001). The improvement rate of the JOA score was 80.8%±18.1%. The fusion time of the grafted bone was 3–8 months, with an average of 5.7±1.5 months. In total, 11 patients presented with postoperative dysphagia and three with irritating cough. However, none of them exhibited other major complications. Conclusions Anterior retropharyngeal atlantodentoplasty can anatomically reduce the atlantoaxial joint with a satisfactory clinical outcome in patients with irreducible atlantoaxial dislocation with atlantodental bony obstruction.

Methods: The clinical data of 26 patients diagnosed with irreducible atlantoaxial dislocation complicated by atlantodental bony obstruction were analyzed retrospectively. All patients underwent anterior retropharyngeal atlantodentoplasty, followed by posterior occipitocervical fusion. Details including surgical duration and blood loss volume were recorded. Radiographic data such as the anterior atlantodental interval, O–C2 angle, space available for the cord, clivus–canal angle, and cervical medullary angle, and clinical data including the Japanese Orthopedic Association (JOA) score were assessed. The fusion time of the grafted bone and the development of complications were examined. Results: In patients undergoing anterior retropharyngeal atlantodentoplasty, the surgical duration and blood loss volume were 120.1±16.4 minutes and 100.6±33.5 mL, respectively. The anterior atlantodental interval decreased significantly after the surgery (p <0.001). The O–C2 angle, space available for the cord, clivus–canal angle, and cervical medullary angle increased significantly after the surgery (p <0.001). The JOA score during the latest follow-up significantly increased compared with that before the surgery (p <0.001). The improvement rate of the JOA score was 80.8%±18.1%. The fusion time of the grafted bone was 3–8 months, with an average of 5.7±1.5 months. In total, 11 patients presented with postoperative dysphagia and three with irritating cough. However, none of them exhibited other major complications. Conclusions Anterior retropharyngeal atlantodentoplasty can anatomically reduce the atlantoaxial joint with a satisfactory clinical outcome in patients with irreducible atlantoaxial dislocation with atlantodental bony obstruction.

Methods: The clinical data of 26 patients diagnosed with irreducible atlantoaxial dislocation complicated by atlantodental bony obstruction were analyzed retrospectively. All patients underwent anterior retropharyngeal atlantodentoplasty, followed by posterior occipitocervical fusion. Details including surgical duration and blood loss volume were recorded. Radiographic data such as the anterior atlantodental interval, O–C2 angle, space available for the cord, clivus–canal angle, and cervical medullary angle, and clinical data including the Japanese Orthopedic Association (JOA) score were assessed. The fusion time of the grafted bone and the development of complications were examined. Results: In patients undergoing anterior retropharyngeal atlantodentoplasty, the surgical duration and blood loss volume were 120.1±16.4 minutes and 100.6±33.5 mL, respectively. The anterior atlantodental interval decreased significantly after the surgery (p <0.001). The O–C2 angle, space available for the cord, clivus–canal angle, and cervical medullary angle increased significantly after the surgery (p <0.001). The JOA score during the latest follow-up significantly increased compared with that before the surgery (p <0.001). The improvement rate of the JOA score was 80.8%±18.1%. The fusion time of the grafted bone was 3–8 months, with an average of 5.7±1.5 months. In total, 11 patients presented with postoperative dysphagia and three with irritating cough. However, none of them exhibited other major complications. Conclusions Anterior retropharyngeal atlantodentoplasty can anatomically reduce the atlantoaxial joint with a satisfactory clinical outcome in patients with irreducible atlantoaxial dislocation with atlantodental bony obstruction.

Rare diseases still lack effective treatments, and the development of drugs for rare diseases (known as orphan drugs) is an urgent medical problem. As natural active ingredients in living organisms, some biomacromolecule drugs have good biocompatibility, low immunogenicity, and high targeting. They have become one of the most promising fields in drug research and development in the 21st century. However, there are still many obstacles in terms of in vivo delivery. In view of the unique advantages of nanocarriers prepared from polymers, lipids, organic biomimetic and inorganic materials in drug delivery, researchers are committed to building an efficient delivery system with versatility and synergy to solve the bottleneck issues in treating rare diseases with biomacromolecule drugs. Therefore, this article reviews the research progress of nanocarrier delivering proteins, peptides and nucleic acids in the field of rare disease treatment in the past ten years, which provides ideas for researches on biomacromolecule drug nanosystems in the field of treatment of rare diseases.

Objective To study the stress change characteristics of the cervical disc after removing different ranges of the uncinate process by establishing a three⁃dimensional finite element model of the C

Objective To observe the therapeutic effect and mechanism of electroacupuncture at Jiaji(EX-B2)points for lumbar disc degeneration in rats.Methods Thirty SD rats were randomly divided into the sham-operation group,model group and electroacupuncture group,with 10 rats in each group.The rats in the model group and electroacupuncture group were constructed a lumbar disc degeneration model by annulus fibrosus puncture method,and the sham-operation group was only given separation of intervertebral discs without other treatments.After successful modeling,the electroacupuncture group was treated with electroacupuncture at the L4 and L5 bilateral Jiaji points.No treatment was given to the sham-operation group and the model group.At the end of the intervention,the paw withdrawal mechanical threshold(PMWT)was detected by electronic Von Frey filaments,the changes of the structure of lumbar disc in rats were observed by hematoxylin-eosin(HE)staining,the levels of interleukin 1β(IL-1β)and tumor necrosis factor α(TNF-α)in the supernatant of lumbar intervertebral disc tissues were detected by enzyme-linked immunosorbent assay(ELISA),and the ratio of nucleus pulposus cell cycle was detected by flow cytometry,real-time quantitative polymerase chain reaction(RT-PCR)method was used to detect the mRNA expression levels of Fas-associated death domain protein(FADD),cysteinyl aspartate specific protease 8(Caspase-8),B-cell lymphoma/leukemia 2(Bcl-2)-associated X protein(Bax)and Bcl-2 in the nucleus pulposus of lumbar intervertebral disc,the protein expression levels of FADD,Caspase-8,Bax,and Bcl-2 in the nucleus pulposus of lumbar intervertebral disc were detected by Western Blot.Results The overall structure of the intervertebral disc in rats of the model group was abnormal and obvious degeneration was seen;the degeneration of intervertebral disc tissue in the electroacupuncture group was significantly improved compared with that of the model group.Compared with the sham-operation group,the model group showed lower PWMT,and the higher levels of IL-1β and TNF-α,the increased proportion of G0/G1 nucleus pulposus cells and decreased proportion of G2/M nucleus pulposus cells,and the increased mRNA and protein expression levels of FADD,Caspase-8 and Bax and the decreased mRNA and protein levels of Bcl-2,the differences being statistically significant(P＜0.05).Compared with the model group,the electroacupuncture group showed higher PWMT,the lower levels of IL-1β and TNF-α,the decreased proportion of G0/G1 nucleus pulposus cells and the increased proportion of G2/M nucleus pulposus cells,and the decreased mRNA and protein expression levels of FADD,Caspase-8 and Bax and the increased mRNA and protein levels of Bcl-2,the differences being statistically significant(P＜0.05).Conclusion Electroacupuncture at the Jiaji points can alleviate inflammatory reaction,regulate nucleus pulposus cell cycle to improve the structural changes of lumbar disc through regulating the FADD/Caspase-8 signaling pathway to inhibit apoptosis,thereby slowing down rat lumbar disc degeneration.

Based our previous work, twelve purine derivatives were designed and synthesized as dual modulators of GPR119 and DPP-4by conjugating the GPR119 activating and DPP-4 inhibiting fragments with the position 6 and 9 of purine core via an approach of merged pharmacophores. Compound 11, bearing 2-fluoro-4-methylsulphonyl anilide and cyanopyrrolidine moieties, exhibited the most potent GPR119 agonistic activities (EC₅₀ = 0.33 μmol·L^-1, IA = 71.1%) and DPP-4 inhibitory (58.4% inhibition at 10 μmol·L^-1, 21.2% inhibition at 1 μmol·L^-1) activities in the in vitro antidiabetic study. Subsequently, we performed studies on structure activity relationships and molecular docking to guide the further drug design.

OBJECTIVE: To investigate whether Omicron BA.1 breakthrough infection after receiving the SARS-CoV-2 vaccine could create a strong immunity barrier. METHODS: Blood samples were collected at two different time points from 124 Omicron BA.1 breakthrough infected patients and 124 controls matched for age, gender, and vaccination profile. Live virus-neutralizing antibodies against five SARS-CoV-2 variants, including WT, Gamma, Beta, Delta, and Omicron BA.1, and T-lymphocyte lymphocyte counts in both groups were measured and statistically analyzed. RESULTS: The neutralizing antibody titers against five different variants of SARS-CoV-2 were significantly increased in the vaccinated population infected with the Omicron BA.1 variant at 3 months after infection, but mainly increased the antibody level against the WT strain, and the antibody against the Omicron strain was the lowest. The neutralizing antibody level decreased rapidly 6 months after infection. The T-lymphocyte cell counts of patients with mild and moderate disease recovered at 3 months and completely returned to the normal state at 6 months. CONCLUSION Omicron BA.1 breakthrough infection mainly evoked humoral immune memory in the original strain after vaccination and hardly produced neutralizing antibodies specific to Omicron BA.1. Neutralizing antibodies against the different strains declined rapidly and showed features similar to those of influenza. Thus, T-lymphocytes may play an important role in recovery.
Humans ; Antibodies, Neutralizing ; Prospective Studies ; SARS-CoV-2 ; Breakthrough Infections ; COVID-19 Vaccines ; COVID-19 ; T-Lymphocytes ; China/epidemiology* ; Antibodies, Viral

Objective: To investigate and elucidate the clinicopathological and prognostic characteristics of SMARCA4-deficient non-small cell lung cancer. Methods: The clinicopathological and prognostic data were collected in 127 patients with SMARCA4-deficient non-small cell lung cancer diagnosed in Shanghai Pulmonary Hospital, Shanghai, China from January 2020 to March 2022. The variation and expression of biomarkers related to treatment were retrospectively reviewed. Results: One hundred and twenty-seven patients were eligible for enrollment. Among them 120 patients (94.5%) were male and 7 cases (5.5%) were female, while the average age was 63 years (range 42-80 years). There were 41 cases (32.3%) of stage Ⅰ cancer, 23 cases (18.1%) of stage Ⅱ, 31 cases (24.4%) of stage Ⅲ and 32 cases (25.2%) of stage Ⅳ. SMARCA4 expression detected by immunohistochemistry was completely absent in 117 cases (92.1%) and partially absent in 10 cases (7.9%). PD-L1 immunohistochemical analyses were performed on 107 cases. PD-L1 was negative, weakly positive and strongly positive in 49.5% (53/107), 26.2% (28/107) and 24.3% (26/107) of the cases, respectively. Twenty-one cases showed gene alterations (21/104, 20.2%). The KRAS gene alternation (n=10) was most common. Mutant-type SMARCA4-deficient non-small cell lung cancer was more commonly detected in females, and was associated with positive lymph nodes and advanced clinical stage (P<0.01). Univariate survival analysis showed that advanced clinical stage was a poor prognosis factor, and vascular invasion was a poor predictor of progression-free survival in patients with surgical resection. Conclusions: SMARCA4-deficient non-small cell lung cancer is a rare tumor with poor prognosis, and often occurs in elderly male patients. However, SMARCA4-deficient non-small cell lung cancers with gene mutations are often seen in female patients. Vascular invasion is a prognostic factor for disease progression or recurrence in patients with resectable tumor. Early detection and access to treatment are important for improving patient survivals.
Humans ; Male ; Female ; Aged ; Adult ; Middle Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung/pathology* ; B7-H1 Antigen/metabolism* ; Lung Neoplasms/pathology* ; Retrospective Studies ; China ; Prognosis ; Biomarkers, Tumor/analysis* ; DNA Helicases/genetics* ; Nuclear Proteins/genetics* ; Transcription Factors/genetics*

Humans ; Philadelphia Chromosome ; Neoplasms ; Myelodysplastic Syndromes/genetics* ; Disease Progression