BACKGROUND:Cervical rotation-traction manipulation is effective and safe in the treatment of cervical spondylotic radiculopathy,and has been widely used in clinical work.However,its effects on the biomechanics of cervical vertebra and intervertebral disc and the area of intervertebral foramen have not been systematically clarified. OBJECTIVE:Based on the finite element analysis technique,a relevant research and analysis were carried out to provide digital evidence for the mechanism of effect of cervical rotation-traction manipulation in the treatment of cervical spondylotic radiculopathy. METHODS:The CT image data of a volunteer with no neck diseases were selected as the finite element model material at its left-handed physiological limit position.The initial construction of the finite element model was completed by Mimics 19.0 software,Geomagic Studio 2013 software,Hypermash 14.0 software,and ANSYS Workbench 2020 R2 software,respectively.Based on the literature,the grid division of cervical structure and the assignment of elastic modulus and elastic coefficient were completed.Based on the previous work of the team,the mechanical effects of cervical rotation-traction manipulation were simulated on the model.Effects of cervical rotation-traction manipulation on the mechanical parameters of each vertebral body and intervertebral disc in C3-T1 segment and on the cervical lateral foramen area were analyzed. RESULTS AND CONCLUSION:(1)During cervical rotation-traction manipulation,the stress of bone structure was significantly higher than that of soft tissue such as intervertebral disc.(2)When operating the technique,the stress at the top of each cervical vertebra was higher,the stress at the bottom was lower,and the stress at the facet joint and transverse process was lower.The stress at the top of the intervertebral disc was lower,the stress at the bottom was higher,but the highest point of the intervertebral disc stress was outside the top.(3)In addition,after loading the lifting force,the projected area of the C6/C7 intervertebral foramen increased significantly compared with that before loading.(4)It is indicated that the cervical rotation-traction manipulation has the mechanical characteristics of changing the stress structure of the cervical spine itself,and can expand the C6/7 intervertebral cervical foramen area on the opposite side of the patient's cervical rotation,so as to achieve the purpose of treating cervical spondylotic radiculopathy.

A major challenge facing photodynamic therapy (PDT) is that the activity of the immune-induced infiltrating CD8⁺ T cells is subject to the regulatory T lymphocytes (Tregs), leaving the tumor at risk of recurrence and metastasis after the initial ablation. To augment the antitumor response and reprogram the immunosuppressive tumor microenvironment (TME), a supramolecular photodynamic nanoparticle (DACss) is constructed by the host-guest interaction between demethylcantharidin-conjugated β-cyclodextrin (DMC-CD) and amantadine-terminated disulfide-conjugated FFVLGGGC peptide with chlorin e6 decoration (Ad-ss-pep-Ce6) to achieve intelligent delivery of photosensitizer and immunomodulator for breast cancer treatment. The acid-labile β-carboxamide bond of DMC-CD is hydrolyzed in response to the acidic TME, resulting in the localized release of DMC and subsequent inhibition of Tregs. The guest molecule Ad-ss-pep-Ce6 can be cleaved by a high level of intracellular GSH, reducing photosensitizer toxicity and increasing photosensitizer retention in the tumor. With a significant increase in the CTL/Treg ratio, the combination of Ce6-based PDT and DMC-mediated immunomodulation adequately achieved spatiotemporal regulation and remodeling of the TME, as well as improved primary tumor and in situ lung metastasis suppression with the aid of PD-1 antibody.

BACKGROUND:The evaluation and management of cervical vascular pathologies before orthopedic manual therapy have great significance for reducing risks,ensuring patients'interests and promoting optimal clinical decision-making.However,the research and exploration of this field in China are still in its infancy.In 2020,the International Federation of Orthopaedic Manipulative Physical Therapists(IFOMPT)released the International Framework for Examination of the Cervical Region for potential of vascular pathologies of the neck prior to Orthopaedic Manual Therapy(OMT)Intervention:International IFOMPT Cervical Framework(2020).This framework has important references and guiding values for the clinical practice of cervical manipulation in China. OBJECTIVE:To integrate and interpret the core content of the framework,to provide a reference for the clinical practice of cervical manual therapy in China. METHODS:On the basis of a full study of the framework,the authors interpret the core content of the framework from eight aspects including clinical reasoning,patient history,planning the physical examination,physical examination,risk and benefit.Meanwhile,seven databases including PubMed,EMbase,Cochrane Library,CNKI,WanFang,VIP and China Biomedical Literature Service System databases were searched by computer to screen clinical practice guidelines and expert consensus on neck pain.Through longitudinal comparison of multiple high-quality guidelines and consensus,the authors combine with the clinical practice in China to carry out discussion and analysis. RESULTS AND CONCLUSION:This framework expounds the management strategy and implementation path of cervical vascular disease evaluation before cervical manipulation from multiple dimensions,suggesting that we should improve clinicians'attention to cervical vascular disease evaluation before manipulation,and construct evaluation criteria and implementation path with Chinese clinical characteristics.Meanwhile,we should further carry out basic scientific research with multidisciplinary techniques and promote shared decision-making and teaching model innovation to achieve the best clinical decision.

Objective:To compare the difference of prognosis in ⅢCr stage cervical cancer patients with different T stage and lymph node status who received radical radiotherapy.Methods:Clinical data of 279 patients with ⅢCr stage cervical cancer treated with radical radiotherapy at Zhejiang Cancer Hospital from September 2013 to December 2016 were retrospectively analyzed. According to the latest American Joint Committee on Cancer (AJCC) TNM stage, all patients were divided into T 2a, T 2b, T 3a and T 3b stage groups, and N 1 and N 2 stage groups based on lymph node status. They were also divided into <1.85 cm and ≥1.85 cm groups according to the maximum short diameter of lymph node. In addition, they were assigned into ≤3 and>3 groups according to the number of lymph node metastasis. The differences of progression-free survival (PFS) and overall survival (OS) between patients with different T stage and lymph node status were compared by Kaplan-Meier test and log-rank test. Multivariate survival analysis was performed by Cox regression analysis. Results:Among 279 patients with ⅢCr stage cervical cancer receiving radical radiotherapy, 6 (2.2%) patients were diagnosed with stage T 2a stage, 109 (39.1%) patients with T 2b stage, 13 (4.7%) patients with T 3a stage, and 151 (54.1%) patients with T 3b stage. And 246 (88.2%) patients were diagnosed with N 1 stage and 33 (11.8%) patients with N 2 stage. According to the maximum short diameter of lymph nodes, there were 229 (82.1%) patients in the<1.85 cm group and 50 (17.9%) in the ≥1.85 cm group. According to the number of lymph node metastasis, there were 269 (96.4%) patients in the ≤3 group and 10 (3.6%) in the>3 group. There was no significant difference in the 5-year PFS ( P=0.136) and OS rates ( P=0.050) among patients with different T stages, and patients with T 3a stage had the worst prognosis (5-year OS rate was 38.5%). The 5-year PFS (48.0% vs. 64.2%, P=0.016) and OS rates (52.0% vs. 73.8%, P=0.001) in the ≥1.85 cm group were significantly lower than those in the<1.85 cm group. There was no significant difference in the 5-year PFS (61.0% vs. 63.6%, P=0.796) and OS rates (67.5% vs. 69.7%, P=0.770) between patients with N 1 and N 2 stages. There was no significant difference in the 5-year PFS (61.0% vs. 70.0%, P=0.653) and OS rates (67.3% vs. 80.0%, P=0.447) between patients in the number of metastatic lymph nodes ≤3 and>3 groups. The prognosis of patients with T 2b stage and the maximum short diameter ≥1.85 cm was the worst (5-year OS rate was 31.3%), while patients with T 2b stage and the maximum short diameter <1.85 cm obtained the best prognosis (5-year OS rate was 76.3%). Multivariate analysis showed that the maximum short diameter and radiation dose of lymph nodes were the independent relevant factors for the OS of ⅢCr stage cervical cancer patients (both P<0.05). Conclusions:Among ⅢCr stage cervical cancer patients receiving radical radiotherapy, clinical efficacy and prognosis significantly differ according to different T stage and lymph node status. Current staging system should be optimized to provide effective diagnostic and therapeutic regimens.

Objective:To analyze clinical, immunoserological, and therapeutic features of patients with anti-p200 pemphigoid.Methods:Clinical data were collected from patients with confirmed anti-p200 pemphigoid at the Hospital of Dermatology, Chinese Academy of Medical Sciences from January 2015 to February 2024. Their clinical, immunoserological, and therapeutic characteristics were retrospectively analyzed.Results:A total of 35 patients were included, with a male-to-female ratio of 2.5∶1 (25 males and 10 females) and ages of 57.74 ± 17.12 years. Two (5.71%) patients were accompanied by psoriasis. In these patients, anti-p200 pemphigoid exhibited heterogeneous clinical phenotypes, mimicking classic bullous pemphigoid (20 cases, 57.14%), linear IgA bullous dermatosis (8 cases, 22.86%), or eczema (4 cases, 11.43%). The positive rates of direct immunofluorescence (DIF), indirect immunofluorescence on salt-split skin (ss-IIF), Western blot analysis with dermal extracts as substrates, and Western blot analysis with laminin γ1 C-terminal region (Lnγ1C) as substrates were 100% (24/24), 82.86% (29/35), 100% (35/35), and 80.64% (25/31), respectively. Among the 35 patients, treatment and follow-up information was available for analysis in 33. Six patients (18.18%) received non-glucocorticoid systemic therapy and topical glucocorticoid therapy, with a follow-up period ( M [ Q1, Q3]) of 19.50 (6.50, 69.25) months, and 1 withdrew the drugs. Sixteen patients received systemic glucocorticoids combined with traditional anti-inflammatory drugs, with a follow-up period of 13.50 (4.25, 18.00) months, the initial dose of glucocorticoids was equivalent to 0.30 - 0.50 mg·kg -1·d -1 of prednisone, and the time to disease control was 15.31 ± 5.23 days; among the 16 patients, 3 experienced fluctuations in disease condition which were alleviated by adding dapsone, and 1 discontinued glucocorticoids. Five patients (15.15%) received systemic glucocorticoids combined with immunosuppressants, with a follow-up period of 26.00 (14.00, 90.00) months, the initial dose of glucocorticoids was equivalent to 0.50 - 0.75 mg·kg -1·d -1 of prednisone, and the time to disease control was 10.20 ± 3.27 days; among the 5 patients, 2 received maintenance treatment with glucocorticoids (5 - 10 mg/d prednisone), 2 withdrew the drugs, and 1 relapsed after discontinuing glucocorticoids. One patient (3.03%) received systemic glucocorticoids combined with rituximab therapy, with a follow-up period of 53 months, and discontinued glucocorticoids thereafter. One patient (3.03%) received systemic glucocorticoids combined with dupilumab therapy, which proved to be effective. Four patients (12.12%) received systemic glucocorticoids combined with Janus kinase inhibitors, and 3 responded well. Conclusions:Anti-p200 pemphigoid presented a heterogeneous clinical profile in this series of patients, but scarring and milia were rare. Some patients showed negative results in Western blot analysis with Lnγ1C as substrates. The prognosis of anti-p200 pemphigoid was usually favorable, and most patients could achieve complete remission and ultimately discontinue medication.

Objective:To analyze clinical and immunoserological features of patients with epidermolysis bullosa acquisita (EBA) .Methods:Clinical data were collected from patients with confirmed EBA at the Hospital of Dermatology, Chinese Academy of Medical Sciences from January 2017 to January 2022, and their clinical and immunoserological characteristics were retrospectively analyzed.Results:A total of 20 patients were collected, including 7 males and 13 females, and they were aged 41.85 ± 18.43 years. Ten patients presented with the classical phenotype of EBA, 8 with the inflammatory phenotype of EBA, and 2 with the mixed phenotype of EBA. Mucosal involvement occurred in 19 cases, nail involvement occurred in 4, scarring was observed in 9, and milia in 13. Indirect immunofluorescence on salt-split skin showed IgG deposition on the dermal side in 19 cases. Enzyme-linked immunosorbent assay for type Ⅶ collagen revealed positive results in 19 cases, with a diagnostic sensitivity of 95%. Western blot analysis with dermal extracts as substrates revealed a protein band with a relative molecular mass of 290 000 in 16 cases, with a diagnostic sensitivity of 80%, and multiple autoantibodies against different basement membrane zone antigens were identified in 3 cases. Fifteen patients received systemic glucocorticoids, including 2 receiving combined immunosuppressive agents and 13 receiving combined anti-inflammatory agents with dapsone and colchicine as the first and second commonly used anti-inflammatory agents respectively; among 5 patients receiving non-glucocorticoid therapy, 2 with inflammatory EBA were sensitive to dapsone and colchicine, while the other 3 patients were lost to follow-up. Totally, 17 patients were followed up for an average duration of 26.21 months. Among the 17 patients, 1 achieved complete remission off therapy, 2 achieved complete remission on minimal therapy, and the remaining 14 patients achieved partial remission.Conclusions:The treatment of EBA is challenging, and anti-inflammatory agents such as dapsone and colchicine are often used. Immunoserological tests are of great value in the diagnosis of EBA.

Objective:To explore the application effect of an intelligent teaching robot system of lifting manipulation in cervical spine manipulation teaching.Methods:60 doctors were randomly divided into an experimental group ( n = 30) and a control group ( n = 30). The control group was taught by a certified chief physician using a combination of "PowerPoint presentations, video demonstrations, and operation demonstrations" . Each part is 5 min. The experimental group was taught by the intelligent teaching robot system with a spinning technique. The teaching time is 15 min for both groups. At the end of the two teaching sessions, the two groups were trained five times under different BMIs and passed the system assessment. The qualified rates of pre-traction force, lifting and pulling force, maximum force, pre-traction time, lifting and pulling time, rotation amplitude, and pitch amplitude were compared between the two groups. Results:In normal, there was significant differences between the qualified rates of pre-traction force, lifting and pulling force, maximum force, pre-traction time, lifting and pulling time, rotation amplitude, and pitch amplitude in two groups (all P<0.05). For overweight people, there were significant differences in pre-traction force, pulling force, maximum force, and rotation amplitude (all P <0.05), while there were no significant differences in pre-traction time, pulling time, or pitching amplitude (all P >0.05). In obesity, there were significant differences in pre-traction force, lifting and pulling force, maximum force, and pitch amplitude (all P <0.05), but no significant differences in pre-traction time, lifting and pulling time, or rotation amplitude (all P >0.05). Conclusions:The proposed system can improve the pass rate of spinning manipulation, especially by effectively controlling the pre-traction force, pulling force, and maximum force.

Objective:To analyze the adverse reactions of patients with multidrug-resistant pulmonary tuberculosis treated with linezolid, and to provide reference for clinical rational use of drugs.Methods:A total of 189 patients with multidrug-resistant pulmonary tuberculosis who were admitted to Hunan Chest Hospital between June 2019 and June 2020 were retrospectively included, and were divided into the linezolid group and the control group. The control group was given a standardized anti-tuberculosis treatment without linezolid, and the linezolid group was given linezolid in addition to standardized regimens. The occurrences of hematological toxicity, peripheral neuritis, optic neuritis and other adverse reactions in the two groups after anti-tuberculosis treatment were recorded. The risk factors for adverse reactions of linezolid were analyzed. Statistical analysis was performed using independent samples t test and chi-square test, and logistic regression was used to analyze the risk factors for adverse reactions of linezolid. Results:A total of 189 patients with MDR-TB were included in this study, including 108 in the linezolid group and 81 in the control group. There were no significant differences in baseline characteristics between the linezolid and control groups. The frequencies of leukopenia, anemia, thrombocytopenia, peripheral neuritis and optic neuritis in the linezolid group were 20.4%(22/108), 47.2%(51/108), 21.3%(23/108), 20.4%(22/108) and 13.9%(15/108), respectively, which were all significantly higher than those in the control group (8.6%(7/81), 27.2%(22/81), 9.9%(8/81), 1.2%(1/81) and 4.9%(4/81), respectively), and the differences were all statistically significant ( χ2=4.90, 7.86, 4.40, 15.86 and 4.10, respectively, all P<0.050). Patients older than 45 years of age was independent risk factor for leukopenia (odds ratio ( OR)=3.08, 95% confidence interval ( CI) 1.03 to 9.25, P<0.050) and thrombocytopenia ( OR=2.41, 95% CI 1.09 to 5.35, P<0.050) after linezolid administration. The higher value of white blood cell at baseline ( OR=0.48, 95% CI 0.30 to 0.76, P=0.002) was an independent protective factor for leukopenia associated with linezolid. Conclusions:Pancytopenia, peripheral neuritis and optic neuritis are prone to appear when linezolid is used to treat patients with multidrug-resistant pulmonary tuberculosis. In clinical practice, closely monitoring the adverse reactions during the use of linezolid for anti-tuberculosis treatment is needed.

Objective:To analyze clinical and immunoserological features of patients with anti-p200 pemphigoid.Methods:Clinical data were collected from patients with confirmed anti-p200 pemphigoid in Hospital of Dermatology, Chinese Academy of Medical Sciences from January 2015 to October 2021, and their clinical and immunoserological characteristics were retrospectively analyzed.Results:Seven patients with anti-p200 pemphigoid were included. Indirect immunofluorescence on salt-split skin (IIF-SSS) showed that serum IgG antibodies of the 7 patients were located in the dermis of the salt-split skin, and Western blot analysis with dermal extracts as substrates revealed a protein band with a relative molecular mass of 200 000. Four patients presented with classic bullous pemphigoid-like skin lesions, 2 initially presented with eczematous lesions, and 1 presented with linear IgA bullous dermatosis-like skin lesions. Circulating IgG antibodies could recognize the recombinant laminin γ1 C-terminal region in 6 cases. Four patients received different doses of systemic glucocorticoids, 1 of whom was resistant to high-dose systemic glucocorticoids (equivalent to 1.4 mg·kg -1·d -1 prednisone) ; 2 responded well to minocycline and dapsone; 1 was lost to follow-up. Four patients achieved complete remission and discontinued the treatment at a mean follow-up of 22.5 months; 2 received complete remissiona on minimal therapy at a mean follow-up of 8 months. Conclusion:Patients with anti-p200 pemphigoid presented with heterogeneous clinical manifestations, and the recombinant C-terminal fragment of laminin γ1 can serve as a reliable antigen substrate for the detection of autoantibodies in patients with anti-p200 pemphigoid; some patients can eventually achieve complete remission off treatment.

Objective:To optimize indirect immunofluorescence on salt-split skin (IIF-SSS), and to evaluate its performance in detection of bullous pemphigoid (BP) antibodies.Methods:Normal human foreskin and non-foreskin skin tissues were used to prepare salt-split substrates under 3 different experimental conditions: traditional group rotated at 4 ℃ for 48 - 72 hours, low-temperature immersion group soaked at 4 ℃ for 48 - 72 hours, room-temperature immersion group soaked at 25 ℃ (range: 23 - 27 ℃) for 24 hours. Serum samples were obtained from 20 patients with bullous pemphigoid (BP) in Hospital of Dermatology, Chinese Academy of Medical Sciences between August 2019 and August 2020, and subjected to IIF on the intact skin or salt-split substrates by using a multiple dilution method. Paired-sample t test was used for comparisons of means between two paired samples. Results:No dermal-epidermal separation was observed in the substrates prepared in the low-temperature immersion group at 48 - 72 hours, while dermal-epidermal separation occurred in the lower lamina lucida of the foreskin and non-foreskin substrates in the room-temperature immersion group and the traditional group. For the 20 patients with BP, the reciprocal end-point titers ( M[ Q1, Q3]) detected with the salt-split non-foreskin skin and salt-split foreskin in the room-temperature immersion group, and with the salt-split non-foreskin skin in the traditional group were 5 120 (2 560, 17 920), 1 280 (640, 2 560), 1 280 (640, 2 560), respectively. Moreover, 19 (95%) patients with BP showed that the reciprocal end-point titers detected with the substrates in the room-temperature immersion group were 1 - 5 times those in the traditional group ( t = 8.04, P<0.001), suggesting that the performance of salt-split skin in the room-temperature immersion group was superior to that in the traditional group in the detection of BP antibodies; however, there was no significant difference in the reciprocal end-point titers of BP antibodies between the salt-split foreskin in the room-temperature immersion group and salt-split non-foreskin skin in the traditional group ( t<0.001, P>0.05). The reciprocal end-point titers in 20 BP sera detected by conventional IIF on the intact non-foreskin skin and foreskin were 320 (160, 640) and 480 (160, 1 120), respectively; the reciprocal end-point titers detected by IIF on the salt-split foreskin and non-foreskin skin in the room-temperature immersion group, as well as on the salt-split non-foreskin skin in the traditional group, were all consistent with or 1 - 7 times higher than those detected by conventional IIF ( t = 6.47, 14.83, 5.26, respectively, all P<0.001) . Conclusion:The soaking method at room temperature 25 ℃ (23 - 27 ℃) for preparing salt-split substrates has advantages of short duration and simple procedure, and the sensitivity of IIF-SSS using the substrates prepared by this method is equal or superior to the traditional salt-split method for detecting BP antibodies.