Asthma is a chronic inflammatory respiratory disease accompanied with airway inflammation, airway remodeling and bronchial hyperresponsiveness. Chemokines are important for the recruitment of immune cells to the lung, which play an important role in the formation and development of asthma. Targeting the chemokine receptors to anti-inflammation and anti-asthma is a new strategy and some candidate drugs are discovered recently. This review is focused on the development of chemokine receptor antagonists for anti-asthma, which will promote the compound designations.

ObjectiveTo establish the rat model of multi-infarct dementia. MethodsSephadex (4 mg/ml, 8 mg/ml) was injected into the internal carotid artery through the common carotid artery. Neurological deficits were measured 24 h after the operation, and Morris water maze test as well as Nissl stain were observed 26～30 d after the operation. ResultsThere was significant difference between the model groups injected sephadex of 8 ml/ml and 4 mg/ml in the neurologic deficits. In the following experiment, the rats injected sephadex of 8 mg/ml were only used as model. For the water maze test, the escape latency was longer (P＜0.01) and the frequency across target area reduced (P＜0.01) in the model, while the apoptotic Nissl body could be observed. ConclusionA model of multi-infarct dementia could be established with the sephadex in rats.

This study is to investigate the influence and the expression of CMTM family of testosterone on spermatogenesis suppression in the male rats treated by gossypol and cyclophosphamide. Gossypol (50 mg kg(-1)) and cyclophosphamide (20 mg kg(-1)) were administered to male rats to induce spermatogenesis suppression. Testosterone propionate was administrated at the dose of 5 mg kg(-1) every other day for 6 times. Sperm was collected from the left caudal epididymis, the count and motility of sperm were analyzed by CASA. Morphological change of testis tissue was observed with HE staining. The expression of CMTM family was examined by Western blotting assay. Gossypol (50 mg kg(-1)) and cyclophosphamide (20 mg kg(-1)) decreased the count and motility of sperm, and the pathological change of testis tissue was also observed. But, testosterone (5 mg kg(-1)) had positive effect. Furthermore, CMTM4 down-expressed remarkably in the gossypol and cyclophosphamide treated rats, the expression of the CMTM4 was up-expressed after testosterone administration. On the contrary, the expression of CMTM2 increased significantly only in gossypol treated male rats, but not in cyclophosphamide treated male rats. The expression of CMTM2 was down-expressed after testosterone administration. However, no obvious change of CMTM2 was observed in cyclophosphamide treated rats. Testosterone did not influence the expression of CKLF1, CMTM3 and CMTM5, the CMTM6, CMTM7 and CMTM8 of CMTM family were not detected in testis tissue. These demonstrated that the spermatogenesis effect of testosterone (5 mg kg(-1)) was associated with the expression of CMTM family, and CMTM2 and CMTM4 may take part in the spermatogenesis process.

Objective To discuss the clinical feature ,diagnosis and treatment of the occult cerebrospinal fluid rhinorrhea after tracheotomy in patients with severe traumatic brain injury .Methods The clinical data of 18 cases of the occult cerebrospinal fluid rhinorrhea after tracheotomy in patients with severe traumatic brain injury were retro -spectively analyzed .Results 15 cases showed involuntary swallowing movements ,frequent stimulus-likecough, abnormal increased secretions in the oral and nasal;3 cases performance of aspiration ,hypoxemia ,respiratory distress . After a three -dimensional thin skull CT , cisternography , nasal endoscopic examination can confirm the diagnosis . After the treatment with replacing the tracheostomy tube with a balloon ,continuous lumbar drainage ,endoscopic repair leak,the cerebrospinal fluid rhinorrhea were cured .Conclusion Patients with occult cerebrospinal fluid rhinorrhea performance the diversity and easily missed ,early detection and timely treatment can prevent cerebrospinal fluid rhi-norrhea delayed healing and intracranial infection and promote patient recovery .

Objective:We designed and applied a novel, bionic megaprosthesis for distal femur, which substituted the hinged articulation with an artificial ligament and a constrained tibial insert in order to maintain articular stability and reduce stress and the risks of wearing, loosening and breakage.Methods:We reviewed the cases of distal femoral osteosarcoma in children population who were initially treated in our center during 2019. Twelve cases of bionic distal femoral prosthesis (bionic group) and 21 cases of fixed-hinge distal femoral prosthesis (control group) were included. In the bionic group, there were six female and six male with the mean age as 8.8±2.6 y. One patient had pathological fracture. Staging according to Enneking system included 1 case of stage IIA, 10 cases of stage IIB and 1 case of stage III. In the control group, there were seven female and fourteen male with the mean age as 8.6±2.2 y. Pathological fracture was seen in three cases. Staging included 15 cases of stage IIB and 6 cases of stage III.We investigated the peri-operative safety, oncological outcome, complication profiles and post-operative functional status of the bionic prosthesis by comparing the baseline data, operative data, and oncological and prosthetic outcomes between the two groups.Results:The two groups were comparable in terms of baseline data including gender, age, height, weight and onset duration, and operative data including duration of operation (126.7±27.9 min vs 143.3±38.9 min, P=0.203), intra-operative hemorrhage (162.5±212.3 ml vs 247.6±175.6 ml, P=0.224) and duration of wound drainage (6.3±2.4 d vs 6.4±3.4 d, P=0.908). The mean follow-up duration of bionic group was 16.0±4.7 months, during which time three patients had systemic progression and one of them died of disease. Another patient had local recurrence and subluxation of the prosthesis that was treated by amputation. Subluxation might be related to the huge tumor mass and excessive resection of the quadriceps femoris. As for the control group, the mean follow-up duration was 12.7±4.5 months. Three patients had systemic progression and all patients were still alive by last follow-up. Local recurrence was seen in two patients and was treated by excision. No prosthetic complications were seen in the control group. The averaged range of motion (ROM) was greater in the bionic group than that in the control group (120.6°±13.6° vs 92.0°±7.7°, P<0.05), but the MSTS 93 scores were similar between groups (29.1±0.9 vs 29.5±0.6, P=0.337). Conclusion:Compared with the fixed-hinge distal femoral prosthesis, the bionic prosthesis had good peri-operative safety, did not increase the risks of prosthetic complications, and could achieve a better range of motion and a similar functional status based on the results of short-term follow-up.

BACKGROUND:Rheumatoid arthritis is an autoimmune disease, and traditional treatment methods are difficult to effectively solve the patient's lack of immune tolerance mechanisms. With the development of stem cel s in regenerative medicine, stem cel therapy has become a hot spot in the treatment of autoimmune diseases.
Currently, studies on cel transplantation for the treatment of rheumatoid arthritis are rarely reported.
OBJECTIVE:To study the influence of umbilical cord mesenchymal stem cel therapy on the changes of Th1/Th2 and Treg in rheumatoid arthritis patients, thereby seeking new therapies for rheumatoid arthritis.
METHODS:We selected 180 cases of rheumatoid arthritis, including 27 patients as control group undergoing non-steroidal anti-inflammatory drugs and anti-rheumatic drugs and 153 patients as cel treatment group undergoing intravenous infusion of 40 mL umbilical cord mesenchymal stem cel s at a density of 4×107. Dosing regimen was same in the two groups. The 76 of 153 patients accepted second cel therapy at 3-4 months after the first cel therapy. After fol ow-up of 3 and 6 months, clinical effectiveness evaluation (DAS28, HAQ, ACR20), rheumatoid factor, anti-CCP antibodies, T cel subsets, Th cytokine were detected;for patients with second cel therapy, T cel subsets and Treg were detected at 8 months after treatment.
RESULTS AND CONCLUSION:(1) At 3 months after treatment, the DAS28, HAQ and ACR20 scores were significantly lower in the cel treatment group than the control group (P<0.01). (2) At 3 and 6 months after cel therapy, the DAS28 and HAQ scores were significantly decreased in the cel treatment group (P<0.01), and these scores were decreased continuously after second cel therapy (P<0.01). (3) Interferon-γlevel in cel s did not change obviously at 3-6 months after treatment, but the interleukin-4 level was gradual y increased at 6 months after treatment (P<0.05). (4) The number of Treg cel s was significantly increased at 3-6 months after treatment (P<0.01), which was closely related to ACR, especial y ACR70 percentage (P<0.05);the ratio of CD4+Treg was increased significantly at 3 months after treatment (P<0.05), and this increasing trend was also maintained at 6 and 8 months after treatment, but there was no significant difference (P>0.05). (5) B cel levels were significantly decreased at 6 months after treatment (P>0.05);the rheumatoid factor value was significantly decreased at 3-6 months after treatment (P<0.05). (6) There was no change in anti-CCP antibody and interleukin-17 levels at 3-6 months after treatment. These findings indicate that after treatment with umbilical cord mesenchymal stem cel s, the Th1/Th2 tends to balance and Treg level is elevated in rheumatoid arthritis patients, which are directly related to clinical trials and symptomatic relief. Therefore, standard rheumatism medication combined with umbilical cord mesenchymal stem cel transplantation can improve immune network effects, adjust the immune tolerance and prevent il ness progress in rheumatoid arthritis patients.

To study the umbilical cord mesenchymal stem cells impact of inflammatory factors in rheumatoid arthritis patients.Methods:94 cases of patients with RA hospitalized in our department from April 2011 to December 2012 were treated with umbilical cord mesenchymal stem cells (MSCs) UC,during which the cell therapy scholastic ethics was committed approvally and patients′informed consents were separately signed .94 patients were directly intravenous infusion with 40 ml UC-MSCs ( 4×107 cells/ml),including 57 cases with two UC-MSCs therapy.We used multifunctional flow lattice Luminex 200 analysis to detect contents of 13 kinds of factors in serum such as TNF alpha,IFN-gamma,IL-1β,IL-4,IL-6,IL-8,IL-10,ie,and detected CPR,ESR,assessment DAS28,HAQ,and ARA.Follow-up treatments were performed after 1 week,3 months,6 months ( two cells treatment of 60 cases).Results:①DAS28,HAQ grading standards,were decreased (P<0.01) in 3 months and 6 months before the patients treatment ,2 times than one continue treatment decreased ( P<0.01 );the ESR and CRP in 1 week dropped significantly after treatment ( P<0.01),3 months,6 months before the treatment also decreased (P<0.05).②IL-6,TNF alpha were in falling levels after 1 week,3 months and 6 months treatment ,( P<0.05 ).Conclusion: We proved the inflammatory factors directly related with clinical indicators and symptoms of RA patients .94 cases of patients with other inflammatory factor (IL-17,IL-4,IL-10,etc.) also had some change,we still needed further observation.According to drug rheumatism guide at the same time , collaborative using with UC-MSCs could make RA patients improve local and systemic inflammatory response ,prevent disease progression.

Objective To investigate the proliferative inhibition effect and mechanism of total saponins from marsdenia tenacissima on human liver cancer HepG2 cells. Methods Human liver cancer HpeG2 cells cultured conventionally were divided into the marsdenia tenacissima saponins A control group, the experimental group and the blank control group. The experimental group was treated with different mass concentrations of total saponins from marsdenia tenacissima (0.14, 0.29, 0.58, 1.15, 2.13 mg/ml), while the marsdenia tenacissima saponins A control group was treated with marsdenia tenacissima saponins A (1.0 mg/ml), and the blank control group was established stimultaneously. The methyl thiazolyl tetrazolium (MTT) method was used to detect the effect of total saponins from marsdenia tenacissima on the activity of HepG2 cells, and the cell morphology was observed by using inverted microscopy. The cell apoptosis rate was detected by using flow cytometry from Annexin V-FITC/PI staining. The expressions of bcl-2, bax and p53 were analyzed by using Western blot after the drug effect. Results The results of cell activity test showed that total saponins from marsdenia tenacissima could inhibit the proliferation of HepG2 cells at the concentration of 0.29, 0.58, 1.15, 2.13 mg/ml, which was positively correlated with the concentration. The half maximal inhibitory concentration (IC 50) of cell growth inhibition of total saponins from marsdenia tenacissima on HepG2 cells was 0.75 mg/ml. Under inverted microscopy, the adherent cells were significantly reduced, the cells fell off into clusters and the debris was increased after the effect of total saponins from marsdenia tenacissima. Moreover, flow cytometry showed that total saponins from marsdenia tenacissima could increase the late apoptosis rate of HepG2 cells (P< 0.01). Western blot showed that the expression of bcl-2 was 0.62±0.16, 0.31±0.15, 0.84±0.09 and 1.00±0.11 respectively in the experimental group (total saponins from marsdenia tenacissima 0.58 mg/ml and 2.13 mg/ml), the marsdenia tenacissima saponins A control group and the blank control group;the expression of bax protein was 0.75±0.10, 0.83±0.12, 1.00±0.14 and 0.15±0.02, respectively in the above four groups; the expression of p53 protein was 0.63±0.08, 0.78±0.11, 1.00±0.13 and 0.18±0.02 respectively in the above four groups. The protein expression of bcl-2 was decreased and the protein expressions of bax and p53 were increased in the experiment group, and there was a statistical difference between the experiment group and the blank control group (P< 0.05). Conclusions Total saponins from marsdenia tenacissima can upregulate the expression of bax by upregulating the expression of p53 gene, and inhibit the expression of bcl-2, which would cause the cascade reaction to induce the apoptosis of HepG2 cells. Its inhibitory effect can be realized through mitochondrial pathmay to induce apoptosis.

Objective:To describe the design, manufacture and use of three-dimensional (3D)-printed endoprosthesis for reconstruction after metaphysis-involved intercalary tumor resection and to evaluate its outcome.Methods:Forty-three patients who received metaphysis-involved intercalary tumor resection followed by 3D-printed endoprosthetic reconstruction in Musculoskeletal Tumor Center, Peking University People's Hospital between January 2018 and December 2021 were retrospectively reviewed. There were 25 males and 18 males with an average age of 20.1±15.2 years (range, 4-58 years). The pathological diagnosis included 24 cases of osteosarcomas, 6 cases of Ewing sarcomas, 5 cases of chondrosarcomas, 2 cases of pleomorphic undifferentiated sarcomas, 3 cases of soft-tissue sarcomas (liposarcoma, synovial sarcoma, malignant peripheral nerve sheath tumor for each) and 3 others (adamantinoma, recurrent aneurysmal bone cyst and recurrent osteofibrous dysplasia for each). The tumors located at femur in 25 patients (58%), including 14 lesions involving distal femoral metaphysis and 11 lesions involving both proximal and distal metaphysis; the tumors located at tibia in 11 patients (26%), including 4 lesions involving distal tibial metaphysis, 5 lesions involving proximal tibial metaphysis and 2 lesions involving both proximal and distal tibial metaphysis; the tumors located at humerus in 7 patients (16%), including 1 lesion involving distal humeral metaphysis, 3 lesions involving proximal humeral metaphysis and 3 lesions involving both proximal and distal humeral metaphysis. The endoprosthesis was designed in a semi-modular fashion and consisted of three parts: a diaphysis-fixing component, a semi-modular lap joint component, and a custom-made 3D-printed metaphysis-fixing component which was designed as two types with 3D-printed porous bone-contacting surfaces according to the osteotomy plane (Type I on meta-diaphyseal region, Type II on meta-epiphyseal region). The functional outcome was assessed using Musculoskeletal Tumor Society (MSTS) 93 system.Results:All surgeries were accomplished sucessfully. The median resection length and the distance from osteotomy plane to adjacent joint was 16.0 (13.0, 22.0) cm and 4.5 (3.5, 6.0) cm, respectively. 59 metaphysis-fixing components were installed in 43 patients. Type I components were used in single and dual ends of endoprosthesis in 12 and 6 cases respectively. Type II components were used in single and dual ends in 15 and 5 cases respectively. Hybrid endoprosthesis with Type I and II components were used in 5 cases. The mean follow-up time was 26.0 (17, 37) months (range, 12-54 months). The mean MSTS 93 score was 29.0 (28.0, 30.0) points (range, 21-30 points). Implant failures were found in 5 patients, including 2 cases of aseptic loosening (loosening was observed in the cementing diaphysis-fixing stems while no evidence of loosening in metaphysis-fixing components) and 3 cases of local tumor progression. The 2-year implant survival rate was 90.3% (95% CI: 0.81, 0.99). Conclusion:Using 3D-printed intercalary endoprosthesis for reconstruction after intercalary resection of metaphysis-involved bone tumor shows satisfactory functional outcome and implant survival. Moreover, by assembling endoprosthetic components according to the different osteotomy plane, the semi-modularized endoprosthesis also provids a comprehensive and individualized reconstruction for patients with metaphysis-involved intercalary tumor.

Objective To evaluate the safety and efficacy of denosumab in treatment of patients with pelvic giant cell tumor of bone (GCTB) during perioperative period. Methods This is a retrospective observational study. Twenty-three patients diagnosed with pelvic GCTB undergoing perioperative denosumab treatment in Musculoskeletal Tumor Center of Peking University People's Hospital from January 2014 to December 2016 were reviewed. The subjective adverse reactions and mandibular X-ray films were used to assess the drug safety. As for efficacy, imaging findings (including X-ray, CT, magnetic resonance imaging) were reviewed. MSTS-93 scoring system was applied in the postoperative functional assessment. Histological response rate, objective response rate, clinical benefit rate and event-free survival rate were all used to deficit the efficacy of denosumab in the treatment of pelvic GCTB combined with surgery. All the results of postoperative were compared statistically with pelvic GCTB patients who underwent surgery in the same hospital from 1999 to 2009. Results All the patients were firstly diagnosed as classic GCTB except for one case which was malignant pelvic GCTB. All patients received denosumab preoperatively and/or postoperatively, and the average number of medications was 8.43. According to the surgical patterns, patients were divided into intralesional surgery group (13 cases) and wide resection group (10 cases). The follow-up was 5-47 months(mean:27.30 months),recurrence was observed in 2 cases in the intralesional surgery group, none in the wide resection group. After drug administration, 13 cases were partial response, 7 cases were stable disease, the objective response rate was 65.0 % (13/20), and the histologically clearance rate of giant cells was 85.0 % (17/20). No case of osteonecrosis of the jaw was observed in this study, and all laboratory indicators were normal. The average postoperative MSTS-93 score was 26.87. Compared with pelvic GCTB patients who underwent surgical treatment from 1999 to 2009, in the intralesional surgery group, there was no significant difference in the recurrence rate [15.4 % (2/13) vs. 30.8 % (4/13), P = 0.514], but the limb function was significantly increased (P= 0.002). Conclusions Denosumab combined with surgery plays an important role in the multidisciplinary treatment of pelvic GCTB. The neoadjuvant strategy can reduce patient's intraoperative blood loss by shrinking the tumor size which makes the intralesional curettage surgery possible, and also diminishing the recurrence rate. But more attention should be paid to secondary malignant GCTB during the use of denousmab.