Objective To evaluate the effect and safety of thymosin combined with biapenem in the treatment of severe lower respiratory tract infection of gram negative bacilli.Methods 54 patients with severe lower respiratory tract infection of gram negative bacilli were randomly divided into study group (group A) and control group (group B),group A was treated with thymosin and biapenem,group B biapenem.All patients were treated for 7 ～ 14 days in a course.The clinical effect,treatment time of biapenem,the bacterial clearance rate and adverse drug reaction betweeen two groups were compared.Results The clinical effective rate of group A and B were 84.6％ and 82.1％,respectively,there was no statistical difference (P ＞ 0.05).Treatment time of biapenem in group A and B was (8.2 ±3.4) days and (13.2 ± 3.6) days,respectively,there was statistical difference (P ＜ 0.05).The bacterial clearance rate of group A and B were 86.7％ and 80.7％,respectively,there was no statistical difference between two groups (P ＞ 0.05).Conclusion The treatment time of thymosin combined with biapenem treatment of gram-negative bacilli severe respiratory tract infection was shorter than that of biapenem alone treatment,and it was safe,effective,and worthy of ciinical application.

BACKGROUND:The mechanism underlying orthodontic-induced external root resorption is not yet clear, and it differs individual y. Kidney deficiency has been proved to be related to bone diseases which mediated by different cytokines. Interleukin-17 is an important cytokine involved in external root resorption. So figuring out whether kidney deficiency and interleukin-17 are related to root resorption wil be helpful for etiological research.
OBJECTIVE:To explore the relationship between kidney deficiency physique, interleukin-17 and root resorption during orthodontic treatment in rats.
METHODS:Thirty-six Wistar rats were selected and equivalently randomized into two groups, fol owed by modeled into kidney deficiency (kidney deficiency group) or injected with normal saline (control group), respectively. Afterwards, the right maxil ary of each rat served as an orthodontic force model, and the left maxil ary as a non-orthodontic force model. Al rats were respectively sacrificed under general anesthesia at the 3, 7 and 14 days after given orthodontic force. Then, the mesial surface of the root of maxil ary first molars and the expression level of interleukin-17 were observed through hematoxylin-eosin staining and immunohistochemical method.
RESULTS AND CONCLUSION:Histological observation showed that significantly increasing root resorption in a time-dependent manner could be observed, and there were various absorbed lacunae of osteoclasts on the enamel in the kidney deficiency orthodontic force group. The alveolar bone resorption and widened periodontal membrane appeared in the control orthodontic force group. While no remarkable root and alveolar bone resorptions were found in the other two non-orthodontic force groups. The expression level of interleukin-17 in the kidney deficiency orthodontic force group was higher than that in the control orthodontic force group;the expression level of interleukin-17 in the kidney deficiency non-orthodontic force group was higher than that in the control non-orthodontic force group. In conclusion, kidney deficiency patients are easy to develop root resorption, the mechanism of which is maybe relevant to the upregulation of interleukin-17.

Objective:To study the clinical effect of internal combined with external fixation in the treatment of pelvic fracture and its effect on the serum alkaline phosphatase (ALP),tumor necrosis factor-a (TNF-α) and transforming growth factor-β (TGF-β).Methods:Eighty-six patients with pelvic fractures admitted in our hospital from August 2014 to July 2015 were selected and divided into the observation group and control group according to the admission order.Conventional internal fixation was used in the control group,and the internal combined with extemal fixation was performed in the observation group.The clinical curative effect,operative time,blood loss,fracture healing time and incidence of complication were compared between two groups.The levels of serum ALP,TNF-α and TGF-β in the two groups were compared before and after treatment between two groups.Results:The excellent rate of observation group was significantly higher than that of the control group [81.40％ (35/43) vs 41.86％ (18/43)] (P ＜0.05).The operative time,blood loss and fracture healing time in the observation group were significantly shorter or less than those of the control group (P＜0.05).There was no significant difference in the serum ALP,TNF-α and TGF-β levels between the two groups before treatment (P＞0.05).After treatment,the serum ALP levels in the two groups were significantly higher than before treatment (P＜0.05).The levels of TNF-α and TGF-β were significantly lowe than those before treatment(P＜0.05),the ALP levels in the observation group was significantly higher than that of the control group (P ＜0.05),and the levels of TNF-c and TGF-β were significantly lower than those of the control group 0.05).The incidence of complications of observation group was significantly lower than that of the control group [0.00％ (0/43) vs 11.63％ (5/43)] (P ＜0.05).Conclusion:Internal and external fixation was effective and safe in the treatment of pelvic fractures,which could significantly increase the serum ALP level and reduce the levels of TNF-α and TGF-β.

Objective:To investigate the diagnostic value of circular RNA circ_100367 in thyroid cancer (THCA) and its relationship with immune-related factors.Methods:According to the data chip provided by the National Center for Biotechnology Information (NCBI) website, the differentially expressed circRNAs in THCA were analyzed, then circ_100367 was included in this study. The serum of 175 THCA patients and healthy people were collected, and the expression levels of circ_100367 and its linear transcript DCAF8 mRNA in serum samples were detected by qRT-PCR, and the correlation between circ_100367 and DCAF8 was calculated. The correlation between the expression of circ_100367 and the clinicopathological characteristicsof the patients, immune infiltration level and immunosuppressive factor PD-1 was analyzed.Results:Compared with serum of healthy people (1.00±0.37) , expression level of circ_100367 in serum of THCA patients was significantly increased (1.37±0.41) ( t=8.80, P<0.001) , and there was no significant difference in DCAF8 mRNA expression ( t=1.67, P=0.095) , but circ_100367 was positively correlated with DCAF8 mRNA expression ( r=0.17, P=0.028) . Analysis of expression and clinicopathological characteristics of circ_100367 showed that compared with patients in M0 group (1.26±0.40) , circ_100367 was overexpressed in M1 and Mx patients (1.43±0.40) ( t=2.63, P=0.009) ; compared with N0 patients (1.24±0.36) , circ_100367 was overexpressed in serum of N1 and Nx patients (1.45±0.42) ( t=3.48, P=0.001) ; compared with serum of patients with negative lymph node detection (1.28±0.36) , circ_100367 was overexpressed in serum of positive patients (1.42±0.43) ( t=2.14, P=0.034) ; compared with T1+T2 stage patients (1.30±0.37) , circ_100367 expression was overexpressed in serum ofT3+T4 patients (1.40±0.43) ( t=2.22, P=0.028) . Analysis of the expression and immune infiltration levels of circ_100367 found that highly expressed circ_100367 was associated with CD8+ T cells ( r=0.25, P=0.024) , macrophages ( r=0.22, P=0.038) , CD4+ T cells ( r=0.25, P=0.020) and B cell ( r=0.23, P=0.033) levels. The expression of circ_100367 was also positively correlated with the immunosuppressive factor PD-1 ( r=0.19, P=0.011) . Conclusion:circ_100367 can be used as a marker for the diagnosis of THCA and its expression is strongly correlated with immune-related factors.

Objective:To explore the effectiveness and safety of tirofiban in patients with reocclusive ischemic stroke after intravenous thrombolysis with alteplase.Methods:Eighty-four patients with re-occlusive ischemic stroke after intravenous thrombolysis with alteplase, admitted to our hospital from January 2018 to May 2020, were prospectively chosen; these patients were divided into tirofiban group and routine (non-tirofiban) group ( n=42). In addition to thrombolysis, patients in the routine group received intensive lipid-lowering, collateral circulation improvement, blood glucose control, and early rehabilitation therapy; after thrombolysis for 24 h, patients without intracranial hemorrhage were given oral aspirin, 0.1 g/d, for 90 d. After thrombolysis and re-occlusion, patients in the tirofiban group were intravenously pumped with 0.4 μg/(kg·min), which was changed to 0.1 μg/(kg·min) after 30 min for 24 h; at 24 h after thrombolysis, brain CT was reexamined: tirofiban was discontinued for patients with intracranial hemorrhage, and intravenous pumping of tirofiban was continued for patients without intracranial hemorrhage for 24 h. Effectiveness was evaluated by comparing the general clinical data, National Institutes of Health Stroke Scale (NIHSS) scores 7 d after treatment, and modified Rankin Scale (mRS) scores 90 d after treatment between the two groups. Safety was assessed by comparing the intracranial hemorrhage, symptomatic intracranial hemorrhage, and mortality within 90 d of treatment between the two groups. Results:There were no significant differences in age, gender, underlying diseases, risk factors, baseline NIHSS scores, time from onset to start of treatment, infarction sites, and TOAST classification between the 2 groups ( P>0.05). NIHSS scores 7 d after treatment ([10.05±4.73] min vs. [7.93±4.68] min), mRS scores 90 d after treatment (3.48±1.48 vs.2.55±1.93), and good prognosis rate 90 d after treatment (21.4% vs. 42.9%) showed significant differences between the routine group and tirofiban group ( P<0.05). In terms of safety, there were no significant differences in intracranial hemorrhage rate (4.76% vs. 7.14%), symptomatic intracranial hemorrhage incidence (2.38% vs. 2.38%) and mortality (2.38% vs. 2.38%) between the 2 groups ( P>0.05). Conclusion:It is safe and effective for tirofiban in patients with re-occlusive ischemic stroke after intravenous thrombolysis with alteplase.

Objective　To investigate N terminal pro B type natriuretic peptide (NT-proBNP),glial fibrillary acidic protein (GFAP)and hypoxia inducible factor-1 (hypoxia inducible factor-1α,HIF-1α) expression and there significance in inflammatory injury in patients with cerebral hemorrhage.Methods　We selected 80 patients with acute intracerebral hemorrhage treated in our hospital from January 2018 to December 2019 as the observation group and 80 healthy people who underwent physical examination in our hospital in the same period as the control group.After routine treatment,NT-proBNP,GFAP and HIF-1α in patients serum and cerebrospinal fluid were detectedα、Tumor necrosis factor-α(TNF-α) interleukin-6 (IL-6),and correlation analysis was carried out.Results　NT-proBNP,GFAP and HIF-1α in serum and cerebrospinal fluid of patients in the observation group、TNF-α and IL-6 levels in the control group were higher than those in the control group (P<0.05).NT-proBNP,GFAP and HIF-1α in serum and cerebrospinal fluid of the observation group after treatment,as well as TNF-α and IL-6 levels were lower than those before treatment (P<0.05).NT-proBNP,GFAP and HIF-1α in serum and cerebrospinal fluid increased with the aggravation of the disease、TNF-α and IL-6 levels were positively correlated with the degree of intracerebral hemorrhage (P<0.05).NT-proBNP,GFAP and HIF-1α in serum and cerebrospinal fluid were associated with inflammatory injury in intracerebral hemorrhage.There was a significant positive correlation with IL-6 level (P<0.05).NT-proBNP,GFAP and HIF-1α.It was closely related to inflammatory injury in patients with intracerebral hemorrhage and was an independent risk factor for intracerebral hemorrhage complicated with inflammatory injury (P<0.05).Conclusion　The levels of NT-proBNP,GFAP and HIF-1α are closely related to inflammatory injury and prognosis in patients with cerebral hemorrhage.The detection of NT-proBNP,GFAP and HIF-1α levels has certain clinical value in judging the disease and prognosis.

Objective:This study aimed to explore the status of radiological Kashin-Beck disease (KBD) among school-aged children in Chamdo City, Tibet, through a 3-year monitoring survey, providing epidemiological evidence for prevention and control strategies.Methods:The target areas for this study were Luolong, Bianba, and Basu counties in Chamdo City, Tibet Autonomous Region, identified as having the most severe historical cases of KBD. Children aged 7-12 years attending school were enrolled as study subjects. Anteroposterior X-ray films of the right-hand were taken, and radiological diagnoses were made based on the "Diagnosis of Kashin-Beck Disease" criteria (WS/T 207-2010). Two experienced researchers independently reviewed the X-rays, and intra- and inter-group consistency were assessed using weighted Kappa values and percentage agreement. Cross-sectional surveys were conducted in 2017 and 2020 to describe the X-ray detection rates of KBD, and logistic regression analysis was employed to construct a predictive model of risk factors for radiological KBD cases.Results:In 2017, a total of 5,711 children aged 7-12 years in Chamdo City, Tibet, participated in the baseline cross-sectional survey (average age 9.2 years, 48.0% female), with 28 cases of radiological KBD. The age- and gender-standardized prevalence rate was 0.527%. In 2020, 6,771 participants (average age 9.3 years, 49.5% female) underwent a second cross-sectional survey, with 9 cases of radiological KBD and a standardized prevalence rate of 0.134%. Logistic regression analysis indicated that older age [ OR=2.439, 95% CI(1.299, 4.580), P=0.006] and female gender [ OR=8.157, 95% CI(1.016, 65.528), P=0.048] were independent risk factors for radiological KBD cases. Conversely, higher residential altitude, under the premise of Tibet's high altitude, was a protective factor [ OR=0.995, 95% CI(0.990, 0.999), P=0.032). Conclusion:The radiographically positive detection rate of KBD among school-aged children in Chamdo City, Tibet Autonomous Region, is at an extremely low level and showing a declining trend, reaching the historical standard in 2020. Considering the absence of positive signs in affected children, it suggests that local KBD has been effectively eliminated.

Osteoporotic thoracolumbar fracture in the elderly will seriously reduce their quality of life and life expectancy. For osteoporotic thoracolumbar fracture in the elderly, spinal reconstruction is necessary, which should comprehensively consider factors such as the physical condition, fracture type, clinical characteristics and osteoporosis degree. While there lacks relevant clinical norms or guidelines on selection of spinal reconstruction strategies. In order to standardize the concept of spinal reconstruction for osteoporotic thoracolumbar fracture in the elderly, based on the principles of scientificity, practicality and progressiveness, the authors formulated the Clinical guideline for spinal reconstruction of osteoporotic thoracolumbar fracture in elderly patients ( version 2022), in which suggestions based on evidence of evidence-based medicine were put forward upon 10 important issues related to the fracture classification, non-operative treatment strategies and surgical treatment strategies in spinal reconstruction after osteoporosis thoracolumbar fracture in the elderly, hoping to provide a reference for clinical treatment.

Drug optimization, which improves drug potency/specificity by structure‒activity relationship (SAR) and drug-like properties, is rigorously performed to select drug candidates for clinical trials. However, the current drug optimization may overlook the structure‒tissue exposure/selectivity-relationship (STR) in disease-targeted tissues vs. normal tissues, which may mislead the drug candidate selection and impact the balance of clinical efficacy/toxicity. In this study, we investigated the STR in correlation with observed clinical efficacy/toxicity using seven selective estrogen receptor modulators (SERMs) that have similar structures, same molecular target, and similar/different pharmacokinetics. The results showed that drug's plasma exposure was not correlated with drug's exposures in the target tissues (tumor, fat pad, bone, uterus), while tissue exposure/selectivity of SERMs was correlated with clinical efficacy/safety. Slight structure modifications of four SERMs did not change drug's plasma exposure but altered drug's tissue exposure/selectivity. Seven SERMs with high protein binding showed higher accumulation in tumors compared to surrounding normal tissues, which is likely due to tumor EPR effect of protein-bound drugs. These suggest that STR alters drug's tissue exposure/selectivity in disease-targeted tissues vs. normal tissues impacting clinical efficacy/toxicity. Drug optimization needs to balance the SAR and STR in selecting drug candidate for clinical trial to improve success of clinical drug development.