Objective To observe the temporary loss(re-falling)of knee range of motion(ROM)during rehabilitation after arthroly-sis for post-traumatic knee stiffness,and analyze the factors related to it. Methods From July,2016 to September,2019,64 patients(68 knees)in Beijing Bo'ai Hospital accepted minimally inva-sive arthrolysis for post-traumatic knee stiffness,and were followed up for twelve months.ROM of flexion and extension of knee was measured before operation,and one,six and twelve weeks,and six and twelve months af-ter operation;while they were asssessed with Hospital for Special Surgery Knee Score(HSS).Multivariate Logis-tic regression was performed on re-falling. Results The ROM and HSS score improved as a whole after operation;however,HSS score improved constantly,but ROM decreased six weeks after operation compared with that one weeks after operation,involving 46 knees of 44 cases.Arthrolysis longer than 12 months from primary injuries,multiple complicated fracture and history of infection were the risk factors for re-falling(OR＞8.058,P＜0.05). Conclusion Minimally invasive arthrolysis is effective on knee function after arthrolysis for post-traumatic knee stiff-ness.However,re-falling of ROM may happen during rehabilitation.Delay of operation,multiple complicated fracture and history of infection may increase the risk of re-falling.

Objective:To analyze the drug resistance characteristics of Klebsiella pneumoniae in the nasopharynx of hospitalized patients in North China from 2022 to 2023. Methods:From November 2022 to July 2023, nasopharyngeal swabs were collected from 100 inpatients in Affiliated Hospital of North China University of Science and Technology, and Klebsiella pneumoniae was isolated and cultured. At the same time, the clinical data of the patients were collected, including gender, age, department, clinical diagnosis of disease type, etc. The minimum inhibitory concentration of strains was detected by an automatic bacterial drug sensitivity system. The drug resistance genes, ST types, capsule serotypes and population structure of the strains were analyzed by whole genome sequencing and data analysis. Results:Klebsiella pneumoniae was isolated from 55 nasopharyngeal swabs of 100 inpatients(55.00%). Among the 55 inpatients with Klebsiella pneumoniae in the nasopharynx, 70.91% (39/55) were male, with an age distribution concentrated between 61 and 80 years old (58.18%, 32/55), and 50.91% (28/55) were in intensive care units (ICU). The main underlying disease type was nervous system disease (49.09%, 27/55). The results of drug sensitivity showed that the non-susceptibility rates of 55 strains of Klebsiella pneumoniae to cephalosporins, quinolones, aztreonam and nitrofurantoin were all more than 80.00%. Twenty-eight carbapenem-resistant Klebsiella pneumoniae strains (50.91%), 47 extended-spectrum β-lactamase producing strains (85.45%), and 48 multi-drug-resistant strains (87.27%) were detected. A total of 11 antibiotic resistance genes were detected, including carbapenems (carrying rate 76.36%) and extended-spectrum β-lactamase (carrying rate 96.36%). The 55 strains could be divided into 17 ST types, and the most common type was ST11 (25.45%). The 55 strains were divided into 18 capsular serotypes, among which K102 was the most prevalent (23.64%). OXA-1_ST307_K102 (21.82%) and KPC-2_ST5492_K125 (18.18%) were the dominant clones, distributed in the Department of Neurosurgery and ICU. The result of whole genome sequence analysis showed that there were four clusters with high homology among the 55 strains. The strains from the ICU formed two independent clusters, and strains from the Neurology ICU and Neurosurgery department formed one cluster respectively. Conclusion:The carrying rate of Klebsiella pneumoniae in the nasopharynx of inpatients is high, and the drug resistance of the strains is serious. There are many types of drug-resistant genes.

Objective:To analyze the drug resistance characteristics of Klebsiella pneumoniae in the nasopharynx of hospitalized patients in North China from 2022 to 2023. Methods:From November 2022 to July 2023, nasopharyngeal swabs were collected from 100 inpatients in Affiliated Hospital of North China University of Science and Technology, and Klebsiella pneumoniae was isolated and cultured. At the same time, the clinical data of the patients were collected, including gender, age, department, clinical diagnosis of disease type, etc. The minimum inhibitory concentration of strains was detected by an automatic bacterial drug sensitivity system. The drug resistance genes, ST types, capsule serotypes and population structure of the strains were analyzed by whole genome sequencing and data analysis. Results:Klebsiella pneumoniae was isolated from 55 nasopharyngeal swabs of 100 inpatients(55.00%). Among the 55 inpatients with Klebsiella pneumoniae in the nasopharynx, 70.91% (39/55) were male, with an age distribution concentrated between 61 and 80 years old (58.18%, 32/55), and 50.91% (28/55) were in intensive care units (ICU). The main underlying disease type was nervous system disease (49.09%, 27/55). The results of drug sensitivity showed that the non-susceptibility rates of 55 strains of Klebsiella pneumoniae to cephalosporins, quinolones, aztreonam and nitrofurantoin were all more than 80.00%. Twenty-eight carbapenem-resistant Klebsiella pneumoniae strains (50.91%), 47 extended-spectrum β-lactamase producing strains (85.45%), and 48 multi-drug-resistant strains (87.27%) were detected. A total of 11 antibiotic resistance genes were detected, including carbapenems (carrying rate 76.36%) and extended-spectrum β-lactamase (carrying rate 96.36%). The 55 strains could be divided into 17 ST types, and the most common type was ST11 (25.45%). The 55 strains were divided into 18 capsular serotypes, among which K102 was the most prevalent (23.64%). OXA-1_ST307_K102 (21.82%) and KPC-2_ST5492_K125 (18.18%) were the dominant clones, distributed in the Department of Neurosurgery and ICU. The result of whole genome sequence analysis showed that there were four clusters with high homology among the 55 strains. The strains from the ICU formed two independent clusters, and strains from the Neurology ICU and Neurosurgery department formed one cluster respectively. Conclusion:The carrying rate of Klebsiella pneumoniae in the nasopharynx of inpatients is high, and the drug resistance of the strains is serious. There are many types of drug-resistant genes.

Objective:To investigate the early clinical characteristics of elderly patients with severe burns and the risk factors on prognosis.Methods:This study was a retrospective case series study. Clinical data of 124 elderly patients with severe burns who met the inclusion criteria and were admitted to the 12 hospitals from January 2015 to December 2020 were collected, including 4 patients from the Fourth People's Hospital of Dalian, 5 patients from Fujian Medical University Union Hospital, 22 patients from Guangzhou Red Cross Hospital of Jinan University, 5 patients from Heilongjiang Provincial Hospital, 27 patients from the First Affiliated Hospital of Naval Medical University, 9 patients from the First Affiliated Hospital of Nanchang University, 10 patients from Affiliated Hospital of Nantong University, 9 patients from Tongren Hospital of Wuhan University & Wuhan Third Hospital, 12 patients from the 924 th Hospital of PLA, 6 patients from Zhangjiagang First People's Hospital, 4 patients from Taizhou Hospital of Zhejiang Province, and 11 patients from Zhengzhou First People's Hospital. The patients' overall clinical characteristics, such as gender, age, body mass index, total burn area, full-thickness burn area, inhalation injury, causative factors, whether combined with underlying medical diseases, and admission time after injury were recorded. According to the survival outcome within 28 days after injury, the patients were divided into survival group (89 cases) and death group (35 cases). The following data of patients were compared between the two groups, including the basic data and injuries (the same as the overall clinical characteristics ahead); the coagulation indexes within the first 24 hours of injury such as prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time, D-dimer, fibrinogen degradation product (FDP), international normalized ratio (INR), and fibrinogen; the blood routine indexes within the first 24 hours of injury such as white blood cell count, platelet count, neutrophil-to-lymphocyte ratio, monocyte count, red blood cell count, hemoglobin, and hematocrit; the organ function indexes within the first 24 hours of injury such as direct bilirubin, total bilirubin, urea, serum creatinine, aspartate aminotransferase, alanine aminotransferase, total protein, albumin, globulin, blood glucose, triglyceride, total cholesterol, alkaline phosphatase, creatine kinase, electrolyte indexes (potassium, sodium, chlorine, calcium, magnesium, and phosphorus in blood), uric acid, myoglobin, and brain natriuretic peptide; the infection and blood gas indexes within the first 24 hours of injury such as procalcitonin, C-reactive protein, pH value, oxygenation index, base excess, and lactate; treatment such as whether conducted with mechanical ventilation, whether conducted with continuous renal replacement therapy, whether conducted with anticoagulation therapy, whether applied with vasoactive drugs, and fluid resuscitation. The analysis was conducted to screen the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns. Results:Among 124 patients, there were 82 males and 42 females, aged 60-97 years, with body mass index of 23.44 (21.09, 25.95) kg/m 2, total burn area of 54.00% (42.00%, 75.00%) total body surface area (TBSA), and full-thickness burn area of 25.00% (10.00%, 40.00%) TBSA. The patients were mainly combined with moderate to severe inhalation injury and caused by flame burns. There were 43 cases with underlying medical diseases. The majority of patients were admitted to the hospital within 8 hours after injury. There were statistically significant differences between patients in the 2 groups in terms of age, total burn area, full-thickness burn area, and inhalation injury, and PT, APTT, D-dimer, FDP, INR, white blood cell count, platelet count, urea, serum creatinine, blood glucose, blood sodium, uric acid, myoglobin, and urine volume within the first 24 hours of injury (with Z values of 2.37, 5.49, 5.26, 5.97, 2.18, 1.95, 2.68, 2.68, 2.51, 2.82, 2.14, 3.40, 5.31, 3.41, 2.35, 3.81, 2.16, and -3.82, respectively, P<0.05); there were statistically significant differences between two groups of patients in whether conducted with mechanical ventilation and whether applied with vasoactive drugs (with χ2 values of 9.44 and 28.50, respectively, P<0.05). Age, total burn area, full-thickness burn area, serum creatinine within the first 24 hours of injury, and APTT within the first 24 hours of injury were the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns (with odds ratios of 1.17, 1.10, 1.10, 1.09, and 1.27, 95% confidence intervals of 1.03-1.40, 1.04-1.21, 1.05-1.19, 1.05-1.17, and 1.07-1.69, respectively, P<0.05). Conclusions:The elderly patients with severe burns had the injuries mainly from flame burns, often accompanied by moderate to severe inhalation injury and enhanced inflammatory response, elevated blood glucose levels, activated fibrinolysis, and impaired organ function in the early stage, which are associated with their prognosis. Age, total burn area, full-thickness burn area, and serum creatinine and APTT within the first 24 hours of injury are the independent risk factors for death within 28 days after injury in this population.

Objective To investigate the effect and mechanism of sodium cantharidate on the proliferation,migration and invasion of esophageal carcinoma EC9706 cells.Methods Esophageal cancer EC9706 cells were randomly divided into blank control group,low-dose sodium cantharidate group,medium-dose sodium cantharidate group,high-dose sodium canthari-date group and cisplatin group.The EC9706 cells in the low-,medium-and high-dose sodium cantharidate groups were given fi-nal mass concentration of 1.0,2.5 and 5.0 mg·L-1 sodium cantharidate intervention,respectively.The EC9706 cells in the cisplatin group were treated with the final mass concentration of 140 mg·L-1 cisplatin,and the cells in the control group was cultured in Dulbecco's modified Eagle's medium.The cell proliferation rate in each group was detected by cell counting reagent-8 method,the mobility of EC9706 cells in each group was detected by scratch test,the invasion rate of EC9706 cells in each group was detected by Transwell method,and the levels of Wnt3a and β-catenin mRNA in EC9706 cells in each group were detected by real-time quantitative polymerase chain reaction method,and the levels of Wnt3a and β-catenin protein in EC9706 cells in each group were detected by Western blot.Results At 24,48 and 72 h of cultivation,the proliferation rate of EC9706 cells in the low-dose sodium cantharidate group,medium-dose sodium cantharidate group,high-dose sodium canthari-date group and cisplatin group was significantly lower than that in the blank control group(P＜0.05);the proliferation rate of EC9706 cells in the low-dose sodium cantharidate group and medium-dose of sodium cantharidate group was significantly higher than that in the high-dose sodium cantharidate group and cisplatin group(P＜0.05);the proliferation rate of EC9706 cells in the low-dose sodium cantharidate group was significantly higher than that in the medium-dose sodium cantharidate group(P＜0.05);there was no significant difference in the proliferation rate of EC9706 cells between the high-dose sodium cantharidate group and cisplatin group(P＞0.05);the proliferation rate of EC9706 cells in the low-dose sodium cantharidate group,medium-dose sodium cantharidate group,high-dose sodium cantharidate group and cisplatin group was significantly decreased with the extension of culture time(P＜0.05).The mobility rate and invasion rate of EC9706 cells in the low-dose sodium cantharidate group,medium-dose sodium cantharidate group,high-dose sodium cantharidate group and cisplatin group were significantly lower than those in the blank control group(P＜0.05);the mobility rate and invasion rate of EC9706 cells in the low-dose sodium cantharidate group and medium-dose sodium cantharidate group were significantly higher than those in the high-dose sodium cantharidate group and cisplatin group(P＜0.05);the migration rate and invasion rate of EC9706 cells in the low-dose sodium cantharidate group were significantly higher than those in the medium-dose sodium cantharidate group(P＜0.05);there was no significant difference in the mobility rate and invasion rate of EC9706 cells between the high-dose sodium cantharidate group and cisplatin group(P＞0.05).The relative expression levels of Wnt3a and β-catenin mRNA and protein in EC9706 cells in the low-dose sodium cantharidate group,medium-dose sodium cantharidate group,high-dose sodium cantharidate group and cisplatin group were significantly lower than those in the blank control group(P＜0.05);the relative expression levels of Wnt3a and β-catenin mRNA and protein in EC9706 cells in the low-dose sodium cantharidate group and medium-dose sodium cantharidate group were significantly higher than those in the high-dose sodium cantharidate group and cisplatin group(P＜0.05);the relative expressions levels of Wnt3a and β-catenin mRNA and protein in EC9706 cells in the low-dose sodium cantharidate group were significantly higher than those in the medium-dose sodium cantharidate group(P＜0.05);there was no significant difference in the relative expression levels of Wnt3a and β-catenin mRNA and protein in EC9706 cells between the high-dose sodium cantharidate group and cisplatin group(P＞0.05).Conclusion Sodium cantharidate can significantly inhibit the proliferation,migration and invasion of esophageal carcinoma EC9706 cells,and its mechanism may be related to the inhibition of the Wnt3a/β-catenin pathway.

ObjectiveTo observe the architectural parameter changes of the muscles around the knee in middle-aged and elderly women with early knee osteoarthritis (KOA) by musculoskeletal ultrasound, and to clarify the indicators of muscles that affect early KOA. MethodsFrom January to August, 2022, 20 healthy middle-aged and elderly healthy women (controls) and 20 middle-aged and elderly women with unilateral early KOA (KOA group) were recruited through Beijing Bo'ai Hospital, to measure muscle thickness of the popliteus muscle, the muscle thickness and the pennation angle of the quadriceps, as rectus femoris, vastus intermedius, vastus lateralis, vastus medialis longus and vastus medialis oblique. ResultsCompared with the healthy limb of KOA group, and the controls, the muscle thickness of vastus medialis longus, vastus medialis oblique and popliteus muscle of the affected limb of KOA group became thinner (t > 2.133, P < 0.05); the proportion of thickness of vastus medialis oblique to thickness of vastus lateralis became smaller (t > 3.660, P < 0.05). The pennation angle was smaller in the affected limb of KOA group than in the matched dominant side of the controls (t = 3.101, P < 0.05). Logistic regression analysis showed that the muscle thickness of vastus medialis oblique (OR = 0.235, 95%CI 0.068 to 0.805, P = 0.021) and popliteus muscle (OR = 0.387, 95%CI 0.152 to 0.980, P = 0.045) were related to the onset of early KOA. ConclusionThe thickness of vastus medialis longus, vastus medialis oblique and popliteus muscle decrease, and the balance of the strength of vastus medialis oblique and vastus lateralis weakens in the affected limbs of the middle-aged and elderly women with early KOA. The thickness of vastus medialis oblique and popliteus muscle are protective factors for onset of KOA.

Pulmonary fibrosis (PF) is the pathological structure of incurable fibroproliferative lung diseases that are attributed to the repeated lung injury-caused failure of lung alveolar regeneration (LAR). Here, we report that repetitive lung damage results in a progressive accumulation of the transcriptional repressor SLUG in alveolar epithelial type II cells (AEC2s). The abnormal increased SLUG inhibits AEC2s from self-renewal and differentiation into alveolar epithelial type I cells (AEC1s). We found that the elevated SLUG represses the expression of the phosphate transporter SLC34A2 in AEC2s, which reduces intracellular phosphate and represses the phosphorylation of JNK and P38 MAPK, two critical kinases supporting LAR, leading to LAR failure. TRIB3, a stress sensor, interacts with the E3 ligase MDM2 to suppress SLUG degradation in AEC2s by impeding MDM2-catalyzed SLUG ubiquitination. Targeting SLUG degradation by disturbing the TRIB3/MDM2 interaction using a new synthetic staple peptide restores LAR capacity and exhibits potent therapeutic efficacy against experimental PF. Our study reveals a mechanism of the TRIB3-MDM2-SLUG-SLC34A2 axis causing the LAR failure in PF, which confers a potential strategy for treating patients with fibroproliferative lung diseases.

Langerhans cell histiocytosis(LCH)and Langerhans cell sarcoma(LCS)are characterized by clone proliferation of Langerhans-type cells, which may occur concurrently or sequentially with T-cell acute lymphoblastic leukemia (T-ALL) and other Lymphoid neoplasms. A 15-year old female patient diagnosed with T-ALL developed LCH involving multiple systems during maintenance chemotherapy of T-AL. After treated with chemotherapy with improved result, the patient showed progression of the illness and refractory to the second-line treatment. We found c.G35A (p.G12D)mutation in the KRAS gene and used the targeted drug Trametinib for treatment. The treatment proved effective, leading to partial remission within a week. Three months after Trametinib treatment, the patient developed new lymphadenopathy. Biopsy revealed the existence of LCS. The disease progressed quickly, and the patient died 7 days after diagnosis of LCS. The case of patients with T-ALL then developing LCH and LCS sequentially is extraordinarily rare. The causes of the case is unclear and may be related to cell transdifferentiation, clonal evolution, and chemotherapy. Targeted drugs can contain this disease for a short time.

Objective:To understand the clinical characteristics and prognosis of Langerhans cell histiocytosis (LCH) with skin-limited lesion.Methods:A retrospective analysis was performed on clinical characteristics and prognosis of 16 skin-limited LCH patients, out of 578 LCH patients who were hospitalized in Beijing Children′s Hospital during December 2013 to June 2018.Results:A total of 16 skin-limited LCH cases, accounted for 2.7% of all 578 cases, were included.Among which, sex ratio (male vs.female) was 1.28∶1.00.Median ages of skin eruption occurrence and of diagnosis of the disease were 3.5 months (3 days to 2 years and 5 months) and 6 months (2 months 14 days to 2 years and 8 months) in this group.Among the 16 cases, seborrheic dermatitis-like lesions(11 cases, 68.7%) was the most common, and the trunk was most frequently involved[75.0% (12 cases)]. Serine/threonine protein kinase gene V600E [ BRAF (p.V600E)] mutation was detected in pathological specimens from 10 skin-limi-ted cases, with 9 cases being positive.Plasma samples from 5 positive cases were further detected for BRAF (p.V600E) mutation, and 4 positive results were gained.Of all 16 patients, 11 cases (68.7%) were treated.Remission were achieved in 3-6 months from treatment start in patients treated whether according to the Histiocyte Society′s LCH-2009 protocol for 25 weeks(6 cases, 37.5%), or with topical mometasonefuroate for 3 months (3 cases, 18.8%). Two patients(12.5%) with solitary cutaneous lesions underwent excision biopsy (one face and one prepuce) and were considered to be in remission immediately after surgery.None of these patients suffered from the recurrence of the disease.The remaining 5 patients (31.3%) with skin-limited LCH were just evaluated regularly, and achieved remission in 3-6 months of commencing observation.Among these untreated patients, 1 with consistently positive BRAF (p.V600E) mutation in plasma had bone involvement in the 24 th month of assessment, and was then treated based on the Histiocyte Society′s LCH-2009 Protocol.No clinical or imageological evidence supporting disease progression was found on this patient.Median follow-up period was 32.8 months (2.9-63.9 months). Except one patient, none of the rest cases had active disease till follow-up ended.Two-year event free survival(EFS) of this research was (92.3± 7.4)%.There was no significant difference between EFS of treated group and that of observation group( χ2=1.250, P=0.264). Conclusions:Skin-limited LCH often occurs in infants and newborns, with strong heterogeneity in clinical manifestations, laboratory indicators, and pathogenesis.Seborrheic dermatitis-like lesions were the most common cutaneous type.The prognosis of the patients is excellent despite progressing into multisystem involvement can be seen in a few patients.

Objective:To investigate the clinical and gene variant characteristics of benign familial infantile epilepsy in generations of three families.Methods:The clinical data of the three benign familial infantile epilepsy patients with PRRT2 gene variant who were diagnosed and their family members were collected from Children′s Hospital Affiliated to Zhengzhou University between 2018 and 2019. All coding exons from the patients and their parents were screened by targeted next-generation sequencing, and detected variants were verified by Sanger sequencing.Results:In all the patients, a cluster of seizures was observed before one year old,but interictal clinical conditions were normal. The electroencephalograms were all normal in interictal stage. The father of proband 1 presented with convulsion onset at the age of eight months and showed remission before one year old. The grandpa, mother and uncle of proband 2 also presented with convulsion onset in their babyhood of life and showed remission before one year old. The mother of proband 3 presented with convulsion onset in their babyhood of life and showed remission before three years old. Proband 1 carried heterozygous c.937G>C variant in the PRRT2 gene which is inherited from his father. Proband 2 carried c.1075_c.1076insC variant inherited from his mother. A deletion of PRRT2 gene exon 2 was detected in both of proband 3 and her mother. The three variants had not been reported in the Human Gene Mutation Database.Conclusions:Benign familial infantile epilepsy is a kind of inherited epilepsy characterized by early onset of seizure in babyhood with better prognosis, a cluster of focal seizures with or without secondary generalization, and cessation of seizure mostly before two or three years of age. The variants c.937G>C, c.1075_c.1076insC and the deletion of exon 2 in the PRRT2 gene have enriched the gene variant spectrum of benign familial infantile epilepsy.