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Miao-Miao Zhang, Xiao-Chun Yu, Feng-Li Lu, Ke-Ke Lu Department of Emergency, The Fifth People’s Hospital of Yuhang District, Hangzhou, Zhejiang, 311100, People’s Republic of ChinaCorrespondence: Ke-Ke LuDepartment of Emergency, The Fifth People’s Hospital of Yuhang District, Hangzhou, No. 60 Baojian Road of Linping Street, Yuhang District, Hangzhou, 311100, People’s Republic of ChinaTel +86 571 86163516Email lukekeht@163.comObjective: This study aimed to explore the application effect of lean management in rabies vaccination.Methods: Lean management in rabies vaccination was implemented from July 2020. A total of 2306 patients vaccinated from January to June 2020 were enrolled as routine management group, and 2718 patients vaccinated from July to November 2020 were enrolled as lean management group. The relationship between potential factors and rabies vaccination with 1:1 propensity score matching (PSM) was analysed. The compliance, waiting time for vaccination, and satisfaction of patients of routine and lean management group were statistically analyzed. The changes in the three indicators before and after the implementation and their application effects were compared.Results: Compliance rate in lean management group (98.72%) was significantly higher than that in routine management group (93.87%) (χ2=32.902, P< 0.001). The waiting time for vaccination was also significantly shortened (t = 9.209, P < 0.001), and the satisfaction of patients significantly improved (X2 = 39.611, P < 0.001).Conclusion: Implementing lean management in all aspects of rabies vaccination can significantly improve patient compliance and work efficiency of nursing staff and improve the patient medical experience.Keywords: lean management, rabies, vaccination, compliance, satisfaction rate

Yu-Xue Zhao,1 Xiao-Chun Yu,1 Jun-Hong Gao,1 Ming-Jiang Yao,2,3 Bing Zhu1 1Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, 100700, People’s Republic of China; 2Institute of Basic Medical Sciences, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, 100091, People’s Republic of China; 3Key Laboratory of Pharmacology of Chinese Materia Medica, Beijing, 100091, People’s Republic of ChinaCorrespondence: Yu-Xue Zhao; Bing ZhuInstitute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, No. 16 Dong-zhi-men-nei South Street, Dongcheng District, Beijing, 100700, People’s Republic of ChinaTel +86-10-64089363Email claricezhao@live.cn; zhubing@mail.cintcm.ac.cnAbstract: Paclitaxel-induced peripheral neuropathy (PIPN) is a common and intractable side effect of the conventional chemotherapeutic agent paclitaxel. Acupuncture has been reported as an effective alternative therapy in treatment of PIPN in both basic studies and clinical trials. However, there is a lack of comprehensive surveys to summarize the action of acupuncture in management of PIPN. In this review, we briefly demonstrate the basic pathology of PIPN, which includes the activation of ion channels, mitochondrial dysfunction, disruption of axonal transport and also neuro-inflammatory involvement. Meanwhile, we review both the clinical and basic studies as an emphasis to give a general overview of the therapeutic effect of acupuncture against PIPN. Finally, we summarize the current known mechanisms underlying the action of acupuncture against PIPN mainly at peripheral and spinal levels, which include various neurotransmitters, multiple receptors, different types of enzymes and molecules. In conclusion, acupuncture could be considered as a potential alternative therapy in treatment of PIPN, and further clinical and experimental studies are called for in the future.Keywords: paclitaxel, peripheral neuropathy, acupuncture

Yu-Xue Zhao, 1 Ming-Jiang Yao, 2, 3 Qun Liu, 1 Juan-Juan Xin, 1 Jun-Hong Gao, 1 Xiao-Chun Yu 1 1Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing 100700, People’s Republic of China; 2Institute of Basic Medical Sciences, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing 100091, People’s Republic of China; 3Key Laboratory of Pharmacology of Chinese Materia Medica, Beijing 100091, People’s Republic of ChinaCorrespondence: Yu-Xue Zhao; Xiao-Chun YuInstitute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Dongcheng District, Beijing 100700, People’s Republic of ChinaEmail claricezhao@live.cn; yuxc@mail.cintcm.ac.cnBackground and Purpose: Neuropathic pain is a major side-effect of paclitaxel (PTX) chemotherapy. Although the precise mechanisms responsible for this pain are unclear, the activation of neuroglia and upregulation of the TLR4/NF-κB pathway are known to be involved. In this study, we determined whether electroacupuncture (EA) could limit mechanical hypersensitivity resulting from the chemotherapeutic drug PTX in rats, and investigated the potential mechanisms involved.Methods: Rats intraperitoneally received a cumulative dose of 8 mg/kg PTX (2 mg/kg per day) or vehicle control on alternate days (day 0, 2, 4 and 6). EA treatment (10 Hz, 1 mA) was applied at bilateral ST36 acupoints in rats once every other day on days 0– 14. For sham EA, needles were inserted at ST36 acupoints without electrical stimulation. Mechanical allodynia was measured by mechanical withdrawal latency (MWL) of paws to a mechanical stimulus every 2 days. Protein expression of TLR4 and NF-κB p65, as well as TMEM119 and GFAP (indicators of microglia and astrocytes, respectively) in spinal cord was quantified by Western blot analysis. Levels of inflammatory cytokines IL-1β and TNF-α in spinal cord and serum were detected by ELISA.Results: Mechanical allodynia induced by PTX in both paws (right and left) of rats was significantly attenuated by EA but not sham EA treatment. In addition, EA, but not sham EA, inhibited the activation of both microglia (TMEM119) and astrocytes (GFAP) in lumbar spinal cord. Moreover, Western blot analysis revealed that protein expression of TLR4 and NF-κB in spinal cord was suppressed by EA but not sham EA treatment. PTX significantly increased inflammatory cytokines in spinal cord and serum, which were ameliorated by EA treatment but not by sham EA.Conclusion: These results indicate that EA treatment attenuates PTX-induced mechanical allodynia. The putative mechanism corroborating this finding could be related to the suppression of activated microglia and astrocytes in spinal cord, as well as the inhibition of the activated TLR4/NF-κB signaling pathway by EA treatment.Keywords: electroacupuncture, neuropathic pain, paclitaxel, TLR4/NF-κB pathway, neuroglia

Background: Surgical treatment for hinge failure in mega-prosthesis continues to be a challenge. This study introduces a new method for treating hinge failure by using a unilateral prosthesis and hinge revision., Case Presentation: We here present two patients who underwent mega-prosthesis reconstruction after resection of osteosarcoma in the distal femur. To address the issue of knee hyperextension after mega-prosthesis reconstruction, one patient underwent three revision surgeries, two surgeries were performed using the original hinge, and one surgery involved a newly designed hinge. To resolve the problem of dislocation, one patient underwent three revisions, with the first two revisions not involving hinge replacement and the third revision involving a newly designed hinge. Two replacements of unilateral prosthesis and hinge renovations were successful., Conclusions: Unilateral prosthesis and newly designed hinge device revision are effective in treating the failure of old-fashioned mega-prosthesis hinges., (© 2024 The Author(s). Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Background: Revision of tumor-type prosthetic fractures is very challenging in clinical work. Traditional repair methods may not be able to meet the needs of complex cases or cause greater bone damage. Therefore, more effective and reliable solutions need to be found., Case Presentation: This study presents a novel revision technique for managing fractures of tumor-type total elbow prostheses. A 57-year-old female patient was diagnosed with a left distal humeral bone tumor accompanied by pathological fracture and underwent customized tumor-type total elbow prosthesis arthroplasty. After 5 years, she experienced pain and encountered difficulty in flexing the left elbow while lifting heavy objects. The X-ray examination revealed a fracture of the distal humeral prosthesis. As a response, the elbow joint was initially explored, and the damaged component of the prosthesis was extracted. Subsequently, we utilized 3D printing technology to design a split-piece sleeve prosthesis and effectively restored the fractured left distal humerus implant. During the 2-year follow-up, The X-ray demonstrated satisfactory positioning of the prosthesis, which remained securely affixed without any indications of loosening. The Mayo Elbow Performance Score (MEPS) reached 80 points, the Musculoskeletal Tumor Society (MSTS) attained a score of 28 points, and the range of motion of the elbow was measured between 25° and 110°, revealing favorable functional outcomes., Conclusion: The utilization of a 3D printed split-piece sleeve prosthesis presents a viable clinical treatment strategy for addressing fractures in tumor-type elbow prostheses., (© 2024 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

The aim of this study was to clarify the anti-fatigue effect of peanut oligopeptides (POPs) in mice and to investigate its possible underlying mechanism. A total of 150 male ICR mice were randomly assigned into five groups: control, whey protein (0.50 g/kg·bw), and three peanut peptide groups (0.25, 0.50, and 1.00 g/kg·bw). All the mice were treated with intra-gastric administration for 30 days. Following the intervention, a weight-loaded swimming test, blood lactate concentration, glycogen content, the activities of antioxidant factors and energy metabolism enzymes, and the function of mitochondria in the skeletal muscle were examined. The results show that POP intervention significantly prolonged the exhaustive swimming time, decreased blood lactate concentration levels, regulated the process of energy metabolism, and increased the level of antioxidant enzymes, muscle glycogen, and expressions of mtTFA and NRF-1 in the mitochondria of the gastrocnemius muscle. The results suggest that POPs produce an anti-fatigue effect in the animals, and they may exert this effect through the mechanism of improving the animals' antioxidant capacity to reduce oxidative damage levels and regulating the process of energy metabolism.

Background: Improvements in screening and imaging technologies and treatment of liver disease have influenced the trend in diagnosis for stage I liver cancer. In this article, recent trends in age, incidence, tumour size, and survival of different stages of liver cancer are analysed., Methods: Surveillance, Epidemiology, and end results data from the National Cancer Institute were used to analyse trends in age-adjusted incidence rate, mean tumour size at diagnosis, age at diagnosis, and 5-year survival probability for stage I liver cancer., Results: Stage I cases of liver cancer increased most tremendously over the study period, with a greater increase from 2004 to 2012 following a smaller increase from 2012 to 2015. Moreover, the mean age of stage I liver cancer increased by 1.72 years from 2004 to 2015. The 5-year-overall survival for stage I liver cases worsened from 97.9% to 83.7% from 2004 to 2011, whereas the 10-year survival probability for stage I cases worsened from 97.3% in 2004 to 79.6% in 2006. Comparing with higher stage cases, stage I liver cancer were more likely to be females, be married, live in metro areas, receive chemotherapy, and carry medical insurance., Conclusions: The incidence of stage I liver cancer has increased over the study period, with an increase in age of diagnosis, decrease in tumour size, and generally stable overall survival rate with slight decrease. These trends emphasized the importance of early detection of liver cancer and regular screening and better treatment for high-risk populations.RESEARCH HIGHLIGHTSImprovements in screening and imaging technologies and treatment of liver disease have influenced the trend in diagnosis for liver cancer.Stage I cases of liver cancer increased most tremendously over the study period, with a greater increase from 2004 to 2012 following a smaller increase from 2012 to 2015.These trends emphasized the importance of early detection of liver cancer and regular screening and better treatment for high-risk populations.

Background: Surgical treatment for recurrent bone tumors in the extremities still presents a challenge. This study was designed to evaluate the clinical value of microwave ablation in the treatment of recurrent bone tumors., Methods: We present 15 patients who underwent microwave ablation for recurrent bone tumors during the last 7 years. The following parameters were analyzed for outcome evaluation: general condition, surgical complications, local disease control, overall survival, and functional score measured using the Musculoskeletal Tumor Society (MSTS) 93 scoring system., Results: Percutaneous microwave ablation in one patient with osteoid osteoma and another with bone metastasis resulted in postoperative pain relief. Thirteen patients received intraoperative microwave ablation before curettage or resection, including those with giant cell tumors of bone (6), chondroblastoma (2), osteosarcoma (2), undifferentiated sarcoma (1), and bone metastases (2). All patients achieved reasonable local tumor control in the mean follow-up of 29.9 months. The functional score was 24.1 for the 15 patients 6 months after the operation. Four patients had tumor metastasis and died, whereas 3 patients with tumors survived, and the remaining 8 patients without the disease survived., Conclusions: Microwave ablation represents an optional method for local control in treating recurrent bone tumors in the extremities., (© 2022. The Author(s).)

Objective: This study proposes a system for classifying the aseptic loosening of distal femoral endoprostheses and discusses reconstruction methods for revision surgery, based on different classification types., Methods: We retrospectively analyzed the data of patients who received revision surgery for aseptic loosening in distal femoral tumor endoprosthesis from January 2008 to December 2020 at 3 bone tumor treatment centers in China. Based on the patient imaging data, we proposed a classification system for the aseptic loosening of distal femoral endoprostheses and discussed its revision surgery strategy for various bone defects., Results: A total of 31 patients were included in this study, including 21 males and 10 females aged 15-75 y (average: 44.3 y). First-revision surgery was performed on 24 patients, whereas second-revision surgery was conducted on 7 patients. The 31 patients were classified into different types based on the degree of aseptic loosening: Type I, 12 patients (38.7%); Type IIa, 7 patients (22.5%); Type IIb, 7 patients (22.5%); Type III, 4 patient (12.9%); and Type IV, 1 patient (3.2%). For type I, 11 patients underwent revisions with standard longer-stem prostheses (one with the original prosthesis), and one patient had the original prosthesis plus cortical allograft strut. For type II (a and b), 10 patients underwent revisions with original prosthesis or longer-stem prosthesis and 4 patients combined with cortical allograft strut. For type III, one patient underwent revision with a longer-stem prosthesis and the other 3 patients with a custom short-stem prosthesis. For type IV, only one patient underwent revision with a custom short-stem prosthesis., Conclusions: Aseptic loosening of the distal femoral prosthesis can be divided into 4 types: type I, type II (a, b), type III and type IV. The reconstruction methods of our centers for different types of bone defects can offer some reference value in the revision of aseptic loosening., (© 2022. The Author(s).)

Background: Helicobacter pylori ( H. pylori ) infects about 50% of the world population and is the major cause of chronic gastritis, peptic ulcers, and gastric cancer. Chronic H. pylori infection induces gastric mucosal precancerous lesions mostly in adulthood, and it is debatable whether these pathological conditions can occur in childhood and adolescents as well. Since this is a critical issue to determine if intervention should be offered for this population group, we investigated the gastric mucosal precancerous lesions in pediatric patients in an area in central China with a high prevalence of H. pylori and gastric cancer., Aim: To investigate the relationship of H. pylori infection and gastric mucosal precancerous lesions in children and adolescents in central China., Methods: We screened 4258 ward-admitted children and adolescent patients with upper gastrointestinal symptoms, and finally enrolled 1015 pediatric patients with H. pylori infection and endoscopic and histological data. H. pylori infection status was determined by rapid urease test and histopathological examination. Both clinical and pathological data were collected and analyzed retrospectively. Occurrence of gastric mucosal precancerous lesions, inflammatory activity and degree of inflammatory cell infiltration between H. pylori -positive and -negative groups were compared., Results: Among the 1015 eligible children and adolescents, the overall H. pylori infection rate was 84.14% (854/1015). The infection rate increased with age. The incidence of gastric mucosal precancerous lesions in H. pylori- infected children was 4.33% (37/854), which included atrophic gastritis (17 cases), intestinal metaplasia (11 cases) and dysplasia (9 cases). In H. pylori -negative patients, only 1 atrophic gastritis case [0.62%, (1/161)] was found ( P < 0.05). Active inflammation in H. pylori -infected patients was significantly higher than that in non-infected patients, and the H. pylori -infected group showed more severe lymphocyte and neutrophil granulocyte infiltration ( P < 0.001). In addition, endoscopy revealed that the most common findings in H. pylori -positive patients were antral nodularity, but in H. pylori -negative patients only superficial gastritis was observed., Conclusion: In children and adolescents, gastric mucosal precancerous lesions occurred in 4.33% of H. pylori- infected patients in central China. These cases included atrophic gastritis, intestinal metaplasia, and dysplasia. The data revealed an obvious critical issue requiring future investigation and intervention for this population group., Competing Interests: Conflict-of-interest statement: All authors declare that there are no conflicts of interests related to this work., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Helicobacter pylori ( H. pylori ) has characteristics of family cluster infection; however, its family-based infection status, related factors, and transmission pattern in central China, a high-risk area for H. pylori infection and gastric cancer, have not been evaluated. We investigated family-based H. pylori infection in healthy households to understand its infection status, related factors, and patterns of transmission for related disease prevention., Aim: To investigate family-based H. pylori infection status, related factors, and patterns of transmission in healthy households for related disease prevention., Methods: Blood samples and survey questionnaires were collected from 282 families including 772 individuals. The recruited families were from 10 selected communities in the greater Zhengzhou area with different living standards, and the family members' general data, H. pylori infection status, related factors, and transmission pattern were analyzed. H. pylori infection was confirmed primarily by serum H. pylori antibody arrays; if patients previously underwent H. pylori eradication therapy, an additional 13 C-urea breath test was performed to obtain their current infection status. Serum gastrin and pepsinogens (PGs) were also analyzed., Results: Among the 772 individuals examined, H. pylori infection rate was 54.27%. These infected individuals were from 246 families, accounting for 87.23% of all 282 families examined, and 34.55% of these families were infected by the same strains. In 27.24% of infected families, all members were infected, and 68.66% of them were infected with type I strains. Among the 244 families that included both husband and wife, spouse co-infection rate was 34.84%, and in only 17.21% of these spouses, none were infected. The infection rate increased with duration of marriage, but annual household income, history of smoking, history of alcohol consumption, dining location, presence of gastrointestinal symptoms, and family history of gastric disease or GC did not affect infection rates; however, individuals who had a higher education level showed lower infection rates. The levels of gastrin-17, PGI, and PGII were significantly higher, and PGI/II ratio was significantly lower in H. pylori -infected groups than in H. pylori -negative groups., Conclusion: In our study sample from the general public of central China, H. pylori infection rate was 54.27%, but in 87.23% of healthy households, there was at least 1 H. pylori -infected person; in 27.24% of these infected families, all members were infected. Type I H. pylori was the dominant strain in this area. Individuals with a higher education level showed significantly lower infection rates; no other variables affected infection rates., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: The objective is to observe the synergistic and attenuating effect of electroacupuncture (EA) on aconitine (ACO) in improving heart failure (HF) and to explore its underlying mechanism for calcium regulation., Methods: Twenty-four male Sprague-Dawley rats were randomly divided into four groups: normal control (NC) ( n  = 6), HF( n  = 6), ACO ( n  = 6), and ACO + EA ( n  = 6). The maximum rates of left ventricular pressure rising and declining (±dp/dtmax), arrhythmia, the left ventricular systolic pressure (LVSP), ejection fraction (LVEF), and fractional shortening (LVFS) were measured by physiological recorder and ultrasound, respectively. Protein expressions of sarcoplasmic/endoplasmic reticulum Ca 2+ ATPase (SERCA2a), phospholamban (PLB), and Na + -Ca 2+ exchange (NCX1) in the left ventricle tissue were detected by fluorescence immunoblotting., Results: Compared with the NC group, LVSP, ±dp/dtmax, LVEF, and LVFS were decreased in the HF group; compared with the HF group, LVSP, ±dp/dtmax, LVEF, and LVFS were significantly increased in the ACO + EA group. Compared with the ACO group, the incidence and the degree of arrhythmia were significantly reduced in the ACO + EA group. Compared with the NC group, the activity of SERCA2a was decreased, and the expression of PLB and NCX1 was enhanced in the HF group; compared with the HF group and ACO group, the activity of SERCA2a was increased, and the expression of PLB and NCX1 was significantly attenuated in the ACO + EA group., Conclusions: EA plays a synergistic and attenuated role in ACO improving HF, and the mechanism may be related to the enhancement of the SERCA2a activity and the decrease of the expression of PLB and NCX1 in cardiomyocytes., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Chen Zhou et al.)

Objective: To measure the full-length anteroposterior and lateral radiographs of lower limbs after the resection of a tumor in the distal femur and tumor-type knee prosthesis replacement and to analyze the factors leading to aseptic loosening of the prosthesis., Methods: A total of 26 cases of tumor-type knee prosthesis replacement or revision due to the distal femoral tumor at our hospital from January 2007 to December 2019 were retrospectively analyzed. The patients were divided into the loosening and unloosening groups depending on whether aseptic loosening occurred after surgery. Full-length anteroposterior and lateral radiographs of lower limbs were used to measure bone resection length, length of prosthesis, distance of proximal apex of the medullary stem of the femoral prosthesis from the maximum arc of the anterior femoral arch, diameter of the medullary stem, etc. Data were analyzed, and the risk factors for aseptic loosening of the prosthesis were explored., Results: The ratio of the prosthetic length to the femoral length (63.72 ± 5.21) and the ratio of the femoral medullary stem diameter to the femoral diameter (26.03 ± 8.45) were smaller in the loosening group than in the unloosening group. The difference was statistically significant (p < 0.05). The distance between the apex of the medullary stem and the maximum arc of the anterior femoral arch was significantly shorter in the loosening group (3.47 ± 2.96) than in the unloosening group, and the difference was statistically significant (p < 0.05). The measurement of the lower limb alignment showed significant differences between the loosening and unloosening groups in terms of HKAA, mLDFA, and distance between the lower limb alignment and the center of the knee joint (p < 0.05). The logistic regression analysis showed that less than 30% ratio between the medullary stem diameter and the femoral diameter, less than 3 cm distance between the apex of the medullary stem and the maximum curvature of the anterior arch of the femur, distance between the lower limb alignment and the center of the knee joint, and presence of varus knee and valgus knee after the surgery were the risk factors for aseptic loosening of the prosthesis., Conclusions: The diameter of the femoral medullary stem of the prosthesis, the apex position of the prosthetic stem, and the lower limb alignment are the risk factors for aseptic loosening of the prosthesis., (© 2022 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Label-free sensors are highly desirable for biological analysis and early-stage disease diagnosis. Optical evanescent sensors have shown extraordinary ability in label-free detection, but their potentials have not been fully exploited because of the weak evanescent field tails at the sensing surfaces. Here, we report an ultrasensitive optofluidic biosensor with interface whispering gallery modes in a microbubble cavity. The interface modes feature both the peak of electromagnetic-field intensity at the sensing surface and high- Q factors even in a small-sized cavity, enabling a detection limit as low as 0.3 pg/cm 2 The sample consumption can be pushed down to 10 pL due to the intrinsically integrated microfluidic channel. Furthermore, detection of single DNA with 8 kDa molecular weight is realized by the plasmonic-enhanced interface mode., Competing Interests: The authors declare no competing interest., (Copyright © 2022 the Author(s). Published by PNAS.)

Objective: To propose a simple and practical clinical classification for tenosynovial giant cell tumor (TGCT) of the knee., Methods: A retrospective study was conducted to verify the value and significance of this clinical classification. TGCT growth patterns, knee joint capsule, and bone erosion were applied to establish this novel clinical classification. Seventy-eight patients who underwent surgery for TGCT from 2008 to 2016 were identified. This novel clinical classification was retrospectively applied to patients' existing classification, and patients with different TGCT types were statistically compared to verify the significance of the clinical classification., Results: The clinical classification included three types and four subtypes. Type 1: localized TGCT, Subtype 1a: localized intra-articular TGCT, Subtype 1b: localized extra-articular TGCT. Type 2: diffuse TGCT, Subtype 2a: diffuse intra-articular TGCT with bone normal, Subtype 2b: diffuse intra-articular TGCT with bone destruction. Type 3: diffuse TGCT across the knee joint capsule. The mean follow-up time for the 78 patients was 59.6 months. Twenty-one patients were in Subtype 1a, four were Subtype 1b, 38 were Subtype 2a, seven were Subtype 2b, and eight were Type 3. Oncological results and surgical complications differed significantly (P = 0.000, P = 0.000). The mean Musculoskeletal Tumor Society functional scores differed significantly at 27.8 for Type 1 patients, 22.9 for Type 2 patients, and 17.0 for Type 3 patients (P = 0.000)., Conclusions: This clinical classification can be easily used to evaluate TGCT of all knees prior to surgery or other treatments and can help determine surgical options., (© 2021 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Chlorpromazine hydrochloride (CH) and N -acetyl- p -amino-phenoltriptolide (APAP) are typical acentral dopamine receptor antagonists and antipyretic analgesics in clinical applications, respectively. However, it has been reported that these 2 drugs could cause liver damage. Lysophosphatidylcholines (LPCs) have multiple physiological functions and are metabolized primarily in the liver, where it undergoes significant changes when the liver is damaged. In the study, 15 LPCs in the rat serum with CH- and APAP-induced liver injury were quantified based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry, and multivariate statistical analyses including principal component analysis (PCA) and orthogonal partial least squares discriminate analysis (OPLS-DA) were combined to understand CH- and APAP-induced liver injury from the perspective of LPC metabolic profiling. The quantitative results showed that there were significant changes in 10 LPCs and 5 LPCs after CH- and APAP-administration, separately. The results of PCA and OPLS-DA indicated that CH- and APAP-induced liver injury could be well distinguished by the LPC metabolic profiling, and 7 LPCs and 1 LPC biomarkers that could characterize CH- and APAP-induced liver damage in turn had been screened. This study will not only provide a new perspective for the clinical diagnosis of CH- and APAP-induced liver injury, but also offer a reference for further study of their hepatotoxicity mechanisms.

There are many unknown genetic factors that lead to infertility in nonobstructive azoospermia men. Here, we performed whole-exome sequencing in blood samples obtained from 40 azoospermia patients with meiotic arrest and found a novel c.151&#95;154del (p.D51fs) frame-shift mutation in exon 3 of the testis expressed 11 (TEX11) gene in one patient. Sanger sequencing analysis of the patient and 288 fertile men was performed to validate the mutation. Immunohistochemical analysis showed TEX11 expression in late-pachytene spermatocytes and in round spermatids in fertile human testes. In contrast, testes of the patient with TEX11 mutation underwent meiotic arrest and lacked TEX11 expression. Western blotting of human embryonic kidney (HEK293) cells transfected with a vector for the p.D51fs TEX11 variant detected no TEX11 expression. In conclusion, we identified a novel frame-shift mutation in the TEX11 gene in an azoospermia patient, emphasizing that this gene should be included in genetic screening panels for the clinical evaluation of azoospermia patients., Competing Interests: None

Drug resistance is a key factor in the treatment failure of clinical non-small cell lung cancer (NSCLC) patients after adjuvant chemotherapy. Here, our results provide the first evidence that eukaryotic translation initiation factor 2b subunit delta (EIF2B4)-Stratifin (SFN) fusion and increased SFN expression are associated with chemotherapy tolerance and activation of the phosphatidylinositol 3 kinase/v-akt murine thymoma viral oncogene (PI3K/Akt) signaling pathway in NSCLC patients, suggesting that SFN might have potential prognostic value as a tumor biomarker for the prognosis of patients with NSCLC., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Major, trace and rare earth element (REE) geochemistry of the late Cretaceous lower Zhoutian Formation from the Jitai Basin of Southeast China were measured by inductively coupled plasma mass spectrometry (ICP-MS) analysis to infer the provenance of the sediments and to reconstruct the palaeoenvironment and palaeoclimate. The wide range of Sr/Cu ratios point to a fluctuating palaeoclimate, and the negative correlation between the FeO/MnO and Al 2 O 3 /MgO ratios and the Sr/Cu ratio indicates that the late Cretaceous climate during the lower Zhoutian Formation in the Jitai Basin can be divided into two parts. The lower part experienced two cooling periods, whilst the upper part was dominated by warm-humid climate. Mostly corresponding trends of the B/Ga, Sr/Ba and Sr/Cu ratios show that the salinity changed consistently with the late Cretaceous climate during the lower Zhoutian Formation in the Jitai Basin. During the lower part, the salinity changed from salt water to fresh/brackish water. In the upper part, water was mainly fresh/brackish, and there were many changes from fresh/brackish water to salt water. The relatively stable Ni/Co, V/Cr, V/(V + Ni) and Ce/Ce* data indicate a long period of oxic conditions. The La-Th-Sc, Th-Sc-Zr/10 and La/Th-Hf data of the silt- and sandstones of the lower Zhoutian Formation show that its provenance was mainly a mixture of felsic upper crust sediments and older sedimentary rocks.

This study investigated the antioxidant effects of whey protein peptide on learning and memory in aging C57BL/6N mice. A total of 72 SPF male C57BL/6N mice were used. Twelve mice were randomly selected as the control group, and the other mice were intraperitoneally injected with D-galactose (100 mg/kg body weight for 6 weeks), during which, the mice in the control group were intraperitoneally injected with the same amount of normal saline. After 6 weeks, the blood was taken from the epicanthus and the serum MDA level was measured, according to which, the mice were randomly divided into the model control group, the whey protein group (1.5 g/kg body weight), and three Whey protein peptide (WHP) intervention groups (0.3 g/kg body weight, 1.5 g/kg body weight, 3.0 g/kg body weight). The water solution of the test sample was administered by oral gavage every day. The intervention period was 30 days, during which, the model control group, the whey protein group, and the whey protein peptide group continued receiving intraperitoneal injections of D-galactose, while the control group continued receiving intraperitoneal injections of normal saline. After the intervention, behavioral experiments were conducted in the following order: open field test, water maze test, and new object recognition test. After the behavioral experiment, the morphology of hippocampal formation was observed by HE staining and TUNEL labeling. Oxidative stress-related indexes in the serum, liver, and brain were detected. Expression levels of the cholinergic system-related enzymes and proinflammatory cytokines in brain tissue were detected. Western blot was used to detect the expression of synaptic plasticity-related proteins in the mouse brain. The results showed that WHP could significantly improve the accumulation of MDA and PC, increase the activities of SOD and GSH-Px, resist oxidative stress injury, and enhance the potential of endogenous antioxidant defense mechanisms. WHP can significantly improve the decline of aging-related spatial exploration, body movement, and spatial and non-spatial learning/memory ability. Its specific mechanism may be related to reducing the degeneration of hippocampal nerve cells, reducing the apoptosis of nerve cells, improving the activity of AChE, reducing the expression of inflammatory factors (TNF-α and IL-1β) in brain tissue, reducing oxidative stress injury, and improving the expression of p-CaMKⅡ and BDNF synaptic plasticity protein. These results indicate that WHP can improve aging-related oxidative stress, as well as learning and memory impairment.

Optical microcavities have become an attractive platform for precision measurement with merits of ultrahigh sensitivity, miniature footprint and fast response. Despite the achievements of ultrasensitive detection, optical microcavities still face significant challenges in the measurement of biochemical and physical processes with complex dynamics, especially when multiple effects are present. Here we demonstrate operando monitoring of the transition dynamics of a phase-change material via a self-referencing optofluidic microcavity. We use a pair of cavity modes to precisely decouple the refractive index and temperature information of the analyte during the phase-transition process. Through real-time measurements, we reveal the detailed hysteresis behaviors of refractive index during the irreversible phase transitions between hydrophilic and hydrophobic states. We further extract the phase-transition threshold by analyzing the steady-state refractive index change at various power levels. Our technology could be further extended to other materials and provide great opportunities for exploring on-demand dynamic biochemical processes.

Optical evanescent sensors can non-invasively detect unlabeled nanoscale objects in real time with unprecedented sensitivity, enabling a variety of advances in fundamental physics and biological applications. However, the intrinsic low-frequency noise therein with an approximately 1/f-shaped spectral density imposes an ultimate detection limit for monitoring many paramount processes, such as antigen-antibody reactions, cell motions and DNA hybridizations. Here, we propose and demonstrate a 1/f-noise-free optical sensor through an up-converted detection system. Experimentally, in a CMOS-compatible heterodyne interferometer, the sampling noise amplitude is suppressed by two orders of magnitude. It pushes the label-free single-nanoparticle detection limit down to the attogram level without exploiting cavity resonances, plasmonic effects, or surface charges on the analytes. Single polystyrene nanobeads and HIV-1 virus-like particles are detected as a proof-of-concept demonstration for airborne biosensing. Based on integrated waveguide arrays, our devices hold great potentials for multiplexed and rapid sensing of diverse viruses or molecules.

Radiation therapy is widely used in the treatment of tumor diseases, but it can also cause serious damage to the body, so it is necessary to find effective nutritional supplements. The main purpose of this study is to evaluate the protective effect of whey hydrolysate peptides (WHPs) against 60 Coγ radiation damage in mice and explore the mechanism. BALB/c mice were given WHPs by oral gavage administration for 14 days. Then, some mice underwent a 30-day survival test after 8 Gy radiation, and other mice received 3.5 Gy radiation to analyze the changes in body weight, hematology and bone marrow DNA after three and 14 days. In addition, through further analysis of the level of oxidative stress and intestinal barrier function, the possible mechanism of the radioprotective effect of WHPs was explored. The study found WHPs can prolong survival time, restore body weight, and increase the number of peripheral blood white blood cells and bone marrow DNA content in irradiated mice. In addition, WHPs can significantly improve the antioxidant capacity, inhibit pro-inflammatory cytokines and protect the intestinal barrier. These results indicate that WHPs have a certain radioprotective effect in mice, and the main mechanism is related to reducing oxidative damage.

Phytosterols have been shown to improve blood lipid levels and treat atherosclerosis. This research investigated the effects of phytosterol Alisol B 23-acetate (AB23A) on jejunum lipid metabolism and atherosclerosis. The results show that intragastric administration of AB23A can significantly reduce atherosclerotic plaque area and lipid accumulation in the jejunum of ovariectomized ApoE -/- mice fed a high-fat diet and can also improve the lipid mass spectra of the plasma and jejunum. In vitro studies have shown that AB23A can increase cholesterol outflow in Caco-2 cells exposed to high fat concentrations and increase the expression of ATP-binding cassette transfer proteins G5/G8 (ABCG5/G8), the liver X receptor α (LXRα). Furthermore, inhibition of LXRα can significantly eliminate the active effect of AB23A on decreasing intracellular lipid accumulation. We also confirmed that AB23A has a negative effect on Acyl-CoA cholesterol acyltransferase 2 (ACAT2) in Caco-2 cells cultured in the high concentrations of fat, and we found that AB23A further reduces ACAT2 expression in cells treated with the ACAT2 inhibitor pyripyropene or transfected with ACAT2 siRNA. In conclusion, we confirmed that AB23A can reduce the absorption of dietary lipids in the jejunum by affecting the LXRα-ACAT2-ABCG5/G8 pathway and ultimately exert an anti-atherosclerotic effect.

Long-term hypertension can lead to both structural and functional impairments of the myocardium. Reversing left ventricular (LV) myocardial fibrosis has been considered as a key goal for curing chronic hypertension and has been a hot field of research in recent years. The aim of the present work is to investigate the effect of electroacupuncture (EA) at PC6 on hypertension-induced myocardial fibrosis in spontaneously hypertensive rats (SHRs). Thirty SHRs were randomized into model, SHR + EA, and SHR + Sham EA groups with WKY rats as a normal control. EA was applied once a day for 8 consecutive weeks. The cardiac fibrosis as well as the underlying mechanisms were investigated. After 8 weeks of EA treatment at PC6, the enhanced myocardial fibrosis in SHRs was characterized by an increased ratio of left ventricular mass index (LVMI), collagen volume fraction (CVF), and elevated content of hydroxyproline (Hyp) as well as the upregulated expression of collagen I and collagen III in myocardium tissue of SHRs. All these abnormal alterations in the SHR + EA group were significantly lower compared to the model group. In addition, EA at PC6 significantly improved the pathological changes of myocardial morphology. Meanwhile, the increased levels of angiotensin II (Ang II) and tumor necrosis factor-α (TNFα) and expression of transforming growth factor β1 (TGF-β1), connective tissue growth factor (CTGF), matrix metalloproteinase (MMP)-2, and MMP-9 in the serum or heart tissue of SHRs were also markedly diminished by EA. These results suggest that EA at bilateral PC6 could ameliorate cardiac fibrosis in SHRs, which might be mediated by the regulation of the Ang II - TGF-β 1 pathway., (Copyright © 2020 Xin, Dai, Lu, Zhao, Liu, Cui, Xu, Bai, Jing, Gao and Yu.)

Osteosarcoma is the most common primary malignant bone tumor, occurring mainly in children and adolescents, and the limbs are the main affected sites. At present, limb-salvage treatment is considered as an effective basic standard treatment for osteosarcoma of the limb. China has a vast territory, but the development of technology is not balanced,which requires sufficient theoretical coverage, strong technical guidance and the application of limb-salvage treatment guidelines to the treatment of osteosarcoma. Therefore, to standardize and promote the development of limb-salvage surgery technology and improve the success rate of limb-salvage treatment, this guide systematically introduces limb-salvage techniques for the treatment of patients with limb osteosarcoma through definition of limb-salvage treatment, surgical methods, efficacy evaluation, postoperative treatment and prevention of complications, rehabilitation guidance, and follow-up advice., (© 2020 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Background: Due to the particularity of patients with bone tumors, the risk of periprosthetic infection following megaprosthetic replacement is much higher than that of traditional total knee arthroplasty. Unfortunately, few studies specifically reported the risk factors for periprosthetic infection following megaprosthetic replacement. The purposes of the study were to (1) establish a nomogram model, which can provide a reference for clinicians, and patients to reduce the occurrence of periprosthetic infection (2) explore the risk factors for deep infection of megaprosthesis., Hypothesis: A prediction model can be established and has favorable predictive accuracy., Patients and Methods: One hundred and seventy-seven megaprostheses were identified. There were 61 female patients and 116 male patients with a mean age of 35 years. The following risk factors were analyzed: tumor site, sex, age, material for prosthetic stem, tumor type, smoking, diabetes, length of bone resection, operation time, chemotherapy, BMI, malignant tumor staging and hematoma formation. Finally, based on the multivariate analysis, the independent risk factors were used to develop a nomogram model., Results: Univariate Cox regression analysis showed that the chemotherapy, longer operation time and hematoma formation were risk factors for periprosthetic infection. Multivariate Cox regression analysis showed that the chemotherapy, longer operation time and hematoma formation were significant risk factors for periprosthetic infection. The nomogram model was established using these significant risk factors, with a C-index of 0.766 and an acceptable consistency according to the internal validation, indicating that the prediction model had favorable predictive accuracy., Discussion: This study has important implications for the future investigations of prevention of periprosthetic infection. The nomogram model identifies high-risk patients for whom attached prophylaxis measures are required. Future studies regarding reduction of incidence of periprosthetic infection should pay close attention to these high-risk patients., Level of Evidence: IV, retrospective, cohort study., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Objectives: To investigate the contact stress and the contact area o tibial inserts and bushings with respect to different congruency designs in a spherical center axis and rotating bearing hinge knee prosthesis under gait cycle loading conditions using finite element analysis., Methods: Nine prostheses with different congruency (different degrees of tibiofemoral conformity and different distances between the spherical center and the bushing) designs were developed with the same femoral and tibial components. The models were transferred to finite element software. The peak contact stresses and contact areas on tibial inserts and bushings under the gait cycle loading conditions were investigated and compared., Results: For tibial insert, the peak contact stress was the highest in the low conformity-long group (61.4486 MPa), and it was 1.88 times higher than that in the group with the lowest stress (moderate conformity-short group, 32.754 MPa). The contact area was the largest in the low conformity-long group (420.485 mm 2 ), and it was 1.19 times larger than that in the group with the smallest area (moderate conformity-middle group, 352.332 mm 2 ). For bushing, the peak contact stress was the highest in the high conformity-long group (72.8093 MPa), and it was 3.21 times higher than that in the group with the lowest stress (high conformity-short group, 22.6928 MPa). The contact area was the largest in the low conformity-short group (2.41 mm 2 ), and it was 2.27 times larger than that in the group with the smallest area (high conformity-middle group, 1.063 mm 2 )., Conclusion: The results of our study showed that the congruency of the tibiofemoral surface and bushing surface should be considered carefully in the design of the spherical center axis and rotating bearing hinge knee prosthesis. Different levels of contact performance were observed with different congruency designs. In addition, the influence of contact stress and contact area on the polyethylene wear of rotating hinge knee prostheses should be confirmed with additional laboratory tests., (© 2020 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Sterilization and clarification are essential to produce wine of high quality and stability, microfiltration is a serious candidate for both purposes. In this work, microfiltration of fermented mulberry wine was evaluated for the first time. Four different commercial membranes, of two different materials (PES, PVDF) and two different nominal pore sizes (0.22 μm and 0.45 μm) were employed. Pore blocking model was used to identify the fouling mechanism, foulant constituents were revealed by FT-IR spectra. The effect of microfiltration on permeate quality of mulberry wine was also involved. The results indicated that cake formation was the dominant mechanism during steady-state of mulberry wine microfiltration, independently on the membrane property. The fouling layer was mainly composed of protein and polysaccharides, which induced basically reversible overall filtration resistance. Microfiltration delivered a superior clarity, highly polydisperse and light-color mulberry wine with a satisfactory sterilization stability. It preserved the main basic properties and organic acid contents of mulberry wine while resulted in certain loss of volatile compounds, especially esters and alcohols. This work has provided a scientific reference for producing mulberry wine, a modern functional beverage., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Objective: To investigate the roles played by A2b receptor and the key Ca 2+ signaling components in the mediation of the cardioprotection of electroacupuncture pretreatment in the rats subjected to myocardial ischemia and reperfusion., Methods: SD rats were randomly divided into a normal control (NC) group, ischemia/reperfusion model (M) group, electroacupuncture pretreatment (EA) group, and electroacupuncture pretreatment plus A2b antagonist (EAG) group. The ischemia/reperfusion model was made by ligation and loosening of the left descending branch of the coronary artery in all groups except the NC group. The EA group was pretreated with electroacupuncture at the Neiguan (PC6) point once a day for three consecutive days before the modeling. The elevation of the ST segment, arrhythmia scores, and myocardial infarction size of each group was measured. The relative expression levels of A2b, RyR2, SERCA2a, NCX1, P-PLB(S16)/PLB, and Troponin C/Troponin I proteins in the injured myocardium were detected by multiple fluorescence western blot., Results: The level of ST segment, arrhythmia scores, and infarct size in the M group was significantly higher/larger than that in the NC group after ischemia and reperfusion, while all the three indices mentioned above in the EA group were significantly lower/smaller than those in the M group after reperfusion. The expression of the proteins of adenosine receptor 2b(A2b), ryanodine receptor 2(RyR2), and sarco(endo)plasmic reticulum Ca 2+ -ATPase 2a (SERCA2a) in the EA group was significantly enhanced as compared with the M group, while in the EAG group, the contents of A2b were significantly lower than those in the EA group, and RyR2 was higher in the EAG group. In comparison with the NC group, the relative expression of NCX1 protein in M, EA, and EAG groups was not changed significantly. The ratio of phosphorylated phospholamban (P-PLB) over phospholamban (PLB) in the M group was significantly lower than that in the NC group, and the ratio in the EA group was significantly increased as compared with the M group, while the ratio of Troponin C/Troponin I in the EA group was significantly decreased in comparison with that in other groups., Conclusion: Electroacupuncture pretreatment could reduce ischemia and reperfusion-induced myocardial injury via possibly increasing the A2b content and regulating the key Ca 2+ signaling components, namely inhibiting RyR2 and enhancing P-PLB(S16)/PLB ratio and SERCA2a proteins, so as to diminish the intracellular Ca 2+ overload and consequently lessen the myocardial injury., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2019 Qiu-Fu Dai et al.)

Our previous work indicates the lymphatic network and perivascular spaces or tissues might be involved in the facial intradermal brain-targeted delivery of Evans blue (EB). In this article, we presented the detailed involvement of both, and the linkage between lymphatic network and perivascular spaces or tissues. The in-vivo imaging, the trigeminal transection and immunohistochemistry were used. In-vivo imaging indicated intradermal injection in the mystacial pad (i.d.) delivered EB into the brain at 2-, 6- and 24 h, while intranasal injection (i.n.) delivered EB into the rostral head and intravenous injection (i.v.) diffused EB weakly into the brain. Trigeminal perineurial and epineurial EB occurred along the perivascular spaces or tissues and along brain vessels. EB diffused into the lymphatic vessels and submandibular lymph nodes. Moreover, perineurial and epineurial EB co-located or overlaid with Lyve1 immuno-reactivity and VEGF antibody, and lymphatic network connected with perivascular spaces or tissues, suggesting lymphatic system-perivascular spaces might involve in the EB delivery with i.d. The trigeminal transection reduced the trigeminal epineurial and perineurial EB and brain EB along vessels. EB diffused in the fasciculus and the perineurium, blood and lymphatic vessels in the mystacial pad, mystacial EB overlaid VEGF or Lyve1 antibody. In summary, the dermal-trigeminal-brain perivascular spaces or tissues and the linkage to the lymphatic network mediated the intradermal brain-targeted delivery.

Objectives: To evaluate treatments and prognostic factors for the myxoid liposarcoma in extremities., Methods: We retrospectively reviewed 34 patients histologically diagnosed with myxoid liposarcoma arising in the extremities, treated in our hospital from 2010 to 2017. We recorded tumor locations, max diameter, operations, complications, radiation, chemotherapy, survival, recrudescence, and metastases. Overall survival, treatments, and prognostic factors were subsequently analyzed., Results: The mean age of 34 patients with myxoid liposarcoma in extremities was 49.1 years, and the mean follow-up period was 65.1 months. The median survival time was 190 months. Five of 14 patients accepted recrudescence resection and two patients of 20 patients who underwent primary tumor resection or unplanned operation died of tumor progression. Although no statistical difference was found (X 2 = 3.331, P = 0.068), the lower mortality was confirmed in the patients who accepted primary tumor resection or unplanned operation. Eleven patients with a tumor diameter of 8.6 ± 4.7 cm accepted wide resection, while 23 patients with 17.2 ± 8.8 cm tumors accepted marginal resection. Statistical difference was found between the size of tumors with relatively wide resection and those with relatively marginal resection (F = 9.130, P = 0.005). No recurrence or metastasis occurred in patients who accepted wide resection, while 14 patients presented with local recurrence and 8 patients developed distant metastases among the 23 patients with marginal resection. Seven patients died of metastases, while one patient lived with metastases. No significant difference in survival was found between different surgical methods (X 2 = 0.9460, P = 0.3307). The average diameter of eight patients with distant metastases was 21.7 cm, which was considerable larger than the 12.1 cm of patients without metastasis. This difference was proven significant upon the statistical analysis (F = 9.412, P = 0.004)., Conclusions: Wide resection achieved good local control but was not unambiguously superior in long-term survival. Myxoid liposarcoma tumors with larger diameters were more difficult to be submitted to wide resection and were more likely to present with distant metastasis., (© 2019 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Objective: To observe the process of sacroiliac joint invasion by primary malignant tumors of sacrum and iliac bone, and to explore the methods of surgical resection and reconstruction., Methods: From January 2009 to November 2017, there were nine patients with primary malignant bone tumors involving sacroiliac joints, five males and four females, aged from 16 to 63 years, with an average age of 35 years. Of these there were three cases of primitive neuroectodermal tumors, three cases of chondrosarcoma, and three cases of osteosarcoma. Pelvic ring reconstruction was performed with longitudinal half sacrum, sacroiliac joint and partial iliac bone block excision and screw-rod system combined with bone grafting., Results: The operation time was 155-310 min, with an average of 245 ± 55 min, and the bleeding volume was 1400-8500 ml, with an average of 3111 ± 2189 ml. Follow-up ranged from 5 to 108 months, with a median follow-up of 24 months. Three patients (33.3%) had local recurrence, three patients (33.3%) survived without tumors, and one patient had lung metastasis 2 years after operation, and survived with tumors. Five patients (55.6%) died, of which four died of lung metastasis and one died of brain metastasis. Survival analysis showed that the 3-year overall survival rate was 57%. Bone grafts did not heal in four patients, and bone grafts healed in five patients. The healing time ranged from 5 to 7 months, with an average of 6.2 months., Complications: one patient developed deep infection 2 months after operation; one patient had skin edge necrosis; titanium rod loosening and displacement were found in two patients with nonunion of bone graft, and no fracture of nail rod was found. The MSTS 93 functional score of nine patients ranged from 20% to 50%, with an average of 34%., Conclusion: The tumors around the sacroiliac joint often invade the contralateral bone by ligament, and the en bloc resection and pelvic ring reconstruction for primary malignant bone tumors involving sacroiliac joint was feasible., (© 2019 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Background: Aseptic loosening has become the main cause of prosthetic failure in medium- to long-term follow-up. The objective of this study was to establish and validate a nomogram model for aseptic loosening after tumor prosthetic replacement around knee., Methods: We collected data on patients who underwent tumor prosthetic replacements. The following risk factors were analyzed: tumor site, stem length, resection length, prosthetic motion mode, sex, age, extra-cortical grafting, custom or modular, stem diameter, stem material, tumor type, activity intensity, and BMI. We used univariate and multivariate Cox regression for analysis. Finally, the significant risk factors were used to establish the nomogram model., Results: The stem length, resection length, tumor site, and prosthetic motion mode showed a tendency to be related to aseptic loosening, according to the univariate analysis. Multivariate analysis showed that the tumor site, stem length, and prosthetic motion mode were independent risk factors. The internal validation indicated that the nomogram model had acceptable predictive accuracy., Conclusions: A nomogram model was developed for predicting the prosthetic survival rate without aseptic loosening. Patients with distal femoral tumors and those who are applied with fixed hinge and short-stem prostheses are more likely to be exposed to aseptic loosening.

Slope one is a popular recommendation algorithm due to its simplicity and high efficiency for sparse data. However, it often suffers from under-fitting since the global information of all relevant users/items are considered. In this paper, we propose a new scheme called enhanced slope one recommendation through local information embedding. First, we employ clustering algorithms to obtain the user clusters as well as item clusters to represent local information. Second, we predict ratings using the local information of users and items in the same cluster. The local information can detect strong localized associations shared within clusters. Third, we design different fusion approaches based on the local information embedding. In this way, both under-fitting and over-fitting problems are alleviated. Experiment results on the real datasets show that our approaches defeats slope one in terms of both mean absolute error and root mean square error., Competing Interests: The authors have declared that no competing interests exist.

Background: Anti-malarial drug artesunate (ART), a semi-synthetic derivative of artemisnin, has immunosuppressive effects on several autoimmune diseases, including Systemic lupus erythematosus (SLE), Rheumatoid arthritis (RA), and Colitis. However, molecular mechanisms of ART, especially on follicular helper T cells (Tfh), central players in SLE pathology, are far from clear., Purpose: The object for this work is to investigate the therapeutic effect of ART on lupus-prone MRL/lpr mice and its regulatory function on Tfh cells., Study Design and Methods: MRL/lpr mice were used to explore therapeutic effects of ART on lupus-prone MRL/lpr mice and its regulatory functions on Tfh cells. Then, experiments of renal function were accomplished using the biochemical kits. Effects of ART on histopathology of kidneys, inflammatory factors and autoantibodies were examined using H&E staining, ELISA and real-time PCR. Flow cytometry and western blot analysis were used to examine effects of ART on Tfh differentiation and Jak2-Stat3 signaling pathway., Results: Upon oral administration, ART significantly prolonged the survival of MRL/lpr mice, ameliorated the lupus nephritis symptoms, decreased the levels of anti-dsDNA antibodies deposited in the kidney, and the levels of pathogenic cytokines (IL-6, IFN-γ and IL-21). After ART treatment, T-cell compartment in the spleen of MRL/lpr mice was restored in terms of reduction in the number of Tfh cells and in the maintenance of the ratio of Tfr to follicular regulatory T cells (Tfh). In addition, ART has significantly inhibited the phosphorylation levels of Jak2 and Stat3 in the MRL/lpr mice., Conclusion: ART showed therapeutic effects on lupus-prone MRL/lpr mice by inhibiting the differentiation of Tfh cells as well as altering the activation status of Jak2-Stat3 signaling cascade., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Meiosis is a specialized type of cell division that creates haploid germ cells and ensures their genetic diversity through homologous recombination. We show that the H3K4me3 reader ZCWPW1 is specifically required for meiosis prophase I progression in male but not in female germ cells in mice. Loss of Zcwpw1 in male mice caused a complete failure of synapsis, resulting in meiotic arrest at the zygotene to pachytene stage, accompanied by incomplete DNA double-strand break repair and lack of crossover formation, leading to male infertility. In oocytes, deletion of Zcwpw1 only somewhat slowed down meiosis prophase I progression; Zcwpw1 -/- oocytes were able to complete meiosis, and Zcwpw1 -/- female mice had normal fertility until mid-adulthood. We conclude that the H3K4me3 reader ZCWPW1 is indispensable for meiosis synapsis in males but is dispensable for females. Our results suggest that ZCWPW1 may represent a previously unknown, sex-dependent epigenetic regulator of germ cell meiosis in mammals.

Objective: Calcium dobesilate (CaD), an effective drug for the treatment of diabetic microvascular complications, especially diabetic retinopathy, is widely used in the clinic. Interestingly, several studies have indicated that CaD is therapeutic for diabetic kidney disease (DKD). Recently, evidence has indicated that altered vascular endothelial growth factor (VEGF) expression and decreased autophagy are the main pathological mechanisms of proteinuria. Thus, this study was conducted to explore the effect of CaD on restoring autophagy in DKD and the possible signaling pathway between VEGF and autophagy. Methods: Obese mice with spontaneous diabetes (KK-Ay) and high-fat diet- and streptozotocin-induced diabetic mice (HFD/STZ) were used in this study. Biochemical staining, western blotting, and immunohistochemistry were conducted to determine the angioprotective effect of CaD and the underlying mechanism between autophagy and VEGF/VEGFR. Results: Our results showed that CaD was capable of reducing albuminuria and restoring renal histological changes in KK-Ay and HFD/STZ-induced diabetic mice. CaD restored autophagy by decreasing the protein expression of LC3 II, Atg5, and beclin 1 and increasing the expression of P62. Moreover, CaD reduced the activation of the autophagy-related PI3K/AKT/mTOR pathway possibly via decreasing VEGF and downregulating VEGF receptor 2. Conclusion: Overall, CaD, as a novel potential therapeutic drug for DKD, plays a key role in protecting renal function and restoring autophagy by blocking VEGF/VEGFR2 and inhibiting the PI3K/AKT/mTOR signaling pathway.

Objectives: To evaluate the validity of a modified scoring system (MSS) for inferring the bony quality of tumor-bearing diaphyses and predicting the risk of reconstructive failure after devitalized bone replantation (DBR)., Methods: In this retrospective cohort study, we reviewed the records of 30 patients surgically treated for diaphyseal malignancies between 1996 and 2015. There were 18 male and 12 female subjects; the average age was 34.0 ± 24.5 years (8-82 years). Tumor locations comprised the femur (21), the humerus (4), the tibia (3), the radius (1), and the fibula (1). Histological diagnoses included osteosarcoma (13), metastases (4), Ewing sarcoma (3), chondrosarcoma (3), malignant fibrohistiocytoma (2), periosteal osteosarcoma (1), Langerhans cell sarcoma (1), lymphoma (1), rhabdomyosarcoma (1), and malignant giant cell tumor (1). All primary tumors were rated as stage IIB. Twenty patients underwent DBR. Prosthetic procedures and segmental autografting/allografting were performed in 7 and 3 cases, respectively. MSS (comprising 5 elements: pain, tumor location, bone destruction, localized dimension, and longitudinal dimension) for each patient was calculated in accordance with their preoperative presentations. Outcome measurements included oncological results, outcomes of reconstructions, complications, and functional preservation, presented using the musculoskeletal tumor society (MSTS) scale., Results: Follow up was available in 29 cases for an average duration of 61.0 ± 49.9 months (12-152 months). Infection occurred in 2 patients (6.9%), primary nonunion in 6 (27.3%), metastases in 9 (31.9%), recurrences in 4 (13.8%), and deaths in 7 (24.1%); 1 subject underwent amputation due to recurrence following endoprosthetic replacement (3.4%). In the DBR group, fractures occurred in 4 cases (21.1%) and nonunion in 5 (25%); internal fixation was related to nonunion (nails, 44.4% vs plates, 9.1%, P = 0.02). MSS was associated with fractures of devitalized autografts (11.0 ± 1.2 vs 8.3 ± 1.8, P = 0.01); the system was efficacious in predicting chances of fractures of these grafts (P = 0.02). MSS ≥ 10 (with false positive rate ≤ 6.7%) suggested increased fracture probability (≥22.7%) after DBR; therefore, 10 was considered a cutoff value., Conclusions: Diaphyseal malignancies with MSS ≥10 may contraindicate DBR for increased chances of reconstructive failure. In this situation, alternative procedures are advisable. Further investigations are warranted to assess the efficacy of MSS in implying the validity of DBR for diaphyseal malignancies., (© 2019 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Background: The optimal reconstructive method after diaphyseal malignant bone tumor resection remains controversial. This multicenter clinical study was designed to investigate the clinical value and complications of segmental prosthesis in the repair of diaphyseal defects., Methods: We present 49 patients from three clinical centers treated with wide resection for primary or metastatic bone tumors involving the diaphysis of the femur, tibia, humerus, or ulna, followed by reconstruction using a modular intramedullary segmental prosthesis., Results: Enrolled patients included 23 men and 26 women with a mean age of 63.3 years. Of these, seven patients had primary bone tumors and 42 patients had metastatic lesions. At the mean follow-up of 13.7 months, 17 patients were alive, 31 patients were deceased due to tumor progression, and one patient was dead of another reason. There were eight nononcologic complications (two with radial nerve injury, three with delayed incision healing, two with aseptic loosening in the proximal humerus prosthetic stem and one with structural failure) and three oncologic complications (three with primary tumor recurrence) among all patients. The incidence of complications in primary tumor patients (4/7, 57.1%) was higher than that in patients with metastatic tumors (7/42, 16.7%) (p = 0.036). Aseptic loosening and mechanical complications were not common for patients with primary tumors, although the reconstruction length difference was statistically significant (p = 0.023). No statistically significant differences were observed in limb function, while the mean musculoskeletal tumor society score was 21.2 in femora, 19.6 in humeri, and 17.8 in tibiae (p = 0.134)., Conclusions: Segmental prostheses represent an optional method for the reconstruction of diaphyseal defects in patients with limited life expectancy. Segmental prostheses in the humerus experienced more complications than those used to treat lesions in the femur.

Objectives: To investigate the association between the number of metastases to the spine and survival in patients with metastatic spinal cord compression (MSCC), as well as the prognosis difference between patients with solitary spinal metastasis (SSM) and multiple spinal metastases (MSM)., Methods: Three institutional databases were searched to identify all patients who had undergone spinal surgery for metastatic spinal tumors between March 2002 and June 2010. As well as age and gender, preoperative medical conditions were collected from medical records, including primary tumor, preoperative Frankel score, other bone metastases, preoperative Karnofsky performance status (KPS), number of involved vertebrae, pathological fracture metastasis site, serum albumin, sphincter dysfunction and the time of developing motor deficits before surgery. Survival data were obtained from medical records or via telephone follow-ups. Univariate and multivariate predictors of overall survival for each group were assessed using the Cox proportional hazards model., Results: The median postoperative survival time was 6.0 ± 0.6 months (95% confidence interval [CI] 4.8-7.2) in patients with SSM and 7.0 ± 1.0 months (95% CI 5.1-8.9) in patients with MSM (P = 0.238). The difference in survival was not significant between groups. Furthermore, univariate analysis showed that the number of spinal metastases had no significant association with survival (P = 0.075). Primary tumor (P = 0.004) and preoperative KPS (P < 0.001) were independent prognostic factors in the whole cohort; primary tumor (P = 0.020), time of developing motor deficit (P = 0.041) and preoperative KPS (P = 0.038) were independent prognostic factors in patients with SSM; while preoperative KPS (P = 0.001) and serum album level (P < 0.001) were independent prognostic factors in patients with MSM., Conclusion: The number of spinal metastases has not proven to be useful in predicting the prognosis for patients with MSCC. Consequently, more aggressive operations should be considered for patients with multiple spinal metastases., (© 2019 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Objective: To investigate whether visceral metastases have a significant impact on survival in patients with metastasis-related spinal cord compression (MSCC), and to determine the difference in prognosis between patients with and without visceral metastases., Methods: Three institutional databases were searched to identify all patients who had undergone spinal surgery for spinal metastases between March 2002 and June 2010. Data on patient characteristics including pre- and post-operative medical conditions, were collected from medical records or by telephone follow-up. Survival data were obtained either from medical records or by searching a governmental cancer registry., Results: The mean age of study patients was 59.6 ± 10.5 years (range, 18-84 years), of whom 102 were male and 67 female. The median and mean postoperative survival times were 7.0 ± 0.5 (95% CI 6.0-8.0) months and 12.6 ± 1.2 (95% CI 10.1-15.0) months, respectively, in all patients, being 5.0 ± 0.5 (95% CI 4.0-6.0) months and 10.8 ± 2.4 (95% CI 6.1-15.5) months, respectively, for patients with visceral metastases and 7.0 ± 0.8 (95% CI 5.4-8.6) months and 13.0 ± 1.4 (95%CI 10.3-15.6) months, respectively, for patients without visceral metastases (P = 0.87). These survival times did not differ significantly between groups. Multivariate Cox proportional hazard regressions showed that visceral metastases had no statistically significant association with survival (P = 0.277), whereas rate of growth of primary tumor (P = 0.003), preoperative Karnofsky performance status (KPS) (P < 0.001), change in KPS (P < 0.001), and Frankel grade (P = 0.091) were independent prognostic factors in the whole cohort (P = 0.005). Changes in KPS (P = 0.001) and major complications (P = 0.003) were significantly associated with survival in patients with visceral metastases, whereas rate of growth of primary tumor (P = 0.016), change in KPS (P = 0.001), and preoperative KPS (P < 0.001) were significantly associated with survival in patients without visceral metastases., Conclusions: Visceral metastases do not appear to predict the prognosis of patients with MSCC; thus, more aggressive surgery should be considered in patients with MSCC who have visceral metastases. Additionally, prognostic factors differ according to visceral metastases status in these patients., (© 2019 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

The role of protein structural disorder in biological functions has gained increasing attention in the past decade. The bacterial acid-resistant chaperone HdeA belongs to a group of "conditionally disordered" proteins, because it is inactive in its well-structured state and becomes activated via an order-to-disorder transition under acid stress. However, the mechanism for unfolding-induced activation remains unclear because of a lack of experimental information on the unfolded state conformation and the chaperone-client interactions. Herein, we used advanced solution NMR methods to characterize the activated-state conformation of HdeA under acidic conditions and identify its client-binding sites. We observed that the structure of activated HdeA becomes largely disordered and exposes two hydrophobic patches essential for client interactions. Furthermore, using the pH-dependent chemical exchange saturation transfer (CEST) NMR method, we identified three acid-sensitive regions that act as structural locks in regulating the exposure of the two client-binding sites during the activation process, revealing a multistep activation mechanism of HdeA's chaperone function at the atomic level. Our results highlight the role of intrinsic protein disorder in chaperone function and the self-inhibitory role of ordered structures under nonstress conditions, offering new insights for improving our understanding of protein structure-function paradigms., (© 2019 Yu et al.)

Although an accurate evaluation of the distribution of ultrafine particulate matter in air is of utmost significance to public health, the usually used PM 2.5 index fails to provide size distribution information. Here we demonstrate a low-profile and cavity-free size spectrometer for probing fine and ultrafine particulate matter by using the enhanced particle-perturbed scattering in strong optical evanescent fields of a nanofiber array. The unprecedented size resolution reaches 10 nm for detecting single 100-nm-diameter nanoparticles by employing uniform nanofibers and controlling the polarizations of the probe light. This size spectrometry was tested and used to retrieve the size distribution of particulate matter in the air of Beijing, yielding mass concentrations of nanoparticles, as a secondary exercise, consistent with the officially released data. This nanofiber-array probe shows potential for the full monitoring of air pollution and for studying early-stage haze evolution and can be further extended to explore nanoparticle interactions., Competing Interests: The authors declare no conflict of interest.

Objective: To assess the value of immunoglobulin heavy/light chain (HLC) immunoassay on therapeutic response in patients with multiple myeloma(MM). Methods: A total of 45 newly diagnosed MM patients were retrospectively enrolled in Peking Union Medical College Hospital from 2013 to 2016, whose 115 serum samples were consecutively collected. HLC was tested to evaluate response and compare with other methods for M protein detection. Results: ①There were 30 males and 15 females in total of whom the monoclonal immunoglobulin was IgG in 27 (IgGκ∶IgGλ 12∶15) and IgA (IgAκ∶IgAλ 9∶9) in 18. The arerage age of the studied population was 59 (range 43-80) . ② In 34 patients with serum sample at diagnosis, 32 (94.1%) had abnormal HLC ratio (rHLC) while 2 patients with IgG had normal rHLC. The percentages of abnormal rHLC was 81.8% (18/22) at partial response、50.0%(9/18) at very good complete response and 16.0%(4/25) at complete response. ③In 25 patients reaching CR, there were 13 with IgG and 12 with IgA. 4 patients equally split of IgG and IgA had abnormal rHLC at complete response. ④By monitoring the rHLC of some patients consecutively, we found that the remission of rHLC was to some extent behind the remission of SPE and IEF, or even rFLC. Conclusion: Immunoglobulin HLC detection is one feasible method for minimal residual disease detection.

Aims: To study the protective effects of late remote ischaemic preconditioning (RIPC) against myocardial ischaemia/reperfusion (I/R) injury and determine whether Stat5 is involved in this protection by using cardiomyocyte-specific Stat5 knockout mice (Stat5-cKO)., Methods and Results: Mice were exposed to lower limb RIPC or sham ischaemia. After 24 h, the left anterior descending artery (LAD) was ligated for 30 min, then reperfused for 180 min. The myocardial infarct size (IS), apoptotic rate of cardiomyocytes, and serum myocardial enzymes were measured to evaluate for cardioprotective effects. Heart tissues were harvested to determine the cardiomyocytes' anti-apoptotic and survival signaling. When compared with the Stat5fl/fl mice without RIPC, Stat5fl/fl mice with RIPC (Stat5fl/fl+RIPC + I/R) displayed a decreased myocardial IS/LV (16 ± 1.5 vs. 30.1 ± 3.1%, P < 0.01; IS/ area at risk (AAR), 42.2 ± 3.5 vs. 69.2 ± 4.9%, P < 0.01), a reduced cardiomyocyte apoptotic rate (2.1 ± 0.37 vs. 5.5 ± 0.53%, P < 0.01), and lower creatine kinase (CK), lactate dehydrogenase (LDH), and creatine kinase-MB (CK-MB) levels. To the contrary, the Stat5-cKO mice (Stat5fl/fl; Tnnt2Cremice with Doxycycline treatment for 7 days) did not exhibit any effect of RIPC-induced cardioprotection. Activation of STAT5 protein was significantly higher in the Stat5fl/fl+RIPC + I/R group than in the Stat5fl/fl+I/R group, while there was no significant difference between the Stat5-cKO + RIPC + I/R and the Stat5-cKO + I/R group. Further analyses with heart tissues detected decreased protein expressions of cytochrome c (Cyt c) and cleaved Caspase-3 in the Stat5fl/fl+RIPC + I/R mice, along with increased anti-apoptotic molecules, including B-cell lymphoma-extra large (Bcl-xL) and B-cell lymphoma-2 (Bcl-2); such changes were not noted in the Stat5-cKO + RIPC + I/R mice. Additionally, RIPC increased cardiac hypoxia inducible factor-1 (HIF-1α) and interleukin-10 (IL10) protein levels and caused activation of AKT, phosphatidylinositol 3 kinase (PI3K), and vascular endothelial growth factor in the heart of the Stat5fl/fl mice. However, these changes were completely inhibited by the absence of Stat5., Conclusions: These results suggest that RIPC-induced late cardioprotection against myocardial I/R injury is Stat5-dependent and is correlated with the activation of anti-apoptotic signaling and cardiomyocyte-survival signaling.