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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.)

Abstract: Objective: This study aimed to explore the impact of heat stress (HS) on glutamate transmission-dependent expression levels of interleukin-1β (IL-1β) and IL-18 in BV-2 microglial cells. Methods: BV-2 microglial cells were cultured in vitro , with cells maintained at 37°C serving as the control. The HS group experienced incubation at 40°C for 1 h, followed by further culturing at 37°C for 6 or 12 h. The experimental group was preincubated with glutamate, the glutamate antagonist riluzole, or the mGluR5 agonist, 2-chloro-5-hydroxyphenylglycine (CHPG), before HS. Glutamate content in BV-2 culture supernatant was assessed using colorimetric assay. Moreover, mRNA expression levels of EAAT3 and/or mGluR5 in BV-2 cells were determined via quantitative polymerase chain reaction. Interleukins (IL-1β and IL-18) in cell culture supernatant were measured using enzyme-linked immunosorbent assay. Western blot analysis was employed to assess protein levels of IL-1β and IL-18 in BV-2 cells. Results: HS induced a significant release of glutamate and increased the expression levels of mGluR5 and EAAT3 in BV-2 cells. It also triggered the expression levels and release of proinflammatory factors, such as IL-1β and IL-18, synergizing with the effects of glutamate treatment. Preincubation with both riluzole and CHPG significantly reduced HS-induced glutamate release and mitigated the increased expression levels and release of IL-1β and IL-18 induced by HS. Conclusion: The findings confirmed that microglia could be involved in HS primarily through glutamate metabolisms, influencing the expression levels and release of IL-1β and IL-18., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Shock Society.)

Background: Patient adherence status to the newly introduced family-based Helicobacter pylori (H. pylori) infection control and management strategy remains unclear, so are its influencing factors. We aim to investigate family members' adherence and its influencing factors during the family-based H. pylori infection management practice for related disease prevention., Materials and Methods: Based on our previously family-based H. pylori survey in 2021, 282 families including 772 individuals were followed up 2 years after the initial survey to compare if the investigation and education might improve family member's adherence. The participant's adherence to H. pylori infection awareness, retest, treatment, publicity, gastroscopy, and hygiene habits were followed up, and their influencing factors were also analyzed., Results: The overall participant's adherence to recommendations on H. pylori awareness, retest, treatment, publicity, gastroscopy, and hygiene habits were 77% (187/243), 67.3% (138/205), 60.1% (211/351), 46.5% (107/230), 45.6% (159/349), and 39.1% (213/545), respectively; and all showed improvements compared with their prior survey stages. The top reasons for rejection to treatment, retest, and gastroscopy were forgetting or unaware of H. pylori infection (30.3%), busy (32.8%), and asymptomatic (67.9%), respectively. Independent risk factor for low adherence to treatment was occupation (e.g., staff: OR 4.49, 95% CI 1.34-15.10). Independent favorable factors for treatment adherence were individuals at the ages of 18-44 years (OR 0.19, 95% CI 0.04-0.89) and had a large family size (e.g., four family members: OR 0.15, 95% CI 0.06-0.41); for retest adherence, it was individuals at the ages of 60-69 years (OR 0.23, 95% CI 0.06-0.97); for gastroscopy adherence, it was individuals at the age of 60-69 years (OR 0.46, 95% CI 0.28-0.75), and with gastrointestinal symptoms (OR 0.57, 95% CI 0.36-0.90)., Conclusions: Family-based H. pylori management increases individual adherence to treatment, retest, and awareness, and there are also improved adherence to gastroscopy, publicity, and personal hygiene recommendations; further efforts are required to enhance the individual adherence rate for related disease prevention., (© 2024 John Wiley & Sons Ltd.)

Microglia-mediated inflammation is involved in the pathogenesis of Alzheimer's disease (AD), whereas human fibroblast growth factor 21 (hFGF21) has demonstrated the ability to regulate microglia activation in Parkinson's disease, indicating a potential therapeutic role in AD. However, challenges such as aggregation, rapid inactivation, and the blood-brain barrier hinder its effectiveness in treating AD. This study develops targeted delivery of hFGF21 to activated microglia using BV2 cell membrane-coated PEGylated liposomes (hFGF21@BCM-LIP), preserving the bioactivity of hFGF21. In vitro, hFGF21@BCM-LIP specifically targets Aβ 1-42 -induced BV2 cells, with uptake hindered by anti-VCAM-1 antibody, indicating the importance of VCAM-1 and integrin α4/β1 interaction in targeted delivery to BV2 cells. In vivo, following subcutaneous injection near the lymph nodes of the neck, hFGF21@BCM-LIP diffuses into lymph nodes and distributes along the meningeal lymphatic vasculature and brain parenchyma in amyloid-beta (Aβ 1-42 )-induced mice. Furthermore, the administration of hFGF21@BCM-LIP to activated microglia improves cognitive deficits caused by Aβ 1-42 and reduces levels of tau, p-Tau, and BACE1. It also decreases interleukin-6  (IL-6) and tumor necrosis factor-α (TNF-α) release while increasing interleukin-10 (IL-10) release both in vivo and in vitro. These results indicate that hFGF21@BCM-LIP can be a promising treatment for AD, by effectively crossing the blood-brain barrier and targeting delivery to brain microglia via the neck-meningeal lymphatic vasculature-brain parenchyma pathways., (© 2024 Wiley‐VCH GmbH.)

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.)

An efficient method for the synthesis of M 2 B 10 H 14 (M = Na and K) has been developed. The two possible formation mechanisms of the B 10 H 14 2- anion are proposed, in which the NH 2 BH 3 - anion acts as a proton abstractor and a hydride donor. Furthermore, the B 10 H 13 - and B 10 H 15 - intermediates were detected.

Objective: To observe the effect of electroacupuncture (EA) at "Neiguan" (PC 6) on myocardial fibrosis in spontaneously hypertensive rats (SHR), and explore preliminarily the mediating role of cholinergic anti-inflammatory pathway (CAP) and its downstream nuclear factor κB (NF-κB) signaling pathway., Methods: Six 12-week-old WKY male rats were employed as the normal group. Eighteen 12-week-old SHR were randomly divided into 3 groups, i.e. a model group, an EA group and a blocking group (EA after blocking α7 nicotinic acetylcholine receptor [α7nAchR]), with 6 rats in each one. In the EA group, EA was delivered at "Neiguan"(PC 6) and the site 0.5 cm from its left side, with disperse-dense wave, 2 Hz/15 Hz in frequency and 1 mA in current intensity. One intervention took 30 min and was given once every 2 days, lasting 8 weeks. In the blocking group, prior to each EA, the α7nAchR specific blocker, α-bungartoxin was injected intravenously in the tails of the rats. After EA intervention, the systolic blood pressure (SBP), the diastolic blood pressure (DBP) and the mean arterial pressure (MAP) were measured with non-invasive blood pressure monitor. Using echocardiogram, the left ventricular (LV) anterior wall end-diastolic thickness (LVAWd) , LV posterior wall end-diastolic thickness (LVPWd) and the LV end-diastolic internal diameter (LVIDd) were measured. The level of hydroxyproline (Hyp) in the myocardial tissue was determined by using alkaline hydrolysis, and that of acetylcholine (Ach) was detected by ELISA. With the real-time PCR adopted, the mRNA expression of NF-κB p65, tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 were determined., Results: Compared with the normal group, SBP, DBP, MAP, LVAWd and LVPWd were increased ( P <0.01), and LVIDd was decreased ( P <0.01) in the rats of the model group. SBP, DBP, MAP and LVAWd were dropped ( P <0.01, P <0.05), and LVIDd rose ( P <0.01) in the EA group when compared with those in the model group. The differences in the above indexes were not statistically significant between the blocking group and the model group ( P >0.05). Compared with the normal group, Hyp level and the mRNA expression of NF-κB p65, TNF-α, IL-1β and IL-6 in the myocardial tissue increased ( P <0.01, P <0.05) and Ach level decreased ( P <0.01) in the model group. Hyp level, the mRNA expression of NF-κB p65, TNF-α, IL-1β and IL-6 in the myocardial tissue were reduced ( P <0.05, P <0.01) and Ach level rose ( P <0.01) in the EA group when compared with those in the model group. These indexes were not different statistically between the blocking group and the model group ( P >0.05)., Conclusion: CAP may be involved in ameliorating the pathological damage of myocardial fibrosis during EA at "Neiguan"(PC 6). The underlying effect mechanism is associated with up-regulating the neurotransmitter, Ach and down-regulating mRNA expression of NF-κB p65 and pro-inflammatory factors such as TNF-α, IL-1β and IL-6 in myocardial tissue.

The combination of photo and copper catalysts has emerged as a novel paradigm in organic catalysis, which provides access to the acceleration of chemical synthesis. Herein, we describe an aminoalkylation of amino-dependent olefins with maleimides through a cooperative photo/copper catalytic system. In this report, the strategy allows the generation of a broad complex of functionalized nitrogenous molecules including oxazolidinones, 2-pyrrolidones, imidazolidinones, thiazolidinones, pyridines, and piperidines in the absence of an external photosensitizer and base. The approach is achieved through a photoinduced Cu(I)/Cu(II)/Cu(III) complex species of nitrogen nucleophiles, intermolecular radical addition, and hydrogen atom transfer (HAT) processes. The plausible mechanism is investigated by a series of control experiments and theoretical tests, including radical scavenging experiments, deuterium labeling experiments, ultraviolet-visible absorption, and cyclic voltammetry (CV) tests.

Objective To compare the surgical safety of elderly hospitalized patients in different age groups undergoing general surgery,and provide references for preoperative evaluation and treatment decision-making.Methods The inpatients ≥ 60 years old in the department of general surgery were selected from a national multi-center survey conducted from January to June in 2015 and from January to June in 2016.The patient characteristics and postoperative outcomes were described,and the risk factors for adverse postoperative outcomes of patients in different age groups were explored.Results The elderly patients (≥75 years old) accounted for 17.33%.The non-elderly patient (< 75 years old) group and the elderly patient (≥75 years old) group had significant differences in the proportions of patients with three or more chronical diseases (13.18% vs .5.36%, P <0.001),emergency surgery (16.64% vs .7.62%, P <0.001),American Society of Anesthesiologists score≥3 (48.68% vs .27.28%, P <0.001),and postoperative return to the intensive care unit(33.64% vs .12.00%, P <0.001).The occurrence of postoperative infectious complications showed no significant difference between the two age groups (7.29% vs .6.40%, P =0.410),while severe complications differed between the two groups (6.51% vs .2.60%, P <0.001).Besides,emergency surgery was a common independent risk factor for the two age groups.Conclusions Advanced age is not a contraindication to surgery of elderly patients.With consideration to patient's physical conditions and available surgical resources,elderly patients can still benefit from surgery.

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.

Objective: To investigate the effect of electroacupuncture (EA) at Neiguan (PC 6) on myocardial fibrosis in spontaneously hypertensive rats (SHRs), and to explore the contribution of interleukin-1 β (IL-1 β), insulin-like growth factor 1 (IGF-1), and transforming growth factor β 1 (TGF- β 1) to the effects., Methods: Nine 12-weeks-old Wistar Kyoto (WKY) male rats were employed as the normal group. Twenty-seven SHRs were equally randomized into SHR, SHR+EA, and SHR + sham groups. EA was applied at bilateral PC 6 once a day 30 min per day in 8 consecutive weeks. After 8-weeks EA treatment at PC 6, histopathologic changes of collagen type I (Col I), collagen type 1 (Col 1) and the levels of IGF-1, 1L-1 β, TGF- β 1, matrix metalloproteinase (MMP)-2 and MMP-9 were examined in myocardial tissure respectively., Results: After 8-weeks EA treatment at PC 6, the enhanced myocardial fibrosis in SHRs were characterized by the increased mean fluorescence intensity of Col I and Col 1 in myocardium tissue (P<0.01). All these abnormal alterations above in SHR + EA group was significantly lower compared with the SHR group (P<0.01). Meanwhile, the increased levels of IL-1 β, IGF-1, TGF-β 1 in serum or myocardial tissue of SHRs, diminished MMP 9 mRNA expression in SHRs were also markedly inhibited after 8 weeks of EA treatment (P<0.05 or P<0.01). Furthermore, the contents of IL-1 β, IGF-1, TGF-β 1 in myocardial tissue were positively correlated with the systolic blood pressure and hydroxyproline respectively (P<0.01)., Conclusion: EA at bilateral PC 6 could ameliorate cardiac fibrosis in SHRs, which might be mediated by regulation of 1L-1 β/IGF-1-TGF- β 1-MMP9 pathway., (© 2022. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective To investigate the patterns of perioperative blood transfusion in patients with blood loss during major cardiac surgery,so as to provide data reference for rational and standardized blood use.Methods The adult patients(aged 18 years or above)who underwent vascular surgery,coronary artery bypass grafting surgery,heart valve surgery or surgery for congenital heart disease in a national multicenter(four large hospitals)survey in China,2015-2016 were included in this study.We described their baseline characteristics,postoperative outcomes,and in particular,bleeding and patterns of perioperative blood transfusion(autologous and allogeneic,the latter including red blood cells,plasma,and platelet,or a combination of these components).Results Autologous blood transfusion in operation accounted for the highest proportion(58.84%)in patients undergoing heart valve surgery.The patients undergoing vascular surgery had the largest autologous blood transfusion volume(722 ml)and the highest intraoperative transfusion proportion of allogeneic blood(53.28%),especially that of platelet(39.34%).Compared with the transfusion of red blood cells,the transfusion of other blood components showed concentrated time distribution,and the proportion of plasma transfusion was the highest one day post operation.With the increase in bleeding volume,combined transfusion presented increased proportion and became the dominant transfusion pattern.Conclusions The blood transfusion patterns varied significantly depending on different types of cardiac surgery,different perioperative stages,and different bleeding volumes.It is necessary to formulate the targeted transfusion practice scheme on the basis of understanding the current situation,so as to make better use of blood resources and improve the safety of transfusion.

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).)

In the present study, we explored whether sirtuin-3 (SIRT3) regulates the proliferation and migration of esophageal squamous cell carcinoma (ESCC) and investigated the mechanisms underlying the oncogene role of SIRT3. siRNA was used to transfect Eca109 cells and downregulate SIRT3. The proliferation and migration of Eca109 cells were examined by the CCK-8 assay, colony formation assay, Transwell assay, and scratch test. Quantitative real-time PCR and Western blotting were used to detect SIRT3, hexokinase 2, AKT, and p-AKT in Eca109 cells. Functional assays showed that downregulation of SIRT3 could inhibit the proliferation and migration of ESCC cells. Reduced SIRT3 expression downregulated hexokinase 2 expression and inhibited AKT activation in ESCC. These results indicated that SIRT3 promote ESCC development and progression by regulating hexokinase 2 through the AKT signaling pathway. SIRT3 promote ESCC proliferation and migration by regulating HK-2 through the AKT signaling pathway., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

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).)

The novel polychloromethylation/acyloxylation of 1,6-enynes with chloroalkanes and diacyl peroxides through dual-role designs has been developed to prepare 2-pyrrolidinone derivatives with polychloromethyl units with the use of an inexpensive copper salt under mild conditions. This strategy includes two dual-role designs, not only improving atomic utilization but also allowing a cleaner process. The wide substrate scope and simple reaction conditions demonstrate the practicability of this protocol.

The multi-attribute method (MAM) was conceived as a single assay to potentially replace multiple single-attribute assays that have long been used in process development and quality control (QC) for protein therapeutics. MAM is rooted in traditional peptide mapping methods; it leverages mass spectrometry (MS) detection for confident identification and quantitation of many types of protein attributes that may be targeted for monitoring. While MAM has been widely explored across the industry, it has yet to gain a strong foothold within QC laboratories as a replacement method for established orthogonal platforms. Members of the MAM consortium recently undertook an interlaboratory study to evaluate the industry-wide status of MAM. Here we present the results of this study as they pertain to the targeted attribute analytics component of MAM, including investigation into the sources of variability between laboratories and comparison of MAM data to orthogonal methods. These results are made available with an eye toward aiding the community in further optimizing the method to enable its more frequent use in the QC environment.

Background: Helicobacter pylori (H. pylori) infection and its related diseases are substantial public health burden for highly infected areas. Recently, a novel family-based H. pylori infection control and management (FBCM) strategy is introduced for H. pylori infection prevention and control. However, its cost-effectiveness has not been evaluated. We conducted this health economic evaluation to investigate the cost-effectiveness of FBCM, screen-and-treat, and no-screen strategies in Chinese population., Materials and Methods: Cost-effectiveness analysis was performed using decision tree and Markov model. Parameters required for the model were from published literatures and public databases, including health state utility, screening characteristics, treatment effectiveness, and medical costs for the three strategies. Outcomes were cost, quality-adjusted life year (QALY), incremental cost-effectiveness ratio (ICER). Uncertainty analysis was performed to verify the robustness of this model., Results: To prevent gastric cancer in a cohort of 1 million asymptomatic Chinese families, FBCM and screen-and-treat strategies prevented 1010 and 1201 new gastric cancer cases, reduced 2809 and 3339 gastric cancer-related death, and saved 956,971 and 1,137,549 QALYs, respectively, when compared with no-screen strategy. Cost-effectiveness analysis showed that FBCM strategy cost $9.18/QALY, and screen-and-treat strategy cost $12.08/QALY for gastric cancer prevention when compared with no-screen strategy. One-way sensitivity analysis revealed that screening from younger age by both strategies are more cost-effective. When compared with FBCM strategy, screen-and-treat strategy saved 5.98% gastric cancer cases and 5.78% of gastric cancer deaths, but costed $9348 to reduce a gastric cancer case. Results are not sensitive to any variables, and probabilistic sensitivity analysis confirmed robustness of the results., Conclusions: Both FBCM and screen-and-treat strategies are cost-effective for gastric cancer prevention compared with no-screen strategy. Since FBCM is more practical and convenient, it may be an efficient and excellent cost-effective strategy for gastric cancer prevention in H. pylori and gastric cancer prevalent areas., (© 2022 John Wiley & Sons Ltd.)

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 observe the effect of electroacupuncture (EA) at "Neiguan" (PC 6) on cardiac function of ventriculus sinister in rats with spontaneously hypertensive (SHR), and to explore the mediation effect of endothelin-1 (ET-1)/endothelial nitric oxide synthase (eNOS)., Methods: Six 12-week-old male Wistar Kyoto (WKY) rats were taken as the normal group. Eighteen 12-week-old SHR were randomly divided into a model group, an EA group and a sham EA group, 6 rats in each group. The rats in the EA group were treated with EA (disperse-dense wave, 2 Hz/15 Hz in frequency, 1 mA in current intensity) at "Neiguan" (PC 6), 30 min each time, once a day for 8 weeks. The rats in the sham EA group were treated with superficial needling at "Neiguan" (PC 6) with no electrical stimulation applied. After treatment, the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were tested by echocardiographic analysis. The left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), heart rate (HR), the maximum rate of increase/decrease of left ventricular pressure (±dp/dt max ) were detected. The serum content of ET-1 was detected by ELISA. Western blot was used to evaluate the expression of ETAR, eNOS in myocardial tissue of left ventricular., Results: Compared with the normal group, LVEF, LVFS, +dp/dt max /LVSP and -dp/dt max /LVSP were decreased ( P <0.01, P <0.05), while LVSP, LVEDP, +dp/dt max and -dp/dt max were increased ( P <0.01) in the model group. Compared with the model group, LVEF, LVFS, +dp/dt max /LVSP and -dp/dt max /LVSP were increased ( P <0.01, P <0.05), and LVSP and LVEDP were decreased ( P <0.01) in the EA group. Compared with the normal group, the serum content of ET-1 and the expression of ETAR in myocardial tissue were increased ( P <0.01), whereas expression of eNOS was decreased ( P <0.01) in the model group. Compared with the model group, the serum content of ET-1 and the expression of ETAR in myocardial tissue were decreased ( P <0.05), whereas expression of eNOS was increased ( P <0.05) in the EA group., Conclusion: EA intervention may alleviate hypertensive cardiac function damage by up-regulating the expression of eNOS protein in myocardial tissue, down-regulating the serum content of ET-1 and the expression of ETAR protein in myocardial tissue.

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.)

The lower bioavailability after oral administration limited icariin applications in central nervous system. Icariin/HP-β-cyclodextrin (HP-β-CD) inclusion complex was prepared for acute severe opening traumatic brain injury (TBI) via facial intradermal (i.d.) in the mystacial pad. After fluid percussion-induced TBI, icariin/HP-β-CD at 0.4 mg/kg i.d. preserved more neurons and oligodendrocytes than intranasal injection (i.n.) or intravenous injection via tail vein (i.v.) and decreased microglia and astrocyte activation. Icariin/HP-β-CD i.d. reduced apoptosis in cortical penumbra while i.n. and i.v. showed weak or no effects. Icariin/HP-β-CD i.d. reduced Evans blue leakage and altered CD34, ZO-1, Claudin-5, and beta-catenin expression after TBI. Moreover, icariin/HP-β-CD promoted human umbilical vein endothelial cells proliferation. Thus, Icariin/HP-β-CD i.d. improved TBI, including blood-brain barrier opening. Fluorescein 5-isothiocyanate (FITC) and 3,3'-Dioctadecyloxacarbocyanine perchlorate (DiOC18(3)) mimic HP-β-CD and icariin respectively. FITC and DiOC18(3) were similarly delivered to trigeminal epineurium, perineurium and perivascular spaces or tissues, caudal dura mater, and scattered in trigeminal fasciculus, indicating that icariin/HP-β-CD was delivered to the brain via trigeminal nerve-dura mater-brain pathways. In sum, intradermal injection in mystacial pad might deliver icariin/HP-β-CD to the brain and icariin/HP-β-CD improved acute severe opening TBI.

Purpose: To investigate the different imaging features of contrast-enhanced multidetector-row-computed tomography (MDCT) for distinguishing between silicosis and tuberculosis involving the mediastinal lymph nodes., Methods: 86 silicosis patients and 61 tuberculosis patients with mediastinal lymphadenopathy based on contrast-enhanced MDCT were included. The enhanced patterns, anatomical distribution and calcification features of the enlarged lymph nodes were retrospectively compared between the groups using the Pearson chi-square test or Fisher's exact test., Results: Homogeneous enhancement of the mediastinal lymph nodes was more commonly observed in silicosis (94.2%, 81/86) than in tuberculosis (19.7%, 12/61). Peripheral enhancement was more frequent in tuberculosis (n = 44, 72.1%) than in silicosis involving the mediastinal lymph nodes (n = 1, 1.2%), and multilocular appearance was more frequent in TB than in silicosis. Tuberculosis was more likely to affect regions 1R, 2R, 2L, 3A, 5 and 6 than silicosis (all p < 0.05), especially region 2R. Calcification of the lymph nodes was more common in the silicosis group than in tuberculosis group. The sensitivity, specificity, and accuracy of silicosis with lymphadenopathy with homogeneous enhanced pattern were 94.2%, 80.3% and 88.4%, respectively. The sensitivity, specificity, and accuracy of tuberculosis lymphadenopathy with peripheral enhanced pattern were 72.1%, 98.8%, and 87.7%, respectively., Conclusion: The predominant enhanced patterns, anatomical distribution, and calcification features of mediastinal lymph nodes were different between tuberculosis and silicosis. These radiographic features might help differentiate tuberculosis from silicosis, which provides imaging information for the differential diagnosis of the two diseases in a clinical setting., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Antibiotic resistance emerges as a major issue for Helicobacter pylori (H. pylori) treatment. High-dose dual therapy has recently shown encouraging results in H. pylori eradication, but it has yet to be validated in this H. pylori highly infected area; it is also not known if this concept can be extended to antibiotics other than amoxicillin, and factors that affect the eradication. We investigate if rabeprazole plus amoxicillin or furazolidone regimens could be a first-line therapy for H. pylori eradication, and factors that affect the curing rate., Methods: This is a single-center, prospective, open-label, randomized-controlled trial. Naive patients (n=292) were randomly treated with bismuth-containing quadruple therapy (BQT), rabeprazole plus amoxicillin (RADT), or furazolidone (RFDT) groups. RADT and FADT use three times daily regimens. H. pylori diagnosis and eradication were determined and confirmed by 13 C-urea breath test., Results: In per-protocol (PP) analysis, H. pylori eradication rate was 91.2% in BQT group, 89.6% in RADT, and 51.0% in RFDT group. In intention-to-treat (ITT) analysis, infection was eradicated in 86.7% of patients in BQT group, 85.8% in RADT, and 48.1% in RFDT groups, respectively. Noninferiority was confirmed between BQT and RADT groups. The incidence of side effects in BQT group was significantly higher than that in RADT group. Successful eradication was associated with lower body surface area (BSA) and low body mass index (BMI) in BQT group. Smoking and high BSA index reduced H. pylori eradication rate in RADT group., Conclusions: Rabeprazole-amoxicillin dual therapy is equally effective to the bismuth-containing quadruple therapy for H. pylori eradication with fewer side effects and saves use of one antibiotic per each treatment. Successful eradication is also associated with low BSA and non-smoking condition, which deserves future stratified analysis for refinement and optimization., (© 2022 John Wiley & Sons Ltd.)

All-solid-state K batteries are ideal energy storage devices for grid-scale applications of renewable energies. A novel electrolyte K[B 3 H 7 NH 2 BH 2 NH 2 B 3 H 7 ] with weakly coordinating anions was synthesized. It has a high K + conductivity of 1.01 × 10 -4 S cm -1 at 75 °C, which is probably due to the increased electrostatic potential and size of the anions.

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.)

Chinese hamster ovary (CHO) cell engineering based on CRISPR/Cas9 knockout (KO) technology requires the delivery of guide RNA (gRNA) and Cas9 enzyme for efficient gene targeting. With an ever-increasing list of promising gene targets, developing, and optimizing a multiplex gene KO protocol is crucial for rapid CHO cell engineering. Here, we describe a method that can support efficient targeting and KO of up to 10 genes through sequential transfections. This method utilizes Cas9 protein to first screen multiple synthetic gRNAs per gene, followed by Sanger sequencing indel analysis, to identify effective gRNA sequences. Using sequential transfections of these potent gRNAs led to the isolation of single cell clones with the targeted deletion of all 10 genes (as confirmed by Sanger sequencing at the DNA level and mass spectrometry at the protein level). Screening 704 single cell clones yielded 6 clones in which all 10 genes were deleted through sequential transfections, demonstrating the success of this decaplex gene editing strategy. This pragmatic approach substantially reduces the time and effort required to generate multiple gene knockouts in CHO cells., (© 2021 American Institute of Chemical Engineers.)

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.

Objective: To investigate the mechanism of electroacupuncture (EA) with the involvement of sarcoplasmic reticulum Ca 2+ -ATPase2a (SERCA2a)/phospholamban (PLB) on the synergistic and attenuated effect of aconitine for heart failure., Methods: Thirty SPF-ranked SD rats were randomly divided into a control group, a model group, an EA group, an aconitine group and an EA plus aconitine group, with 6 rats in each group. The rat model of acute heart failure was established by infusion of high-dose propranolol hydrochloride solution into the right femoral vein. After stabilized for 10 min in the modeled rats, EA was exerted at "Neiguan" (PC 6), with disperse-dense wave, 2 Hz/15 Hz in frequency, 3 mA in intensity, for 30 min in the EA group and the EA plus aconitine group; aconitine solution (10 μg/kg) was injected from the left femoral veins in the rats in the aconitine group and the EA plus aconitine group. Hemodynamic indexes such as the left ventricular systolic pressure (LVSP) and the maximum rate of increase/decrease of left ventricular pressure (±dp/dt max ) were detected and arrhythmia types were observed and scored. SERCA2a protein and PLB protein expressions in left ventricular myocardial tissue of rats were detected by multiplex fluorescence Western blot., Results: Compared with the control group, LVSP and ±dp/dt max all were decreased after modeling and at each time point after intervention in the model group ( P <0.01). Compared with the model group, ±dp/dt max was increased in the aconitine group and the EA group at 1 min after intervention ( P <0.01, P <0.05), +dp/dt max was increased at 10 to 60 min after intervention in the aconitine group and at 20 to 60 min after intervention in the EA group ( P <0.01, P <0.05), LVSP was increased at 1 min after intervention in the EA group ( P <0.01), while LVSP and ±dp/dt max were all increased at 1 to 60 min after intervention in the EA plus aconitine group ( P <0.01, P <0.05). Compared with the aconitine group, LVSP and +dp/dt max were increased at 1 min after intervention in the EA group ( P <0.01, P <0.05), LVSP and ±dp/dt max at 1 min after intervention while +dp/dt max at 20 to 60 min after intervention were all increased in the EA plus aconitine group ( P <0.01, P <0.05). Compared with the EA group, +dp/dt max was higher at 10 to 60 min after intervention in the EA plus aconitine group ( P <0.01). Compared with the model group, arrhythmia score was higher in the aconitine group ( P <0.01). Compared with the aconitine group, arrhythmia score was lower in the EA group and the EA plus aconitine group ( P <0.01). As compared with the control group, the expression of SERCA2a protein in the left ventricular cardiomyocytes was decreased ( P <0.01), while the expression of PLB protein was increased in the model group ( P <0.01). Compared with the model group, the expression of SERCA2a protein was increased in both the EA group and the EA plus aconitine group ( P <0.05, P <0.01), and PLB protein expression was decreased in each intervention group respectively ( P <0.01, P <0.05). As compared with the EA group and the aconitine group, the expression of SERCA2a protein was increased and the expression of PLB protein was decreased in the EA plus aconitine group separately ( P <0.05, P <0.01)., Conclusion: The intervention with electroacupuncture achieves the synergism/ attenuation effect of aconitine for the improvements in heart failure probably by up-regulating the expression of SERCA2a and down-regulating the expression of PLB in myocardial tissue.

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

Objective: To observe the influence of electroacupuncture(EA) combined with aconitine on the hemodyna-mics, echocardiogram, and arrhythmias in heart failure rats, so as to explore the facilitation and attenuation effects of EA combined with aconitine., Methods: SD rats were randomly divided into control, model, aconitine and aconitine+EA groups, with 6 rats in each group. Propranolol hydrochloride was used to establish the heart failure model. Rats in the aconitine group were trea-ted with aconitine continuously for 1 h (40 μg/kg). Rats in the aconitine +EA group were given the same treatment as the aconitine group, meanwhile, EA (3 mA, 2 Hz/15 Hz) was applied at "Neiguan"(PC6) for 30 min. Left ventricular catheter and small animal ultrasound imaging system were used to observe the heart hemodynamic indexes such as left ventricular systolic pressure(LVSP), maximal rate for left ventricular pressure rising (+dp/dt max ), and maximal rate for left ventricular pressure declining (-dp/dt max ), ejection fraction (EF) and fractional shortening (FS). The incidence rate of arrhythmia and arrhythmia score was observed by electrocardiogram., Results: Following modeling and compared with the control group, LVSP, +dp/dt max , -dp/dt max , EF and FS in the aconitine group all decreased( P <0.01) and maintained in the model group. The LVSP of rats in the aconitine group was higher than that of the model group at 15 min after administration of aconitine ( P <0.05), and +dp/dtmax was higher at 15, 60 min after administration ( P <0.05). Since 15 min after administration, EF and FS in the aconitine group were significantly higher than those of the model group ( P <0.01, P <0.05). After EA intervention, compared with the aconitine group, LVSP, +dp/dt max , -dp/dt max in the aconitine+EA group were significantly increased ( P <0.01, P <0.05) during administration and EF and FS in the aconitine+EA group significantly increased at the beginning of administration of aconitine and 30 and 60 min during administration ( P <0.05, P <0.01). The incidence rate of arrhythmia was 100% in the aconitine group, and 50.0% in the rats of aconitine + EA group. The arrhythmia score of aconitine + EA group was significantly lower than that of aconitine group ( P <0.05)., Conclusion: Aconitine has a certain inotropic effect, but it is easy to cause arrhythmia. The combination of EA and aconitine can not only improve the contractile function of the heart in rats with heart failure, but also reduce the toxic reaction of aconitine.

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.

Background: Two critical concerns during Helicobacter pylori (H. pylori) eradication are the successful eradication and recurrence. It is debatable whether whole family-based H. pylori treatment regimen might have any advantage over single-infected patient treatment approach in increasing eradication rate and reducing recurrence rate. We conduct systematic review and meta-analysis to compare the efficacy of these two treatment regimens in order to provide clinical practice a better option for H. pylori eradication., Methods: Randomized controlled trials evaluating H. pylori eradication and recurrence in whole family-based treatment group (WFTG) versus single-infected patient treatment group (SPTG) were collected from published literature up to July 2020 from common databases. Pooled results were analyzed using either fixed-effect or random-effect model. Results were expressed as the odds ratio (OR) and 95% confidence interval (CI)., Results: A total of 1751 relevant articles were identified, and 12 studies were eligible for analysis. Among them: (a) Eight articles including 1198 patients were selected to analyze H. pylori eradication rate, pooled result showed that eradication rate of WFTG was higher than that of SPTG (OR=2.93; 95% CI 1.68-5.13). Stratified analysis showed that H. pylori eradication rate in WFTG were higher over SPTG in children subgroup, but had no difference in spouse subgroup. (b) Six studies including 881 patients were analyzed for recurrence rate between the two groups, pooled analysis showed that the overall recurrence rate of WFTG was lower than that of SPTG (OR=0.3; 95% CI 0.19-0.48). Stratified analysis showed that the recurrence rate in WFTG was lower over SPTG at 6, 12, 18, and more than 24 months post-treatment subgroups., Conclusion: Whole family-based H. pylori treatment can partially increase eradication rate and reduce recurrence rate over single-infected patient treatment approach, the results provide clinical practice a novel notion for H. pylori eradication and infection prevention., (© 2021 John Wiley & Sons Ltd.)

AINTEGUMENTA-like (AIL) proteins are members of the APETALA 2/ETHYLENE RESPONSE FACTOR (AP2/ERF) domain family of transcription factors involved in plant growth, development, and abiotic stress responses. However, the biological functions of AIL members in pumpkin (Cucurbita moschata Duch.) remain unknown. In this study, we identified 12 AIL genes in the pumpkin genome encoding proteins predicted to be localized in the nucleus. Phylogenetic analysis showed that the AIL gene family could be classified into six major subfamilies, with each member encoding two AP2/ERF domains separated by a linker region. CmoAIL genes were expressed at varying levels in the examined tissues, and CmoANT genes showed different expression patterns under auxin (IAA), 1-naphthylphthalamic acid (NPA), and abscisic acid (ABA) treatments. Ectopic overexpression of CmoANT1.2 in Arabidopsis increased organ size and promoted growth of grafted plants by accelerating graft union formation. However, there was no significant difference at the graft junction for WT/WT and WT/ANT under IAA or NPA treatments. Taken together, the results of this study provide critical information about CmoAIL genes and their encoded proteins, and suggest future work should investigate the functions of CmoANT1.2 in the grafting process in pumpkin., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

The Multi-Attribute Method (MAM) Consortium was initially formed as a venue to harmonize best practices, share experiences, and generate innovative methodologies to facilitate widespread integration of the MAM platform, which is an emerging ultra-high-performance liquid chromatography-mass spectrometry application. Successful implementation of MAM as a purity-indicating assay requires new peak detection (NPD) of potential process- and/or product-related impurities. The NPD interlaboratory study described herein was carried out by the MAM Consortium to report on the industry-wide performance of NPD using predigested samples of the NISTmAb Reference Material 8671. Results from 28 participating laboratories show that the NPD parameters being utilized across the industry are representative of high-resolution MS performance capabilities. Certain elements of NPD, including common sources of variability in the number of new peaks detected, that are critical to the performance of the purity function of MAM were identified in this study and are reported here as a means to further refine the methodology and accelerate adoption into manufacturer-specific protein therapeutic product life cycles.

Background: Central injection of corticotrophin-releasing factor (CRF) mimics the effect of stress on gastrointestinal (GI) responses, including inhibition of GI motility. This study was designed to explore the effects of electroacupuncture (EA) on disordered jejunal motility in a rat model of stress induced by intracisternal (IC) injection of CRF., Methods: A stress model was established by IC injection of CRF in Sprague-Dawley rats. GI motility was evaluated by assessing gastric emptying (GE), gastrointestinal transit (GIT) and jejunal motility in vivo. EA was performed at ST36. The functional roles of CRF receptor subtype 1 and subtype 2 (CRFr1 and CRFr2) were examined by IC administration of the corresponding selective CRF antagonists. Protein expression of CRFr1 and CRFr2 in the hypothalamus and jejunum was detected by Western blotting., Results: IC injection of CRF significantly inhibited GE, GIT and jejunal motility. EA treatment remarkably improved the disturbed GI motility. Intriguingly, the disordered jejunal motility induced by central CRF was abolished by IC injection of a selective CRFr2 antagonist, indicating the essential role of central CRFr2 in mediating the stress-induced jejunal motor disorder. EA at ST36 decreased central and peripheral expression of CRFr2, which might be one of the potential mechanisms underlying the beneficial effect of EA on jejunal dysmotility in this rat model of stress., Conclusion: This study suggested that EA at ST36 could ameliorate disordered jejunal motility induced by stress, and that this might be associated with the down-regulation of CRFr2.