As the population is aging rapidly,the incidence of Alzheimer's disease(AD)is increasing year by year.The World Health Organization stresses that early prevention plays a key role in reducing the incidence of AD.Subjective cognitive decline(SCD)is an early window of AD development,and timely intervention can effectively slow down the progression of the disease or prevent it from developing into dementia,thus reducing the burden on the society.White matter hyperintensity(WMH)can effectively reflect white matter changes and provide strong evidence to identify SCD.In this paper,we review the recent research progress in WMH and SCD,reveal the problems in the current research on WMH,explain the correlation between WMH and SCD in terms of physiopathology and cognitive function,and put forward several suggestions for the future research.
Humans ; White Matter/pathology* ; Cognitive Dysfunction/pathology* ; Alzheimer Disease/pathology* ; Magnetic Resonance Imaging

Objective To explore the effects of Rhodiola salidroside on regulating the mitogen-activated protein kinase(MAPK)/extracellular signal-regulated kinase(ERK)/mammalian target of rapamycin(mTOR)signaling pathway and explore its impact on hippocampal neuron autophagy and apoptosis induced by oxygen-glucose deprivation/reperfusion(OGD/R).Methods The mouse hippocampal neuronal cell line HT22 was cultured in vitro and randomly divided into control group,OGD/R group,salidroside group,tert-butylhydroquinone(TBHQ)group,and salidroside+TBHQgroup.Except for control group,cell models were established by OGD/R induction in other groups.Cells in corresponding groups were treated with Rhodiola salidroside(500 μmol/L)and/or MAPK activator TBHQ(50 μmol/L)for 24 h.The lactate dehydrogenase(LDH)release rates were measured,cell apoptosis was detected by flow cytometry,and cell viability was assessed by MTT assay.Acridine orange(AO)staining was used to detect autophagy.Enzyme-linked immunosorbent assay(ELISA)was used to measure the expression levels of inflammatory cytokines including interleukins(IL)-6,IL-8,and IL-17,and tumor necrosis factor-α(TNF-α).Western blotting was performed to detect the expression levels of proteins related to apoptosis,autophagy,and the MAPK/ERK/mTOR signaling pathway.Results Salidroside(500 μmol/L)significantly enhanced the viability of OGD/R-induced HT22 cells(P＜0.05),without obvious effect on the viability of normally cultured HT22 cells(P＞0.05).Compared with control group,OGD/R group showed significantly increased LDH release rates,apoptosis rates,autophagosome formation rates,levels of IL-6,IL-8,IL-17 and TNF-α,expressions of Bcl-2-associated X protein(Bax),Cleaved Caspase-3,Caspase-3 and Beclin-1 protein,ratios of microtubule-associated protein 1 light chain 3(LC3)-Ⅱ/LC3-Ⅰ,phosphorylation(p)-p38 MAPK/p38 MAPK,and p-ERK1/2/ERK1/2(P＜0.05),while cell viability and p-mTOR/mTOR ratio were significantly decreased(P＜0.05).Compared with OGD/R group,salidroside group had significantly reduced LDH release rates,apoptosis rates,autophagosome formation rates,levels of IL-6,IL-8,IL-17,and TNF-α,expressions of Bax,Cleaved Caspase-3,Caspase-3,Beclin-1 protein,and ratios of LC3-Ⅱ/LC3-Ⅰ ratio,p-p38 MAPK/p38 MAPK,and p-ERK1/2/ERK1/2(P＜0.05),while cell viability and p-mTOR/mTOR ratio were significantly increased(P＜0.05).The change of indicators in TBHQgroup showed an opposite trend to those in salidroside(P＜0.05).Compared with salidroside group,salidroside+TBHQgroup had significantly increased LDH release rates,apoptosis rates,autophagosome formation rates,levels of IL-6,IL-8,IL-17 and TNF-α,expressions of Bax,Cleaved Caspase-3,Caspase-3,Beclin-1 protein,and ratios of LC3-Ⅱ/LC3-Ⅰ,p-p38 MAPK/p38 MAPK,and p-ERK1/2/ERK1/2(P＜0.05),while cell viability and p-mTOR/mTOR ratio were significantly decreased(P＜0.05).Conclusion Salidroside may inhibit OGD/R-induced hippocampal neuron autophagy and apoptosis by blocking the activation and transmission of MAPK/ERK/mTOR signaling pathway.

Objective To investigate the protective effect of long non-coding RNA(lncRNA)small nucleolar RNA host gene 12(SNHG12)on neuronal damage induced by oxygen glucose deprivation/reoxygenation(OGD/R)by targeting microRNA(miR)-140-3p.Methods Human cortical neurons(HCN)were used to establish an OGD/R model,which was separated into OGD/R group,negative control(NC)group,SNHG12 group,SNHG12+miR-NC group,and SNHG12+miR-140-3p mimics group.Normal cultured HCN were also taken as the control(Ctrl)group.There were 6 repetitions in each group.Cell proliferation,apoptosis,lactate dehydrogenase(LDH)activity,mitochondrial membrane potential,lncRNA SNHG12 and miR-140-3p expression levels,and the interaction of lncRNA SNHG12 and miR-140-3p were detected.Results Compared with the control group,the survival rate of HCN,mitochondrial membrane potential,and lncRNA SNHG12 expression were lower in the OGD/R group,while the LDH activity,apoptosis rate,and miR-140-3p expression were higher(P＜0.05).Compared with the OGD/R group and NC group,the survival rate of HCN,mitochondrial membrane potential,and lncRNA SNHG12 expression were higher in the SNHG12 group,while the LDH activity,apoptosis rate,and miR-140-3p expression were lower(P＜0.05).Compared with the SNHG12+miR-NC group,the survival rate of HCN,mitochondrial membrane potential,and lncRNA SNHG12 expression were lower in the SNHG12+miR-140-3p mimics group,while the LDH activity,apoptosis rate,and miR-140-3p expression were higher(P＜0.05).Dual luciferase activity showed a targeted relationship between lncRNA SNHG12 and miR-140-3p(P＜0.05).Conclusion LncRNA SNHG12 may exert a protective effect against OGD/R-induced neuronal damage by inhibiting miR-140-3p.

Objective To observe the effect of multi-modal hand hygiene(HH)intervention on HH compliance,as well as the relationship between HH compliance and the healthcare-associated(HA)case infection incidence.Methods From 2014 to 2022,the infection control team in a tertiary first-class hospital implemented multi-modal HH intervention for health care workers(HCWs).The changing trend of HH monitoring data,the correlation be-tween HH compliance rate and HA case infection incidence were analyzed retrospectively.Results The consump-tion of HH products in the wards showed a stable upward trend;HH compliance rate increased from 64.98％in 2014 to 85.01％in 2022(P＜0.001),and HA case infection incidence decreased from 1.21％to 0.83％(P＜0.05).HH compliance rate was negatively correlated with HA case infection incidence(r=-0.369,P=0.027).HH compliance rates in different regions and job posts in each quarter were increased(P＜0.001).For 5 different HH moments in each quarter,HH compliance rate fluctuated slightly before sterile manipulation and after touching patient;presented rising trend after touching surroundings around patient,and decreased before touching patient and after touching patient's body fluid since 2020(P＜0.001).Conclusion Multi-modal HH intervention can im-prove the HH compliance of HCWs,improving their HH awareness is conducive to reducing HA case infection incidence.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Rheumatoid arthritis (RA) is an autoimmune disease driven by antigens and mediated by T cells. Collagen II (CII) and fibrinogen (Fib) are the two main antigens in the pathogenesis of RA. The antigen produced after citrulline modification (Cit) is also one of the inducements to induce the body to produce a pathogenic anti-citrulline protein antibody (ACPA). To provide a reference for RA-related research, this study intends to establish an RA animal model by using CII, Cit-CII, Fib, and Cit-Fib antigens, emulsification with complete Freund's adjuvant and immunization with DBA/1 mice, respectively, to compare the pathological characteristics of RA models induced by different antigens from the aspects of pathology, imaging and serum biochemistry. Animal welfare and experimental process are in accordance with the regulations of the Experimental Animal Ethics Committee of the China Academy of Chinese Medical Sciences. The results showed that the CII, Cit-CII, and Cit-Fib induced mice all had symptoms such as joint redness and swelling, and toe deformation and the clinical score and incidence rate were higher than those of the normal group. The CII group had the most serious lesions, with a incidence rate of 100%, and the Cit-CII and Cit-Fib groups had mild symptoms, with a incidence rate of 25% and 37.5%, respectively; pathological and imaging examination results showed that the joints of mice in CII-induced group showed severe synovial inflammation, cartilage and bone destruction, while those in Cit-CII and Cit-Fib group showed only slight inflammatory infiltration, joint cavity stenosis and bone destruction; the results of serum antibody detection showed that CII, Cit-CII and Cit-Fib groups all produced high levels of anti-cyclic citrullinated peptide (CCP) antibodies, among which, Cit-Fib group > Cit-CII group > CII group > Fib group, and both Cit-CII and Cit-Fib groups produced high levels of citrullinated epitope-specific antibodies, while the total IgG level was the highest in CII group; serum ELISA and RT-PCR analysis of joint tissue showed that the expression of pro-inflammatory factors and bone destruction-related molecules increased most significantly in the CII-induced group, followed by Cit-Fib and Cit-CII. The above results showed that among the four different antigens, the symptoms and conditions of arthritis in RA mice induced by CII were the most serious, and IgG instead of anti-CCP antibody was its typical immunological feature, and CII could be the first choice for the model of RA mice; Cit-Fib has certain immunogenicity, can partially induce the symptoms and conditions of RA arthritis in mice, and produce high-level anti-CCP antibody and anti-Cit-Fib antibody, which is more suitable for the study of citrulline-related RA; although Cit-CII has certain immunogenicity, the incidence, and severity of RA arthritis induced by Cit-CII in mice are low.

The approach combining disease, syndrome, and symptom was employed to investigate the characteristic changes of blood stasis syndrome in a rat model of steroid-induced osteonecrosis of the femoral head(SONFH) during disease onset and progression. Seventy-two male SD rats were randomized into a healthy control group and a model group. The rat model of SONFH was established by injection of lipopolysaccharide(LPS) in the tail vein at a dose of 20 μg·kg~(-1)·d~(-1) on days 1 and 2 and gluteal intramuscular injection of methylprednisolone sodium succinate(MPS) at a dose of 40 mg·kg~(-1)·d~(-1) on days 3-5, while the healthy control group received an equal volume of saline. The mechanical pain test, tongue color RGB technique, gait detection, open field test, and inclined plane test were employed to assess hip pain, tongue color, limping, joint activity, and lower limb strength, respectively, at different time points within 21 weeks of modeling. At weeks 2, 4, 8, 12, 16, and 21 after modeling, histopathological changes of the femoral head were observed by hematoxylin-eosin(HE) staining and micro-CT scanning; four coagulation items were measured by rotational thromboelastometry; and enzyme-linked immunosorbent assay(ELISA) was employed to determine the levels of six blood lipids, vascular endothelial growth factor(VEGF), endothelin-1(ET-1), nitric oxide(NO), tissue-type plasminogen activator(t-PA), plasminogen activator inhibitor factor-1(PAI-1), bone gla protein(BGP), alkaline phosphatase(ALP), receptor activator of nuclear factor-κB(RANKL), osteoprotegerin(OPG), and tartrate-resistant acid phosphatase 5b(TRAP5b) in the serum, as well as the levels of 6-keto-prostaglandin 1α(6-keto-PGF1α) and thromboxane B2(TXB2) in the plasma. The results demonstrated that the pathological alterations in the SONFH rats were severer over time. The bone trabecular area ratio, adipocyte number, empty lacuna rate, bone mineral density(BMD), bone volume/tissue volume(BV/TV), trabecular thickness(Tb.Th), trabecular number(Tb.N), bone surface area/bone volume(BS/BV), and trabecular separation(Tb.Sp) all significantly increased or decreased over the modeling time after week 4. Compared with the healthy control group, the mechanical pain threshold, gait swing speed, stride, standing time, and walking cycle of SONFH rats changed significantly within 21 weeks after modeling, with the greatest difference observed 12 weeks after modeling. The time spent in the central zone, rearing score, and maximum tilt angle in the open field test of SONFH rats also changed significantly over the modeling time. Compared with the healthy control group, the R, G, and B values of the tongue color of the model rats decreased significantly, with the greatest difference observed 11 weeks after modeling. The levels of total cholesterol(TC), total triglycerides(TG), low-density lipoprotein-cholesterol(LDL-C), and apoprotein B(ApoB) in the SONFH rats changed significantly 4 and 8 weeks after modeling. The levels of VEGF, ET-1, NO, t-PA, PAI-1, 6-keto-PGF1α, TXB2, four coagulation items, and TXB2/6-keto-PGF1α ratio in the serum of SONFH rats changed significantly 4-16 weeks after modeling, with the greatest differences observed 12 weeks after modeling. The levels of BGP, TRAP5b, RANKL, OPG, and RANKL/OPG ratio in the serum of SONFH rats changed significantly 8-21 weeks after modeling. During the entire onset and progression of SONFH in rats, the blood stasis syndrome characteristics such as hyperalgesia, tongue color darkening, gait abnormalities, platelet, vascular, and coagulation dysfunctions were observed, which gradually worsened and then gradually alleviated in the disease course(2-21 weeks), with the most notable differences occurred around 12 weeks after modeling.
Rats ; Male ; Animals ; Femur Head/pathology* ; Plasminogen Activator Inhibitor 1/adverse effects* ; Vascular Endothelial Growth Factor A ; Femur Head Necrosis/pathology* ; Rats, Sprague-Dawley ; Steroids ; Pain ; Cholesterol

Hepatic cystic echinococcosis is a chronic parasitic disease caused by the infection with the larvae of Echinococcus granulosus in human or animal liver tissues. As a chronic active infectious disease, tuberculous empyema mainly invades the pleural space and then causes visceral and parietal pleura thickening. It is rare to present comorbidity for hepatic cystic echinococcosis and tuberculous empyema. This case report presents a case of hepatic cystic echinococcosis complicated with tuberculous empyema misdiagnosed as hepatic and pulmonary cystic echinococcosis, aiming to improve clinicians’ ability to distinguish this disorder.

The dry eye is a common ocular surface disease caused by multiple factors with multiple pathogenesis. With the increasing morbidity of dry eye in our country year by year, dry eye has gradually attracted people's attention. The pathogenesis of dry eye is more complicated whose critical influencing factors include inflammation, corneal and conjunctival epithelial cell changes, tear film composition changes, corneal nerve changes, and meibomian gland dysfunction and so on. The tear film hypertonicity leads to the hypertonicity of the ocular surface epithelial cells, stimulating the cascade of inflammation, which is the most critical part among the pathogenesis of dry eye. A variety of inflammatory mediators and immune cells are involved in this process, and more and more people have reached a consensus that the dry eye is an antigen-specific autoimmune inflammatory disease and they are closely correlated with each. In clinical treatment, various anti-inflammatory drugs and drugs promoting tear secretion mark the rapid development of drug therapy for dry eye to some extent, but dry eye treatment is not only to improve symptoms, but to carry out treatment according to specific etiology. Recently, researches on the immune mechanism of dry eye have been increasing. This article reviewed on the immune progress of dry eye to realize the clinical significance and systematically understand the role of which in the occurrence and development of dry eye.

Objective: To investigate the efficacy and safety of a new cervical artificial disc prosthesis in the treatment of cervical degenerative diseases. Methods: The clinical data of 18 patients with single-level cervical degenerative diseases who underwent three dimensional printed anatomical bionic cervical disc replacement at Department of Spinal Surgery,Honghui Hospital,Xi'an Jiaotong University from May 2019 to July 2020 were analyzed retrospectively. There were 7 males and 11 females,aged (45±8) years old(range:28 to 58 years).The surgical segment was located at C_3－4 level in 2 cases, C_4－5 level in 5 cases, C_5－6 level in 9 cases, and C_6－7 level in 2 cases.The clinical and radiographic outcomes were recorded and compared at preoperative,postoperative times of one month and twelve months.The clinical assessments contained Japanese orthopedic association (JOA) score,neck disability index (NDI) and visual analogue scale (VAS).Imaging assessments included range of motion (ROM) of cervical spine, prosthesis subsidence and prosthesis anteroposterior migration.Repeated measurement variance analysis was used for comparison between groups,and paired t test was used for pairwise comparison. Results: All patients underwent the operation successfully and were followed up for more than 12 months.Compared with preoperative score,the JOA score,NDI and VAS were significantly improved after surgery (all P<0.01).There was no significant difference in postoperative ROM compared with 1-and 12-month preoperative ROM (t=1.570,P=0.135;t=1.744,P=0.099). The prosthesis subsidence was (0.29±0.13) mm (range: 0.18 to 0.50 mm) at 12-month postoperatively.The migration of prosthesis at 12-months postoperatively were (0.71±0.20) mm (range: 0.44 to 1.08 mm).There was no prosthesis subsidence or migration>2 mm at 12-month postoperatively. Conclusion: Three dimensional printed anatomical biomimetic cervical artificial disc replacement has a good early clinical effect in the treatment of cervical degenerative diseases, good mobility can be obtained while maintaining stability.
Adult ; Biomimetics ; Cervical Vertebrae/surgery* ; Female ; Follow-Up Studies ; Humans ; Intervertebral Disc/surgery* ; Intervertebral Disc Degeneration/surgery* ; Male ; Middle Aged ; Range of Motion, Articular ; Retrospective Studies ; Total Disc Replacement/methods* ; Treatment Outcome