Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

ObjectiveTo establish the Shanghai twin birth cohort （STBC） and analyze the effects of genetic factors， shared environment， and non-shared environment interactions on birth health and growth and development of newborns. MethodsBased on the population-wide birth cohort in Shanghai， a comprehensive survey was conducted on the families with double and multiple babies born after January 1， 2015 to collect information on birth health， growth and development， and the family environment of the babies. ResultsBy December 31， 2021， a total of 7 195 pairs （14 405 cases） of twins were successfully included in the STBC survey. The average birth length of twins was 47.2 cm and average birth weight was 2 465.3 g. Heterozygous twins accounted for 69.05% and preterm babies accounted for 57.07%. The average age of the mothers of twins was 31.82 years， and the average age of the fathers was 33.87 years， with more than 80% of the parents having a college degree or above. 44.50% of the mothers used assisted reproductive technologies， 7.40% had illnesses during pregnancy， and 15.90% were exposed to passive smoking during pregnancy. During the survey period， the average monthly increase in the length of the twin infants was 2.09 cm， and the average monthly weight gain was 0.53 kg. ConclusionThe incidence of adverse outcomes such as maternal cesarean section rate， preterm birth， and low birth weight is higher in the twin birth population. Information on birth health as well as growth and development in childhood and adolescence in the twin birth population is collected based on STBC， which can provide a solid data foundation for studying children’s chronic non-communicable diseases， psychological and behavioral disorders and other complex health problems caused by the combined effects of genetics and the environment.

Natural products are important sources for the discovery of anti-tumor drugs. Evodiamine is the main alkaloid component of the traditional Chinese herb Wu-Chu-Yu, and it has weak antitumor activity. In recent years, a number of highly active antitumor candidates have been discovered with a significant progress. This article reviews the research progress of evodiamine-based antitumor drug design strategies, in order to provide reference for the development of new drugs with natural products as leads.

ObjectiveTo design a prospective nested case-control study based on a city-wide birth cohort of Shanghai， so as to understand their health status and explore the influencing factors of birth defects. MethodsBased on the birth registration covering the entire city of Shanghai， the nested case-control study of children with severe birth defects was designed. Children born with severe birth defects were selected as the case group， and healthy children were matched as the control group. Basic information， health status， maternal pregnancy history， and survival outcome of children both in the case group and the control group were collected through medical history review and home visits. The logistic regression model was used for multivariate analysis. ResultsA total of 18 875 infants born between January 1， 2011， and December 31， 2021， were included， among which 11 500 （60.93%） were children with severe birth defects and 7 375 （39.07%） were healthy children. The logistic regression model analysis showed that being male （OR=1.20， 95%CI：1.13‒1.29）， non-Shanghai residency （OR=1.16， 95%CI： 1.06‒1.25）， multiple births （OR=8.41， 95%CI：6.25‒11.30）， artificial insemination （OR=2.31， 95%CI：1.34‒3.99）， in vitro fertilization （IVF） （OR=1.85， 95%CI：1.44‒2.38）， maternal exposure to radiation （OR=1.83， 95%CI：1.07‒3.14）， maternal illness during pregnancy （OR=1.61， 95%CI：1.49‒1.74）， experiencing a traumatic event during pregnancy （OR=2.34， 95%CI：1.88‒2.92）， paternal chemical exposure （OR=1.88， 95%CI：1.32‒2.69）， paternal radiation exposure （OR=1.65， 95%CI： 1.18‒2.33）， family history of birth defects （OR=8.18， 95%CI： 3.96‒16.89）， being overweight before pregnancy （OR=1.16， 95%CI： 1.07‒1.27）， being obese before pregnancy （OR=1.15， 95%CI：1.03‒1.30）， and being excessively obese before pregnancy （OR=1.52， 95%CI：1.26‒1.83） were risk factors for the occurrence of birth defects. Analysis by type of birth defect found that prematurity was a risk factor for cardiac malformations and cheilopalatoschisis （OR=27.87， 95%CI： 20.84‒37.27）， especially ranking first in cardiac malformations. ConclusionAfter controlling for influencing factors， maternal overweight， obesity， and excessive obesity before pregnancy， artificial insemination， and IVF are independent risk factors for the occurrence of birth defects. Choosing a healthy lifestyle， improving physical and mental health during pregnancy， and controlling BMI during pregnancy are beneficial in reducing the risk of birth defects.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive dysfunction and behavioral impairment, and there is a lack of effective drugs to treat AD clinically. Existing medications for the treatment of AD, such as Tacrine, Donepezil, Rivastigmine, and Aducanumab, only serve to delay symptoms and but not cure disease. To add insult to injury, these medications are associated with very serious adverse effects. Therefore, it is urgent to explore effective therapeutic drugs for AD. Recently, studies have shown that a variety of enzyme inhibitors, such as cholinesterase inhibitors, monoamine oxidase (MAO)inhibitors, secretase inhibitors, can ameliorate cholinergic system dysfunction, Aβ production and deposition, Tau protein hyperphosphorylation, oxidative stress damage, and the decline of synaptic plasticity, thereby improving AD symptoms and cognitive function. Some plant extracts from natural sources, such as Umbelliferone, Aaptamine, Medha Plus, have the ability to inhibit cholinesterase activity and act to improve learning and cognition. Isochromanone derivatives incorporating the donepezil pharmacophore bind to the catalytic active site (CAS) and peripheral anionic site (PAS) sites of acetylcholinesterase (AChE), which can inhibit AChE activity and ameliorate cholinergic system disorders. A compound called Rosmarinic acid which is found in the Lamiaceae can inhibit monoamine oxidase, increase monoamine levels in the brain, and reduce Aβ deposition. Compounds obtained by hybridization of coumarin derivatives and hydroxypyridinones can inhibit MAO-B activity and attenuate oxidative stress damage. Quinoline derivatives which inhibit the activation of AChE and MAO-B can reduce Aβ burden and promote learning and memory of mice. The compound derived from the combination of propargyl and tacrine retains the inhibitory capacity of tacrine towards cholinesterase, and also inhibits the activity of MAO by binding to the FAD cofactor of monoamine oxidase. A series of hybrids, obtained by an amide linker of chromone in combine with the benzylpiperidine moieties of donepezil, have a favorable safety profile of both cholinesterase and monoamine oxidase inhibitory activity. Single domain antibodies (such as AAV-VHH) targeted the inhibition of BACE1 can reduce Aβ production and deposition as well as the levels of inflammatory cells, which ultimately improve synaptic plasticity. 3-O-trans-p-coumaroyl maslinic acid from the extract of Ligustrum lucidum can specifically inhibit the activity of γ-secretase, thereby rescuing the long-term potentiation and enhancing synaptic plasticity in APP/PS1 mice. Inhibiting γ-secretase activity which leads to the decline of inflammatory factors (such as IFN-γ, IL-8) not only directly improves the pathology of AD, but also reduces Aβ production. Melatonin reduces the transcriptional expression of GSK-3β mRNA, thereby decreasing the levels of GSK-3β and reducing the phosphorylation induced by GSK-3β. Hydrogen sulfide can inhibitGSK-3β activity via sulfhydration of the Cys218 site of GSK-3β, resulting in the suppression of Tau protein hyperphosphorylation, which ameliorate the motor deficits and cognitive impairment in mice with AD. This article reviews enzyme inhibitors and conformational optimization of enzyme inhibitors targeting the regulation of cholinesterase, monoamine oxidase, secretase, and GSK-3β. We are hoping to provide a comprehensive overview of drug development in the enzyme inhibitors, which may be useful in treating AD.

Objective To observe the effects of indobufen tablets combined with clopidogrel tablets on levels of serum myocardial injury indexes and incidence of major adverse cardiovascular events(MACE)in elderly patients with coronary heart disease after percutaneous coronary intervention(PCI).Methods The elderly patients with coronary heart disease after PCI were divided into treatment group[clopidogrel 75 mg(qd)combined with indobufen 200 mg(qd)]and control group[clopidogrel 75 mg(qd)combined with aspirin 100 mg(qd)]according to cohort method.All patients were treated for 3 months.The total effective rate,serum myocardial injury indexes[N terminal pro B type natriuretic peptide(NT-proBNP),cardiac troponin Ⅰ(cTn Ⅰ)],coagulation-fibrinolysis indexes[fibrinogen(FIB),prothrombin time(PT),antithrombin Ⅲ(AT-Ⅲ)]and platelet function indexes[platelet distribution width(PDW)]were compared between two groups.Occurrence of bleeding events and MACE within 6 months were compared between the two groups.The safety was evaluated.Results There were 32 cases in control group and 32 cases in treatment group.After treatment,the total effective rates in treatment group and control group were 93.75％(30 cases/32 cases)and 78.13％(25 cases/32 cases),without significant difference(P＞0.05).After treatment,NT-proBNP levels in treatment group and control group were(202.65±30.77)and(283.52±31.42)pg·mL-1,cTn Ⅰ levels were(0.06±0.01)and(0.12±0.03)ng·mL-1,FIB levels were(3.17±0.51)and(3.84±0.59)g·L-1,PT were(15.87±1.23)and(14.92±1.35)s,AT-Ⅲ levels were(138.95±14.18)％and(125.17±14.96)％,PDW were(17.04±2.04)％and(19.13±2.32)％,the differences were statistically significant(all P＜0.05).The incidences of bleeding events in treatment group and control group were 6.25％and 15.63％,adverse drug reactions were 9.38％and 15.63％,respectively,the differences of above indexes were statistically significant between two groups(all P＞0.05).The total incidences of MACE in treatment group and control group were 6.25％and 25.00％,respectively(P＜0.05).Conclusion Indobufen tablets combined with clopidogrel tablets can reduce levels of serum myocardial injury indexes in elderly patients with coronary heart disease after PCI,improve coagulation-fibrinolysis function and reduce the incidence of MACE.

The emerging and re-emerging arthropod-borne infectious diseases pose a serious threat to global public health security. Field and laboratory studies of arthropods of medical importance are essential and critical for the prevention and control of arthropod-borne infectious diseases. Various institutions or universities in China have been conducting research in the field or laboratory study of arthropods of medical importance, but up to 2023, it is still lacking detailed biosafety guidelines or recommendations that can guide the related work for arthropods of medical importance. In order to proactively address potential biosafety issues in the field or laboratory activities related to arthropods of medical importance, improve the standardization of arthropod biosafety classification, operations, and protection, and ensure the safety of practitioners, an expert consensus on the biosafety recommendation of arthropods of medical importance in field and laboratory has been developed, aiming to guide the future work of arthropods and ensure the national biosafety and biosecurity of China.

Objective To study the damage mechanism of diacetylmorphine(DAM)on BV-2cells.Methods BV-2 cells with the ability to divide and proliferate were selected as experimental objects,BV-2 cells were treated with 30,60 and 120 mg/L DAM,respectively.The cells were cu?tured for 4,8,16,32 and 48 h.The damage degree and proliferation inhibition rate of BV-2 cells were detected by trypan blue and thiazole blue(MTT)method.The effects of DAM on BV-2 cell cycle and apoptosis were detected with flow cytometry.The c-Fos,Bax,caspase-9,BDNF,HSP-70 and TrkB protein level in BV-2 cells were detected by ELISA.Results Trypan blue and MTT detection showed that the death cells increased significantly with the increase of DAM concentration and prolonged action time and the inhibition rate of BV-2 cells was significantly higher than that of the control group.Cell cycle showed that the number of G0/G1 phase cells in DAM group was significantly increased,the number of G2 phase cells was significantly decreased,and the apoptosis rate was increased.ELISA showed that the protein levels of caspase-9,c-Fos and Bax in DAM groups were significantly higher than those in the control group.On the contrary,BDNF,HSP-70 and TrkB protein levels were significantly lower than those in the control group.Conclusion The damage mechanism of DAM on BV-2 cells is related to up-regulating damage protein level,down-regulating protection protein level,damaging cell membrane structure,inhibiting cell division,leading to cell apoptosis and death.

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.

The effect of porcine SIRT5 on replication of foot and mouth disease virus type O(FMDV-O)and the underlying regulatory mechanism were investigated.Western blot and RT-qPCR analyses were employed to monitor expression of endoge-nous SIRT5 in PK-15 cells infected with FMDV-O.Three pairs of SIRT5-specific siRNAs were synthesized.Changes to SIRT5 and FMDV-O protein and transcript levels,in addition to virus copy numbers,were measured by western blot and RT-qPCR analyses.PK-15 cells were transfected with a eukaryotic SIRT5 expression plasmid.Western blot and RT-qPCR analyses were used to explore the impact of SIRT5 overexpression on FMDV-O replication.Meanwhile,RT-qPCR analysis was used to detect the effect of SIRT5 overexpression on the mRNA expression levels of type I interferon-stimulated genes induced by SeV and FMDV-O.The results showed that expression of SIRT5 was up-regulated in PK-15 cells infected with FMDV-O and siRNA interfered with SIRT5 to inhibit FMDV-O replication.SIRT5 overexpression promoted FMDV-O replication.SIRT5 over-expression decreased mRNA expression levels of interferon-stimulated genes induced by SeV and FMDV-O.These results suggest that FMDV-O infection stimulated expression of SIRT5 in PK-15 cells,while SIRT5 promoted FMDV-O rep-lication by inhibiting production of type I interferon-stimula-ted genes.These findings provide a reference to further ex-plore the mechanism underlying the ability of porcine SIRT5 to promote FMDV-O replication.