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 efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To analyze the influence of target-controlled infusion with different target concentrations of propofol and remifentanil on elderly patients undergoing painless fiberoptic bronchoscopy.Methods Elderly patients undergoing painless fiberoptic bronchoscopy were divided into low-dose group,middle-dose group and high-dose group.Target-controlled infusion with remifentanil and propofol was performed in low-dose group,middle-dose group and high-dose group,and the target effect-site concentrations of remifentanil all were 3.0 ng·mL-1,and the target effect-site concentrations of propofol were 3.0,4.0 and 5.0 μg·mL-1,respectively.The examination began when the target effect-site concentrations of propofol and remifentanil both reached the target concentrations.The anesthesia effect,anesthesia quality(anesthesia time,patient comfort and operator anesthesia satisfaction),recovery time,intubation time and the safety was evaluated.Results The low-dose,middle-dose and high-dose groups included 31,36 and 35 patients,respectively.The excellent and good rate of anesthesia in low-dose group,middle-dose group and high-dose group were 67.74％(21 cases/31 cases),77.78％(28 cases/36 cases)and 82.86％(29 cases/35 cases),respectively.The difference between middle-dose group and high-dose group and low-dose group was statistically significant(all P＜0.05).In the low-dose group,the middle-dose group and the high-dose group,the satisfaction of anesthesia were(6.13±1.19),(7.48±1.25)and(6.50±1.07)min,respectively;the recovery time were(7.01±1.64),(7.58±1.30)and(9.42±1.58)min,respectively;the intubation time were(9.94±2.02),(10.76±1.97)and(13.18±2.25)min,respectively.There were statistically significant differences between low-dose group and middle-dose group and high-dose group(all P＜0.05).The duration of anesthesia in low-dose group,middle-dose group and high-dose group were(31.18±4.26),(29.96±5.08)and(28.74±5.43)min,respectively;the comfort level were(8.95±0.49),(9.03±0.41)and(9.12±0.38)min,respectively;the incidence of hypotension was 12.90％,5.56％and 14.29％;the incidence of physical activity was 16.13％,8.33％and 5.71％;the incidence of cough was 19.35％,13.89％and 11.43％,respectively,The satisfaction of anesthesiologists in the meddle-dose group was significantly higher than that in the low-dose group and the high-dose group,and the differences were statistically significant(all P＜0.05).Conclusion Target-controlled infusion with propofol at a target effect-site concentration of 4.0 μg·mL-1 and remifentanil at a target effect-site concentration of 3.0 ng·mL-1 has the optimal anesthesia quality,the shortest recovery time and intubation time and good safety in elderly patients with painless fiberoptic bronchoscopy.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

A patient with a history of sulfonamide allergy and dermatomyositis was admitted to the hospital due to secondary infection.After admission,a comprehensive examination confirmed the presence of Pneumocystis jirovecii pneumonia(PJP)along with cytomegalovirus(CMV)and Klebsiella pneumoniae infections.Clinical pharmacists actively participated in the treatment process by referring to relevant clinical guidelines.For patients with Pneumocystis jirovecii infection,compound sulfamethoxazole(TMP-SMX)should be considered as the primary choice,while desensitization treatment is recommended for those with a history of sulfonamide allergy.Prior to treatment,the patient had pre-existing liver insufficiency and was on long-term glucocorticoid therapy,with complex medications.The clinical pharmacists provided individualized pharmaceutical care for this case,assisting clinicians in formulating scientifically and reasonably tailored drug treatment plans.They also offered new insights and references for selecting appropriate drugs considering the patient's previous sulfonamide allergies.After sulfonamide desensitization,the patients were administered a combination of TMP-SMX and carpofungin for anti-PJP treatment,along with ganciclovir for anti-CMV treatment,resulting in favorable therapeutic outcomes.

Objective To investigate the acupoint selection rules of obesity complicated with type 2 diabetes mellitus(T2DM)through R language data mining technology.Methods CNKI,Wanfang,VIP,CBM,PubMed,Embase,Cochrane Library,web of science and other major databases were searched by computer.From the establishment of the database to January 2024,the clinical research literature on acupuncture and moxibustion for the treatment of obesity with T2DM was included.Microsoft Excel 2021 was used to establish a database of acupoint prescriptions.R 4.3.2 and Rstudio software were used to analyze the frequency,meridian tropism,specific acupoints,correlation analysis,association rules and cluster analysis of acupoints.Results A total of 81 articles were included,and 117 prescriptions were extracted.It involves 82 acupoints,and the total frequency of acupoint usage is 1 072 times.The top five acupoints with the highest frequency were Zusanli(ST36),Zhongwan(RN12),Weiwanxiashu(EX-B3),Pishu(BL20),Tianshu(ST25).The meridian selection is mainly based on the stomach meridian of foot yangming,ren meridian,foot taiyang bladder meridian and foot taiyin spleen meridian.The five-shu points are the specific points with the highest frequency of use.Correlation analysis showed that there were three groups of strongly related acupoint groups.The core acupoints were obtained by association rule analysis.Cluster analysis and machine voting were performed on acupoints with frequency ≥ 10 by function,and a total of four cluster acupoint groups were obtained.Conclusion Through R language data analysis,the principle of acupoint selection for acupuncture and moxibustion in the treatment of obesity complicated with T2DM is mainly based on abdominal local acupoints,combined with visceral syndrome differentiation and empirical point selection,which provides effective treatment ideas for acupuncture and moxibustion in the treatment of obesity complicated with T2DM.

Cervical spondylotic radiculopathy(CSR)is a condition caused by the degeneration of cervical intervertebral discs and facet joints,primarily manifesting as the pain,sensory abnormalities,and motor dysfunction in the cervical nerve innervation area of neck,shoulder,and upper limb.For the treatment of CSR,tendon-bone syndrome differentiation in traditional Chinese medicine often faces the issues of conceptual confusion and non-standard syndrome differentiation.Based on the traditional tendon-bone syndrome differentiation and by integrating modern anatomical insights,Professor LIN Ding-Kun,an esteemed scholar of Traditional Chinese Medicine,proposed a classification system for the cervical spine that includes the categories of tendons,joints,bones and marrow.This paper explored the thoughts of Professor LIN for the tendon-bone syndrome differentiation of CSR,summarized the targets of manual therapy,and proposed the four kinds of pathological changes such as tendon overstrain,joint dislocation,bone lesion,and marrow injury,as well as the four techniques of traditional Chinese medicine manipulations,i.e.relaxation of tendons,reduction of joints,protection of marrow,and treatment of bones.The aim is to improve the syndrome-differentiation and treatment for CSR with orthopedic and traumatologic manipulations,and to provide reference for clinical practice.

The pathogenesis of rheumatoid arthritis patients exerts the features of wind-damp and stasis obstruction,sinew injury and bone damage,therefore,the therapy of dispelling wind and removing dampness,dredging blood vessels,unblocking meridians and collaterals,invigorating spleen and kidney,and strengthening muscles and bones was proposed,hereinafter referred to as Qushi Tongmai method.Under the guidance of Qushi Tongmai method,rheumatoid arthritis can be treated with Chinese medicine based on the modification of empirical formulas such as Kunduan Yimu Formula,Nanxu Yimu Granules and Santeng Shujin Formula,and classical formulas such as Guizhi Shaoyao Zhimu Decoction,Huangqi Guizhi Wuwu Decoction and Banxia Xiexin Decoction according to the deficiency and excess of healthy qi and pathogenic qi as well as the specific symptoms.Moreover,the soft exact,external treatment and functional exercise can be also included.The Chinese medicine therapy combined with the soft exact,external treatment and functional exercise constitutes a unique Chinese medicine system for the prevention and treatment of rheumatoid arthritis.The results of a series of clinical and experimental studies indicated that Qushi Tongmai method exerts efficiency-enhancing and toxin-reducing effect in the treatment of rheumatoid arthritis,and the establishment of Qushi Tongmai method is a theoretical innovation in exerting the advantages of Chinese medicine in the prevention and treatment of rheumatoid arthritis.

The male patient,one day old,was admitted to the hospital due to hypoglycemia accompanied by apnea appearing six hours after birth.The patient had transient hypoglycemia early after birth,and acute heart failure suddenly occurred on the eighth day after birth.Laboratory tests showed significantly reduced levels of adrenocorticotropic hormone and cortisol,and pituitary magnetic resonance imaging was normal.Genetic testing results showed that the patient had probably pathogenic compound heterozygous mutations of the TBX19 gene(c.917-2A＞G+c.608C＞T),inherited respectively from the parents.The patient was conclusively diagnosed with congenital isolated adrenocorticotropic hormone deficiency caused by mutation of the TBX19 gene.Upon initiating hydrocortisone replacement therapy,cardiac function rapidly returned to normal.After being discharged,the patient continued with the hydrocortisone replacement therapy.By the 18-month follow-up,the patient was growing and developing well.In neonates,unexplained acute heart failure requires caution for possible endocrine hereditary metabolic diseases,and timely cortisol testing and genetic testing should be conducted.[Chinese Journal of Contemporary Pediatrics,2024,26(3):321-324,V]

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.