The study aims to investigate and compare the effects of probiotics and docosahexaenoic acid (DHA) with the Alzheimer's disease (AD) therapeutic drug donepezil on the learning cognition and brain damage related indexes in AD mice, and to provide experimental basis for its treatment of AD. All animal experiments were approved by the Ethics Committee of the Henan University of Chinese Medicine (ethics number DWLL2018080003). Fifty male C57BL/6J mice were randomly assigned to one of five groups: sham-operated, model, donepezil (10 mg·kg^-1), probiotic (2.7×10⁹ CFU·d^-1), and DHA (0.104 g·kg^-1). Except for the sham-operated group, the AD animal model was established by injecting Aβ_25-35 (200 μmol·L^-1) in the lateral ventricle, followed by gavage administration for 4 weeks. In all mouse groups, learning memory ability, neuronal morphology in the hippocampus, apoptosis of primary hippocampal cells, and immune cell levels were detected. The levels of Aβ_1-42, Aβ_1-40, p-Tau, AchE, Ach, oxidative stress, glial cell activation, and the inflammatory factors IL-1β, IL-10, and TNF-α in the brain tissue of mice were also detected. 16S rDNA sequencing was used to further investigate the effects of donepezil and probiotics on AD. Donepezil, probiotics and DHA improved cognitive deficits and enhanced learning memory in Aβ_25-35-induced mice by increasing locomotion time, locomotion distance, autonomic alternation rate, and shortening the time to reach the plateau; it significantly attenuated Aβ_25-35-induced brain injury and neuroinflammation in mice by decreasing Aβ_1-42, Aβ_1-40, p-Tau, AchE, IL-1β, TNF-α, and MDA and increasing the levels of Ach, IL-10, GSH-Px, and T-SOD in brain tissues, as well as decreasing the activation of glial cells, and had a modulatory effect on immune cells. 16S rDNA sequencing shows that both donepezil and probiotics restore flora homeostasis and that differential bacteria are strongly associated with cognition, AD pathology, and neuroinflammation. Combining all indicators, donepezil and probiotics were more effective than DHA. All in all, donepezil, probiotics and DHA ameliorate Aβ_25-35-induced cognitive dysfunction and brain damage in mice by modulating immune cells, reducing the number of apoptotic cells and glial cell activation in the brain, and decreasing the levels of oxidative stress and inflammatory factor expression, among which the effects of donepezil and probiotics were better than those of DHA, and the therapeutic effects of donepezil and probiotics on AD were closely related to the modulation of gut microbiome.

AIM: To evaluate the necessity of slit-lamp biomicroscopy(referred to here as “slit-lamp”)training from the student's perspective and reach a consensus on slit-lamp training in medical students during ophthalmology clerkship.METHODS: A controlled before-after clerkship study was performed on 117 students of the class of 2017 enrolled in clinical medicine at Sun Yat-sen University. All medical students underwent slit-lamp training during ophthalmology clerkship. We evaluated the students' cognition, perceived need and recommendations for slit-lamp teaching, using a self-completed questionnaire survey and compared the students' scores in these aspects before and after their ophthalmology clerkships. Additionally, the efficiency of slit-lamp training was evaluated by subjective student assessment after the ophthalmology clerkship. Each item was scored on a five-point Likert Scale. Statistical analysis was performed by IBM SPSS(Version 20.0; SPSS Inc., Chicago, IL, USA).RESULTS: A total of 116(99.1%)medical students completed the survey. The average score before clerkship was 19.99±3.03, which indicated a high level of cognition regarding slit-lamp utility; However, this score significantly increased to 22.97±2.37 after clerkship(P<0.001). The average score regarding perceived need was also higher for post-clerkship students than for pre-clerkship students(24.62±3.15 vs. 23.60±2.36, P=0.009). Moreover, 86.2% of post-clerkship students reported that hands-on slit-lamp practice could help promote clerkship quality. More than three-quarters of the surveyed students tended to agree that slit-lamp practice time should be increased(76.7% and 77.6% before and after clerkship, respectively).CONCLUSION: A hands-on approach to slit-lamp training is more favored by medical students in ophthalmology clerkships, and this training should be recommended in ophthalmology clerkships given its potential usefulness for improving clerkship quality.

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ²=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.
Male ; Humans ; Middle Aged ; Reverse Transcriptase Inhibitors/therapeutic use* ; HIV Infections/drug therapy* ; Drug Resistance, Viral/genetics* ; China/epidemiology* ; Mutation ; HIV-1/genetics* ; Protease Inhibitors/therapeutic use* ; Genotype

The exploration of drug toxicity and mechanisms is a vital component in ensuring the safe use of drugs in clinical practice, as this topic has attracted widespread concern. The intestinal flora holds great significance for drug metabolism, efficacy and mechanism, and is an instrumental metabolic organ that facilitates material information transfer and biotransformation. However, an increasing number of studies have shown that intestinal bacteria are closely related to the toxicity of specific drugs. On the one hand, drugs are transformed into toxic metabolites under the influence of intestinal bacteria, thus inducing direct drug toxicity. On the other hand, the composition and function of the intestinal flora are altered under drug influence, resulting in disruption of endogenous metabolic pathways. Consequently, this disruption compromises the intestinal barrier and affects other organs, leading to indirect drug toxicity. This review meticulously compiles recent examples of drug toxicity attributed to intestinal bacteria, explores in depth the contention that metabolic enzymes of gut microbiota may be of great influence on oral drug toxicity, and outlines prospective avenues for future research on gut microbiota and drug toxicity and mechanisms. This not only provides novel perspectives for the judicious clinical utilization of drugs but also offers insights for the safety assessment of innovative pharmaceuticals.

Objective:To assess the clinical effectiveness and safety of Omalizumab for treating pediatric allergic asthma in real world in China.Methods:The clinical data of children aged 6 to 11 years with allergic asthma who received Omalizumab treatment in 17 hospitals in China between July 6, 2018 and September 30, 2020 were retrospectively analyzed.Such information as the demographic characteristics, allergic history, family history, total immunoglobulin E (IgE) levels, specific IgE levels, skin prick test, exhaled nitric oxide (FeNO) levels, eosinophil (EOS) counts, and comorbidities at baseline were collected.Descriptive analysis of the Omalizumab treatment mode was made, and the difference in the first dose, injection frequency and course of treatment between the Omalizumab treatment mode and the mode recommended in the instruction was investigated.Global Evaluation of Treatment Effectiveness (GETE) analysis was made after Omalizumab treatment.The moderate-to-severe asthma exacerbation rate, inhaled corticosteroid (ICS) dose, lung functions were compared before and after Omalizumab treatment.Changes in the Childhood Asthma Control Test (C-ACT) and Pediatric Asthma Quality of Life Questionnaire (PAQLQ) results from baseline to 4, 8, 12, 16, 24, and 52 weeks after Omalizumab treatment were studied.The commodity improvement was assessed.The adverse event (AE) and serious adverse event (SAE) were analyzed for the evaluation of Omalizumab treatment safety.The difference in the annual rate of moderate-to-severe asthma exacerbation and ICS reduction was investigated by using t test.The significance level was set to 0.05.Other parameters were all subject to descriptive analysis.A total of 200 allergic asthma patients were enrolled, including 75.5% ( n=151) males and 24.5% ( n=49) females.The patients aged (8.20±1.81) years. Results:The median total IgE level of the 200 patients was 513.5 (24.4-11 600.0) IU/mL.Their median treatment time with Omalizumab was 112 (1-666) days.Their first dose of Omalizumab was 300 (150-600) mg.Of the 200 cases, 114 cases (57.0%) followed the first Omalizumab dosage recommended in the instruction.After 4-6 months of Omalizumab treatment, 88.5% of the patients enrolled ( n=117) responded to Omalizumab.After 4 weeks of treatment with Omalizumab, asthma was well-controlled, with an increased C-ACT score [from (22.70±3.70) points to (18.90±3.74) points at baseline]. Four-six months after Omalizumab administration, the annual rate of moderate-to-severe asthma exacerbation had a reduction of (2.00±5.68) per patient year( t=4.702 5, P<0.001), the median ICS daily dose was lowered [0 (0-240) μg vs. 160 (50-4 000) μg at baseline] ( P<0.001), the PAQLQ score was improved [(154.90±8.57) points vs. (122.80±27.15) points at baseline], and the forced expiratory volume in one second % predicted (FEV 1%pred) was increased [(92.80±10.50)% vs. (89.70±18.17)% at baseline]. In patients with available evaluations for comorbidities, including allergic rhinitis, atopic dermatitis or eczema, urticaria, allergic conjunctivitis and sinusitis, 92.8%-100.0% showed improved symptoms.A total of 124 AE were reported in 58 (29.0%) of the 200 patients, and the annual incidence was 0(0-15.1) per patient year.In 53 patients who suffered AE, 44 patients (83.0%) and 9 patients (17.0%) reported mild and moderate AE, respectively.No severe AE were observed in patients.The annual incidence of SAE was 0(0-1.9) per patient year.Most common drug-related AE were abdominal pain (2 patients, 1.0%) and fever (2 patients, 1.0%). No patient withdrew Omalizumab due to AE. Conclusions:Omalizumab shows good effectiveness and safety for the treatment of asthma in children.It can reduce the moderate-to-severe asthma exacerbation rate, reduce the ICS dose, improve asthma control levels, and improve lung functions and quality of life of patients.

Objective:To seek any correlation between cortical activity and the swallowing of dysphagia patients with infratentorial stroke, and to observe any effect of three-needle acupuncture of the tongue on such activity.Methods:Thirty infratentorial stroke survivors with dysphagia were randomly divided into a tongue three-needle group and a sham acupuncture group, each of 15. Functional near-infrared spectroscopy was used to monitor changes in the concentration of oxygenated hemoglobin (ΔHbO 2) at rest, during acupuncture (or sham acupuncture), during real or sham electro-acupuncture, and at rest after the acupuncture or sham acupuncture treatment. The Modified Rankin Scale, a Penetration-Aspiration Scale (PAS), and the Functional Oral Intake Scale were employed to assess overall functional disability and the swallowing of both groups. Results:At rest the average ΔHbO 2 concentrations recorded in the left primary motor cortex, the left dorsolateral prefrontal cortex and the left premotor cortex in both groups were positively correlated with the PAS scores. During the acupuncture ΔHbO 2 concentration in the right inferior frontal gyrus and the left middle temporal gyrus increased significantly in the tongue three-needle group. It decreased significantly in the left somatosensory cortex and the left primary motor cortex. Conclusion:Three-needle acupuncture of the tongue induces changes in cortical activity in infratentorial stroke survivors with dysphagia, suggesting a potential technique for improving disordered swallowing.

To understand the current quality status and rearing situation of Bombyx Batryticatus, the authors collected 102 batches of Bombyx Batryticatus from different main producing areas and five major Chinese medicine markets from 2016 to 2018, and measured the properties and quality of the silk gland, to clarify the quality status of Bombyx Batryticatus from different producing areas and markets. In addition, 35 batches of Bombyx Batryticatus from 2019 to 2022 were used to verify the silk gland after revision. Moreover, Beauveria Bassiana was inoculated in the silkworm of 4-5 instars, and standardized rearing was carried out until they die. The death rate and the quality of Bombyx Batryticatus were measured to determine the differences in Bombyx Batryticatus of different instars, and explore the rationality of the infection age of Bombyx Batryticatus in Chinese Pharmacopoeia(2020). The results revealed that in the 102 batches of Bombyx Batryticatus, the qualification rate of silk gland was low; the content of total ash far exceeded the standard; the content of beauvericin varied greatly. The qualification rate of the silk gland of the 35 batches of Bombyx Batryticatus was only 47.49%, which could be increased to 73.00% if the number of silk gland was 2 to 4. The death rate of Bombyx Batryticatus at different infection ages was quite different, with uneven quality. Generally, the yield of Bombyx Batryticatus inoculated on the first day of the fifth instar was high with good quality. Therefore, in combination with the quality and actual production of Bombyx Batryticatus, the following suggestions were proposed for revision of Bombyx Batryticatus in Chinese Pharmacopoeia(2025): The number of silk gland should be revised as 2-4 bright brown or bright black silk glands, after which, the quality of Bombyx Batryticatus could be guaranteed, and the "quality identification based on character" could also be reflected scientifically; the content determination index that the content of beauvericin shall not be less than 0.017% should be added to better control the quality of Bombyx Batryticatus; the infection age should be revised as the first day of the fifth instar to narrow the age span, which could better fit the actual production and ensure the quality of Bombyx Batryticatus.
Animals ; Bombyx ; Medicine, East Asian Traditional ; Silk ; Larva

Objective:To explore the method of developing a canal-shaped implant template using a combined automatic pre-planning and 3D printing technology, and assess its impact on dose and efficacy improvement.Methods:Retrospective analysis of 15 patients with advanced cervical cancer admitted to the Affiliated Cancer Hospital of Guangxi Medical University from September 2020 to September 2022 was performed. Patients had characteristics such as vaginal stump recurrence, tumor eccentric growth, and previous hysterotomy, etc. Three-dimensional images were obtained by CT scan after automatic pre-planning. The PMT 3D software was used to analyze digital imaging and communications in medicine (DICOM) radiotherapy data, capture the coordinates of the pre-planned stay points to establish the implant channel, and generate the size and shape of the canal-shaped implant template based on patients' physiological structure. Dosimetric parameters, such as conformity index (CI), were evaluated. The changes of tumor size before and after treatment were analyzed by paired t-test. Results:Fifteen patients were treated with the canal-shaped implant template. The CI was 0.74±0.26, the total radiation dose (HR-CTV) D 90% (EQD 2, α/β=10) was (85.5±6.8) Gy, and the D 2 cm3 (EQD 2, α/β=3)for bladder, rectum, small intestine, and colon were (72.2±4.2), (65.8±6.1), (65.2±4.4), and (69.8±3.7) Gy, respectively, meeting clinical needs. After the treatment, the tumor volume was significantly decreased. The template had a good fit with the vaginal cavity, and a small amount of air gap on the sidewall did not affect the dose. Non-parallel needle insertion increased the utilization of the cavity space and implant needles. Conclusion:The method of developing the canal-shaped implant template using automatic pre-planning and 3D printing technology is efficient and effective, meets the requirements of modern precise radiotherapy, and has practical clinical value.

Inflammation is the key pathogenic feature of heart failure （HF）， and its overexpression can cause myocardial hypertrophy， apoptosis and fibrosis， aggravating the process of HF. Macrophages are important immune cells in human body with high heterogeneity， which involve in inflammation response and maintain heart homeostasis. Macrophage polarization is a dynamic process. Under the stimulation of different microenvironment， it can polarize two subsets， including classically activated M1 type and alternatively activated M2 type， which are antagonistic to each other. When macrophages polarize into the pro-inflammatory phenotype （M1）， the inflammatory response is initiated， the anti-inflammatory phenotype （M2） plays a role in inhibiting inflammation and repairing tissue. At the same time， in different stages of development of HF， M1 and M2 macrophages can be transformed into each other， which is similar to the connotation of Yin-yang restriction， balance and transformation of traditional Chinese medicine （TCM） theory. Based on this， this paper intends to clarify the relationship between M1 and M2 macrophages by Yin-yang theory， proposing that the clinical prevention and treatment of HF should pay attention to regulating micro and macro inflammatory responses， regulating macrophage polarization， and achieving the balance between anti-inflammatory and pro-inflammation， which is consistent with the balance of Yin-yang in TCM theory. It can provide a new target and direction for TCM treatment of HF.

OBJECTIVE: To explore the mechanism underlying the hepatoprotective effect of dihydromyricetin (DMY) against lipid accumulation in light of the lipophagy pathway and the inhibitory effect of DMY on HepG2 cell proliferation. METHODS: LO2 cells were cultured in the presence of 10% FBS for 24 h and treated with 100 μg/mL DMY, or exposed to 50% FBS for 24 h followed by treatment with 50, 100, or 200 μg/mL DMY; the cells in recovery group were cultured in 50% FBS for 24 h and then in 10% FBS for another 24 h. Oil red O staining was used to observe the accumulation of lipid droplets in the cells, and the levels of TC, TG, and LDL and activities of AST, ALT and LDH were measured. The expression of LC3 protein was detected using Western blotting. AO staining and transmission electron microscopy were used to determine the numbers of autophagolysosomes and autophagosomes, respectively. The formation of autophagosomes was observed with MDC staining, and the mRNA expression levels of LC3, ATG7, AMPK, mTOR, p62 and Beclin1 were determined with q-PCR. Flow cytometry was performed to analyze the effect of 50, 100, and 200 μg/mL DMY on cell cycle and apoptosis of HepG2 cells; DNA integrity in the treated cells was examined with cell DNA fragmentation test. RESULTS: DMY treatment and pretreatment obviously inhibited lipid accumulation and reduced the levels of TC, TG, LDL and enzyme activities of AST, ALT and LDH in LO2 cells (P < 0.05). In routinely cultured LO2 cells, DMY significantly promoted the formation of autophagosomes and autophagolysosomes and upregulated the expression of LC3 protein. DMY obviously attenuated high FBS-induced inhibition of autophagosome formation in LO2 cells, up- regulated the mRNA levels of LC3, ATG7, Beclin1 and AMPK, and downregulated p62 and mTOR mRNA levels (P < 0.05 or 0.01). In HepG2 cells, DMY caused obvious cell cycle arrest, inhibited cell proliferation, and induced late apoptosis and DNA fragmentation. CONCLUSION DMY reduces lipid accumulation in LO2 cells by regulating the AMPK/ mTOR-mediated lipophagy pathway and inhibits the proliferation of HepG2 by causing cell cycle arrest and promoting apoptosis.
AMP-Activated Protein Kinases/metabolism* ; Autophagy ; Beclin-1 ; Cell Proliferation ; Flavonols ; Hep G2 Cells ; Humans ; Lipids ; RNA, Messenger ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism*