BACKGROUND:Neuregulin 1 has been shown to be characterized in cell proliferation,differentiation,and vascular growth.Human amniotic mesenchymal stem cells are important seed cells in the field of tissue engineering,and have been shown to be involved in tissue repair and regeneration. OBJECTIVE:To construct human amniotic mesenchymal stem cells overexpressing neuregulin 1 and investigate their proliferation and migration abilities,as well as their effects on wound healing. METHODS:(1)Human amniotic mesenchymal stem cells were in vitro isolated and cultured and identified.(2)A lentivirus overexpressing neuregulin 1 was constructed.Human amniotic mesenchymal stem cells were divided into empty group,neuregulin 1 group,and control group,and transfected with empty lentivirus and lentivirus overexpressing neuregulin 1,or not transfected,respectively.(3)Edu assay was used to detect the proliferation ability of the cells of each group,and Transwell assay was used to detect the migration ability of the cells.(4)The C57 BL/6 mouse trauma models were constructed and randomly divided into control group,empty group,neuregulin 1 group,with 8 mice in each group.Human amniotic mesenchymal stem cells transfected with empty lentivirus or lentivirus overexpressing neuregulin-1 were uniformly injected with 1 mL at multiple local wound sites.The control group was injected with an equal amount of saline.(5)The healing of the trauma was observed at 1,7,and 14 days after model establishment.Histological changes of the healing of the trauma were observed by hematoxylin-eosin staining.The expression of CD31 on the trauma was observed by immunohistochemistry. RESULTS AND CONCLUSION:(1)Human amniotic mesenchymal stem cells overexpressing neuregulin-1 were successfully constructed.The mRNA and protein expression of intracellular neuregulin 1 was significantly up-regulated compared with the empty group(P<0.05).(2)The overexpression of neuregulin 1 promoted the migratory ability(P<0.01)and proliferative ability of human amniotic mesenchymal stem cells(P<0.05).(3)Human amniotic mesenchymal stem cells overexpressing neuregulin 1 promoted wound healing in mice(P<0.05)and wound angiogenesis(P<0.05).The results showed that overexpression of neuregulin 1 resulted in an increase in the proliferative and migratory capacities of human amniotic mesenchymal stem cells,significantly promoting wound healing and angiogenesis.

Objective To construct large medical model named by "Huaxi HongYi"and explore its application effectiveness in assisting medical record generation. Methods By the way of a full-chain medical large model construction paradigm of "data annotation - model training - scenario incubation", through strategies such as multimodal data fusion, domain adaptation training, and localization of hardware adaptation, "Huaxi HongYi" with 72 billion parameters was constructed. Combined with technologies such as speech recognition, knowledge graphs, and reinforcement learning, an application system for assisting in the generation of medical records was developed. Results Taking the assisted generation of discharge records as an example, in the pilot department, after using the application system, the average completion times of writing a medical records shortened (21 min vs. 5 min) with efficiency increased by 3.2 time, the accuracy rate of the model output reached 92.4%. Conclusion It is feasible for medical institutions to build independently controllable medical large models and incubate various applications based on these models, providing a reference pathway for artificial intelligence development in similar institutions.

The main protease (M^pro) of SARS-CoV-2 is an attractive target in anti-COVID-19 therapy for its high conservation and major role in the virus life cycle. The covalent M^pro inhibitor nirmatrelvir (in combination with ritonavir, a pharmacokinetic enhancer) and the non-covalent inhibitor ensitrelvir have shown efficacy in clinical trials and have been approved for therapeutic use. Effective antiviral drugs are needed to fight the pandemic, while non-covalent M^pro inhibitors could be promising alternatives due to their high selectivity and favorable druggability. Numerous non-covalent M^pro inhibitors with desirable properties have been developed based on available crystal structures of M^pro. In this article, we describe medicinal chemistry strategies applied for the discovery and optimization of non-covalent M^pro inhibitors, followed by a general overview and critical analysis of the available information. Prospective viewpoints and insights into current strategies for the development of non-covalent M^pro inhibitors are also discussed.

italic>Anoectochilus roxburghii liquid (spray, a hospital preparation of Wu Mengchao Hepatobiliary Hospital of Fujian Medical University) has shown a good clinical treatment effect during the COVID-19 pandemic, but its material basis and mechanism of action are still unclear. In this study, network pharmacology and molecular docking methods were used to predict the molecular mechanism of A. roxburghii liquid against COVID-19, and pharmacodynamic experiments in vitro were conducted to study the interaction between the current targets with clear preventive and therapeutic effects and the key components of A. roxburghii liquid. UPLC-MS and database were used to compare and analyze the active ingredients in the liquid, and 17 potential active ingredients with good drug-like properties were screened by in vivo pharmacokinetics process in SwissADME database. SwissTargetPrediction and GeneCards were searched to find 93 common targets. Cytoscape 3.8.2 software was used to construct the "component-target" network map, and the Metascape platform was used for gene function annotation and pathway enrichment analysis. It was found that the extract could regulate the positive response to external stimuli, inflammatory response, cytokine production and other biological processes by binding the active ingredients such as isorhamnetin, kaempferol, luteolin, quercetin and apigenin to the common targets (NOS3, MPO, MMP3, etc.), and play an anti-COVID-19 role. In the angiotensin-converting enzyme 2 (ACE2) activity inhibition assay, it was found that the stock solution of A. roxburghii liquid (for spray), and the supernatant after removing polysaccharides (mainly containing flavonoids) could to some extent inhibit the activity of ACE2. Crucially, in the experiment of 2019-nCOV-S pseudovirus infecting HEK-293T-ACE2 cells, we found that A. roxburghii liquid may exert anti-COVID-19 effects by blocking the binding of SARS-CoV-S protein to ACE2.

Objective To investigate the clinical value of thyroid globulin antibody(TgAb)and thyroid peroxidase antibody(TPOAb)in the diagnosis and treatment of papillary thyroid microcarcinoma(PTMC).Methods A total of 346 patients with thyroid nodules who underwent surgical treatment in the hospital from August 2012 to October 2021 were selected as the research objects.According to the postoperative pathologi-cal results,the patients were divided into the benign nodule group,PTMC group and non-micro papillary thy-roid carcinoma(PTC)group.The general data of the patients and thyroid function indexes[free triiodothyro-nine(FT3),free tetraiodothyronine(FT4),thyroid stimulating hormone(TSH),TgAb and TPOAb]before and after operation were collected,the tumor recurrence or lymph node metastasis after operation were ob-served,and the relationship between serum TgAb and TPOAb and the risk and prognosis of PTMC was ana-lyzed.Results The positivity rate of TgAb in the PTMC and non-micro PTC groups was significantly higher than that in the benign nodule group(P<0.05).The TPOAb positivity rate was not significantly different among the three groups(P>0.05).Only the TSH level in the PTMC group was higher than that in the non-micro PTC group(P<0.05).Multivariate logistic analysis showed that younger age,higher TSH and positive TgAb were independent risk factors for PTMC and non-micro PTC(P<0.05).However,the risk of PTC didn't increase with increasing TgAb titres.The positivity rate of TgAb in the PTMC and non-micro PTC groups didn't change significantly within one month after operation,but decreased in one year after operation(P<0.05).The TPOAb positivity rate decreased after operation,but the difference was not statistically sig-nificant(P>0.05).In the PTMC group,four cases had tumor recurrence or lymph node metastasis,and the TgAb level increased by 88.4%,49.5%,5.7%and 84.0%respectively when the tumor recurred or metasta-sized.Among them,the TPOAb level increased by 51.6%,30.0%and 2.9%respectively in three cases and decreased by 53.9%in one case.In the PTMC group,there were 11 patients with cervical lymph node enlarge-ment,and there was no statistical difference in TgAb and TPOAb levels when the condition changed(P>0.05).Conclusion TgAb is a risk factor for PTMC,and can be followed up regularly during the diagnosis and treatment of PTMC.The specificity of TPOAb is not as good as that of TgAb,and appropriate follow-up can be chosen during the course of the disease.

Objective To investigate the difference of depressive symptoms between adolescents and adults,and to provide possible basis for early detection of adolescent depression.Methods From July 2021 to June 2022,a total of 4 096 patients with"depression"in the psychiatric clinic of the First Affiliated Hospital of Chongqing Medical University were selected as the research objects.They were divided into the adolescent group(n=2 439)and adult group(n=1 657)according to their ages,and the results of self-rating depression scale(SDS)and symptom checklist 90(SCL-90)were collected and analyzed.Results There were significant differences in nationality,residence,native place,family history and degree of depression between the two groups(P<0.05).The adolescent group has more severe depressive symptoms,which were mainly manifes-ted in negative ideas,obsessive-compulsive symptoms,hostile and interpersonal relationship,and psychotic symptoms(P<0.05).The adult group showed more obvious in sleep(P<0.05).Conclusion Early inter-vention should be carried out for adolescents'depressive symptoms such as negative thoughts.

The quality control of traditional Chinese medicine(TCM)is the core issue to ensure the modernization,industrialization and internationalization of TCM.Compared with other detection methods,electrochemical analysis method has many advantages such as high sensitivity,fast detection speed and low cost,making it an important means of quality control for TCM and having broad development prospects.This article reviewed the research progress of electrochemical methods in quality control of TCM in recent years,discussed the application of electrochemical fingerprinting technique in identification of TCM,and comprehensively summarized the application of electrochemical technology in analyzing effective components and harmful substances in TCM,including flavonoids,alkaloids,quinones,glycosides,heavy metals and pesticide residues.Finally,the development prospects of electrochemical methods in the field of quality control of TCM were discussed.

Acute cerebral infarction(ACI)has the characteristics of onset nasty and high mortality,and thus the rapid determination of the occurrence and development of ACI plays a key role in the diagnosis,treatment and prognosis of ACI patients.It has shown that the serum level of human haptoglobin(Hp)is related to ACI.In this study,surface enhanced Raman scattering(SERS)combined with immune recognition was applied to establish a quantitative analysis method for serum Hp.Firstly,the SERS substrate of silver nanoparticles was prepared on silicon wafer,and 4-mercaptobenzoic Acid(MBA)was used as a Raman probe by forming Ag—S bond and connecting it on the surface of nanoparticles.The carboxyl group of MBA was linked to amino group of self-made high-affinity antibody through forming CO—NH structure thus forming a SERS self-assembled chip of Hp(Ag/MBA/anti-Hp).Hp in serum could be specifically captured by antibodies on SERS substrate,which caused the shift of SERS characteristic peak of MBA.The results showed that there was a good linear relationship between the logarithm of Hp concentration and the SERS characteristic peak shift of MBA.The detection range was 1-1000 ng/mL(R2=0.988).The Hp concentrations in serum of 90 ACI patients were determined by this method,and the results were consistent with those of ELISA method,which proved the practicability and accuracy of this method.This method was highly specific,simple and convenient,which could realize the specific recognition and quantitative analysis of serum Hp,so as to be an effective means for clinical detection of serum Hp,thus providing a reference for the treatment and prognosis of ACI.

Objective To explore the dynamic changes and mechanisms of neurological and cognitive functions in mice with traumatic brain injury (TBI). Methods Totally 60 12⁃month⁃old Balb/ c mice were divided into control group (10 in group) and TBI group (50 in group). TBT model mice were divided into 5 subgroups according to the time of model construction, including model 1 day, model 1 day, model 3 day, model 7 day, model 14 days and model 28 days group with 10 in each group. At the 29th day of the experiment, neurological scores and step down tests were carried out. After the test, the mice were sacrificed for brains which were detected by immunohistochemistry staining, inflammatory cytokine tests and Western blotting. Results Compared with the control group, the neurological scores of mice in TBI group increased, and then decreased after the 7th day when the scores reached the peak. However, the latency of step down errors was lower than control group, and the number of step down errors was higher than control group which had no changes. Compared with the control group, the expression of lonized calcium⁃binding adapter molecule 1(IBA1), chemokine C⁃X3⁃C⁃motif ligand1 (CX3CL1), C⁃X3⁃C chemokine receptor 1(CX3CR1), NOD⁃like receptor thermal protein domain associated protein 3 (NLRP3), and phosphorylation nuclear factor(p⁃NF)⁃κB in TBI group increased and reached to the peak at the 7th day, and then started to decrease. At the same time, the levels of inflammatory cytokines interleukin⁃6(IL⁃6) and tumor necrosis factor⁃α(TNF⁃α) first increased to the peak, and then began to decrease. However, compared with the control group, the expression of amyloid β(Aβ) protein and p⁃Tau protein in the model group continued to increase at all time. Conclusion The TBI model caused continuous activation of microglia along with inflammatory response, which first increased and then decreased, resultsing in neurological scores changes. In addition, the inflammatory response may act as a promoter of Aβ protein deposition and Tau protein phosphorylation, leading to cognitive impairment in mice.

ObjectiveCellular temperature imaging can assist scientists in studying and comprehending the temperature distribution within cells, revealing critical information about cellular metabolism and biochemical processes. Currently, cell temperature imaging techniques based on fluorescent temperature probes suffer from limitations such as low temperature resolution and a limited measurement range. This paper aims to develop a single-cell temperature imaging and real-time monitoring technique by leveraging the temperature-dependent properties of single-molecule quantum coherence processes. MethodsUsing femtosecond pulse lasers, we prepare delayed and phase-adjustable pairs of femtosecond pulses. These modulated pulse pairs excite fluorescent single molecules labeled within cells through a microscopic system, followed by the collection and recording of the arrival time of each fluorescent photon. By defining the quantum coherence visibility (V) of single molecules in relation to the surrounding environmental temperature, a correspondence between V and environmental temperature is established. By modulating and demodulating the arrival times of fluorescent photons, we obtain the local temperature of single molecules. Combined with scanning imaging, we finally achieve temperature imaging and real-time detection of cells. ResultsThis method achieves high precision (temperature resolution<0.1°C) and a wide temperature range (10-50°C) for temperature imaging and measurement, and it enables the observation of temperature changes related to individual cell metabolism. ConclusionThis research contributes to a deeper understanding of cellular metabolism, protein function, and disease mechanisms, providing a valuable tool for biomedical research.