The rapid development of artificial intelligence （AI） technology provides new opportunities for the modernisation of traditional Chinese medicine （TCM） diagnosis. By analysing the foundation， research progress and difficulties of the combination of AI and TCM diagnosis， it is concluded that AI has made remarkable development in intelligence-driven modernization of TCM tongue diagnosis， pulse diagnosis， listening and smelling diagnosis and text processing， and there are useful explorations in the field of constructing data-driven TCM diagnostic model and multidisciplinary integration of TCM diagnostic models. However， the current integration of AI technology in TCM diagnosis still faces many challenges， such as the scarcity and uneven quality of clinical data， the limited ability of AI algorithms to express TCM thinking model of syndrome differentiation and empirical knowledge， and the possible existence of ethical and privacy issues. By systematically sorting out the current research status and development direction of AI-empowered TCM diagnostics， it is proposed to promote the application of AI technology in TCM diagnostics in four aspects， namely， strengthening the construction of TCM big data and talent cultivation， encouraging cross-disciplinary cooperation， improving the legal and ethical framework， and promoting the popularity of the technology in primary care， so as to enhance the modernisation of TCM diagnostics.

The catalytic activity of 3-mercaptopyruvate (3MP) sulfurtransferase (MPST) converts 3MP to hydrogen sulfide (H₂S). However, the regulatory mechanisms governing MPST and its impact on the brain remain largely unexplored. Our study reveals the neuroprotective role of endothelial MPST-generated H₂S, regulated by protein phosphatase 2A (PP2A). Bioinformatics analysis and RNA sequencing demonstrated that endothelial PP2A is associated with neurodegenerative disease pathways. Cerebral ischemic mice exhibited significant inactivation of endothelial PP2A, evidenced by the reduction of PP2Acα in the brain endothelium. Mice with endothelium-specific null PP2A (PP2A^EC-cKO) exhibited neuronal loss, cognitive dysfunction, and long-term potentiation deficits. Postnatal inactivation of endothelial PP2A also contributes to cognitive dysfunction and neuronal loss. However, regaining endothelial PP2A activity by overexpressing Ppp2ca rescued neuronal dysfunction. Mechanistically, PP2A deficiency is intricately linked to the MPST-H₂S signaling pathway. A robust reduction in endothelial MPST-dependent H₂S production followed PP2A deficiency. Exogenous H₂S treatment and AAV-mediated overexpression of MPST in brain endothelial cells significantly mitigated neuronal dysfunction in PP2A^EC-cKO mice. Furthermore, PP2A deficiency promotes an increase in calcium influx and calpain2 phosphorylation, subsequently leading to MPST degradation. The PP2A activator (FTY720) and MPST activator (3MP sodium) both remarkably restored endothelial MPST-dependent H₂S production, subsequently rescuing ischemia-induced neurological deficits. In conclusion, our study demonstrates that endothelial PP2A deficiency leads to MPST degradation by activating calpain2, thus damaging neuronal function.

Objective:To explore the prognostic differences and influencing factors between pancreatic cancer originated from intraductal papillary mucinous neoplasm (IPMN)-termed IC-Ds-and pancreatic cancer concomitant with IPMN (C-PDACs).Methods:Clinical data of 382 patients with pathologically confirmed IPMN who underwent surgical resection in the Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Naval Medical University from January 2016 to January 2022 were collected. According to pathological diagnosis, patients were divided into the IC-Ds group ( n=288) and the C-PDACs group ( n=94). The IC-Ds group was further divided into the colloid carcinoma subgroup and the ductal adenocarcinoma subgroup based on pathological typing. Data including age, gender, preoperative CA19-9 level, surgical margin status, lymph node metastasis, pathological grade, T stage, postoperative adjuvant chemotherapy, and survival follow-up were recorded. The median follow-up time was 35.00 months for IC-Ds patients and 29.00 months for C-PDACs patients. Clinicopathological characteristics and prognostic factors were compared between the IC-Ds and C-PDACs groups, as well as between the colloid carcinoma and ductal adenocarcinoma subgroups. Kaplan-Meier curves for overall survival were generated. Results:There were no significant differences in age, gender, R1 resection margin between the IC-Ds group and the C-PDACs group. However, in the C-PDACs group, 70 cases (74.47%) had elevated preoperative CA19-9, 40 cases (42.55%) had lymph node metastasis, 25 cases (26.60%) were pathologically confirmed as poorly differentiated carcinoma after surgery, and 54 cases (57.45%) received postoperative adjuvant chemotherapy; the proportions of all these indicators were higher than those in the IC-Ds group (90/288, 31.25%; 72/288, 25.00%; 32/288, 11.11%; 105/288, 36.46%). In contrast, the proportion of T1 stage in the IC-Ds group was higher (40.97% vs 20.21%), and all these differences were statistically significant (all P value <0.05). Among the 288 patients in the IC-Ds group, 97 cases (33.68%) were colloid carcinoma and 191 cases (66.32%) were ductal adenocarcinoma. There were no significant differences in age, gender, R1 resection margin, proportion of poorly differentiated carcinoma between the two subgroups. However, in the ductal adenocarcinoma subgroup, 67 cases (35.08%) had elevated preoperative CA19-9, 56 cases (29.32%) had lymph node metastasis confirmed by postoperative pathology, and 80 cases (41.88%) received postoperative adjuvant chemotherapy; all these proportions were significantly higher than those in the colloid carcinoma subgroup (23/97, 23.71%; 16/97, 17.02%; 25/97, 26.60%). In addition, the ductal adenocarcinoma subgroup had higher proportions of T2 and T3/T4 stages, while the proportion of T1 stage in the colloid carcinoma subgroup (60/97, 61.86%) was significantly higher than that in the ductal adenocarcinoma subgroup (58/191, 30.37%), with all differences being statistically significant (all P value <0.05). The median survival time was 47.00 months (95% CI 42.91-51.09) in the IC-Ds group and 34.00 months (95% CI 29.67-38.33) in the C-PDACs group. For the IC-Ds subgroups, the median survival time was 59.00 months (95% CI 50.79-67.21) in the colloid carcinoma subgroup and 42.00 months (95% CI 35.15-48.85) in the ductal adenocarcinoma subgroup. Significant differences in median survival time were observed between the IC-Ds and C-PDACs groups, between the colloid carcinoma and ductal adenocarcinoma subgroups, and between the ductal adenocarcinoma subgroup and the C-PDACs group (all P value <0.01). Conclusions:IC-Ds has a better prognosis than C-PDACs, and there is significant heterogeneity within IC-Ds, indicating different biological behaviors between the two types, which requires the development of targeted diagnosis and treatment strategies.

[Objective]To investigate the effect of blue light on emmetropization in guinea pigs,explore the potential mechanisms and assess its application in myopia prevention and control.[Methods]Three-week-old male guinea pigs(n=20)were randomly assigned to the white light group and the blue light group.Refraction and ocular biological parameters were measured every 2 weeks until the experiment ended at week 8.And the 4D-data-independent acquisition(4D-DIA)proteomics technology was used to analyze retina from both the blue light and white light groups,exploring protein composition,expression differences,and biological functions.[Results]After 2 weeks,Guinea pigs exposed to white light gradually tended towards emmetropia,showing a statistically significant difference in refractive error compared to the blue light group(P<0.001).From week 4,the axial length of the blue light group was significantly shorter than that of the white light group(P<0.05).Meanwhile,the vitreous chamber length in the blue light group was significantly smaller than that of the white light group from week 2(P<0.05).A total of 161 differentially expressed proteins were identified by proteomics technology in the retina,with 98 proteins upregulated and 63 proteins downregulated.These proteins were primarily enriched in biosynthetic pathways such as vesicle transport,redox reaction,niacin and nicotinamide metabolism and NAD+metabolism.[Conclusions]Guinea pigs raised under blue light exhibit hyperopic drift and slowed axial elongation,which slows the procession of emmetropization.Based on the 4D-DIA technology,the differentially expressed proteins between the blue light and white light groups are primarily involved in NAD+metabolism,niacin and nicotinamide metabolism.Especially in NAD+salvage synthesis,nicotinamide phosphoribosyl transferase(NAMPT)is upregulated,while sirtuin 2(SIRT2)is downregulated.It provides new insights into the mechanism of blue light in emmetropization and a theoretical basis for myopia prevention and control.

Objective:To explore the prognostic differences and influencing factors between pancreatic cancer originated from intraductal papillary mucinous neoplasm (IPMN)-termed IC-Ds-and pancreatic cancer concomitant with IPMN (C-PDACs).Methods:Clinical data of 382 patients with pathologically confirmed IPMN who underwent surgical resection in the Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Naval Medical University from January 2016 to January 2022 were collected. According to pathological diagnosis, patients were divided into the IC-Ds group ( n=288) and the C-PDACs group ( n=94). The IC-Ds group was further divided into the colloid carcinoma subgroup and the ductal adenocarcinoma subgroup based on pathological typing. Data including age, gender, preoperative CA19-9 level, surgical margin status, lymph node metastasis, pathological grade, T stage, postoperative adjuvant chemotherapy, and survival follow-up were recorded. The median follow-up time was 35.00 months for IC-Ds patients and 29.00 months for C-PDACs patients. Clinicopathological characteristics and prognostic factors were compared between the IC-Ds and C-PDACs groups, as well as between the colloid carcinoma and ductal adenocarcinoma subgroups. Kaplan-Meier curves for overall survival were generated. Results:There were no significant differences in age, gender, R1 resection margin between the IC-Ds group and the C-PDACs group. However, in the C-PDACs group, 70 cases (74.47%) had elevated preoperative CA19-9, 40 cases (42.55%) had lymph node metastasis, 25 cases (26.60%) were pathologically confirmed as poorly differentiated carcinoma after surgery, and 54 cases (57.45%) received postoperative adjuvant chemotherapy; the proportions of all these indicators were higher than those in the IC-Ds group (90/288, 31.25%; 72/288, 25.00%; 32/288, 11.11%; 105/288, 36.46%). In contrast, the proportion of T1 stage in the IC-Ds group was higher (40.97% vs 20.21%), and all these differences were statistically significant (all P value <0.05). Among the 288 patients in the IC-Ds group, 97 cases (33.68%) were colloid carcinoma and 191 cases (66.32%) were ductal adenocarcinoma. There were no significant differences in age, gender, R1 resection margin, proportion of poorly differentiated carcinoma between the two subgroups. However, in the ductal adenocarcinoma subgroup, 67 cases (35.08%) had elevated preoperative CA19-9, 56 cases (29.32%) had lymph node metastasis confirmed by postoperative pathology, and 80 cases (41.88%) received postoperative adjuvant chemotherapy; all these proportions were significantly higher than those in the colloid carcinoma subgroup (23/97, 23.71%; 16/97, 17.02%; 25/97, 26.60%). In addition, the ductal adenocarcinoma subgroup had higher proportions of T2 and T3/T4 stages, while the proportion of T1 stage in the colloid carcinoma subgroup (60/97, 61.86%) was significantly higher than that in the ductal adenocarcinoma subgroup (58/191, 30.37%), with all differences being statistically significant (all P value <0.05). The median survival time was 47.00 months (95% CI 42.91-51.09) in the IC-Ds group and 34.00 months (95% CI 29.67-38.33) in the C-PDACs group. For the IC-Ds subgroups, the median survival time was 59.00 months (95% CI 50.79-67.21) in the colloid carcinoma subgroup and 42.00 months (95% CI 35.15-48.85) in the ductal adenocarcinoma subgroup. Significant differences in median survival time were observed between the IC-Ds and C-PDACs groups, between the colloid carcinoma and ductal adenocarcinoma subgroups, and between the ductal adenocarcinoma subgroup and the C-PDACs group (all P value <0.01). Conclusions:IC-Ds has a better prognosis than C-PDACs, and there is significant heterogeneity within IC-Ds, indicating different biological behaviors between the two types, which requires the development of targeted diagnosis and treatment strategies.

Objective:To investigate whether intestinal rehabilitation therapy (IRT)could optimize the effectiveness of IRT in patients with short bowel syndrome (SBS) caused by acute mesenteric ischemia (AMI) with chronic multivessel lesions.Methods:Clinical data of 18 hospitalized patients diagnosed with AMI leading to SBS and undergoing IRT at the Eastern Theater General Hospital of the People's Liberation Army from Jan 2012 to Oct 2023 was retrospectively analyzed.Result:Following IRT, the revascularization group showed significantly greater increases in ASMI and grip strength compared to the control group [(0.28±0.26) kg/m 2vs. (0.02±0.21) kg/m 2, P=0.033, and (0.97±0.33) kg vs. (0.48±0.34) kg, P=0.007, respectively]. Similarly, the increase in EN intake was significantly higher in the revascularization group compared to the control group [(572.5±93.6) ml/d vs. (375.2±176.3) ml/d, P=0.012], accompanied by a greater improvement in intestinal nitrogen absorption rate [(25.06±14.06)% vs. (13.84±4.62)%, P=0.034] and a more substantial decrease in GSRS scores [(-15.88±3.94) vs. (-6.33±5.13), P=0.030]. Moreover, there were significant differences in the composition of EN formulations between the two groups after IRT ( P=0.046). Additionally, SF-36 scores at discharge were significantly higher in the revascularization group than that in the control group for five indicators including BP, GH, VT, SF, and MH ( P<0.05). Conclusions:For patients with SBS resulting from AMI by chronic multivessel lesions, revascularization therapy may not leading to higher growth in weight and hematological nutritional indicators during IRT, but it is beneficial for improving muscle function, improving EN absorption, increasing the likelihood of PN independence, relieving gastrointestinal symptoms, and enhancing overall quality of life.

OBJECTIVE To investigate the effects of nasal administration of non-mitogenic acid fibroblast growth factor(NMFGF1) loaded nanoparticles(NMFGF1-NPs) on the improvement of cognitive function in vascular dementia(VD) mice and its mechanism. METHODS Nanoparticles containing NMFGF1(NMFGF1-NPs) were prepared by water-in-water emulsion technique and characterized. The mice were divided into sham group, VD model group, blank-NPs group, NMFGF1 solution group and NMFGF1-NPs group after repeated cerebral ischemia-reperfusion to establish VD test model, and then given the corresponding form of drug intervention by nasal cavity. After drug intervention, Morris water maze was used to evaluate the learning and memory function of the animals in each group from the perspective of behavior. Meanwhile, the morphology, arrangement and apoptosis index(AI) of hippocampal neurons in each group were evaluated by pathological methods such as HE staining, FJB staining and Tunel apoptosis staining. In addition, ELISA and Western blotting were used to investigate the molecular mechanism of NMFGF1-NPs improving VD by nasal administration. RESULTS The morphology of NMFGF1-NPs was round. The encapsulation rate of NMFGF1-NPs respectively was (87.76±5.89)%. Morris water maze results showed that the behavioral indexes of mice in VD model group were significantly different from those in sham operation group(P<0.01). At the same time, the pathological results showed that the neurons in the CA1 region of the hippocampus in the VD model group were disordered, the cells morphology and structure were missing, and the AI was significantly increased compared with that in the sham operation group(P<0.01). Meanwhile, compared with the VD model group, the NMFGF1-NPs treatment group showed significant improvement in various behavioral indexes, and the hippocampal neuron cells were intact and orderly, and the AI index was significantly decreased(P<0.01). ELISA and Western blotting analysis showed that compared with that of VD model group and other intervention groups, the content of MDA in the brain of NMFGF1-NPs treatment group was significantly decreased. While the content of SOD, NO and the expressions of Nrf2, SOD-1 and GSTO1/2 was significantly increased (P<0.01). CONCLUSION Nasal administration of NMFGF1-NPs can play the role of antioxidant stress damage by activating Nrf2/ARE signal pathway, and ultimately improve the learning and cognitive function of VD mice.

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.
Animals ; Antiviral Agents ; pharmacology ; therapeutic use ; Betacoronavirus ; drug effects ; physiology ; Binding Sites ; drug effects ; Cell Line ; Coronavirus Infections ; drug therapy ; virology ; Crotonates ; pharmacology ; Cytokine Release Syndrome ; drug therapy ; Drug Evaluation, Preclinical ; Gene Knockout Techniques ; Humans ; Influenza A virus ; drug effects ; Leflunomide ; pharmacology ; Mice ; Mice, Inbred BALB C ; Orthomyxoviridae Infections ; drug therapy ; Oseltamivir ; therapeutic use ; Oxidoreductases ; antagonists & inhibitors ; metabolism ; Pandemics ; Pneumonia, Viral ; drug therapy ; virology ; Protein Binding ; drug effects ; Pyrimidines ; biosynthesis ; RNA Viruses ; drug effects ; physiology ; Structure-Activity Relationship ; Toluidines ; pharmacology ; Ubiquinone ; metabolism ; Virus Replication ; drug effects