The traditional Chinese medicine （TCM） myocardial infarction （MI） unit is a standardized， regulated， and continuous integrated care unit guided by TCM theory and built upon existing chest pain centers or emergency care units. This unit emphasizes multidisciplinary collaboration and forms a restructured clinical entity without altering current departmental settings， offering comprehensive diagnostic and therapeutic services with full participation of TCM in the treatment of MI. Its core medical model is patient-centered and disease-focused， providing horizontally integrated TCM-based care across multiple specialties and vertically constructing a full-cycle treatment unit for MI， delivering prevention， treatment， and rehabilitation during the acute， stable， and recovery phases. Additionally， the unit establishes a TCM-featured education and prevention mechanism for MI to guide patients in proactive health management， reduce the incidence of myocardial infarction， and improve quality of life.

OBJECTIVE To study the safety of Shuangshu decoction in rats and its efficacy in improving functional dyspepsia （FD） in rats. METHODS In safety test， 40 rats were divided into blank control group， Shuangshu decoction low-dose， medium- dose and high-dose groups [108， 216， 324 g/（kg·d）， calculated by raw medicine， the same applies below]； they were given relevant medicine intragastrically， for continuous 14 days. The mortality and toxic reactions of rats were recorded， and the organ indexes of the liver， kidney， spleen， lung and heart of rats were calculated； the pathological morphological changes in the liver， kidney， spleen， lung， heart， stomach， duodenum， and colon were observed to evaluate the acute toxicity of Shuangshu decoction. Another 40 rats were grouped and administered in the same way for 30 consecutive days. The mortality and toxic reactions of the rats were recorded， and the corresponding organ indexes were calculated. The pathological morphological changes in the corresponding organs were observed， and blood routine and serum biochemical indicators were measured， in order to assess the subacute toxicity of Shuangshu decoction. In pharmacodynamic experiments: 50 rats were divided into blank control group， model group， and Shuangshu decoction low-， medium-， and high-dose groups （9.45， 18.9， 37.8 g/kg）， with 10 rats in each group. Except for blank control group， rats in all other groups were used to establish the FD rat model by subcutaneous injection of loperamide （3.5 mg/kg）. Rats in each group were administered the corresponding drug solution/normal saline intragastrically， once a day， for 14 consecutive days. After the last medication， fecal moisture content， intestinal propulsion rate， gastric emptying rate and serum level of motilin were all detected， and interstitial cell of Cajal （ICC） ultrastructure of rats was observed in colon tissue. RESULTS The safety experiments showed that no death occurred in each dose group， and no significant difference was found in organ coefficient， routine blood and serum biological index， compared to blank control group （P＞0.05）； no abnormality was found in organ appearance and pathological sections. The results of the pharmacodynamic experiments showed that， compared with the blank control group， the fecal moisture content， gastric emptying rate， intestinal propulsion rate， and serum motilin levels in the model group were significantly decreased （P＜0.05）； in the colonic tissue， the mitochondria in the ICC exhibited severe swelling with the disappearance of cristae， and the endoplasmic reticulum was dilated. Compared with model group， the rats in Shuangshu decoction high-dose group showed significant increases in the above quantitative indicators （P＜ 0.05）； additionally， there was a large number of mitochondria in the ICC of the colonic tissue， with clear cristae and regular arrangement. CONCLUSIONS Shuangshu decoction is safe and has a beneficial improving effect on FD rats； its mechanism of action may be related to the regulation of gastrointestinal hormone expression to promote gastric emptying and intestinal propulsion， as well as the repair of mitochondrial structure in ICCs to restore gastrointestinal function.

ObjectiveTo observe the clinical efficacy and safety of Modified Guomin Decoction （加味过敏煎， MGD） in patients with mild to moderate atopic dermatitis （AD） of the traditional Chinese medicine （TCM） pattern of heart fire and spleen deficiency， and to explore its possible mechanisms. MethodsIn this randomized， double-blind， placebo-controlled study， 72 patients with mild to moderate AD and the TCM pattern of heart fire and spleen deficiency were randomly divided into a treatment group and a control group， with 36 cases in each group. The treatment group received oral MGD granules combined with topical vitamin E emulsion， while the control group received oral placebo granules combined with topical vitamin E treatment. Both groups were treated twice daily for 4 weeks. Clinical efficacy， TCM syndrome scores， Visual Analogue Scale （VAS） for pruritus， Dermatology Life Quality Index （DLQI） scores， Scoring Atopic Dermatitis （SCORAD） and serum biomarkers， including interleukin-33 （IL-33）， interleukin-1β （IL-1β）， immunoglobulin E （IgE）， and tumor necrosis factor-α （TNF-α） were compared before and after treatment. Safety indexes was also assessed. ResultsThe total clinical effective rates were 77.78% （28/36） in the treatment group and 38.89% （14/36） in the control group， with cure rates of 19.44% （7/36） and 2.78% （1/36）， respectively. The treatment group showed significantly better clinical outcomes compared to the control group （P＜0.05）. The treatment group exhibited significant reductions in total TCM syndrome scores， including erythema， edema， papules， scaling， lichenification， pruritus， irritability， insomnia， abdominal distension， and fatigue scores， as well as reductions in VAS， DLQI， SCORAD， and serum IgE and IL-33 levels （P＜0.05 or P＜0.01）. Compared to the control group， the treatment group had significantly better improvements in all indicators except for insomnia （P＜0.05）. No adverse events occurred in either group. ConclusionMGD is effective and safe in treating mild to moderate AD patients with heart fire and spleen deficiency pattern. It significantly alleviates pruritus， improves TCM syndromes and quality of life， and enhances clinical efficacy， possibly through modulation of immune responses.

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

OBJECTIVE To prepare berberine/piperine co-loaded self-microemulsion drug delivery system （BBR/PIP- SMEDDS）， evaluate its physicochemical properties， in vitro release and pharmacokinetic characteristics. METHODS The drug loading mass ratio of berberine （BBR） and piperine （PIP） in the preparation was determined by the everted intestinal sac method. The oil-phase， emulsifier and co-emulsifier were determined by solubility detection， compatibility evaluation and pseudo-ternary phase diagram， respectively. The formulation of blank self-microemulsion drug delivery system （SMEDDS） was optimized and verified by central composite design-response surface methodology with the amount of oil-phase and the mass ratio of emulsifier to co-emulsifier as factors， and the comprehensive score of particle size and Zeta potential as response value. According to the optimal prescription， BBR/PIP-SMEDDS was prepared by adding excessive BBR and PIP raw materials under magnetic stirring， and its physicochemical properties， in vitro release behavior and pharmacokinetic characteristics in rats were investigated. RESULTS The drug loading mass ratio of BBR and PIP was 1∶1. The optimal prescription included oil-phase （ethyl oleate） accounted for 18.54%， emulsifier （Tween-80） accounted for 52.16%， and co-emulsifier （polyethylene glycol 400） accounted for 29.30%. Three verification experiments showed that the average particle size of blank SMEDDS was （16.49±0.49） nm； the Zeta potential was （－16.22±0.77） mV； the comprehensive score was 0.97， the relative deviation of which from the predicted value （0.95） was 2.11%. The prepared BBR/PIP-SMEDDS was an oil-in-water microemulsion， which was a golden yellow oily liquid with a spherical shape. The average particle size was （32.90±0.38） nm， and the Zeta potential was （－19.17±0.70） mV. The encapsulation efficiency of BBR was （90.44±0.88）% ， and the drug loading was （10.18±0.17） mg/g. The encapsulation efficiency of PIP was （87.48±1.13）%， and the drug loading was （9.41±0.17） mg/g. BBR/PIP-SMEDDS had good stability at low temperature （4 ℃ ） in the dark， centri-fugation and dilution. The results of in vitro release showed that the cumulative release percentage of BBR in simulated intestinal fluid for 24 h was significantly higher than that of the raw drug after the preparation of SMEDDS. The pharmacokinetic results in rats showed that the peak concentration and area under the drug- concentration time curve （AUC0－）t of BBR/PIP-SMEDDS were 4.61 and 7.07 times higher than those of the raw drug respectively， and the relative bioavailability was 707.484%. CONCLUSIONS BBR/PIP-SMEDDS is successfully prepared， and the in vitro release and bioavailability of the preparation are greatly improved compared with the raw material.

Background Atmospheric fine particulate matter (PM_2.5) can disrupt the metabolic homeostasis of the liver and accelerate the progression of liver diseases, but there are few studies on the effects of sub-chronic PM_2.5 exposure on the liver metabolome. Objectives To investigate the effects of sub-chronic exposure to concentrated PM_2.5 on hepatic metabolomics in mice by liquid chromatography-mass spectrometry (LC-MS), and to identify potentially affected metabolites and metabolic pathways. Methods Twelve male C57BL/6J (6 weeks old) mice were randomly divided into two groups: a concentrated PM_2.5 exposure group and a clean air exposure group. The mice were exposed to concentrated PM_2.5 using the "Shanghai Meteorological and Environmental Animal Exposure System" at Fudan University. The exposure duration was 8 h per day, 6 d per week, for a total of 8 weeks. The mice's liver tissues were collected 24 h after the completion of exposure. LC-MS was performed to assess changes in the hepatic metabolome. Orthogonal partial least squares discriminant analysis and t-test were employed to identify differentially regulated metabolites between the two groups under the conditions of variable important in projection (VIP)≥1.0 and P<0.05. Metabolic pathway enrichment analysis was performed using MetaboAnalyst 5.0 software and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Results A total of 297 differentially regulated metabolites were identified between the concentrated PM_2.5 exposure group and the clean air group. Among these metabolites, 142 were upregulated and 155 were downregulated. A total of 38 metabolic pathways were altered, with 7 pathways showing significant perturbation (P<0.05). These pathways involved amino acid metabolism, glucose metabolism, nucleotide metabolism, as well as cofactor and vitamin metabolism. The 7 significant metabolic pathways were pantothenic acid and coenzyme A biosynthesis; purine metabolism; amino sugar and nucleotide sugar metabolism; arginine biosynthesis; alanine, aspartate and glutamate metabolism; aminoacyl-tRNA biosynthesis; and fructose and mannose metabolism. Conclusion The results from metabolomics analysis suggest that sub-chronic exposure to PM_2.5 may disrupt hepatic energy metabolism and induce oxidative stress damage. Aspartic acid, succinic acid, ornithine, fumaric acid, as well as purine and xanthine derivatives, were identified as potential early biomarkers of hepatic response to sub-chronic PM_2.5 exposure.

Objective To investigate the present situation of radiation environment in Beijing and provide data support for monitoring and management of radiation environment in Beijing. Methods The γ radiation dose rate of environmental surface as well as the radioactive levels of aerosol, sediment, surface water, and soil samples were monitored in Beijing from 2015 to 2022. The radioactive levels of various environmental elements in this area were presented using statistical charts and statistical tables, and the related issues were discussed. Results The automatic monitoring and cumulative monitoring results of γ radiation dose rate were in the range of local natural background fluctuation. The radioactive levels of beryllium-7, lead-210, and polonium-210 in aerosols were low in summer and high in winter. The radioactive levels of total α, total β, and beryllium-7 in sediments were low in winter and high in summer. The activity concentration of radionuclide potassium-40 in aerosols and sediments did not change significantly with seasons. The total α and total β radioactivity levels of surface water fluctuated within the range of background. These values of reservoir water were within the limits specified in the Hygienic Standard for Drinking Water (GB 5749—2006). Natural radionuclides in soil were within the range of natural background fluctuation, and artificial radionuclides in soil were within the range of normal fluctuation over the years. Conclusion From 2015 to 2022, the environmental surface γ radiation dose rate as well as aerosol, sediment, surface water, and soil radioactivity levels in Beijing were generally low, all of which fluctuated within the environmental background.

[Objective]To explore the expression of transcription factor KLF16 in nonalcoholic fatty liver disease(NAFLD)and its effect on lipid metabolism.[Methods]An animal model of NAFLD was constructed in mice induced by a high-fat diet.The mice were divided into normal diet group(ND)and high fat diet group(HFD).NAFLD cell model was constructed by primary mouse liver cells induced by oleic acid.The cells were divided into control group(Control group)and oleic acid induction group(OA group).Real-time fluorescence quantitative PCR(RT-qPCR)and Western blot were used to detect KLF16 expression in NAFLD animal and cell models.In vitro and in vivo models of KLF16 knockdown were constructed by injection of adeno-associated virus(AAV)into mouse tail veins and transient transfection of cell siRNA.Hematoxylin-eosin staining(HE)and other methods were used to detect changes in lipid deposition in NAFLD models be-fore and after KLF16 knockout.RT-qPCR was used to detect the expression of key genes of lipid metabolism in both cellu-lar and animal NAFLD models before and after KLF16 knockdown.Western blot assay was used to detect the expression of endoplasmic reticulum stress protein in NAFLD model before and after KLF16 knockdown.[Results]The expression level of KLF16 was up-regulated in HFD group and OA group,and lipid deposition was increased in OA group after KLF16 was depressed.There was no change in TC level in hepatocytes between groups(P>0.05),and TG level was increased in differ-ent degrees(P<0.05,P<0.001).At the same time,the change of KLF16 expression also caused the change of ER stress protein expression in OA group.[Conclusion]The transcription factor KLF16 may alleviate lipid deposition in nonalcoholic fatty liver disease by endoplasmic reticulum stress.

Objective:To verify the feasibility of using Elekta accelerated go live (AGL) standard process for the acceptance of multiple accelerators.Methods:The beams of three accelerators were adjusted by PTW Beamscan three-dimensional water tank to reach the AGL standard. Dose verification was performed for three accelerators that met AGL standards. A simple field test example from Cancer Hospital Chinese Academy of Medical Sciences was used to compare the MapCheck 3 surface dose measurement results with the surface dose calculated by the same accelerator model. Images of 10 patients including head and neck, esophagus, breast, lung and rectum were randomly selected. volumetric-modulated arc therapy (VMAT) and intensity modulated radiation therapy (IMRT) treatment techniques were used for planning design, and the measured dose of ArcCheck was compared with the planned dose calculated by the same accelerator model. One-way ANOVA was used to statistically analyze the passing rates of two-dimensional and three-dimensional dose verification.Results:The 6 MV X-ray percentage depth dose at 10 cm underwater (PDD 10) of three accelerators was 67.45%, 67.36%, 67.47%, and the maximum deviation between the three accelerators was 0.11%. The 6 MV flattenting filter free (FFF) mode X-ray PDD 10 was 67.33%, 67.20%, 67.20%, and the maximum deviation between the three accelerators was 0.13%. All required discrete point doses on each energy 30 cm×30 cm Profile spindle of the three accelerator X-rays deviated less than ±1% from the standard data. Absolute γ analysis was performed on the results of MapCheck 3 two-dimensional dose matrix validation. Under the 10% threshold of 2 mm/3% standard, the average passing rate of the test cases in Cancer Hospital Chinese Academy of Medical Sciences was above 99%, and the difference was not statistically significant ( P>0.05). Absolute γ analysis was performed on the ArcCheck verification results. Under the 10% threshold, the pass rate of 2 mm/3% was all above 95%, the maximum average passing rate of the three accelerators with different energy and different treatment techniques was 0.28% (6 MV, VMAT), 0.19%(6 MV FFF, VMAT), 0.56% (6 MV, IMRT) and 0.05% (6 MV FFF, IMRT), and the difference was not statistically significant ( P>0.05). Conclusion:Compared with traditional accelerator acceptance process, the acceptance time of each accelerator is shortened by 4-6 weeks by using the AGL standard process, and the radiotherapy plan of patients can be interchangeably executed among different accelerators.

ObjectiveTo observe the mechanism of Jiawei Guizhi Fuling decoction （JGFD） in alleviating sciatic nerve injury in painful diabetic peripheral neuropathy （PDPN） rats by regulating mitophagy through the PTEN-induced putative kinase 1 （PINK1）/Parkin signaling pathway. MethodThe PDPN model was established by intraperitoneal injection of streptozotocin （STZ）. After modeling， the rats were randomly divided into JGFD high， medium， and low dose groups （JGFD-H， JGFD-M， JGFD-L； 39.6， 19.8， 9.9 g·kg^-1·d^-1， respectively）， a positive drug group （lipoic acid capsules， LA； 50 mg·kg^-1·d^-1）， and a model group （PDPN）. A blank control group （CON） was established. Drug intervention was administered continuously for 8 weeks after modeling. Measurements included body weight and fasting blood glucose of PDPN rats at weeks 0， 2， 4， and 8， mechanical pain threshold and thermal pain threshold at weeks 0 and 8， and motor nerve conduction velocity at week 8. Hematoxylin-eosin （HE） staining was used to observe the morphology of sciatic nerve tissue. The ultrastructure of mitochondria and autophagosomes was observed by transmission electron microscopy. Western blot was performed to detect the protein expression levels of PINK1， Parkin， p62， Beclin-1， and LC3 in sciatic nerve tissue. Additionally， real-time quantitative PCR （Real-time PCR） was performed to detect the mRNA expression levels of PINK1， Parkin， p62， Beclin-1， and LC3 in sciatic nerve tissue. ResultCompared with the CON group， the PDPN group showed a significant decrease in body weight at all time points， a significant increase in fasting blood glucose， significantly shortened mechanical pain and thermal pain thresholds， and significantly reduced motor nerve conduction velocity. The protein and mRNA expression of PINK1， Parkin， Beclin-1， and microtubule-associated protein light chain 3（LC3） in sciatic nerve tissue was significantly reduced， while p62 protein and mRNA expression was significantly increased （P<0.01）. Pathological changes included edema of sciatic nerve fibers， segmental demyelination， loose and disordered arrangement of the myelin sheath layers， significant swelling of mitochondria， reduced electron density， disappearance of cristae， and absence of typical autophagosome and autolysosome structures. Compared with the PDPN group， each JGFD dose group showed a significant increase in body weight and a significant reduction in fasting blood glucose （P<0.05， P<0.01）. The mechanical pain threshold and thermal pain threshold were significantly prolonged， and motor nerve conduction velocity was significantly increased across all JGFD and LA groups. The expression levels of PINK1， Parkin， Beclin-1， and LC3 proteins and mRNA in sciatic nerve tissue were significantly increased， while p62 protein and mRNA expression levels were significantly decreased （P<0.05， P<0.01）. Pathological damage to the sciatic nerve was alleviated to varying degrees， with a relatively intact myelin sheath morphology and intact or slightly edematous outer mitochondrial membrane. Autophagolysosome structures were observed in the JGFD-M and JGFD-H groups. Compared with the LA group， the JGFD-H group showed a significant increase in body weight， a significant reduction in fasting blood glucose， a significant increase in motor nerve conduction velocity， a significant increase in PINK1 protein expression and PINK1， Parkin， and Beclin-1 mRNA expression in sciatic nerve tissue， and a significant decrease in p62 mRNA expression （P<0.05， P<0.01）. ConclusionJGFD may alleviate sciatic nerve injury in PDPN rats by activating mitophagy through the regulation of the PINK1/Parkin signaling pathway.