ObjectiveTo observe the effects of Danggui Shaoyaosan on macrophage polarization and renal inflammation in db/db mice with diabetic kidney disease （DKD）， and to explore its renal protective effects and underlying mechanisms. MethodsEight db/m mice were assigned to the normal group， and forty db/db mice were randomly divided into a model group， low-， medium-， and high-dose Danggui Shaoyaosan groups （8.39， 16.77， 33.54 g·kg^-1）， and an irbesartan group （0.025 g·kg^-1）. All mice were administered treatment by gavage for 12 consecutive weeks. General conditions of the mice were observed during the intervention. At the end of the 12-week intervention， 24-h urine samples were collected using metabolic cages， after which the mice were anesthetized for sample collection. Blood was collected by enucleation and centrifuged to obtain serum for the determination of glycated serum protein （GSP）， serum creatinine （SCr）， blood urea nitrogen （BUN）， total cholesterol （TC）， and triglycerides （TG）. The urinary albumin-to-creatinine ratio （UACR） was measured. Renal pathological changes were observed using hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum tumor necrosis factor-α （TNF-α）， interleukin-10 （IL-10）， and monocyte chemoattractant protein-1 （MCP-1） levels. Immunofluorescence （IF） was performed to detect F4/80 expression in renal tissue， and immunohistochemistry （IHC） was used to assess CD206 expression. Real-time quantitative polymerase chain reaction （Real-time PCR） was employed to measure the mRNA expression of TNF-α， IL-10， inducible nitric oxide synthase （iNOS）， and arginase-1 （Arg-1）. Western blot analysis was used to detect the protein expression of iNOS， Arg-1， CD86， and CD206 in renal tissue. ResultsCompared with the normal group， the model group showed increased levels of GSP， UACR， SCr， BUN， TC， and TG， elevated levels of the inflammatory factor TNF-α and the chemokine MCP-1， and decreased IL-10 levels （P<0.01）. Pathological examination revealed glomerular hypertrophy， mesangial cell proliferation with marked mesangial expansion， inflammatory cell infiltration， vacuolar degeneration of renal tubular epithelial cells， prominent glycogen deposition， and increased collagen fiber deposition. In addition， relative F4/80 fluorescence intensity was enhanced， CD206 expression in the glomeruli and renal interstitium was reduced， and TNF-α and iNOS mRNA expression was increased. IL-10 and Arg-1 mRNA expression was decreased， iNOS and CD86 protein expression was increased， and Arg-1 and CD206 protein expression was decreased （P<0.05， P<0.01）. Compared with the model group， the Danggui Shaoyaosan groups and the irbesartan group showed decreased levels of GSP， UACR， SCr， BUN， TC， and TG， reduced serum TNF-α and MCP-1 levels， and increased IL-10 levels. Renal pathological damage was improved to varying degrees. Relative F4/80 fluorescence intensity was reduced， CD206 expression in the glomeruli and renal interstitium was increased， and TNF-α and iNOS mRNA expression was decreased. IL-10 and Arg-1 mRNA expression was increased， iNOS and CD86 protein expression was reduced， and Arg-1 and CD206 protein expression was increased （P<0.05， P<0.01）. ConclusionDanggui Shaoyaosan can improve renal function and alleviate renal pathological damage in db/db mice. Its mechanism may be related to inhibiting M1 pro-inflammatory macrophage polarization， promoting M2 anti-inflammatory macrophage polarization， reducing inflammatory responses， delaying the progression of renal fibrosis， improving renal pathological injury， and thereby exerting renal protective effects.

ObjectiveTo investigate the effect of Danggui Shaoyaosan on the expression of Toll-like receptor 4/nuclear factor-kappa B p65/NOD-like receptor protein 3 （TLR4/NF-κB p65/NLRP3） signaling pathway in the renal tissues of db/db mice with spontaneous diabetes， and to explore the potential mechanism by which Danggui Shaoyaosan alleviates inflammation in diabetic kidney disease （DKD）. MethodsThirty db/db mice were divided into five groups： A model group， Danggui Shaoyaosan low- （16.77 g·kg^-1·d^-1）， medium- （33.54 g·kg^-1·d^-1）， and high-dose （67.08 g·kg^-1·d^-1） intervention groups， as well as an irbesartan group （0.025 g·kg^-1·d^-1） by the random number table method， with 6 mice in each group. Additionally， 6 db/m mice were assigned to the normal group. After 8 weeks of intervention， the following parameters were determined by corresponding methods： body weight， fasting blood glucose （FBG）， 24-hour urinary protein （24 h-UTP）， and serum creatinine （SCr） levels， renal histopathological analysis by hematoxylin-eosin （HE） staining， Masson staining， and periodic acid-Schiff （PAS） staining， the protein and mRNA expression levels of TLR4， NF-κB p65， NLRP3， tumor necrosis factor-alpha （TNF-α）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， interleukin-10 （IL-10）， and interleukin-18 （IL-18） by Western blot and Real-time quantitative polymerase chain reaction （Real-time PCR）， as well as TLR4， NF-κB p65， and NLRP3 protein expression in renal tissues by immunohistochemistry （IHC）. ResultsCompared with the normal group， the model group exhibited increased body weight， FBG， 24 h-UTP， and SCr levels （P<0.05）； disordered renal structure， thickened basement membrane， and interstitial inflammatory cell infiltration， elevated TLR4， NF-κB p65， NLRP3， TNF-α， IL-1β， IL-6， and IL-18 expression； as well as decreased IL-10 expression （P<0.05）. Compared with the model group， these pathological changes and biochemical abnormalities were reversed in the medicine intervention groups to varying degrees （P<0.05）. ConclusionDanggui Shaoyaosan may delay DKD progression by alleviating renal inflammatory response and reducing urinary protein excretion via modulating the TLR4/NF-κB p65/NLRP3 signaling pathway.

Objective To analyze the relationship between serum levels of Clara cell protein 16(Cc16),E-selectin(CD62E),the severity of neonatal respiratory distress syndrome(NRDS)and lung ultrasound scores.Methods A total of 200 neonates with NRDS were selected in this study.The severity of the disease was assessed using oxygenation index(P/F).The neonates were divided into three groups:the mild group(46 cases),the moderate group(65 cases)and the severe group(89 cases).The serum levels of Cc16 and CD62E were compared between the three groups.In addition,based on the lung ultrasound scores,neonates were divided into the low-score group(score＜12 points,n=127),the medium-score group(score 12-24 points,n=51)and the high-score group(score>24 points,n=22).The receiver operating characteristic(ROC)curve was used to evaluate the predictive efficacy of the combined detection of serum Cc16,CD62E and lung ultrasound score for severe NRDS.Results Compared with the mild group,the serum levels of Cc16 and CD62E,and lung ultrasound scores were higher in the moderate group and the severe group(P＜0.05).Compared with the low lung ultrasound score group,the serum levels of Cc16 and CD62E were higher in the moderate lung ultrasound score group and the high lung ultrasound score groups(P＜0.05).Cc16 and CD62E were positively correlated with the severity of NRDS(rs=0.679 and 0.680,P＜0.01),and they were also positively correlated with lung ultrasound scores(r=0.692 and 0.685,P＜0.01).ROC analysis showed that the combined detection of Cc16,CD62E and lung ultrasound scores had a relatively high diagnostic value for severe NRDS(P＜0.05).Conclusion The serum levels of Cc16 and CD62E in NRDS neonates are positively correlated with disease severity and lung ultrasound scores.

Objective: To observe the clinical efficacy and safety of Yiqi Tongluo Decoction in the intervention of early traditional Chinese medicine (TCM) syndromes after ischemic cerebrovascular disease (ICVD) intervention. Methods: From October 2020 to July 2023, a randomized, double-blind, placebo-controlled study was conducted to include 60 patients with qi deficiency, blood stasis, and phlegm obstruction syndrome after ICVD interventional therapy. They were assigned to the Yiqi Tongluo Decoction treatment group (30 cases) and the TCM placebo routine treatment control group (30 cases) according to the randomized block design. Both groups received routine standardized treatment of Western medicine, including dual antiplatelet, lipid regulation, and control of risk factors for cerebrovascular disease. The treatment group was treated with Yiqi Tongluo Decoction based on the control group. The course of treatment was 60 days and follow-up was carried out 2 and 6 months after the operation. The improvement of qi deficiency syndrome, blood stasis syndrome, phlegm syndrome score and TCM syndrome score, modified Rankin score (mRS), Barthel index (BI) score, Fatty acid-binding protein 4 (FABP4) level, incidence of transient ischemic attack (TIA) and ischemic stroke (IS) and incidence of adverse reactions, Head and neck CT angiography (CTA) or digital subtraction angiography (DSA) examination were collected. The clinical efficacy of the patients 2 months after the operation was taken as the main outcome index to preliminarily evaluate the early and long-term efficacy of Yiqi Tongluo Decoction after the ICVD intervention. The early and long-term clinical efficacy and safety of Western medicine standardized treatment combined with TCM Yiqi Tongluo Decoction on patients with qi deficiency, blood stasis and phlegm obstruction syndrome after ICVD intervention were evaluated. The safety of Yiqi Tongluo Decoction in the treatment of patients after ICVD intervention with white blood cell (WBC), C-reactive protein (CRP), fibrinogen (FIB), plasminogen time (PT), recurrence of cerebral ischaemia and restenosis in patients at 2 and 6 months after treatment were evaluated. Results: Compared to the control group, the TCM syndrome scores for qi deficiency, blood stasis and phlegm syndrome in the treatment group reduced significantly, the clinical efficacy improved significantly, the mRS score and FABP4 were reduced, and the BI score was increased. Adverse events such as cerebral ischaemia were fewer in the treatment group than in the control group, but the difference was not statistically significant; levels of CRP, WBC and PT were reduced, and levels of FIB were reduced at 6 months post-treatment, all P<0.01, and images were intuitively compared. The treatment group was superior to the control group. Conclusion Yiqi Tongluo Decoction combined with Western medicine standard treatment can improve the early clinical efficacy of ICVD patients with qi deficiency, blood stasis and phlegm obstruction syndrome after interventional surgery, improve neurological impairment and daily living ability, reduce the state of qi deficiency syndrome, blood stasis syndrome and phlegm syndrome after interventional surgery, and improve the clinical efficacy of TCM. At the same time, it can reduce the level of FABP4, the target of atherosclerosis and restenosis after interventional surgery, reduce the level of inflammation after interventional surgery in patients with ICVD, regulate coagulation function, and reduce the incidence of long-term recurrence of cerebral ischemia after interventional surgery, with good safety.

Objective To analyze the main epidemiological characteristics of fungal infection in this hospital in the past 7 years,and to provide reference for clinical treatment and prevention and control strategies of fun-gal infection.Methods The fungal data and clinical data of related patients isolated from clinical samples in Peking Union Medical College Hospital from early January 2018 to the end of May 2024 were selected,and the main epidemiological characteristics of fungal infection in this hospital were identified and described through multi-angle statistical analysis.Results A total of 4 479 patients with filamentous fungal infection were en-rolled.The proportion of male patients[57.5％(2 576/4 479)]was higher than that of female patients[42.5％(1 903/4 143)],mainly distributed in internal medicine,Intensive Care Unit(ICU)and emergency de-partment,among which internal medicine accounted for the highest proportion[50.0％(2 241/4 479)].About 90.0％of the specimens were from the lower respiratory tract,in addition to specimens from skin and soft tis-sue,tissue,ear and blood culture.In terms of seasonal distribution,there are more patients in winter.The fun-gi were mainly composed of Aspergillus,Mucor,Cerdosporium,Fusarium and Penicillium,among which As-pergillus was the most abundant,accounting for 74.6％of the total.Aspergillus fumigatus was the most a-bundant Aspergillus,accounting for 42.5％of the total Aspergillus(1 418/3 340).Among the related infec-tions caused by mold,Aspergillus was the most common in the lower respiratory tract,accounting for 76.8％.Among them,Aspergillus fumigatus accounted for the highest proportion(33.6％).98.6％of the molds infected the ear were Aspergillus,of which Aspergillus niger and Aspergillus terreus were the most common.Skin infections are mainly caused by Sporothrix schenckii,Trichophyton rubrum,Microsporum ca-nis.The results of in vitro drug sensitivity test showed that the four common Aspergillus isolated in this hos-pital were sensitive to voriconazole,and amphotericin B had better antifungal activity against Mucorales in vitro.Conclusion Based on the main epidemiological characteristics of fungal infections in this hospital,it is recommended that special attention be paid to the admission of patients in the respiratory department during the peak infection period in autumn and winter.In the treatment of fungal infections in different regions and on different body parts,attention should be paid to the differences in the distribution of bacterial species.

Objective To analyze the acupoint selection law of acupuncture and moxibustion for pediatric cerebral palsy based on data mining techniques.Methods Clinical research literature about acupuncture and moxibustion for the treatment of pediatric cerebral palsy was retrieved from CNKI,Wanfang Data,VIP,CBM,PubMed,Web of Science,Embase and Cochrane Library from the establishment of the databases to April 1,2024.Excel 2021 was used to establish a database of prescription acupoints.The frequency of use of acupoints,attributed to the meridians,parts and specific acupoints were under statistically analysis,and SPSS Modeler 18.0 and SPSS Statistics 27.0 were used to conduct the association rules analysis,factor analysis and clustering analysis of acupoints.Results A total of 579 articles were included,579 prescriptions were extracted,containing 245 acupoints with the frequency of 6 422 times.The high-frequency acupoints were Zusanli,Baihui,Hegu,Sanyinjiao and Quchi,etc.The commonly used meridians were Governor Vessel,gall bladder meridian,stomach meridian,large intestine meridian and bladder meridian;mostly used acupoints were in the lower limbs,head and neck,upper limbs,waist and back.The association rules analysis showed that the top combinations were"Hegu-Quchi","Zusanli-Quchi","Zusanli-Quchi-Hegu","Hegu-Quchi-Zusanli";clustering analysis showed that 6 valid clusters were extracted;factor analysis extracted 7 valid common factors.Conclusion Acupuncture and moxibustion treatment for pediatric cerebral palsy is based on the principle of strengthening the brain,improving intelligence and tonifying the five zang organs,reflecting the principle of matching acupoints far and near.The core combination of acupoints is"Zusanli-Quchi-Hegu".

Objective:To verify the clinical efficacy of using radial extracorporeal shock wave therapy(rESWT)with a combination of low-to-moderate energy flow density(EFD)in the treatment of erectile dysfunction(ED).Method:Thirty-six patients with ED were randomly divided into two groups,with 18 patients in each group.The rESWT group received 16 sessions of rESWT(twice weekly for 8 weeks),while the control group took oral tadalafil 5 mg once daily for 8 weeks.The 5-item International Index of Erectile Function(IIEF-5)and Erection Hardness Score(EHS)were evaluated before treatment,at 1 month and 2 months during treatment,and at 1 month,3 months,and 6 months after the completion of treatment.Result:The overall comparison of IIEF-5 and EHS scores between the rESWT group and the control group at various time points showed significant differences(P<0.001).For the rESWT group,the IIEF-5 score after 1 month of treatment was significantly higher than that before treatment(P<0.001)but lower than that of the control group(P<0.05).After 2 months,it was significantly higher than at 1 month(P<0.001)with no differ-ence compared to the control group(P>0.05).There were no significant differences were observed at the 1-month and 3-month follow-ups compared to the 2-month treatment(P>0.05).At 3 months of follow-up,the score was higher than that of the control group(P<0.05).At 6 months of follow-up,the score was higher than that before treatment(P<0.05).For the control group,the IIEF-5 score,there were no differences be-tween 1 and 2 months of treatment(P>0.05),but both were significantly higher than before treatment(P<0.001).At 1 month of follow-up,the score was lower than at 2 months of treatment(P<0.01).There was no difference in EHS between the rESWT group and the control group(P>0.05),but the rESWT group was treat-ed for 2 months and followed up for 1 month,which was higher than that before treatment(P<0.05).Conclusion:The combined use of low-to-moderate EFD rESWT can achieve the same efficacy comparable to Tadalafil in ED treatment and demonstrates superior durability of response,indicating its broader clinical appli-cation.

Checkpoint blockade immunotherapy has emerged as a transformative approach in cancer treatment by activating tumor-infiltrating T cells. However, the efficacy of PD-L1 blockade is restricted in "cold" tumors, which are characterized by low immunogenicity, presenting a challenge to immunotherapy. This study introduces an innovative strategy, utilizing cathepsin-cleavable N-(2-hydroxypropyl) methacrylamide (HPMA) polymer-assisted combined photodynamic therapy (PDT) and PD-L1 degradation for the first time, effectively treating T cell-deficient tumors. The degradable main-chain polymer, conjugated with photosensitizer porphyrin, facilitates the accumulation of reactive oxygen species (ROS), triggering immunogenic cell death (ICD) and promoting cytotoxic T lymphocytes (CTLs) infiltration into tumors. Multivalent peptide antagonists of PD-L1 promote PD-L1 degradation in lysosomes through receptor crosslinking, overcoming the adaptive cycling of PD-L1 to the tumor cell surface. These findings demonstrate that polymer-assisted PDT and PD-L1 crosslinking degradation represent a potential novel strategy for anti-tumor immunotherapy, providing valuable tools for expanding immunotherapy applications in immunosuppressive cancers.

The continuous emergence of SARS-CoV-2 variants as well as other potential future coronavirus has challenged the effectiveness of current COVID-19 vaccines. Therefore, there remains a need for alternative antivirals that target processes less susceptible to mutations, such as the formation of six-helix bundle (6-HB) during the viral fusion step of host cell entry. In this study, a novel high-throughput screening (HTS) assay employing a yeast-two-hybrid (Y2H) system was established to identify inhibitors of HR1/HR2 interaction. The compound IMB-9C, which achieved single-digit micromolar inhibition of SARS-CoV-2 and its Omicron variants with low cytotoxicity, was selected. IMB-9C effectively blocks the HR1/HR2 interaction in vitro and inhibits SARS-CoV-2-S-mediated cell-cell fusion. It binds to both HR1 and HR2 through non-covalent interaction and influences the secondary structure of HR1/HR2 complex. In addition, virtual docking and site-mutagenesis results suggest that amino acid residues A930, I931, K933, T941, and L945 are critical for IMB-9C binding to HR1. Collectively, in this study, we have developed a novel screening method for HR1/HR2 interaction inhibitors and identified IMB-9C as a potential antiviral small molecule against COVID-19 and its variants.

Plant-derived extracellular vesicles (PDEVs), describe a group of nanoparticles released by plants. These particles are characterized by a lipid bilayer structure containing various proteins, lipids, nucleic acids, and unique metabolites. Although the study on PDEVs is relatively new, having only been around for ten years, they have shown promising development prospects in both basic research and clinical transformation areas. Evidence suggests that PDEVs have excellent application prospects in regulating inflammation and treating tumors. Their distinctive, vesicle-mimicking architecture and stellar biocompatibility render them prime candidates for ferrying various anti-cancer agents, including RNA, proteins, and conventional chemotherapy drugs. Increasingly, studies have shown that PDEVs can be engineered as an innovative platform for combination cancer immunotherapy. Consequently, this paper provides an extensive summary of current developments in engineering methods and strategies for PDEVs in cancer treatment and combined cancer immune therapeutics. The essential characteristics of PDEVs, including the biogenesis process and components, as well as their anti-tumor activity and mechanism, are summarized. Finally, the in vivo safety of PDEVs as delivery vectors and the challenges of scale-up production and clinical transformation are discussed.