By reviewing the physical biological research on the activation of acupoint effects by acupuncture， this paper explains the activation mechanism from the perspective of the generation and transmission of mechanical signals caused by acupuncture， and reveals the physical-chemical coupling processes in the acupoint microenvironment. Future research should focus on locally mechanosensitive cells， further exploring how acupuncture mechanical signals trigger dynamic changes in cells and molecules in the acupoints， and the physical-chemical information transduction mechanism， which will provide scientific evidence for the acupoint activation during acupuncture. Related studies will contribute to a deeper understanding of the scientific principles behind acupuncture and promote its clinical application and development.

Objective To perform single-molecule, real-time sequencing of ceftazidime-avibactam (CAZ-AVI)-resistant Pseudomonas aeruginosa and to investigate the mechanism underlying ceftazidime-avibactam resistance in P. aeruginosa. Methods The susceptibility of 89 P. aeruginosa isolates randomly sampled from clinical specimens in Sanming First Hospital Affiliated to Fujian Medical University from November 2021 through July 2023 to common antimicrobial agents was tested, and the minimum inhibitory concentration (MIC) of CAZ-AVI was determined against P. aeruginosa with a broth microdilution assay, with CAZ-AVI MICs of 8 mg/L and lower defined as susceptible and 16 mg/L and higher as resistant. The expression of drug-resistant genes ampC, oxa-488, oprD, mexA, oxa-10, oxa-14, vim and tem was quantified in P. aeruginosa using a real-time quantitative reverse transcription PCR (qPCR) assay. CAZ-AVI-susceptible and -resistant P. aeruginosa isolates from the same case were selected for PacBio single-molecule, real-time sequencing, and sequencing results were subjected to genome structure and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotations. Results The 89 P. aeruginosa isolates showed a relatively high level of resistance to meropenem (75.28%) and imipenem (74.16%) and the highest susceptibility to amikacin (91.01%). There were 49 CAZ-AVI-resistant P. aeruginosa isolates and 40 susceptible isolates. qPCR assay detected lower oprD gene expression in CAZ-AVI-resistant P. aeruginosa isolates [0.104 (2.385)] than in susceptible isolates [0.551 (17.885)] (Z = -2.958, P < 0.01), and there were no significant differences between CAZ-AVI-susceptible and -resistant P. aeruginosa isolates in terms of ampC, oxa-488, mexA or tem gene expression (all P values > 0.05), while oxa-10, oxa-14 and vim gene was expressed in few P. aeruginosa isolates. There were 1 729, 3 936, 3 737 and 3 955 genes in CAZ-AVI-resistant P. aeruginosa isolates PA-762 and PA-M174 and susceptible isolates PA-885 and PA-808 that were annotated to GO terms, with the highest numbers of genes enriched in the molecular function of catalytic activity, high numbers of genes enriched in biological processes of metabolic process, single-organism process and cellular process, and high numbers of genes enriched in cellular components of cell and cell membranes. There were 1 803, 4 084, 3 915 and 4 066 genes in the PA-762, PA-M174, PA-885 and PA-808 isolates enriched in the KEGG signaling pathway, and the majority of genes were enriched in four primary signaling pathways of metabolism, genetic information processing, environmental information processing and cellular process, with the highest number of genes associated with metabolic pathways. Both CAZ-AVI-resistant P. aeruginosa isolates PA-762 and PA-M174 carried multiple efflux pumps systems, including MexAB-OprM, MexCD-OprJ, MexEF-OprN and MexXY-OprM. Single nucleotide substitution was found at position 169 in the DNA sequence of the PA-762 isolate, leading to substitution of serine for glycine at position 57 in the protein sequence, and there are deletions of two bases at positions 307 and 308 in the DNA sequence of the PA-M174 isolate, leading to substitution of threonine for arginine at position 103 in the protein sequence. Conclusion Mutation or downregulation of oprD gene may lead to CAZ-AVI resistance in P. aeruginosa.

Objective To preliminarily explore the potential efficacy of Xuesaitong Soft Capsule(XST)against post-stroke depression(PSD),and to investigate the material basis of XST's anti-PSD effect based on the metabolomics results to analyze its related pharmacokinetic(PK)characteristics and further analyze the pharmacodynamic(PD)equation of representative ingredients.Methods The initial evaluation of drug effica-cy was conducted by detecting the depressive-like behavior and neurotransmitter levels in rats.The Pearson correlation analysis was employed to analyze the correlation between the main metabolites regulated by XST and the saponin components entering the bloodstream.At various time points after drug administration,the blood concentration of ginsenoside Re and the concentration of norepinephrine(NE)in the serum of PSD rats were measured,and the compartment model was fitted accordingly.Furthermore,the liquid chromatography-mass spectrometry was utilized to determine the content of ginsenoside Re in the liver,spleen,kidney,prefron-tal cortex,hippocampus and striatum of PSD rats.Results Ginsenoside Re showed the optimal correlation by the Pearson correlation analysis.Based on its pharmacokinetic parameters,the pharmacodynamic equation with NE was E=160.462 × Ce/(38.663+Ce).The contents of ginsenoside Re in the liver,spleen,kidney,prefron-tal cortex,hippocampus and striatum of rats were(17.23+11.90),(19.05+5.67),(1.95+0.79),(70.13+6.75),(57.03+3.11),and(72.45+5.45)ng/g,respectively.Conclusion XST could improve the depressive-like behaviors in PSD rats by regulating the expression levels of neurotransmitter NE and 5-HT.Ginsenoside Re may be the pharmacodynamical material foundation for XST's preventative treatment of PSD.

Invasive fungal infections (IFIs) have become prominent global health threats, escalating the burden on public health systems. The increasing occurrence of invasive fungal infections is due primarily to the extensive application of chemotherapy, immunosuppressive therapies, and broad-spectrum antifungal agents. At present, therapeutic practices utilize multiple categories of antifungal agents, such as azoles, polyenes, echinocandins, and pyrimidine analogs. Nevertheless, the clinical effectiveness of these treatments is progressively weakened by the emergence of drug resistance, thereby substantially restricting their therapeutic utility. Consequently, there is an imperative need to expedite the discovery of novel antifungal agents. This review seeks to present an exhaustive synthesis of novel antifungal drugs and candidate agents that are either under current clinical investigation or anticipated to progress into clinical evaluation. These emerging compounds exhibit unique benefits concerning their modes of action, antimicrobial spectra, and pharmacokinetic characteristics, potentially leading to improved therapeutic outcomes relative to conventional antifungal regimens. It is anticipated that these novel therapeutic agents will furnish innovative treatment modalities and enhance clinical outcomes in managing invasive fungal infections.

This study retrospectively analyzed 12 patients with transfusion-dependent, non-severe aplastic anemia (TD-NSAA) refractory to cyclosporine A (CsA) , who were treated with lusutrombopag monotherapy. These patients either had a variety of chronic comorbidities or medication-related risks, or they were unresponsive to or intolerant of other thrombopoietin receptor agonists (TPO-RA) . The median treatment duration with lusutrombopag was 4 months (range: 3-11 months) , while the median follow-up period was 8 months (range: 6-11 months) . The overall response (OR) rates at months 3, 6, and the end of follow-up were 50.0%, 58.3%, and 50.0%, respectively, with a median time to OR of 2 months (range: 1-4 months) . Complete response (CR) rates were 8.3%, 16.7%, and 16.7% at the same time points, with a median time to CR of 4 months (range: 2-5 months) . Adverse events were all Grade 1, with an incidence rate of 25.0%. During follow-up, one patient experienced a loss of OR after discontinuing treatment, with a relapse rate of 14.3%; no clonal evolution or mortality was observed. These findings suggest that lusutrombopag is both effective and well-tolerated in CsA-refractory TD-NSAA patients and represents a promising therapeutic option for those with poor treatment tolerability.

OBJECTIVE: To investigate the feasibility and effectiveness of the novel bone hook combined with finger-guided technique in the treatment of irreducible intertrochanteric femoral fractures in elderly. METHODS: Between January 2021 and August 2023, 23 elderly patients with irreducible intertrochanteric femoral fractures were treated with the novel bone hook combined with finger-guided technique. There were 10 males and 13 females; the age ranged from 68 to 93 years (mean, 76.2 years). The time from injury to operation ranged from 36 to 76 hours (mean, 51.2 hours). According to the classification standard proposed by TONG Dake et alin 2021, there were 10 cases of typeⅠA, 1 case of typeⅠB, 6 cases of type ⅡA, 4 cases of type ⅡB, and 2 cases of type ⅡC. The operation time, intraoperative blood loss, intraoperative fluoroscopy frequences, and quality of fracture reduction were recorded. The fracture healing time and occurrence of postoperative complications were observed during follow-up. At last follow-up, the Harris scoring system was used to evaluate the hip joint function. RESULTS: The operation time was 42-95 minutes (mean, 52.1 minutes). The intraoperative blood loss was 40-420 mL (mean, 126.5 mL). Intraoperative fluoroscopy was performed 14-34 times (mean, 20.7 times). According to the criteria proposed by Chang et al, the quality of fracture reduction was rated as good in 20 cases and acceptable in 3 cases. All patients were followed up 6-20 months (mean, 10.2 months). X-ray film showed that all fractures healed with the healing time of 3.0-5.5 months (mean, 4.0 months). At last follow-up, the Harris score of the hip joint ranged from 82 to 97 points (mean, 90.4 points). Among them, 14 cases were rated as excellent and 9 cases as good. No complication such as coxa vara, cutting of the cephalomedullary nail, nail withdrawal, or nail breakage occurred during follow-up. CONCLUSION The treatment of elderly patients with irreducible intertrochanteric femoral fractures by using the novel bone hook combined with finger-guided technique can achieve high-quality fracture reduction and fixation, and has a good effectiveness.
Humans ; Male ; Female ; Aged ; Aged, 80 and over ; Hip Fractures/diagnostic imaging* ; Fracture Fixation, Internal/instrumentation* ; Fracture Healing ; Treatment Outcome ; Operative Time ; Fracture Fixation, Intramedullary/instrumentation* ; Bone Nails ; Postoperative Complications/epidemiology* ; Feasibility Studies ; Fingers

OBJECTIVE: To investigate the effects of combined platelet-rich plasma (PRP) and arterial supercharging technique on the survival rate and functional restoration of cross-body region skin flaps in rabbits. METHODS: Twelve healthy 6-month-old New Zealand White rabbits were randomly assigned to 4 groups ( n=3): sham group, PRP group, anastomosis group, and combined treatment group. An axial skin flap with an area of 12 cm×6 cm on the inner side of the hind limbs of all animals were prepared, with the saphenous artery as the main blood supply. Following the ligation of both the proximal and distal ends of the saphenous artery across all groups, the sham group received no further intervention, the PRP group was subjected to PRP injection, the anastomosis group underwent in situ end-to-end anastomosis of the distal saphenous artery, and the combined treatment group received both in situ distal saphenous artery anastomosis and PRP administration. Flap survival was evaluated and recorded on postoperative days 1, 3, and 7, with survival rates calculated accordingly. On day 7, flap tissue samples were harvested for HE staining to assess basal tissue morphology. Additionally, immunohistochemical staining was conducted to detect the expression of α-smooth muscle actin (α-SMA), vascular endothelial growth factor (VEGF), and CD31 in the flap tissues. RESULTS: At postoperative day 1, no significant difference in flap survival rates were observed among the 4 groups ( P>0.05). At day 3, the PRP group showed no significant difference compared to the sham group ( P>0.05); however, both the anastomosis and combined treatment groups exhibited significantly higher survival rates than the sham group ( P<0.05), the combined treatment group further demonstrated superior survival rates compared to both the PRP and anastomosis groups ( P<0.05). At day 7, the combined treatment group maintained significantly higher survival rates than all other groups ( P<0.05), while both the PRP and anastomosis groups exceeded the sham group ( P<0.05). HE staining at day 7 revealed persistent inflammatory cell infiltration, sheet-like erythrocyte deposition, and disordered collagen fibers in the sham group. The PRP group showed nascent microvessel formation and early collagen reorganization, whereas the anastomosis group displayed mature microvasculature with resolved interstitial edema. The combined treatment group exhibited differentiated microvessels with densely packed collagen bundles. Immunohistochemical analysis at day 7 demonstrated significantly larger relative area percentages of α-SMA, VEGF, and CD31 positive cells in the combined treatment group compared to all other groups ( P<0.05). Both the PRP and anastomosis groups also showed significantly higher values than the sham group ( P<0.05). CONCLUSION The combination of PRP and arterial supercharging techniques significantly enhances flap healing, potentially through mechanisms involving augmented angiogenesis and improved blood supply.
Animals ; Rabbits ; Platelet-Rich Plasma ; Surgical Flaps/blood supply* ; Graft Survival ; Anastomosis, Surgical/methods* ; Ischemia/surgery* ; Arteries/surgery* ; Skin/blood supply* ; Vascular Endothelial Growth Factor A/metabolism* ; Male ; Skin Transplantation/methods*

Recently, diffusion models have emerged as a promising paradigm for molecular design and optimization. However, most diffusion-based molecular generative models focus on modeling 2D graphs or 3D geometries, with limited research on molecular sequence diffusion models. The International Union of Pure and Applied Chemistry (IUPAC) names are more akin to chemical natural language than the Simplified Molecular Input Line Entry System (SMILES) for organic compounds. In this work, we apply an IUPAC-guided conditional diffusion model to facilitate molecular editing from chemical natural language to chemical language (SMILES) and explore whether the pre-trained generative performance of diffusion models can be transferred to chemical natural language. We propose DiffIUPAC, a controllable molecular editing diffusion model that converts IUPAC names to SMILES strings. Evaluation results demonstrate that our model outperforms existing methods and successfully captures the semantic rules of both chemical languages. Chemical space and scaffold analysis show that the model can generate similar compounds with diverse scaffolds within the specified constraints. Additionally, to illustrate the model's applicability in drug design, we conducted case studies in functional group editing, analogue design and linker design.

Objective:To analyze the four lab test results of infectious diseases among patients in a stomatological hospital in Shaanxi Province from 2018 to 2023,so as to provide evidence for clinical prevention and control of infection.Methods:The pa-tients who see a doctor in stomatological hospital from January 2018 to December 2023 were tested for four infectious diseases.HB-sAg and anti-HIV were detected by electrochemical luminescence method,and anti-HCV and anti-TP were detected by ELISA method.Results:There was no statistical difference in the positive rates of HBsAg,anti-HCV and anti-HIV in each year,and the positive rate of anti-TP decreased year by year.There was no statistical difference in the positive rate of anti-HCV between different sexes,and the positive rates of HBsAg,anti-TP and anti-HIV are higher in male than in female.HBsAg and anti-HCV positive pa-tients were mostly concentrated in 51-60 years old.Anti-TP positive patients were mostly concentrated in people over 60 years old and anti-HIV positive patients were mostly concentrated in 41-60 years old.78.38％of HIV-positive patients with oral mucosal dis-eases were initially diagnosed as oral candidiasis.Conclusion:Male and people over 41 years old were the high-risk groups of vari-ous infectious diseases.

Recently,diffusion models have emerged as a promising paradigm for molecular design and optimization.However,most diffusion-based molecular generative models focus on modeling 2D graphs or 3D geom-etries,with limited research on molecular sequence diffusion models.The International Union of Pure and Applied Chemistry(IUPAC)names are more akin to chemical natural language than the simplified molecular input line entry system(SMILES)for organic compounds.In this work,we apply an IUPAC-guided conditional diffusion model to facilitate molecular editing from chemical natural language to chemical language(SMILES)and explore whether the pre-trained generative performance of diffusion models can be transferred to chemical natural language.We propose DiffIUPAC,a controllable molecular editing diffusion model that converts IUPAC names to SMILES strings.Evaluation results demonstrate that our model out-performs existing methods and successfully captures the semantic rules of both chemical languages.Chemical space and scaffold analysis show that the model can generate similar compounds with diverse scaffolds within the specified constraints.Additionally,to illustrate the model's applicability in drug design,we conducted case studies in functional group editing,analogue design and linker design.