Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Neuropathic pain, often featuring allodynia, imposes significant physical and psychological burdens on patients, with limited treatments due to unclear central mechanisms. Addressing this challenge remains a crucial unsolved issue in pain medicine. Our previous study, using protein kinase C gamma (PKCγ)-tdTomato mice, highlights the spinal feedforward inhibitory circuit involving PKCγ neurons in gating neuropathic allodynia. However, the regulatory mechanisms governing this circuit necessitate further elucidation. We used diverse transgenic mice and advanced techniques to uncover the regulatory role of the descending serotonin (5-HT) facilitation system on spinal PKCγ neurons. Our findings revealed that 5-HT neurons from the rostral ventromedial medulla hyperpolarize spinal inhibitory interneurons via 5-HT_2C receptors, disinhibiting the feedforward inhibitory circuit involving PKCγ neurons and exacerbating allodynia. Inhibiting spinal 5-HT_2C receptors restored the feedforward inhibitory circuit, effectively preventing neuropathic allodynia. These insights offer promising therapeutic targets for neuropathic allodynia management, emphasizing the potential of spinal 5-HT_2C receptors as a novel avenue for intervention.
Animals ; Neuralgia/physiopathology* ; Protein Kinase C/metabolism* ; Receptor, Serotonin, 5-HT2C/metabolism* ; Hyperalgesia/physiopathology* ; Mice, Transgenic ; Mice ; Spinal Cord/metabolism* ; Serotonin/metabolism* ; Male ; Neurons/metabolism* ; Mice, Inbred C57BL

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis

OBJECTIVE: To study bioactive compounds from the endophytic fungus Penicillium sp. HJT-A-6 isolated from stem of Rhodiola tibetica, and evaluate its allelopathic activity. METHODS: The chemical constituents were isolated and purified by silica gel, Sephadex LH-20 column chromatography and semi-preparative HPLC. Their structures were elucidated by extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. In addition, the allelopathic activity of compound 1 was evaluated by measuring the seed germination rate of R. tibetica. RESULTS: Two new polyketides 4-hydroxy-3,6-dimethyl-2H-pyran-2-one (1) and penilactone E (2), together with six known compounds walterolactone A (3), 5-hydroxyhexan-4-olide (4), 3-methyl-2-penten-5-olide (5), chaetoquadrin F (6), (Z)-6-acetyl-3-(1,2-dihydroxypropylidene)-5-hydroxy-8-methylchroman-2-one (7) and 4-hydroxy-3-(4-hydroxyhexanoyl)-5-methylfuran-2(5H)-one (8) were isolated from Penicillium sp. HJT-A-6. Compound 1 showed moderate seed-germination-promoting activity at a concentration of 0.001 mg/mL while inhibiting the seed germination at concentrations of 0.1 and 0.01 mg/mL. Compared with the positive drug 6-benzyladenine (6-BA), compound 1 could extend the seed-germination period of R. tibetica (up to 11 d). CONCLUSION Two new compounds were isolated from R. tibetica endophytic fungus Penicillium sp. HJT-A-6. Compound 1 displayed plant hormone-like activity, which inhibited the seed germination of the host plant at high concentrations and promoted the seed germination of the host plant at low concentrations. The results not only enrich the chemical constituents of the endophytic fungi isolated from Rhodiola tibetica, but also provide a theoretical basis for understanding the interaction mechanism between Rhodiola tibetica endophytic fungi and the host plant.

OBJECTIVE: To assess the independent and combined effects of air pollutants, meteorological factors, and greenspace exposure on new tuberculosis (TB) cases. METHODS: TB case data from Shanghai (2013-2018) were obtained from the Shanghai Center for Disease Control and Prevention. Environmental data on air pollutants, meteorological variables, and greenspace exposure were obtained from the National Tibetan Plateau Data Center. We employed a distributed-lag nonlinear model to assess the effects of these environmental factors on TB cases. RESULTS: Increased TB risk was linked to PM _2.5, PM ₁₀, and rainfall, whereas NO ₂, SO ₂, and air pressure were associated with a reduced risk. Specifically, the strongest cumulative effects occurred at various lags: PM _2.5 ( RR = 1.166, 95% CI: 1.026-1.325) at 0-19 weeks; PM ₁₀ ( RR = 1.167, 95% CI: 1.028-1.324) at 0-18 weeks; NO ₂ ( RR = 0.968, 95% CI: 0.938-0.999) at 0-1 weeks; SO ₂ ( RR = 0.945, 95% CI: 0.894-0.999) at 0-2 weeks; air pressure ( RR = 0.604, 95% CI: 0.447-0.816) at 0-8 weeks; and rainfall ( RR = 1.404, 95% CI: 1.076-1.833) at 0-22 weeks. Green space exposure did not significantly impact TB cases. Additionally, low temperatures amplified the effect of PM _2.5 on TB. CONCLUSION Exposure to PM _2.5, PM ₁₀, and rainfall increased the risk of TB, highlighting the need to address air pollutants for the prevention of TB in Shanghai.
China/epidemiology* ; Humans ; Air Pollutants/analysis* ; Tuberculosis/epidemiology* ; Incidence ; Meteorological Concepts ; Particulate Matter/adverse effects* ; Environmental Exposure ; Male ; Female ; Adult ; Air Pollution ; Middle Aged

AIM To optimize the cellulase-assisted ultrasound extraction process for total flavonoids from Plumbago zeylanica L.,and to evaluate their anti-oxidant activity.METHODS With extraction time,liquid-solid ratio,cellulase addition amount,extraction temperature and ultrasonic power as influencing factors,extraction rate of total flavonoids as an evaluation index,the extraction process was optimized by response surface method on the basis of single factor test.Subsequently,The scavenging rates of extract on DPPH,ABTS and OH free radicals were determined.RESULTS The optimal conditions were determined to be 34∶1 for liquid-solid ratio,3％for cellulase addition amount,51 ℃ for extraction temperature,38 min for extraction time,and 400 W for ultrasonic power,the extraction rate of total flavonoids was(33.411±0.97)％.The IC50 values of three free radicals were 0.13,0.042,3.29 mg/mL,respectively.CONCLUSION This reasonable and reliable method can be used for the cellulase-assisted ultrasound extraction of total flavonoids from P.zeylanica with strong anti-oxidant activity.

AIM To study the effects of Jiaotai Pills and their single composition drugs on high-fat diet-induced hypothalamic inflammation in obese mice.METHODS C57BL/6J mice were randomly divided into the normal group(15 mice)and the high-fat group(75 mice).The mice given 12 weeks of high-fat diet feeding were further randomly divided into the model group,the Jiaotai Pills group,the Coptis chinensis group,the Cinnamomum cassia group and the positive metformin group,with 15 mice in each group.After 6 weeks of administration,the mice had their body weight and fasting blood glucose(FBG)levels detected;their hypothalamic expressions of IL-1β,IL-6,TNF-α and Socs3 mRNA detected by RT-qPCR;their hypothalamic expressions of TLR4,MyD88,IKKβ and activated NF-κB protein detected by Western blot;their hypothalamic expressions of Iba1 and GFAP detected by immunohistochemistry;and their ultrastructural changes of nerve tissues observed using transmission electron microscopy(TEM).RESULTS Compared with the model group,each drug group displayed decreased hypothalamic expressions of IL-1β,IL-6,TNF-α and Socs3 mRNA(P＜0.01),and improved number and morphology of nerve cells revealed by TEM.The groups intervened with Jiaotai Pills,or Coptis chinensis,or metformin shared decreased body weight and FBG levels(P＜0.05);decreased protein expressions of TLR4,MyD88,IKKβ and p-NF-κB(P＜0.05);and decreased number of hypothalamic astrocytes and microglia(P＜0.05).Additionally,decreased p-NF-κB protein expression was observed in the Cinnamomum cassia group(P＜0.05).CONCLUSION Jiaotai Pills and their single composition drugs can improve high-fat diet-induced hypothalamic inflammation in obese mice.

Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27％.The number of HAI episodes was 38 032,and case prevalence rate was 1.38％.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66％to 2.35％.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65％.The most common infection site was the lower respiratory tract(44.66％),followed by the urinary tract(12.94％),surgical site(9.32％),upper respiratory tract(7.02％),and bloodstream infection(5.78％).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02％),department of neurosurgery(5.51％),and department(group)of hematology(5.34％).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10％)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76％),Pseudomonas aeruginosa(13.33％),Escherichia coli(12.79％),Acinetobacter baumannii(9.23％),and Staphylococcus aureus(7.88％).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71％.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18％.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46％.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.

AIM To study the effects of Jiaotai Pills and their single composition drugs on high-fat diet-induced hypothalamic inflammation in obese mice.METHODS C57BL/6J mice were randomly divided into the normal group(15 mice)and the high-fat group(75 mice).The mice given 12 weeks of high-fat diet feeding were further randomly divided into the model group,the Jiaotai Pills group,the Coptis chinensis group,the Cinnamomum cassia group and the positive metformin group,with 15 mice in each group.After 6 weeks of administration,the mice had their body weight and fasting blood glucose(FBG)levels detected;their hypothalamic expressions of IL-1β,IL-6,TNF-α and Socs3 mRNA detected by RT-qPCR;their hypothalamic expressions of TLR4,MyD88,IKKβ and activated NF-κB protein detected by Western blot;their hypothalamic expressions of Iba1 and GFAP detected by immunohistochemistry;and their ultrastructural changes of nerve tissues observed using transmission electron microscopy(TEM).RESULTS Compared with the model group,each drug group displayed decreased hypothalamic expressions of IL-1β,IL-6,TNF-α and Socs3 mRNA(P＜0.01),and improved number and morphology of nerve cells revealed by TEM.The groups intervened with Jiaotai Pills,or Coptis chinensis,or metformin shared decreased body weight and FBG levels(P＜0.05);decreased protein expressions of TLR4,MyD88,IKKβ and p-NF-κB(P＜0.05);and decreased number of hypothalamic astrocytes and microglia(P＜0.05).Additionally,decreased p-NF-κB protein expression was observed in the Cinnamomum cassia group(P＜0.05).CONCLUSION Jiaotai Pills and their single composition drugs can improve high-fat diet-induced hypothalamic inflammation in obese mice.

This study aims to comprehensively analyze the material basis of toad visceral oil(hereafter referred to as toad oil), and explore the pharmacological effect of toad oil on atopic dermatitis(AD). Ultra-high performance liquid chromatography-linear ion trap/orbitrap high-resolution mass spectrometry(UHPLC-LTQ-Orbitrap-MS) and gas chromatography-mass spectrometry(GC-MS) were employed to comprehensively identify the chemical components in toad oil. The animal model of AD was prepared by the hapten stimulation method. The modeled animals were respectively administrated with positive drug(0.1% hydrocortisone butyrate cream) and low-and high-doses(1%, 10%) of toad oil by gavage. The effect of toad oil on AD was evaluated with the AD score, ear swelling rate, spleen index, and pathological section results as indicators. A total of 99 components were identified by UHPLC-LTQ-Orbitrap-MS, including 14 bufadienolides, 7 fatty acids, 6 alkaloids, 10 ketones, 18 amides, and other compounds. After methylation of toad oil samples, a total of 20 compounds were identified by GC-MS. Compared with the model group, the low-and high-dose toad oil groups showed declined AD score, ear swelling rate, and spleen index, alleviated skin lesions, and reduced infiltrating mast cells. This study comprehensively analyzes the chemical composition and clarifies the material basis of toad oil. Meanwhile, this study proves that toad oil has a good therapeutic effect on AD and is a reserve resource of traditional Chinese medicine for external use in the treatment of AD.
Animals ; Dermatitis, Atopic/immunology* ; Disease Models, Animal ; Mice ; Male ; Gas Chromatography-Mass Spectrometry ; Humans ; Bufonidae ; Oils/administration & dosage* ; Chromatography, High Pressure Liquid ; Female ; Mice, Inbred BALB C