Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

BACKGROUND:Currently,there are many modeling methods for pelvic organ prolapse animal models,and the commonly used methods are vaginal balloon dilatation,oophorectomy and the combination of the two.There is no study comparing the three modeling methods in detail.OBJECTIVE:To construct and validate a rat animal model of pelvic organ prolapse using three different methods and to identify the advantages and disadvantages of various models.METHODS:Seventy-two 8-week SPF-grade female Sprague-Dawley rats were selected and randomly divided into four groups,namely,vaginal balloon dilatation group,ovariectomy group,ovariectomy combined with vaginal balloon dilatation group(the combined group),and the sham-operated group(no ovariectomy and no vaginal dilatation).The vaginal wall tissues of rats were collected at 4,8 and 12 weeks after the operation for hematoxylin-eosin staining,Masson staining,EVG staining and immunohistochemical staining of α-smooth muscle actin,Vimentin and matrix metalloproteinase 9 detection,and the pelvic floor muscle tissues were taken at 4,8 and 12 weeks after the operation for hematoxylin-eosin staining,Masson staining and EVG staining.RESULTS AND CONCLUSION:(1)Hematoxylin-eosi staining showed that there was no significant difference in the decrease of vaginal epithelial layer thickness in the vaginal balloon dilatation group compared with the sham-operated group,(P＞0.05),while the thickness of the vaginal epithelial layer was significantly reduced in the ovariectomy group and the ovariectomy combined with vaginal balloon dilation group(P＜0.001),and the reduction was more significant in the ovariectomy combined with vaginal balloon dilation group,remained stable at 8 weeks after surgery and lasted until 12 weeks.(2)The changes in the content of collagen fibers and elastic fibers in the vaginal wall stained by Masson and EVG staining were the same as the changes in the thickness of the vaginal epithelial layer stained by hematoxylin-eosin,and there were no changes in collagen fibers and elastic fibers in the pelvic floor muscle tissues of the treatment groups.(3)At 4,8 and 12 weeks after treatment,there was no significant difference in the expression levels of α-smooth muscle actin,Vimentin and matrix metalloproteinase 9 in the vaginal wall tissue of the balloon dilation group compared with the control group(P＞0.05),whereas the expression levels of α-smooth muscle actin and Vimentin were significantly decreased in the ovariectomy group and ovariectomy combined with vaginal balloon dilation group(P＜0.01)and the expression of matrix metalloproteinase 9 showed a significant increase(P＜0.01),with a more pronounced increase in the ovariectomy combined with vaginal balloon dilation group,and the increase reached a stable state at 8 weeks after surgery and could persist up to 12 weeks.To conclude,vaginal balloon dilatation could not maintain the degeneration of pelvic organ prolapse formed by the vaginal wall for a long period,and both ovariectomy and the combined method can be used.Ovariectomy combined with vaginal balloon dilatation can significantly accelerate and aggravate the formation of typical histological features of pelvic organ prolapse in vaginal wall tissues,effectively shorten the experimental period,and improve the efficiency.These effects reach a stable state at 8 weeks after surgery and can be sustained up to 12 weeks,which is practical and convenient for the study of pelvic organ prolapse animal models.

BACKGROUND:Currently,there are many modeling methods for pelvic organ prolapse animal models,and the commonly used methods are vaginal balloon dilatation,oophorectomy and the combination of the two.There is no study comparing the three modeling methods in detail.OBJECTIVE:To construct and validate a rat animal model of pelvic organ prolapse using three different methods and to identify the advantages and disadvantages of various models.METHODS:Seventy-two 8-week SPF-grade female Sprague-Dawley rats were selected and randomly divided into four groups,namely,vaginal balloon dilatation group,ovariectomy group,ovariectomy combined with vaginal balloon dilatation group(the combined group),and the sham-operated group(no ovariectomy and no vaginal dilatation).The vaginal wall tissues of rats were collected at 4,8 and 12 weeks after the operation for hematoxylin-eosin staining,Masson staining,EVG staining and immunohistochemical staining of α-smooth muscle actin,Vimentin and matrix metalloproteinase 9 detection,and the pelvic floor muscle tissues were taken at 4,8 and 12 weeks after the operation for hematoxylin-eosin staining,Masson staining and EVG staining.RESULTS AND CONCLUSION:(1)Hematoxylin-eosi staining showed that there was no significant difference in the decrease of vaginal epithelial layer thickness in the vaginal balloon dilatation group compared with the sham-operated group,(P＞0.05),while the thickness of the vaginal epithelial layer was significantly reduced in the ovariectomy group and the ovariectomy combined with vaginal balloon dilation group(P＜0.001),and the reduction was more significant in the ovariectomy combined with vaginal balloon dilation group,remained stable at 8 weeks after surgery and lasted until 12 weeks.(2)The changes in the content of collagen fibers and elastic fibers in the vaginal wall stained by Masson and EVG staining were the same as the changes in the thickness of the vaginal epithelial layer stained by hematoxylin-eosin,and there were no changes in collagen fibers and elastic fibers in the pelvic floor muscle tissues of the treatment groups.(3)At 4,8 and 12 weeks after treatment,there was no significant difference in the expression levels of α-smooth muscle actin,Vimentin and matrix metalloproteinase 9 in the vaginal wall tissue of the balloon dilation group compared with the control group(P＞0.05),whereas the expression levels of α-smooth muscle actin and Vimentin were significantly decreased in the ovariectomy group and ovariectomy combined with vaginal balloon dilation group(P＜0.01)and the expression of matrix metalloproteinase 9 showed a significant increase(P＜0.01),with a more pronounced increase in the ovariectomy combined with vaginal balloon dilation group,and the increase reached a stable state at 8 weeks after surgery and could persist up to 12 weeks.To conclude,vaginal balloon dilatation could not maintain the degeneration of pelvic organ prolapse formed by the vaginal wall for a long period,and both ovariectomy and the combined method can be used.Ovariectomy combined with vaginal balloon dilatation can significantly accelerate and aggravate the formation of typical histological features of pelvic organ prolapse in vaginal wall tissues,effectively shorten the experimental period,and improve the efficiency.These effects reach a stable state at 8 weeks after surgery and can be sustained up to 12 weeks,which is practical and convenient for the study of pelvic organ prolapse animal models.

ObjectiveSpinal cord injury (SCI) directly impairs the regulatory function of the autonomic nervous system, induces intestinal dysfunction, and significantly reduces patients’ quality of life. Preclinical studies have shown that electroacupuncture (EA) therapy can regulate the brain-gut axis and is used to treat central nervous system diseases such as major depressive disorder, Alzheimer’s disease and Parkinson’s disease. Recent research has established that fecal microbiota transplantation (FMT) from EA-treated SCI rats restored intestinal motility and colonic morphology. However, it remains unclear whether the regulation of gut microbiota by EA therapy directly contributes to neural repair after SCI. This study aims to explore whether gut microbiota mediates the neuroprotective effect of EA in the treatment of SCI and its possible mechanism. MethodsThe study employed RNA transcriptome analysis of spinal cord tissue to characterize gene expression profiles and to identify key signaling pathways following EA treatment for SCI. Hematoxylin-Eosin (HE) staining and Nissl staining were used to observe the morphological changes in spinal cord tissue. Western blot (WB) and enzyme-linked immunosorbent assay (ELISA) were applied to detect the effects of EA on the expression of proteins related to nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) -dependent pyroptosis. Using 16S rDNA sequencing, the study observed alterations in gut microbiota diversity and community composition in SCI rats. Prior to establishing SCI models, rats were pretreated with an antibiotic cocktail to induce gut dysbiosis, and the effects on intestinal function and spinal cord neural repair were evaluated. FMT was performed to investigate the regulatory effects of post-EA FMT on motor function, general status, liver and spleen indices, and NLRP3-mediated pyroptosis in SCI rats. ResultsEA improved motor function and reduced regulated neuronal cell death in SCI rats. Transcriptomic analysis demonstrated the activation of immune- and inflammation-related pathways post-SCI, including NOD-like receptors, nuclear factor-kappa B(NF-κB), and Toll-like receptor (TLR) pathways. EA primarily influenced intestinal inflammation and autoimmune functions. 16S rDNA sequencing illustrated that EA did not alter the diversity of gut microbiota. However, EA altered the gut microbiota composition in SCI rats, increasing Lactobacillus and Akkermansia genera while rebalancing the Firmicutes/Bacteroidetes ratio. Furthermore, depletion of gut microbiota by antibiotics disrupted the intestinal barrier, reduced the expression of intestinal barrier proteins Zonula Occludens-1 (ZO-1) and Occludin, elevated serum lipopolysaccharide-binding protein (LBP) levels, exacerbated spinal cord tissue damage, and hindered motor function recovery in SCI rats. FMT from donors treated with EA reduced LBP levels in the intestine, blood, and spinal cord of rats, inhibited the TLR4 myeloid differentiation primary response protein 88 (MyD88)-NF‑κB pathway and NLRP3-dependent pyroptosis, and improved motor function. On the other hand, FMT treatment resulted in decreased body weight and food intake, whereas FMT using EA-treated donors effectively alleviated these alterations. ConclusionEA effectively alleviated neuroinflammatory responses in rats with SCI, primarily through regulating the gut microbiota and suppressing the NLRP3-dependent pyroptosis signaling pathway.

ObjectiveSpinal cord injury (SCI) directly impairs the regulatory function of the autonomic nervous system, induces intestinal dysfunction, and significantly reduces patients’ quality of life. Preclinical studies have shown that electroacupuncture (EA) therapy can regulate the brain-gut axis and is used to treat central nervous system diseases such as major depressive disorder, Alzheimer’s disease and Parkinson’s disease. Recent research has established that fecal microbiota transplantation (FMT) from EA-treated SCI rats restored intestinal motility and colonic morphology. However, it remains unclear whether the regulation of gut microbiota by EA therapy directly contributes to neural repair after SCI. This study aims to explore whether gut microbiota mediates the neuroprotective effect of EA in the treatment of SCI and its possible mechanism. MethodsThe study employed RNA transcriptome analysis of spinal cord tissue to characterize gene expression profiles and to identify key signaling pathways following EA treatment for SCI. Hematoxylin-Eosin (HE) staining and Nissl staining were used to observe the morphological changes in spinal cord tissue. Western blot (WB) and enzyme-linked immunosorbent assay (ELISA) were applied to detect the effects of EA on the expression of proteins related to nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) -dependent pyroptosis. Using 16S rDNA sequencing, the study observed alterations in gut microbiota diversity and community composition in SCI rats. Prior to establishing SCI models, rats were pretreated with an antibiotic cocktail to induce gut dysbiosis, and the effects on intestinal function and spinal cord neural repair were evaluated. FMT was performed to investigate the regulatory effects of post-EA FMT on motor function, general status, liver and spleen indices, and NLRP3-mediated pyroptosis in SCI rats. ResultsEA improved motor function and reduced regulated neuronal cell death in SCI rats. Transcriptomic analysis demonstrated the activation of immune- and inflammation-related pathways post-SCI, including NOD-like receptors, nuclear factor-kappa B(NF-κB), and Toll-like receptor (TLR) pathways. EA primarily influenced intestinal inflammation and autoimmune functions. 16S rDNA sequencing illustrated that EA did not alter the diversity of gut microbiota. However, EA altered the gut microbiota composition in SCI rats, increasing Lactobacillus and Akkermansia genera while rebalancing the Firmicutes/Bacteroidetes ratio. Furthermore, depletion of gut microbiota by antibiotics disrupted the intestinal barrier, reduced the expression of intestinal barrier proteins Zonula Occludens-1 (ZO-1) and Occludin, elevated serum lipopolysaccharide-binding protein (LBP) levels, exacerbated spinal cord tissue damage, and hindered motor function recovery in SCI rats. FMT from donors treated with EA reduced LBP levels in the intestine, blood, and spinal cord of rats, inhibited the TLR4 myeloid differentiation primary response protein 88 (MyD88)-NF‑κB pathway and NLRP3-dependent pyroptosis, and improved motor function. On the other hand, FMT treatment resulted in decreased body weight and food intake, whereas FMT using EA-treated donors effectively alleviated these alterations. ConclusionEA effectively alleviated neuroinflammatory responses in rats with SCI, primarily through regulating the gut microbiota and suppressing the NLRP3-dependent pyroptosis signaling pathway.

Toxoplasma gondii is a single-celled parasite that infects nearly all warm-blooded animals, including humans (Montoya and Liesenfeld, 2004). It occurs worldwide and can persist for a lifetime in mammals. Humans get infected by eating undercooked meat of animals containing the tissue cysts of this parasite. In immune-competent individuals, T. gondii infection usually does not cause significant clinical symptoms, whereas in pregnant or immunocompromised individuals, T. gondii infection (toxoplasmosis) can cause more serious problems like abortion and even death (Dunn et al., 1999; Wang et al., 2017). A combination of pyrimethamine and sulfadiazine is usually used to treat toxoplasmosis, although it is generally inefficient and causes side effects (Alday and Doggett, 2017). Worse still, there is a lack of vaccines to prevent T. gondii infection in humans or animals.
Toxoplasma/enzymology* ; Animals ; Humans ; Toxoplasmosis ; Mitochondria/enzymology* ; Protozoan Proteins/metabolism*

BACKGROUND: Urolithiasis is a widespread disease with a high prevalence worldwide. This study aims to evaluate the disease burden of urolithiasis and its trends from 1990 to 2021 globally, based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 database. METHODS: The numbers and age-standardized rates (ASRs) of incidence, disability-adjusted life years (DALYs), and mortality of urolithiasis were extracted from GBD 2021 to represent the disease burden. Joinpoint regression analyses were conducted to assess the temporal trends in the burden of urolithiasis. The male-to-female ASR ratio indices were used to evaluate sex disparities. Additionally, we explored the relationship between the ASR ratio and the sociodemographic index (SDI). RESULTS: The total numbers of incidence, DALY, and mortality of urolithiasis were 105,983,780 cases (95% uncertainty interval [UI] = 88,349,356-128,645,155 cases), 693,444 cases (95% UI = 567,765-850,490 cases), and 17,672 cases (95% UI = 13,932-21,241 cases), respectively, in 2021. There is an increasing trend in the number of these measures globally, whereas the ASRs have decreased over the past 30 years. The age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) were significantly higher in males than in females in 2021. The sex disparities in the age-standardized DALY rate (ASDR) and ASMR of urolithiasis were negatively correlated with the SDI. In 2021, the ASIR of urolithiasis was 964.70 (95% UI = 801.26-1175.09) per 100,000 people in China, which is much lower than the global average (1242.84 [95% UI = 1034.94-1506.99] per 100,000 people). Compared with the global average, a more pronounced decline in ASIR was observed in China from 1793.16 (1446.0-2235.14) in 1990 to 964.70 (801.26-1175.09) per 100,000 people in 2021. CONCLUSIONS Urolithiasis poses a significant healthcare burden worldwide. More robust global and national strategies are warranted to address the prevention and treatment, especially in low SDI countries and regions.
Humans ; Urolithiasis/mortality* ; Male ; Female ; Incidence ; Global Burden of Disease ; Disability-Adjusted Life Years ; Adult ; Middle Aged ; Risk Factors ; Sex Factors

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.

Objective To explore the safety of establishing the veno-arterial extracorporeal membrane oxygenation(VA-ECMO)pipeline through percutaneous puncture and the effectiveness of high-risk percutaneous coronary intervention(HR-PCI)under VA-ECMO assistance.Methods In this single-center retrospective study,patients who underwent HR-PCI assisted by VA-ECMO at Wuhan Asian Heart Hospital from December 2022 to December 2023 were included.The primary endpoint was the safety of establishing the VA-ECMO pipeline through percutaneous puncture,mainly characterized by extracorporeal membrane oxygenation(ECMO)-related complications,including severe bleeding/hematoma at the wound,arteriovenous fistula,pseudoaneurysm,peripheral arterial dissection,etc.The secondary endpoint was the effectiveness of HR-PCI under VA-ECMO assistance,defined as major adverse cardiovascular and cerebrovascular events(MACCE)at 6-month follow-up,including the composite events of all-cause death,non-fatal myocardial infarction,repeat revascularization,and ischemic stroke.Results Among the 189 patients included in the study,15(7.9％)had severe bleeding/hematoma at the puncture wound caused by VA-ECMO,8(4.2％)had wound infection,1(0.5％)had arteriovenous fistula,4(2.1％)had pseudoaneurysm,3(1.6％)had peripheral arterial dissection,8(4.2％)had systemic embolism,8(4.2％)had acute kidney injury,3(1.6％)had acute neurological injury,and 1(0.5％)died.percutaneous coronary intervention(PCI)was successful in 182 cases(96.3％),and a total of 36 cases(19.0％)had PCI-related complications.164 patients completed 6-month follow-up,among which 4(2.4％)had all-cause death,11(6.7％)had non-fatal myocardial infarction,11(6.7％)had unplanned repeat revascularization,and 2(1.2％)had the composite event of ischemic stroke.Conclusions Ultrasound-guided percutaneous puncture for establishing the VA-ECMO pipeline has high safety,and HR-PCI patients assisted by VA-ECMO have good short-term effects.