Hypoventilation in obesity has four stages, and the first two stages are associated with intermittent nocturnal hypercapnia. We report a 46-year-old man who belongs to Stage 1, with complete washout of nocturnally accumulated carbon dioxide (CO2) and associated concomitant severe obstructive sleep apnea and severe hypoxemia. That condition will lead to progressive right heart dysfunction secondary to persistently nocturnal impaired ventilation and hypoxemia via the pathomechanism of hypoxic pulmonary vasoconstriction and pulmonary vascular remodeling by cytokines and growth factors, supposedly once it is missed for early diagnosis and appropriate PAP therapy is not introduced in time. Early identification and diagnosis of such conditional disease and in-time appropriate treatment are very important before sequelae of disease develop so that we could be able to prevent cardiovascular morbidity and mortality before disease progression.

ObjectiveTo explore the effect of modified Lianpoyin formula （LPYJWF） in the treatment of Helicobacter pylori （Hp）-associated gastric mucosal damage based on mitochondrial autophagy and NLRP3 inflammasome signaling pathway. MethodsA total of 60 eight-week-old Balb/c male mice were assigned via the random number table method into control， model， high-dose LPYJWF （LPYJWF-H， 27.3 g·kg^-1·d^-1）， medium-dose LPYJWF （LPYJWF-M， 13.65 g·kg^-1·d^-1）， low-dose LPYJWF （LPYJWF-L， 6.83 g·kg^-1·d^-1）， and quadruple therapy groups. Except the control group， other groups were modeled for Hp infection. Mice were administrated with LPYJWF at corresponding doses by gavage. Quadruple therapy group was given omeprazole （6.06 mg·kg^-1·d^-1） + amoxicillin （303 mg·kg^-1·d^-1） + clarithromycin （151.67 mg·kg^-1·d^-1） + colloidal pectin capsules （30.3 mg·kg^-1·d^-1） by gavage. The control group was given an equal volume of 0.9% NaCl for 14 days. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of gastric mucosa， and Warthin-Starry （W-S） silver staining was used to detect Hp colonization. Transmission electron microscopy was employed to observe the mitochondrial ultrastructure of the gastric tissue， and immunofluorescence co-localization assay was adopted to detect the expression of mitochondrial transcription factor A （TFAM） and translocase of the outer mitochondrial membrane member 20 （TOMM20）. The water-soluble tetrazolium salt method and thiobarbituric acid method were used to determine the levels of superoxide dismutase （SOD） and malondialdehyde （MDA）， respectively， in the gastric tissue. Western blot was employed to measure the protein levels of PTEN-induced kinase 1 （PINK1）， Parkin， p62， microtubule-associated protein 1 light chain 3 （LC3）， NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein containing a CARD （ASC）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18）. Real-time quantitative PCR was employed to assess the mRNA levels of PINK1， Parkin， p62， and LC3. ResultsCompared with the control group， the model group presented obvious gastric mucosal damage， colonization of a large number of Hp， severe mitochondrial damage， vacuolated structures due to excessive autophagy， reduced TOMM20 and TFAM co-expression in the gastric mucosal tissue， and reduced SOD and increased MDA （P<0.01）. In addition， the gastric tissue in the model group showed up-regulated protein and mRNA levels of PINK1， Parkin， and LC3 and down-regulated protein and mRNA levels of p62 （P<0.01， as well as increased expression of inflammasome-associated proteins NLRP3， ASC， IL-1β， and IL-18 （P<0.01）. Compared with the model group， the LPYJWF and quadruple therapy groups showed alleviated pathological damage of gastric mucosa， reduced Hp colonization， mitigated mitochondrial damage， and increased co-expression of TOMM20 and TFAM. The SOD level was elevated in the LPYJWF-L group （P<0.01）， and the MDA levels became lowered in the LPYJWF and quadruple therapy groups （P<0.05， P<0.01）. Furthermore， the LPYJWF and quadruple therapy groups showed down-regulated mRNA levels of PINK1， Parkin， and LC3 and protein levels of PINK1 and Parkin， and up-regulated mRNA level of p62 （P<0.01）. The LPYJWF-M， LPYJWF-H， and quadruple therapy groups showcased down-regulated LC3 Ⅱ/LC3 Ⅰ level （P<0.05， P<0.01） and up-regulated protein level of p62 （P<0.01）. The expression of inflammasome-associated proteins NLRP3， ASC， IL-1β， and IL-18 were reduced in the LPYJWF and quadruple therapy groups （P<0.05， P<0.01）. ConclusionLPYJWF ameliorates gastric mucosal damage and exerts mucosa-protective effects in Hp-infected mice， which may be related to the inhibition of excessive mitochondrial autophagy， thereby inhibiting the activation of the NLRP3 inflammasome pathway.

ObjectiveTo explore the effect of modified Lianpoyin formula （LPYJWF） in the treatment of Helicobacter pylori （Hp）-associated gastric mucosal damage based on mitochondrial autophagy and NLRP3 inflammasome signaling pathway. MethodsA total of 60 eight-week-old Balb/c male mice were assigned via the random number table method into control， model， high-dose LPYJWF （LPYJWF-H， 27.3 g·kg^-1·d^-1）， medium-dose LPYJWF （LPYJWF-M， 13.65 g·kg^-1·d^-1）， low-dose LPYJWF （LPYJWF-L， 6.83 g·kg^-1·d^-1）， and quadruple therapy groups. Except the control group， other groups were modeled for Hp infection. Mice were administrated with LPYJWF at corresponding doses by gavage. Quadruple therapy group was given omeprazole （6.06 mg·kg^-1·d^-1） + amoxicillin （303 mg·kg^-1·d^-1） + clarithromycin （151.67 mg·kg^-1·d^-1） + colloidal pectin capsules （30.3 mg·kg^-1·d^-1） by gavage. The control group was given an equal volume of 0.9% NaCl for 14 days. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of gastric mucosa， and Warthin-Starry （W-S） silver staining was used to detect Hp colonization. Transmission electron microscopy was employed to observe the mitochondrial ultrastructure of the gastric tissue， and immunofluorescence co-localization assay was adopted to detect the expression of mitochondrial transcription factor A （TFAM） and translocase of the outer mitochondrial membrane member 20 （TOMM20）. The water-soluble tetrazolium salt method and thiobarbituric acid method were used to determine the levels of superoxide dismutase （SOD） and malondialdehyde （MDA）， respectively， in the gastric tissue. Western blot was employed to measure the protein levels of PTEN-induced kinase 1 （PINK1）， Parkin， p62， microtubule-associated protein 1 light chain 3 （LC3）， NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein containing a CARD （ASC）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18）. Real-time quantitative PCR was employed to assess the mRNA levels of PINK1， Parkin， p62， and LC3. ResultsCompared with the control group， the model group presented obvious gastric mucosal damage， colonization of a large number of Hp， severe mitochondrial damage， vacuolated structures due to excessive autophagy， reduced TOMM20 and TFAM co-expression in the gastric mucosal tissue， and reduced SOD and increased MDA （P<0.01）. In addition， the gastric tissue in the model group showed up-regulated protein and mRNA levels of PINK1， Parkin， and LC3 and down-regulated protein and mRNA levels of p62 （P<0.01， as well as increased expression of inflammasome-associated proteins NLRP3， ASC， IL-1β， and IL-18 （P<0.01）. Compared with the model group， the LPYJWF and quadruple therapy groups showed alleviated pathological damage of gastric mucosa， reduced Hp colonization， mitigated mitochondrial damage， and increased co-expression of TOMM20 and TFAM. The SOD level was elevated in the LPYJWF-L group （P<0.01）， and the MDA levels became lowered in the LPYJWF and quadruple therapy groups （P<0.05， P<0.01）. Furthermore， the LPYJWF and quadruple therapy groups showed down-regulated mRNA levels of PINK1， Parkin， and LC3 and protein levels of PINK1 and Parkin， and up-regulated mRNA level of p62 （P<0.01）. The LPYJWF-M， LPYJWF-H， and quadruple therapy groups showcased down-regulated LC3 Ⅱ/LC3 Ⅰ level （P<0.05， P<0.01） and up-regulated protein level of p62 （P<0.01）. The expression of inflammasome-associated proteins NLRP3， ASC， IL-1β， and IL-18 were reduced in the LPYJWF and quadruple therapy groups （P<0.05， P<0.01）. ConclusionLPYJWF ameliorates gastric mucosal damage and exerts mucosa-protective effects in Hp-infected mice， which may be related to the inhibition of excessive mitochondrial autophagy， thereby inhibiting the activation of the NLRP3 inflammasome pathway.

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Objective:To evaluate the application of a two-stage sequential nutritional therapy combined with functional exercise in the preoperative prehabilitation of patients with high-output intestinal fistula(HIF).Methods:A total of 164 HIF patients scheduled for definitive fistula resection in the Department of General Surgery,Eastern Theater Command General Hospital from March 2023 to March 2025 were prospectively enrolled.They were randomly assigned to a control group or an intervention group at a 1:1 ratio,with 82 patients in each group.The control group received conventional nutritional support and basic functional exercise,while the intervention group underwent a two-stage sequential nutritional therapy combined with graded functional exercise.Nutritional indicators,inflammatory markers,functional status,and postoperative recovery were compared between the two groups at 28 days before surgery,1 day before surgery,and 1,3,and 7 days after surgery.Results:On the day before surgery,the nutritional indicators in the intervention group,including albumin[(36.8±4.1)g/L],prealbumin[(213.5±42.1)mg/L],and total protein[(69.3±6.1)g/L],were all significantly higher than those in the control group[albumin(33.1±3.9)g/L,prealbumin(163.2±37.6)mg/L,total protein(63.7±5.9)g/L],with P<0.001.The energy compliance rates on the 21st day before surgery and the day before surgery in the intervention group(85.2%,92.8%)were significantly higher than those in the control group(62.5%,72.4%),with P<0.001.The 6-minute walk distance(6MWD)in the intervention group on the day before surgery and on the 7th day after surgery[(385.1±55.2)m,(346.3±48.4)m]was significantly greater than that in the control group[(315.3±60.7)m,(298.3±51.1)m],with P<0.001.On the 1st day after surgery,the inflammatory markers in the intervention group[CRP(98.7±35.2)mg/L,IL-6(45.3±12.5)pg/mL,PCT(1.2±0.5)ng/mL]were all significantly lower than those in the control group[CRP(152.4±48.6)mg/L,IL-6(89.6±25.4)pg/mL,PCT(2.8±0.9)ng/mL],with P<0.001.Additionally,the time to first ambulation after surgery[(16.8±4.2)h],time to first flatus[(52.4±14.5)h],and ICU stay duration[(3.1±1.6)d]in the intervention group were all significantly shorter than those in the control group,with P<0.001 Conclusion:The two-stage sequential nutritional therapy combined with functional exercise significantly improves the attainment of nutritional targets,suppresses systemic inflammatory response,enhances muscle reserve and exercise tolerance,and effectively shortens the postoperative recovery period in HIF patients.These findings support the use of this combined approach as a targeted and feasible model for preoperative prehabilitation,demonstrating substantial clinical application value.

Hypoventilation in obesity has four stages, and the first two stages are associated with intermittent nocturnal hypercapnia. We report a 46-year-old man who belongs to Stage 1, with complete washout of nocturnally accumulated carbon dioxide (CO2) and associated concomitant severe obstructive sleep apnea and severe hypoxemia. That condition will lead to progressive right heart dysfunction secondary to persistently nocturnal impaired ventilation and hypoxemia via the pathomechanism of hypoxic pulmonary vasoconstriction and pulmonary vascular remodeling by cytokines and growth factors, supposedly once it is missed for early diagnosis and appropriate PAP therapy is not introduced in time. Early identification and diagnosis of such conditional disease and in-time appropriate treatment are very important before sequelae of disease develop so that we could be able to prevent cardiovascular morbidity and mortality before disease progression.

Hypoventilation in obesity has four stages, and the first two stages are associated with intermittent nocturnal hypercapnia. We report a 46-year-old man who belongs to Stage 1, with complete washout of nocturnally accumulated carbon dioxide (CO2) and associated concomitant severe obstructive sleep apnea and severe hypoxemia. That condition will lead to progressive right heart dysfunction secondary to persistently nocturnal impaired ventilation and hypoxemia via the pathomechanism of hypoxic pulmonary vasoconstriction and pulmonary vascular remodeling by cytokines and growth factors, supposedly once it is missed for early diagnosis and appropriate PAP therapy is not introduced in time. Early identification and diagnosis of such conditional disease and in-time appropriate treatment are very important before sequelae of disease develop so that we could be able to prevent cardiovascular morbidity and mortality before disease progression.

This study was aimed at establishing a method of ultra-fast quantitative PCR for Brucella detection.We used an exogenous recombinant plasmid as the internal reference and targeted the T4SS secretion system,an important Brucella viru-lence factor,to design specific primers and probes.The sensitivity,specificity,and repeatability of this method were evaluated,and a standard curve was constructed.The coincidence rate of detection findings with this method versus quantitative PCR was determined.This method markedly decreased the detection time to only 10 minutes.The standard curve demonstrated a good linear relationship(Y=-3.410 7x+38.357,R2=0.998 5)with a low minimum detection limit of 10 copies/μL.The method exhibited good specificity and did not specifically amplify several common clinical bacteria other than Brucella.The de-tection of three concentrations of positive plasmids yielded coefficients of variation(CVs)of 0.20％to 0.91％,thus demonstra-ting the method's excellent repeatability.Furthermore,140 clinical samples were analyzed concurrently with the fluorescence PCR method,which yielded a 100％compliance rate and consistent results.Our findings indicated that the Brucella ultra-fast quantitative PCR was ultrafast;had high sensitivity,high specificity,and good specificity;and can be used for the clinical de-tection of Brucella and emergency investigation of epidemics.Therefore,this method is valuable for the early diagnosis of Bru-cella.

Objective Based on the finite element simulation analysis of the patient's torso-spine model and combined with theoretical calculation data,an individualized scoliosis orthosis was designed,and the effectiveness of the orthosis was verified through three-dimensional(3D)printing.Methods A patient with idiopathic scoliosis was chosen as the research object.Reverse engineering technology and computer-aided technology were used to establish the torso-spine model of the patient.The finite element method was used to analyze the model,and the optimal position and magnitude of the corrective force were determined by combining literature theory calculation.Based on this,an orthosis was designed.To verify the orthopedic effect,the patient's X-rays before and after wearing the orthosis were compared and evaluated,and the patient was followed up 6 months later.Results The optimal position and magnitude of the initial corrective force were determined through theoretical calculations and finite element simulations.Specifically,a 62.95 N corrective force applied to the L3 vertebral body and the left posterior region corresponding to the upper and lower intervertebral discs in the patient's lateral curvature segment of the spine to achieve the optimal orthopedic effect.On this basis,the orthosis was designed,followed by relevant experimental tests before and after wearing the designed orthosis.By comparing X-ray images of the patient before and after wearing the orthosis and combining them with follow-up data six months later,the optimized design of the orthosis met the expected clinical requirements for orthopedic effects.Conclusions The design of orthosis needs to be personalized according to the specific situation of patients with scoliosis.This study takes a patient with idiopathic scoliosis as the research object,providing new ideas and methods for the design of orthosis for patients with idiopathic scoliosis.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.