Background Air pollution and meteorological factors exert complex nonlinear effects on acute symptoms in the population, with intricate interactions among these factors. Traditional statistical methods struggle to simultaneously address complex nonlinear relationships and multicollinearity issues. Objective To delineate the dynamic effects of air pollutants and meteorological parameters on acute symptoms in three distinct populations with the multicollinearity being addressed and to generate reliable scientific evidence for prevention and control of health risk factors. Methods A time-series study design was employed to collect data on air pollution (daily mean temperature, daily precipitation, daily mean relative humidity, and daily mean wind speed), meteorological factors [Air Quality Index (AQI), fine particulate matter (PM_2.5), inhalable particulate matter (PM₁₀), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), carbon monoxide (CO), and 8-hour maximum ozone (O₃)], and acute symptoms such as fever, cough, and sore throat in Jinan from June to December 2023. Key variables were selected using least absolute shrinkage and selection operator (LASSO) regression, followed by generalized additive mixed modeling (GAMM) to analyze the health effects of combined environmental exposures to air pollution and meteorological factors. Linear variables were modeled using linear mixed-effects function, nonlinear variables were smoothed using thin-plate regression splines, and variables with interaction effects were smoothed using low-rank scale-invariant tensor product splines. Fluctuations in independent variables following a normal distribution were treated as sampling errors and incorporated as random effects in the GAMM. Results For fever, the daily mean temperature, daily mean relative humidity, daily mean wind speed, and ambient SO₂ were statistically significant (P<0.05), with daily mean wind speed being a linear influencing factor. When the daily mean temperature was below 3 °C, each 10 °C increase corresponded to a relative risk (RR) of 2.64 (95%CI: 2.50, 2.79). When the daily mean temperature was ≥3 °C, each 10 °C increase corresponded to an RR of 0.86 (95%CI: 0.83, 0.89). Each 10% increase in daily mean relative humidity was associated with an RR of 0.93 (95%CI: 0.89, 0.97). Each 1 m·s⁻¹ increase in daily mean wind speed corresponded to an RR of 1.06 (95%CI: 1.02, 1.10). Within the concentration ranges of <10 μg·m⁻³, 10–<12.5 μg·m⁻³, and ≥12.5 μg·m⁻³, each 1 μg·m⁻³ increase in ambient SO₂ corresponded to RR values of 1.01 (95%CI: 0.98, 1.05), 1.21 (95%CI: 1.17, 1.24), and 0.97 (95%CI: 0.94, 0.99), respectively. For cough, the daily mean temperature, daily mean relative humidity, PM₁₀, and SO₂ were statistically significant (P<0.001), with PM₁₀ being a linear influencing factor. When the daily mean temperature was below 1 °C, each 10 °C increase corresponded to an RR of 1.47 (95%CI: 1.42, 1.52). When the daily mean temperature was ≥1 °C, each 10 °C increase corresponded to an RR of 0.85 (95%CI: 0.82, 0.87). Each 10% increase in daily mean relative humidity was associated with an RR of 0.95 (95%CI: 0.92, 0.98). Each 50 μg·m⁻³ increase in PM₁₀ concentration corresponded to an RR of 1.05 (95%CI: 1.02, 1.08). Within the concentration ranges of <10 μg·m⁻³, 10–<12.5 μg·m⁻³, and ≥ 12.5 μg·m⁻³, each 1 μg·m⁻³ increase in ambient SO₂ corresponded to RR values of 1.00 (95%CI: 0.97, 1.03), 1.12 (95%CI: 1.09, 1.16), and 0.98 (95%CI: 0.95, 1.00), respectively. For sore throat, the daily mean temperature, daily mean relative humidity, daily mean wind speed, PM₁₀, and SO₂ were statistically significant (P<0.05), with daily mean wind speed and PM₁₀ being linear influencing factors. When the daily mean temperature was below 2 °C, each 10 °C increase corresponded to an RR of 1.82 (95%CI: 1.69, 1.96). When the daily mean temperature was ≥2 °C, each 10 °C increase corresponded to an RR of 0.81 (95%CI: 0.77, 0.87). Each 10% increase in daily mean relative humidity was associated with an RR of 0.94 (95%CI: 0.88, 1.00). Within the concentration ranges of <10 μg·m⁻³, 10–<12.5 μg·m⁻³, and ≥12.5 μg·m⁻³, each 1 μg·m⁻³ increase in ambient SO₂ corresponded to RR values of 1.02 (95%CI: 0.97, 1.08), 1.13 (95%CI: 1.08, 1.19), and 0.98 (95%CI: 0.94, 1.02), respectively. Each 1 m·s⁻¹ increase in daily mean wind speed and each 50 μg·m⁻³ increase in PM₁₀ concentration were associated with RR values of 1.06 (95%CI: 1.00, 1.12) and 1.04 (95%CI: 0.98, 1.10), respectively. An interaction effect was observed between daily mean wind speed and PM₁₀: increasing daily mean wind speed non-linearly reduced the impact of PM₁₀, on sore throat whereas PM₁₀ had no significant effect on wind speed. Conclusion This study, by combining LASSO and GAMM, largely eliminates the multicollinearity among selected variables. It reveals complex non-linear effects and interactions between air pollutants, meteorological factors, and acute symptoms in different population groups in Jinan. The symptoms like fever, cough, and sore throat are non-linearly associated with daily mean temperature and SO₂ concentration, while PM₁₀ and wind speed show a linear relationship or interactive effects. These findings provide a new basis for the precise prevention and control of health risk factors.

Objective To investigate the effects of parecoxib sodium on pain and Toll-like receptor 4(TLR4)/p38 mitogen activated protein kinase(p38MAPK)pathway in rats with femoral fracture.Methods Sixty rats were randomly separated into sham operation group,model group,TLR4 inhibitor(TAK-242)group(3 mg/kg),parecoxib sodium group(10 mg/kg),and parecoxib sodium+TLR4 activator lipopolysaccharide group(10 mg/kg parecoxib sodium+15 mg/kg LPS),with 12 rats in each group.Except for the sham operation group,rats in all other groups were used to establish a femoral fracture model by transverse cutting of the mid femur.After 28 days of treatment in each group,X-rays were used to detect the degree of fracture healing in rats.The mechanical pain threshold(PWMT)and thermal pain threshold(PWTL)of rats were measured.ELISA was applied to detect the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and IL-10 in serum.Micro-CT method was applied to detect changes in femoral bone density(BMD),bone volume fraction(BV/TV),trabecular thickness(Tb.Th),and trabecular quantity(Tb.N)in rats.HE staining was applied to observe the pathological changes of bone tissue at the fracture site in rats.Western blot was applied to detect the expression of TLR4/p38MAPK pathway related proteins in bone tissue at the fracture site.Results Compared with the sham operation group,the fracture lines of rats in the model group were obvious,with a small amount of callus growth,the PWMT,PWTL,femoral BMD,BV/TV,Tb.Th,and Tb.N decreased,while the levels of serum IL-6,TNF-α,and IL-10,and the levels of TLR4 and p-p38MAPK/p38MAPK proteins in the bone tissue at the fracture site increased(P＜0.05).Compared with the model group,the fracture lines in the TAK-242 group and the parecoxib sodium group were blurred,and there was an increase in callus growth,the PWMT,PWTL,femoral BMD,BV/TV,Tb.Th,and Tb.N,the serum IL-10 level increased,while the serum IL-6,TNF-αlevels,the TLR4 and p-p38MAPK/p38MAPK protein levels in bone tissue at the fracture site decreased(P＜0.05).LPS could upregulate the phosphorylation levels of TLR4 and p38MAPK,and weaken the relieving effects on anti-inflammatory and pain of parecoxib sodium on fracture rats.Conclusion Paracoxib sodium may alleviate pain and accelerate fracture healing in rats with femoral fractures by inhibiting the TLR4/p38MAPK pathway and suppressing inflammatory responses.

Objective To investigate the effects of parecoxib sodium on pain and Toll-like receptor 4(TLR4)/p38 mitogen activated protein kinase(p38MAPK)pathway in rats with femoral fracture.Methods Sixty rats were randomly separated into sham operation group,model group,TLR4 inhibitor(TAK-242)group(3 mg/kg),parecoxib sodium group(10 mg/kg),and parecoxib sodium+TLR4 activator lipopolysaccharide group(10 mg/kg parecoxib sodium+15 mg/kg LPS),with 12 rats in each group.Except for the sham operation group,rats in all other groups were used to establish a femoral fracture model by transverse cutting of the mid femur.After 28 days of treatment in each group,X-rays were used to detect the degree of fracture healing in rats.The mechanical pain threshold(PWMT)and thermal pain threshold(PWTL)of rats were measured.ELISA was applied to detect the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and IL-10 in serum.Micro-CT method was applied to detect changes in femoral bone density(BMD),bone volume fraction(BV/TV),trabecular thickness(Tb.Th),and trabecular quantity(Tb.N)in rats.HE staining was applied to observe the pathological changes of bone tissue at the fracture site in rats.Western blot was applied to detect the expression of TLR4/p38MAPK pathway related proteins in bone tissue at the fracture site.Results Compared with the sham operation group,the fracture lines of rats in the model group were obvious,with a small amount of callus growth,the PWMT,PWTL,femoral BMD,BV/TV,Tb.Th,and Tb.N decreased,while the levels of serum IL-6,TNF-α,and IL-10,and the levels of TLR4 and p-p38MAPK/p38MAPK proteins in the bone tissue at the fracture site increased(P＜0.05).Compared with the model group,the fracture lines in the TAK-242 group and the parecoxib sodium group were blurred,and there was an increase in callus growth,the PWMT,PWTL,femoral BMD,BV/TV,Tb.Th,and Tb.N,the serum IL-10 level increased,while the serum IL-6,TNF-αlevels,the TLR4 and p-p38MAPK/p38MAPK protein levels in bone tissue at the fracture site decreased(P＜0.05).LPS could upregulate the phosphorylation levels of TLR4 and p38MAPK,and weaken the relieving effects on anti-inflammatory and pain of parecoxib sodium on fracture rats.Conclusion Paracoxib sodium may alleviate pain and accelerate fracture healing in rats with femoral fractures by inhibiting the TLR4/p38MAPK pathway and suppressing inflammatory responses.

Objective To investigate the effect of erector spinae plane block on ultrasound-based hemodynamic parameters of the arteries of the four limbs and biochemical stress indicators in patients with thoracoscopic lobectomy. Methods A total of 120 patients with thoracoscopic lobectomy were randomly divided into study group and control group, with 60 cases in each group.The study group received erector spinae plane block during surgery, while the control group received conventional anesthesia measures.Pulmonary function indicators[peak expiratory flow rate (PEFR), forced vital capacity (FVC), forced expiratory volume in the first second (FEV₁)], ultrasound-based hemodynamic parameters of the arteries of the four limbs (maximum systolic velocity, minimum diastolic velocity, mean velocity, arterial pulsatility index, and arterial resistance index), stress indicators[cortisol (Cor), norepinephrine (NE), angiotensin Ⅱ(Ang Ⅱ), and adrenocorticotropic hormone (ACTH)], and analgesic effect were compared between the two groups at different time points[before anesthesia induction (T₀), after extubation (T₁), and after drainage tube removal (T₂)]. Results FEV₁, FVC and PEFR in both groups were significantly lower at T₁ and T₂ than at T₀, and FEV₁, FVC and PEFR in the study group were significantly higher than those in the control group at T₁ and T₂(P < 0.05).The maximum systolic velocity and arterial resistance index in both groups were significantly lower at T₁ and T₂ than at T₀, while the minimum diastolic velocity, mean velocity and arterial pulsatility index were significantly higher at T₁ and T₂ than at T₀(P < 0.05).The maximum systolic velocity and arterial resistance index in the study group were significantly higher than those in the control group at T₁ and T₂, but the minimum diastolic velocity, mean velocity and arterial pulsatility index were significantly lower than those in the control group (P < 0.05).Cor, ACTH, Ang Ⅱ and NE in both groups were significantly higher at T₂ than at T₀, and Cor, ACTH, Ang Ⅱ and NE in the study group were significantly lower than those in the control group at T₂(P < 0.05).The Prince-Henry pain score, effective compression times, and actual compression times in the study group were significantly lower than those in the control group (P < 0.05). Conclusion Application of erector spinae plane block in thoracoscopic lobectomy causes smaller fluctuations in hemodynamic parameters of the arteries of four limbs and biochemical stress indicators, with a better anesthetic effect.

Objective To investigate the effects of esketamine on hypoxic-ischemic myocardial injury in neonatal rats based on glycogen synthase kinase-3β/NOD-like receptor thermal protein domain-containing protein 3 (GSK-3β/NLRP3) pathway. Methods Thirty neonatal rats were randomly divided into sham operation group, model group and esketamine group, with 10 rats in each group. The rats in the sham operation group underwent a median incision in the neck to expose the bilateral common carotid arteries; the rats in the model group and the esketamine group underwent ligation of the common carotid arteries combined with a hypoxic environment to establish a model ofischemia and hypoxia; the rats in the esketamine group were given esketamine intervention (50 mg/kg). Left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), serum creatine kinase isoenzyme (CK-MB), cardiac troponin I (cTnI), lactate dehydrogenase (LDH), tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1β levels, myocardial injury, myocardial cell apoptosis and apoptosis protein caspase 1/3/9 levels, neutrophil infiltration in myocardial tissue, and changes in GSK-3β and NLRP3 protein levels in myocardial tissue were detected in each group. Results Compared with the sham operation group, the LVEF and LVFS were significantly decreased and the LVEDD and LVESD were significantly increased in the model group, while the LVEF and LVFS were significantly higher and the LVEDD and LVESD were significantly lower in the esketamine group than in the model group (P < 0.05). The serum levels of CK-MB, cTnI, LDH, TNF-α, IL-6, IL-1β, myocardial injury and apoptosis, caspase 1/3/9 protein levels in myocardial tissue sections, neutrophil counts, and GSK-3β and NLRP3 protein levels were significantly increased in the model group, and these indicators were significantly lower in the esketamine group than in the model group (P < 0.05). Conclusion Esketamine improves hypoxic-ischemic myocardial injury in neonatal rats by inhibiting inflammation, and its mechanism of action is related to the GSK-3β/NLRP3 pathway.

OBJECTIVES: To investigate the role of mitochondrial autophagy disorder caused by deletion of E3 ubiquitin ligase Parkin in neuroinflammation in a mouse model of MPTP-induced Parkinson's disease (PD). METHODS: Wild-type (WT) male C57BL/6 mice and Parkin^-/- mice were given intraperitoneal injections with MPTP or PBS for 5 consecutive days, and the changes in motor behaviors of the mice were observed using open field test. The effects of Parkin deletion on PD development and neuroinflammation were evaluated using immunofluorescence and Western blotting. The changes of the PINK 1/Parkin signaling pathway in the midbrain substantia nigra of the mice were examined to explore the molecular mechanism of Parkin-mediated regulation of mitochondrial autophagy and its effect on neuroinflammation in PD mice. RESULTS: Compared with their WT counterparts, the Parkin^-/- mice with MPTP injections exhibited significant impairment of motor function with decreased TH⁺ neurons, increased α-synuclein (α-syn) accumulation, and increased numbers of GFAP⁺ and I-ba1⁺ cells in the midbrain substantia nigra. Parkin deletion obviously affected PINK1/Parkin-mediated mitochondrial autophagy to result in significantly increased mtDNA and upregulated expressions of STING and NLRP3 inflammatosomes in the midbrain substantia nigra of MPTP-treated transgenic mice. CONCLUSIONS Parkin deletion causes mitochondrial autophagy disorder to accelerate PD progression and exacerbates neuroinflammation in mice by affecting the PINK1/Parkin signaling pathway, suggesting the important role of Parkin in early pathogenesis of PD.
Animals ; Ubiquitin-Protein Ligases/genetics* ; Mice ; Mice, Inbred C57BL ; Male ; Parkinson Disease/genetics* ; Protein Kinases/genetics* ; Mitochondria/metabolism* ; Disease Models, Animal ; Autophagy ; Signal Transduction ; Neuroinflammatory Diseases/metabolism* ; Mice, Knockout ; alpha-Synuclein/metabolism* ; Substantia Nigra/metabolism* ; Mitophagy ; Disease Progression

The training of orthopedic residents in Taiwan, China includes post graduate year and specialist training, which contain continuous orthopedic specialist training, humanistic training, and holistic education to ensure the high post competency of orthopedic residents. The training process is oriented towards competency and outcome, emphasizing the cultivation of core competencies. Comprehensive quantitative standards have been established to comprehensively evaluate the post competency of residents through theoretical, technical, and clinical work assessments. In this paper, the literature on medical education and resident training in Taiwan was reviewed. The overall training system, assessment requirements, and humanistic training of orthopedic residents in Taiwan were introduced. In addition, the models of training orthopedic specialists were compared between Taiwan and Mainland of China represented by Peking University Medical Department to provide reference for the training program of orthopedic residents.

Objective To investigate the effect of asiatic acid(AA)on the apoptosis of HT-22 cells induced by sevoflurane(SEVO)by regulating phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT)signaling pathway.Methods Different concentrations of AA(0,5,10,15,20,30 μmol/L)were used to treat HT-22 cells induced by sevoflurane for 24 hours,and CCK-8 was used to detect HT-22 cell viability;HT-22 cells were divided into control group,sevoflurane(SEVO)group,AA low concentration(AA-L,10 μmol/L)group,AA medium concentration(AA-M,15 μmol/L)group,AA high concentration(AA-H,20 μmol/L)group,and AA high concentration+PI13K pathway inhibitor LY294002(AA-H+LY294002,20 μmol/L AA+5 μmol/L LY294002)group.Inverted microscopy was applied to observe changes of cell morphology,ELISA was applied to detect the levels of inflammatory factors TNF-α and IL-6,oxidative stress indicators SOD,GSH-Px,and MDA,ROS detection kit was applied to detect ROS levels,TUNEL kit was applied to detect HT-22 apoptosis,JC-1 method was applied to detect mitochondrial membrane potential,ATP content detection kit was applied to detect ATP content,and Western blot was applied to detect the expressions of Bcl-2,Bax,Caspase-3,p-PI3K,PI3K,p-AKT,and AKT proteins.Results Compared with 0 μmol/L,the activity of HT-22 cells treated with 5-30 μmol/L AA increased in a concentration-dependent manner(P<0.05),concentrations of 10 μmol/L,15 μmol/L,and 20 μmol/L of AA were selected for subsequent experiments.Compared with the SEVO group,the levels of TNF-α,IL-6,MDA,ROS,cell apoptosis rate,and expressions of Bax and Caspase-3 proteins in the AA-L,AA-M,and AA-H groups were reduced,the levels of SOD and GSH-Px,red/green JC-1 fluorescence ratio,content of ATP,the expression of Bcl-2 protein,the phosphorylation levels of PI3K and AKT were increased(P<0.05),and were concentration dependent.LY294002 was able to reverse the protective effect of AA on HT-22 cell damage induced by sevoflurane(P<0.05).Conclusion AA protects HT-22 cells from damage induced by sevoflurane by activating the PI3K/AKT signaling pathway,which provides a theoretical reference for the development of novel drugs to reduce sevofluran-induced neurotoxicity.

Objective:To evaluate the efficacy and safety of Xiao′er Huangjin Zhike Granules in the treatment of cough caused by acute bronchitis in children, which is defined in TCM terms as a syndrome of phlegm-heat obstructing the lung.Methods:This was a block-randomized, double-blind, placebo-controlled, multicenter clinical trial.From January 2022 to September 2023, 359 children aged 3 to 7 years old diagnosed as acute bronchitis (lung-obstructing phlegm-heat syndrome) were enrolled from 21 participating hospitals and randomly assigned to the experimental group and placebo group in a 3︰1 ratio, and respectively treated with Xiao′er Huangjin Zhike Granules and its matching placebo.Cough resolution/general resolution rate after 7 days of treatment was used as the primary efficacy outcome for both groups.Results:(1)On the seventh day of treatment, the rate of cough disappearance/basically disappearance in the experimental group and placebo group were 73.95% and 57.61% retrospectively, which had statistically significance ( P=0.001).(2)After 7 days of treatment, the median duration of cough disappearance/basic disappearance were 5 days and 6 days in the two groups , with a statistically significant difference ( P=0.006).The area under the curve of cough symptom severity time was 7.20 ± 3.79 in the experimental group and 8.20±4.42 in the placebo group.The difference between the two groups was statistically significant ( P=0.039).(3) After 7 days of treatment, the difference between TCM syndrome score and baseline was -16.0 (-20.0, -15.0) points in the experimental group and -15.0 (-18.0, -12.0) points in the placebo group, with significant difference between the two groups ( P=0.004).In the experimental group, the clinical control rate, the markedly effective rate, the effective rate and the ineffective rate were 49.04%, 28.35%, 16.48% and 6.13% severally; and in the placebo group, the clinical control rate, the markedly effective rate, the effective rate and the ineffective rate were 38.04%, 26.09%, 29.35%, and 6.52% separately, which had statistically significant ( P=0.014).(4) There was no significant difference in the incidence of adverse events or adverse reactions during the trial between both groups.Moreover, while adverse reactions in the form of vomiting and diarrhea were occasionally reported, no serious drug-related adverse event or adverse reaction was reported.(5)The tested drug provided good treatment compliance, showing no statistically significant difference from the placebo in terms of compliance rate. Conclusions:Based on the above findings, it can be concluded that Xiao′er Huangjin Zhike Granules provides good safety, efficacy, and treatment compliance in the treatment of cough caused by acute bronchitis, and lung-obstructing phlegm-heat syndrome, in children.

To examine the molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae (CRKP) and investigate the horizontal transmission of blaKPC and blaNDM genes for the prevention and treatment of CRKP. A total of 49 clinically isolated CRKP strains were retrospectively analyzed from January to December 2022 at The First Hospital of Hunan University of Chinese Medicine. Phenotypic screening was performed using modified carbapenem inactivation assay (mCIM) and EDTA-carbapenem inactivation assay (eCIM). Polymerase chain reaction (PCR) was utilized to identify carbapenem resistance genes, β-lactamase resistance genes, and virulence genes, while multi-locus sequence analysis (MLST) was employed to assess the homology of CRKP strains. Conjugation experiments were conducted to infer the horizontal transmission mechanism of blaKPC and blaNDM genes. The results showed that the study included 49 CRKP strains, with 44 carrying blaKPC and 8 carrying blaNDM, Three strains were identified as blaKPC+ blaNDM-CRKP. In this study, 28 out of 49 CRKP strains (57.2%) were found to carry virulence genes. Additionally, one CRKP strain tested positive in the string test and was found to carry both Aerobactin and rmpA virulence genes. MLST results revealed a total of 5 ST types, with ST11 being predominant (41/49, 83.7%). Successful conjugation was observed in all 3 blaKPC-CRKP strains, while only 1 out of 3 blaNDM-CRKP strains showed successful conjugation. The transconjugant exhibited significantly reduced susceptibility to imipenem and cephalosporin antibiotics. In conclusion, the resistance mechanism of CRKP in this study is primarily attributed to the production of KPC enzymes, along with the presence of multiple β-lactamase resistance genes. Additionally, there is a local prevalence of hv-CRKP and blaKPC+ blaNDM-CRKP. blaKPC and blaNDM can be horizontally transmitted through plasmids, with varying efficiency among different strains.