Gout is a crystal-associated arthropathy caused by the deposition of monosodium urate crystals and is closely related to purine metabolic disorders and impaired uric acid excretion. It is clinically characterized by hyperuricemia， recurrent joint swelling and pain， and tophus formation. The disease course is divided into three stages： The hyperuricemia stage， acute attack stage， and chronic gouty arthritis stage. Modern medicine has reached a consensus on its pathology， but traditional Chinese medicine （TCM） lacks a systematic stage-specific understanding of gout pathogenesis and its underlying mechanisms， making it difficult to guide precise syndrome differentiation and treatment. By integrating classical TCM theory， clinical practice， and modern medical understanding， and drawing upon descriptions of Bi syndrome caused by endogenous dampness and turbidity in classical texts such as Huangdi Neijing·Ling Shu and Synopsis of the Golden Chamber， our team proposes the pathogenic concept of gout as ''endogenous dampness leading to Bi syndrome'' and the core pathogenesis of ''spleen deficiency with internal retention of dampness-turbidity''. We systematically elucidate the evolution of pathogenesis across different stages and corresponding therapeutic strategies. This study posits that metabolic byproducts such as urate fall under the category of ''endogenous pathogenic dampness-turbidity''. When genetic or dietary factors lead to metabolic abnormalities， it manifests as ''spleen deficiency with impaired transport and transformation''， resulting in ''internal retention of pathogenic dampness-turbidity''. When damp-turbidity stagnates in the blood vessels， serum uric acid levels rise. When it stagnates in the viscera and limbs， monosodium urate crystals deposit in the joints. Triggered by precipitating factors， this leads to gout attacks—the core pathological process of ''endogenous dampness leading to Bi syndrome''. Based on this theory， the stage-specific pathogenic characteristics of gout are proposed： The hyperuricemia stage is characterized by ''spleen deficiency with impaired transport and transformation， internal retention of pathogenic dampness-turbidity''， the acute attack stage is primarily marked by ''dampness-turbidity and static heat obstructing the limbs and joints''， while the chronic stage is defined by ''spleen deficiency with internal retention of pathogenic dampness-turbidity， intermingled with phlegm-stasis binding''. The treatment principle centers on ''strengthening the spleen and draining dampness'' throughout all stages. During the hyperuricemia stage， treatment focuses on ''strengthening the spleen， draining dampness， and eliminating turbidity''. In the acute attack stage， the treatment should "strengthen the spleen， drain dampness， clear heat， eliminate turbidity， alleviate swelling， and relieve pain''. In the chronic stage， the treatments emphasizes to ''strengthen the spleen， drain dampness， transform turbidity， clear heat， resolve phlegm， and activate blood circulation''. This approach has yielded favorable therapeutic outcomes in clinical practice. This theoretical system clarifies the nature of gout as ''spleen deficiency being the root， dampness-turbidity being the secondary manifestation'' and systematically analyzes its pathogenesis evolution process and characteristics. The constructed stage-based treatment protocol has been validated through clinical and basic research， providing systematic theoretical guidance and a practical framework for the precise TCM management of gout， thereby promoting the modernization of TCM pathogenesis theory related to gout.

ObjectiveThis paper aims to observe the effect of Huazhuo Sanjie Chubi prescription （HSCD） on the gouty bone erosion model rats and investigate its action mechanism. MethodsThirty-six two-month-old male SD rats were randomly divided into the blank group with nine rats and the modeling group with 27 rats. The rats in the modeling group were administered hypoxanthine solution at 300 mg·kg^-1·d^-1 and potassium oxonate solution at 250 mg·kg^-1·d^-1， combined with intra-articular injection of 200 μL monosodium urate （MSU） crystal suspension at 25 g·L^-1 into the right ankle joint （joint injection once every three days）， so as to induce the gouty bone erosion model. After four weeks of modeling， three rats were selected from these two groups to validate the model. The modeled 24 rats were randomly divided into the model group， HSCD group （10.35 g·kg^-1·d^-1）， allopurinol group （20 mg·kg^-1·d^-1）， and inhibitor group （LY294002， 10 mg·kg^-1·d^-1）， with six rats per group. Except for the blank group， rats in all other groups continued to receive hypoxanthine solution at 300 mg·kg^-1 and potassium oxonate solution at 250 mg·kg^-1 via gavage concurrently with administration to maintain modeling intervention. The rats in the HSCD group and allopurinol group received administration by gavage at the above doses. The rats in the inhibitor group received an intraperitoneal injection at the above dose. The rats in the blank group and model group received saline （10.35 g·kg^-1·d^-1） by gavage for four consecutive weeks. After administration， ankle joint swelling of the rats in all groups was observed， and the diameters were measured. Bone volume fraction （BV/TV） and bone surface area to bone volume （BS/BV） were observed and quantitatively analyzed by Micro-CT. Histopathological changes in the ankle joint were observed by hematoxylin-eosin （HE） staining and safranin O-fast green staining. The uric acid in the rats' serum was determined by enzyme colorimetry. The levels of inflammatory factors， including tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， and IL-6 were measured by enzyme-linked immunosorbent assay （ELISA）. The protein expressions of receptor activator of nuclear factor-κB ligand （RANKL） and phosphorylated （p）-phosphatidylinositol-3-kinase （PI3K） in ankle joint tissues of rats were detected by immunofluorescence staining. The mRNA levels of the proteins related to the bone erosion， including RANKL， tartrate-resistant acid phosphatase （TRAP）， cathepsin K （CTSK）， and matrix metalloproteinase-9 （MMP-9） in the ankle joint tissues of rats were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expressions of the proteins related to the bone erosion， including RANKL， CTSK， TRAP， MMP-9， and the proteins related to the PI3K/protein kinase B （Akt） signaling pathway， including PI3K， Akt， mammalian target of rapamycin （mTOR）， p-PI3K， phosphorylated protein kinase B （p-Akt）， and phosphorylated mammalian target of rapamycin （p-mTOR）， were detected by Western blot. ResultsCompared with the blank group， the modeling group showed marked ankle swelling and increased diameter. Micro-CT revealed an uneven articular surface and honeycomb-like bone erosion in the ankle joint. Quantitative analysis showed decreased BV/TV and increased BS/BV （P<0.05）. HE staining revealed a narrowed joint space， rough and discontinuous cartilage surfaces， reduced and unevenly distributed chondrocytes， partial hypertrophy， and blurred tidemarks， confirming successful model establishment. After four weeks of intervention， compared with those in the blank group， the rats in the model group exhibited severe ankle swelling and increased diameters （P<0.05）. Micro‑CT showed that the ankle joint surface was irregular， and bone erosion exhibited a honeycomb‑like morphology. The microstructural parameters of the bone revealed a decreased BV/TV and an increased BS/BV （P<0.05）. Histopathological examination revealed a narrowed joint space and severe articular cartilage destruction. The levels of uric acid in the serum and inflammatory factors （IL-1β， IL-6， and TNF-α） were increased （P<0.05）. The mRNA and protein levels of the proteins related to bone erosion in joint tissue， including RANKL， CTSK， TRAP， and MMP-9， were upregulated （P<0.05）. The ratios of p-PI3K/PI3K， p-Akt/Akt， and p-mTOR/mTOR in the proteins related to the PI3K/Akt signaling pathway were increased （P<0.05）. RANKL and p-PI3K protein fluorescence intensities were elevated （P<0.05）. Compared with those in the model group， the above indicators in all other administration groups showed varying degrees of improvement. The HSCD group and inhibitor groups exhibited more significant effects in reducing ankle swelling， improving bone erosion， bone microstructure （significant decrease in BV/TV and increase in BS/BV）， and the pathology of cartilage erosion， lowering inflammatory factor levels， downregulating the proteins related to the bone erosion， and suppressing activation of the PI3K/Akt/mTOR pathway （P<0.05）. The uric acid levels in rats' serum were reduced in both HSCD and allopurinol groups （P<0.05）. Compared with those in the HSCD group， the rats in the allopurinol group had larger ankle diameters （P<0.05）， more severe bone erosion and bone microstructure damage （P<0.05）， worse improvement of the pathology of cartilage erosion， higher levels of IL-6 and TNF-α （P<0.05）， elevated expressions of the proteins related to the bone erosion， higher expression ratio of proteins related to the PI3K/Akt signaling pathway （P<0.05）， and higher fluorescence intensities of RANKL and p-PI3K proteins （P<0.05）. The inhibitor group achieved comparable results to the HSCD group in improvements of bone microstructure and the reduction of IL-1β and IL-6， stronger suppression of TNF-α and PI3K/Akt/mTOR signaling pathway activation （P<0.05）， but weaker effects on cartilage repair and serum uric acid reduction （P<0.05）. ConclusionHSCD effectively reduces uric acid levels in serum， suppresses inflammatory factor secretion， and downregulates the expressions of proteins related to bone erosion， including RANKL， CTSK， TRAP， and MMP-9 in the joint tissues. Its action mechanism of improving gouty bone erosion may be associated with inhibition of the PI3K/Akt signaling pathway.

Objective:To prevent postoperative myocardial oedema or other causes of acute heart failure in congenital cardiac disease,anticipating delay sternal closure may reduce the number of children requiring cardiopulmonary resuscitation after surgery.The aim of this study was to describe the rate of delay sternal closure after surgery for congenital cardiac disease and to analyse the risk factors that may be associated with it.Methods:We retrospectively reviewed all surgeries with extracorporeal circulation in the cardiothoracic surgery intensive care unit of Shanghai Children's Medical Center in the past five years,from September 2014 to December 2018.The study cohort was divided into the delay sternal closure group (n=418) and the control group (routine chest closure,n=12 188) according to whether a delay sternal closure was applicated.Risk factors associated with delay sternal closure were identified by multivariate Logistic regression analysis.Results:A total of 12 606 cases were eligible,of which 418 (3.32%) were in the delayed sternal closure group.The most common cardiac diagnosis in the delayed sternal group was transposition of the great arteries (26.8%,112/418),whereas the most common cardiac diagnosis in the control group was ventricular septal defect (45.9%,5 599/12 188).All-cause mortality in children in the delayed sternal closure group was 3.3% (14/418) compared with 0.4% (46/12 188) in the control group,with a statistically significant difference ( P<0.05).Multivariate Logistic regression analysis showed that the need for delayed sternal closure were associated with age ( OR 0.164,95% CI 0.079-0.338, P<0.001),positive intropic support before surgery ( OR 0.42,95% CI 0.252-0.699, P=0.001),sex（ OR 0.742，95% CI 0.648-1.098， P<0.05），mean body weight（ OR 1.192，95% CI 1.078-1.318， P<0.001），positive intropic support before surgery（ OR 0.370，95% CI 0.252-0.699， P<0.001），complicated surgery ( OR 0.241,95% CI 0.159-0.367, P<0.001) and extracorporeal circulation diversion time ( OR 6.412,95% CI 4.339-9.475, P<0.001). Conclusion:Delayed sternal closure is an important management strategy for congenital cardiac surgery in infants and children.Delayed sternal closure is associated with age，sex,mean body weight at the time of surgery,positive intropic support before surgery，complicated surgery and extracorporeal circulation diversion time.

Objective:To observe any effect of transcranial direct current stimulation (tDCS) on learning, memory ability and the morphology of neurons in the hippocampus and cortex of rats with cognitive impairment, and also to seek any correlation between the rats′ behavior and the thickness of the granular layer in the CA1 region of the hippocampus.Methods:Thirty Sprague-Dawley rats were randomly divided into an observation group, a model group and a control group, each of 10. Cognitive impairment was induced in the observation and model groups by intraperitoneal injection of scopolamine, while the control group was injected with saline solution over the same period of time. After successful modeling, the observation group was given tDCS, while the model and control groups were connected with electrodes but not given any electrical stimulation. After 16 consecutive days of treatment, behavioral changes of each group were quantified using a shuttle box and a Morris water maze. On the 30th day after the mode-ling, the brains were collected to observe any changes in the morphology of the hippocampal and cortical neurons. The thickness of the hippocampal granular layer was also measured.Results:In the observation group the average rate of electrical impulses after the intervention [(60.5±6.67)/min] was significantly less than in the model group [(145.8±19.31)/min], while the time to find a platform was significantly shorter. The rats of the observation group also crossed the D quadrant of the platform significantly more quickly than the model group, on average. Compared with the control group, the granular layer in the CA1 region of the hippocampus [(93.47±1.07)μm] was significantly thinner on average than in the model group but compared with the model group, the observation group had significantly thicker layers [95.17±1.49)μm] on average. The thickness was negatively correlated with the number of shocks and the time to find the platform, but positively correlated with the number of crossings of the platform in the D quadrant.Conclusions:The degree of impairment generated by intraperitoneal injection of scopolamine correlates with the thickness of the CA1 granular layer of the hippocampus, at least in rats. tDCS can improve the learning and memory of such rats. Its mechanism may be related to promoting structural recovery of hippocampal cortical neurons and increasing the thickness of the granular layer.

Objective:To compare the differences in important parameters between the articulation assessment and training system of intelligently extracted speech with those from the Praat acoustic software and those manually extracted.Methods:The speech of thirty-two normal subjects was captured using the intelligent articulation assessment and training system and using Praat acoustic software. The former analyzed the mean fundamental frequencies (mF0s), the first formant peaks (F1s) and the second formant peak (F2s) of the sustained vowels /a/, /i/ and /u/. The speech parameters collected by the traditional Praat software were extracted and analyzed by professionals. The two tools′ consistency in terms of these important acoustic parameters was analyzed.Results:The results with all 32 subjects when retested returned ICC values above 0.9 with all three vowels with the exception of mF0 for /u/ (ICC=0.75), indicating excellent retest reliability for the articulation assessment and training system. The ICC values also indicated excellent consistency between the two kinds of software in analyzing mF0, F1 and F2 of the three vowels. The mF0, F1, F2, FCR, VAI, tongue spacing, VSA, and mandibular spacing of all three vowels were mostly distributed within the 95% confidence interval of the data points in Bland-Altman plots, indicating the high accuracy of both acoustic analysis systems in speech measurement. The mean fundamental frequency values of the male long vowels /a/, /i/ and /u/ were all significantly lower than for the female long versions.Conclusions:The retest reliability of the articulation assessment and training system was good, and the results of the articulation check in the natural state were in good consistency compared to the Praat check and were interchangeable in the articulation check.

Objective:To analyze the risk factors of performing diaphragm plication(DPL) after congenital heart disease(CHD) surgery as well as the timing and clinical efficacy.Methods:Data regarding children underwent open heart surgery at Shanghai Children′s Medical Center from January 2017 to December 2019 were reviewed.According to whether DPL was performed after CHD operation or not, the children were divided into DPL group and non-diaphragm plication(NDPL)group.Clinical data including age, surgery, cardiopulmonary bypass(CPB)temperature and time of two groups were compared, meanwhile the risk factors of DPL surgery were analyzed.Based on the median of 8 days between open heart surgery and DPL, children in DPL group were divided into early surgery group(less than 8 days), and delayed operation group(no less than 8 days). The parameters of comparison included ventilator using time, hospital stay time, hospitalization expenditure, postoperative infection to evaluate the timing of DPL and effect.Results:There were 10 309 children after CHD, including 95 in DPL group and 10 214 in NDPL group.In DPL group, there were 52 males(54.7%) and 43 females(45.3%), with age 147(52, 318) d, weight(5.5±4.1) kg, height(56.8±25.6) cm, CPB time(136.8±93.4) min and aortic occlusion time(62.5±50.2) min.Compared with NDPL group, DPL group had younger age, shorter height, lighter weight, higher incidence of preoperative special treatment, higher proportion of reoperation, lower CPB temperature, longer CPB time and longer aortic occlusion time.There were significant differences between two groups( P<0.05). Multivariate Logistic regression analysis showed that younger operative age( OR=0.998, 95% CI 0.998~0.999, P<0.001), staging operation( OR=72.977, 95% CI 39.096~136.211, P<0.001), long CPB time( OR=1.006, 95% CI 1.002~1.011, P=0.008), and pulmonary venoplasty( OR=4.219, 95% CI 2.132~8.350, P<0.001) were independent risk factors for DPL after CHD.Early surgery group had lower postoperative infection rate(43.59% vs. 88.38%, P=0.007), shorter ventilator duration[168.0(99.5, 280.5) h vs.309.9(166.2, 644.5) h, P=0.029], shorter hospital stay duration[27.00(20.75, 35.00)d vs.37.00(28.00, 53.00)d, P<0.001], and lower hospitalization cost[158.36(128.99, 203.11) thousand yuan vs.232.95(174.54, 316.47) thousand yuan, P<0.001] than delayed operation group. Conclusion:Younger age, staging operation, long CPB time, and pulmonary venoplasty are independent risk factors for DPL due to diaphragmatic paralysis after pediatric CHD surgery.Early surgical intervention is beneficial for the recovery of children.

Objective:To study the changes of cytokines after cardiopulmonary bypass(CPB)in children with congenital heart disease.Methods:A total of 124 children with congenital heart disease underwent CPB surgery at Shanghai Children′s Medical Center from June 2020 to October 2021 with cytokine detection were enrolled.Twelve kinds of cytokines, white blood cell count(WBC)and neutrophil-to-lymphocyte ratio(NLR), C-reactive protein(CRP)and procalcitonin were detected before and 24 hours after operation.All patients were divided into CPB<120 min group ( n=102)and CPB≥120 min group ( n=22)acoording to CPB time, and were divided into systemic inflammatory response syndrome (SIRS) group, compensatory anti-inflammatory response syndrome (CARS) group and control group according to the changes of cytokines.The changes of cytokines, anti-inflammatory factors and pro-inflammatory factors before and after CPB and the correlation with CPB time were analyzed. Results:There were 65 boys and 59 girls with a body weight of(10.69±8.18)kg and a median age of 317(141, 975)d.After CPB, WBC(×10 9/L)(13.47 vs.8.6), NLR(4.93 vs.0.55), and CRP(mg/L)(81.35 vs.0.8) were significantly higher than those before operation( P<0.001). IL-6(pg/mL)(135.69 vs.6.86), IL-8(pg/mL)(33.33 vs.14.95), and IL-10(pg/mL)(6.05 vs.2.44)were significantly higher than those before operation( P<0.001). Compared with CPB<120 min group, IL-6(pg/mL)(211.88 vs.119.47), IL-8(pg/mL)(71.67 vs. 25.39), and IL-10(pg/mL)(7.69 vs. 4.92)in CPB≥120 min group significantly increased( P<0.001). CRP was negatively correlated with CPB time( r=-0.204, P=0.025), while IL-6( r=0.254, P=0.005), IL-8( r=0.358, P=0.001), IL-10( r=0.198, P=0.03) were positively correlated with CPB time.Twelve children(9.7%)had obvious SIRS, and four cases(3.2%)had early CARS.The mortality of CARS group was significantly higher than that of SIRS group and the control group( P=0.011). Conclusion:Il-6 , IL-8, and IL-10 are significantly increased after CPB in children with congenital heart disease.With the increase of CPB time, IL-6 and IL-8 increase significantly, and the correlation between IL-8 and CPB time is the strongest.Although the proportion of children with early postoperative CARS is small, the mortality is high, which indicates clinical surveillance and treatment need to be strengthened for anti-inflammatory response.

Objective:To explore the relationship between executive function and gait in cases of mild amnestic cognitive impairment (aMCI).Methods:Twenty aMCI hospital patients formed an observation group, while 20 healthy counterparts were the control group. Both groups underwent the Tinetti test, followed by the " normal walking" single-task test and the " normal walking + Go/No-go" dual-task test. The pace, step width, stride length, Go/No-go task response time and accuracy rate were recorded.Results:In the single-task test, there was no significant difference in pace or stride width between the two groups, but the average stride length of the observation group (1.11±0.04)cm was significantly shorter than that of the control group. However, in the dual-task test, the average pace time (0.96±0.08)sec and stride length (1.02±0.06)cm of the observation group were significantly smaller than the control group′s averages, while their step width (0.11±0.02)cm was significantly wider. There was no significant difference between the two groups in the response time in a single (Go/No-go) task, but in the dual-task test, the observation group′s average time was significantly longer than the control group′s and the accuracy was significantly poorer. Both the error rate and the non-response rate were significantly higher than among the control group.Conclusions:Mild amnestic cognitive impairment reduces stride length and pace when walking and impairs executive function.

Objective:To observe the effect of well-designed board sanding training on the upper extremity motor functioning of hemiplegic stroke survivors.Methods:Sixty stroke survivors with hemiplegia were randomly divided into an observation group (30 cases) and a control group (30 cases). All received conventional rehabilitation. The observation group′s training involved intelligent board sanding, while the control group′s training involved traditional sanding.Results:After the treatment, significant improvement was observed in the Fugl-Meyer upper extremity scores, modified Barthel index scores and reported shoulder pain in both groups, with the observation group′s averages significantly better than those of the control group. After the intervention, the average scores of both groups on the modified Ashforth scale had also improved significantly.Conclusions:Supplementing conventional rehabilitation treatment with intelligent board sanding can significantly improve upper extremity motor function and ability in the activities of daily living of stroke survivors with hemiplegia while somewhat relieving shoulder pain. The effect is better than with traditional board sanding.

Lung cancer, which is exacerbated by environmental pollution and tobacco use, has become the most common cause of cancer-related deaths worldwide, with a five-year overall survival rate of only 19% (Siegel et al., 2020; Yang et al., 2020; Yu and Li, 2020). Nearly 85% of lung cancers are non-small cell lung cancers, of which lung adenocarcinoma is the most common subtype accounting for 50% of non-small cell lung cancer cases. At present, radiotherapy is the primary therapeutic modality for lung cancer at different stages, with significant prolongation of survival time (Hirsch et al., 2017; Bai et al., 2019; Shi et al., 2020). Irradiation can generate reactive oxygen species (ROS) through the radiolysis reaction of water and oxygen, cause DNA damage and oxidative stress, and subsequently result in cancer cell death (Kim et al., 2019). Nevertheless, radioresistance seriously hinders the success of treatment for lung cancer, owing to local recurrence and distant metastasis (Huang et al., 2021). Compared with small cell lung cancer, non-small cell lung cancer shows more tolerance to radiotherapy. Therefore, it is of great importance to decipher key mechanisms of radioresistance and identify effective molecular radiosensitizers to improve patient survival.