Traditional Chinese medicine （TCM） has long recognized metabolism-associated fatty liver disease （MASLD）. The Classic of Difficulties （Nan Jing） records that "the accumulation of the liver is called obese Qi". ZHANG Jingyue also stated， "People with spleen and stomach deficiency and weakness or imbalance often suffer from diseases of accumulation". According to syndrome differentiation of the Zang-fu organs， modern physicians generally believe that the key pathogenesis of MASLD lies in the deficiency of spleen and stomach functions. However， MASLD is a chronic and complex disease， and its pathological characteristics cannot be fully explained by a single Zang-Fu syndrome differentiation. The concepts of sweat pores and collateral vessels emerged as early as the Huangdi's Internal Classic （Huang Di Nei Jing）， and later TCM scholars， based on the idea that "sweat pore is the gateway of collateral vessels" proposed the concept of Xuanluo （sweat pores-collateral vessels）. Xuanluo refers to fine structures widely distributed throughout the human body， serving as hubs and channels that regulate the movement and distribution of Qi， blood， and body fluids. By linking the Zang-Fu organs with Xuanluo， a theoretical framework of Qi， blood， and body fluid circulation centered on the "spleen and stomach-Xuanluo" as a whole was established， providing a new perspective for analyzing the essential pathogenesis of MASLD. Combined with the mechanisms involved in the formation and progression of MASLD， the intrinsic correlations between TCM pathogenesis and modern microscopic mechanisms are further analyzed. Modern studies have shown that intestinal microbial dysbiosis and mitochondrial dysfunction are pathological mechanisms involved in the occurrence and development of MASLD， but few have discussed the two as an integrated system. Existing research has confirmed that intestinal microorganisms can affect mitochondrial energy metabolism and oxidative stress through their metabolites， leading to hepatic energy metabolism disorders， oxidative stress （OS）， and inflammation， thereby promoting MASLD progression. Focusing on the correspondence between the "spleen and stomach-Xuanluo" theory and the intestinal microorganism-mitochondrion micro-pathological mechanism， it is proposed that the spleen and stomach share similarities with intestinal microorganisms in the generation of Qi， blood， and body fluids as well as in the regulation of Qi movement， while Xuanluo and mitochondria have commonalities in energy regulation. Moreover， harmonizing the spleen and stomach to ensure unobstructed Xuanluo is the key to maintaining the normal interaction mechanism between intestinal microorganisms and mitochondria. Based on the correlation between the "spleen and stomach-Xuanluo" theory and the intestinal microorganism-mitochondrion interaction， this paper reveals that the essence of MASLD pathogenesis lies in spleen and stomach dysfunction， specifically， failure of the spleen to ascend the clear and failure of the stomach to descend the turbid， resulting in insufficient transformation of Qi and blood， impaired nourishment of Xuanluo， stagnation of Qi and blood， and the long-term formation of phlegm and blood stasis in the liver. Furthermore， it explores the preventive and therapeutic effects of tonifying the spleen and stomach， dredging Xuanluo and collaterals， unblocking the bowels， and regulating Qi in the treatment of MASLD， thereby providing new insights for its prevention and therapy.

Objective With the widespread of transcatheter aortic valve replacement(TAVR)in patients with severe symptomatic aortic stenosis(AS),the life-cycle management has become a major determinant of prognosis.Methods A total of 408 AS patients who underwent successfully TAVR from June 2021 to August 2023 were consecutively enrolled in Hospital Valve Intervention Center.Patients were assigned to the Usual Care(UC)group between June 2021 and October 2022,while patients were assigned to the Heart Multi-parameter Monitoring(HMM)group between November 2022 and August 2023.The primary endpoint was defined as composite endpoint within 6 months post-TAVR,including all-cause death,cardiovascular death,stroke/transient ischemic attack,conduction block,myocardial infarction,heart failure rehospitalization,and major bleeding events.Secondary endpoints were the time interval(in hours)from event occurrence to medical consultation or advice and patient satisfaction.Statistical analysis was performed using Kaplan-Meier and multivariable Cox proportional hazards models.Results The incidence of primary endpoint in HMM group was significantly lower than that in UC group(8.9％vs.17.7％,P=0.016),the driving event was the rate of diagnosis and recognition of conduction block.The average time intervals from event occurrence to receiving medical advice were 3.02 h in HHM group vs.97.09 h in UC group(P＜0.001).Using cardiac monitoring devices and smart healthcare platforms provided significant improving in patients long-term management(HR 0.439,95％CI 0.244-0.790,P=0.006).Conclusions The utilization of cardiac monitoring devices and smart healthcare platforms effectively alerted clinical events and improved postoperative quality of life during long-term management post TAVR.

Targeted radiation therapy using radionuclides is a favored approach for treating tumors.This procedure involves the delivery of drugs to the lesion site via carriers or interventional methods,followed by the emission of radiation energy that selectively irradiates the lesion tissue.This approach minimizes damage to normal tissue and achieves the desired therapeutic effect.Factors such as the type of therapeutic radionuclide,radiation energy,physical half-life,method of preparation,and toxicity determine their clinical application.In this paper,the characteristics and clinical application of therapeutic radionuclides were reviewed to providing reference for the clinical application of targeted therapeutic radionuclides.

Objective:To explore the clinical outcomes of locking compression plating (LCP) in the treatment of periprosthetic fracture (PPF) of the distal femur in the aged patients.Methods:A retrospective study was performed to analyze the 31 aged patients who had been treated at Department of Orthopedic Surgery, The Affiliated Hospital to Nantong University for PPF of the distal femur with LCP between June 2012 and May 2023. There were 27 females and 4 males with an age of (80.2±6.1) years. According to the Unified Classification System (UCS), 18 PPFs were classified as type Ⅴ.3B1 and 6 PPFs as type Ⅴ.3B2 after total knee arthroplasty and 7 PPFs as type Ⅳ.3C after total hip arthroplasty. The patients were fixated with a lateral single plate in 25 cases, and with lateral and medial dual plates in 6 cases. The surgical time, intraoperative blood loss, hospitalization time, postoperative weight-bearing time, fracture healing time, and knee joint function and complications during follow-up were recorded.Results:For the 25 patients undergoing fixation with a lateral single plate, the surgical time was (58.7±7.9) minutes, the intraoperative blood loss (78.0±15.1) mL, the hospitalization time (6.9±1.6) days, the postoperative weight-bearing time (5.9±1.4) days, and the follow-up time 37 (15, 51) months. For the 6 patients undergoing fixation with lateral and medial dual plates, the surgical time was (186.6±9.8) minutes, the intraoperative blood loss (1,256.7±231.2) mL, the hospitalization time (17.8±3.3) days, the postoperative weight-bearing time (3.6±0.6) days, and the follow-up time 17 (16, 21) months. The fracture healing time was (14.9±2.0) and (18.7±2.6) weeks, respectively, for patients fixed with single and double steel plates. By the scoring criteria of the American Hospital for Special Surgery (HSS), the knee joint function was evaluated at the last follow-up as excellent in 10 cases and as good in 15 cases for the 25 patients undergoing fixation with a lateral single plate, and as good for all the 6 patients undergoing fixation with lateral and medial dual plates. No patient experienced such complications as incision infection, bone nonunion, or internal fixation failure during the follow-up period.Conclusions:LCP fixation can achieve satisfactory outcomes in the treatment of PPF of the distal femur in the aged patients. As fixation with a single lateral femoral plate is suitable for most of the aged patients with PPF of the distal femur, it can be used as the first choice. Fixation with dual plates can provide stronger stability, but its indications should be strictly controlled.

As an important advance in the treatment of anti-tumor therapy,immune checkpoint inhibitors significantly prolong the survival of patients with malignant tumors.At the same time,immune-related adverse reactions are also increasing,among which ICIs have increased the risk of acute coronary events,but clinical reports are rare.This paper analyzes the history of a patient with pulmonary small cell neuroendocrine carcinoma who developed acute myocardial infarction after ICIs treatment,suggesting that clinicians should be alert to the occurrence of ICIs-related acute myocardial infarction,and improve the prognosis of patients through early identification and intervention.

Objective To observe the effects of Wuzi Yanzong Pill(WYP)on motor function in a mouse model of Parkinson's disease(PD)and to explore its potential mechanisms.Methods Twenty-four male C57BL/6 mice were randomly divided into control group,model group and WYP group,with 8 mice in each group.Mice in model and WYP group were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine for 7 consecutive days to establish a PD model.From the 1st day of model preparation,mice in WYP group were gavaged with WYP solution[16 g/(kg·d)]twice daily for 14 consecutive days.At the same time,mice in control group and model group were gavaged with 0.9%NaCl solution[50 ml/(kg·d)]twice a day.Gait experiment was utilized to assess the behavioral performance of mice in each group.Immunofluorescence staining was conducted to detect the number of tyrosine hydroxylase(TH)-positive cells in the substantia nigra region,the fluorescence intensity of nuclear factor E2-related factor 2(Nrf2),and the number of NeuN neurons co-labeled with Nrf2 in each group.Western blotting was employed to determine the expression levels of TH,Kelch-like ECH-associated protein 1(Keap-1),Nrf2,and heme oxygenase-1(HO-1)in the brain tissue of mice in each group.Results The gait experiment results showed that,compared with control group,standing time of the left front paw,right front paw,left hind paw,and right hind paw of the mice in model group was significantly shortened(P<0.01),while swinging time of the left front paw,right front paw,left hind paw,and right hind paw was significantly prolonged(P<0.05).Compared with model group,standing time of the left front paw and right hind paw of the mice in WYP group was significantly prolonged(P<0.05),while swing time of the left front paw and right front paw was significantly shortened(P<0.05).Immunofluorescence staining and Western blotting results showed that,compared with control group,in model group the number of TH-positive cells,average fluorescence intensity of Nrf2,and HO-1 levels decreased(P<0.01),while the Keap-1 protein level increased(P<0.01),and the number of Nrf2 expression on NeuN neurons decreased(P<0.001).Compared with model group,the number of TH-positive cells,average fluorescence intensity of Nrf2,HO-1 level,and the number of Nrf2 expression on NeuN neurons in the brain tissue of mice in WYP group increased(P<0.05),while Keap-1 protein level decreased(P<0.05).Conclusions WYP could alleviate the motor dysfunction and protect dopaminergic neurons in PD mice.The underlying mechanism may be related to the regulation of Keap-1/Nrf2/HO-1 pathway to inhibit oxidative stress response.

Objective To investigate the puncture effect of radiofrequency thermocoagulation of semilunar ganglion through the foramen ovale with ultrasound guidance and CT verification in the treatment of V3 branch trigeminal neuralgia(TN).Methods Forty-eight V3 branch TN patients,19 males and 29 females,aged＞18 years,BMI≤28 kg/m2,undergoing radiofrequency thermocoagulation of semilunar ganglion through the foramen ovale were selected.Patients were divided into two groups by random number table method:ultrasound guidance combined with CT verification group(group U)and CT guidance group(group C),24 patients in each groups.According to grouping result,patients received radiofrequency ther-mocoagulation of semilunar ganglion with foramen ovale puncture performed under the ultrasound guidance and CT verification or CT guidance respectively.The success cases of puncture,the number of puncture,ra-diation dose,puncture time,operation time and the occurrence of treatment complications were recorded.Numerical rating scale(NRS)scores and Barrow neurological institute(BNI)scores were recorded before surgery,2,4,12,and 24 weeks after surgery,and good postoperative pain relief rate(BNI Ⅰ or Ⅱ)was calculated.Results All patients in both groups completed puncture operationand radiofrequency thermo-coagulation.Compared with group C,group U had fewer number of puncture,lower radiation exposure,and shorter puncture and surgical times(P＜0.05).Compared with baseline before operation,NRS scores were significantly lower in both groups at 2,4,12,and 24 weeks after surgery(P＜0.05).There was no signif-icant difference in the rate of good pain relief 2,4,12,and 24 weeks after surgery between the two groups.There was no significant difference in the incidence of facial hematoma between the two groups.No other se-rious complications were found in both groups.Conclusion Radiofrequency thermocoagulation of semilunar ganglion through the foramen ovale with ultrasound guidance and CT verification is a safe and feasible method for the treatment of the V3 branch TN.Compared with CT guidance,ultrasound guidance combined with CT verification can significantly improve the puncture accuracy and reduce the radiation exposure related to treatment.

OBJECTIVE: To clarify the epidemiological characteristics and spatial distribution patterns of human norovirus outbreaks in China, identify high-risk areas, and provide guidance for epidemic prevention and control. METHODS: This study analyzed 964 human norovirus outbreaks involving 50,548 cases in 26 provinces reported from 2012 to 2018. Epidemiological analysis and spatiotemporal scanning analysis were conducted to analyze the distribution of norovirus outbreaks in China. RESULTS: The outbreaks showed typical seasonality, with more outbreaks in winter and fewer in summer, and the total number of infected cases increased over time. Schools, especially middle schools and primary schools, are the most common settings of norovirus outbreaks, with the major transmission route being life contact. More outbreaks occurred in southeast coastal areas in China and showed significant spatial aggregation. The highly clustered areas of norovirus outbreaks have expanded northeast over time. CONCLUSION By identifying the epidemiological characteristics and high-risk areas of norovirus outbreaks, this study provides important scientific support for the development of preventive and control measures for norovirus outbreaks, which is conducive to the administrative management of high-risk settings and reduction of disease burden in susceptible areas.
Humans ; Gastroenteritis/epidemiology* ; Norovirus ; Caliciviridae Infections/epidemiology* ; Disease Outbreaks ; China/epidemiology* ; Genotype

This study explores the effect of total flavonoids of Rhododendra simsii(TFR) on middle cerebral artery occlusion(MCAO)-induced cerebral injury in rats and oxygen-glucose deprivation/reoxygenation(OGD/R) injury in PC12 cells and the underlying mechanism. The MCAO method was used to induce focal ischemic cerebral injury in rats. Male SD rats were randomized into sham group, model group, and TFR group. After MCAO, TFR(60 mg·kg~(-1)) was administered for 3 days. The content of tumor necrosis factor-α(TNF-α), interleukin-1(IL-1), and interleukin-6(IL-6) in serum was detected by enzyme-linked immunosorbent assay(ELISA). The pathological changes of brain tissue and cerebral infarction were observed based on hematoxylin and eosin(HE) staining and 2,3,5-triphenyltetrazolium chloride(TTC) staining. RT-qPCR and Western blot were used to detect the mRNA and protein levels of calcium release-activated calcium channel modulator 1(ORAI1), stromal interaction molecule 1(STIM1), stromal intera-ction molecule 2(STIM2), protein kinase B(PKB), and cysteinyl aspartate specific proteinase 3(caspase-3) in brain tissues. The OGD/R method was employed to induce injury in PC12 cells. Cells were randomized into the normal group, model group, gene silencing group, TFR(30 μg·mL~(-1)) group, and TFR(30 μg·mL~(-1))+gene overexpression plasmid group. Intracellular Ca~(2+) concentration and apoptosis rate of PC12 cells were measured by laser scanning confocal microscopy and flow cytometry. The effect of STIM-ORAI-regulated store-operated calcium entry(SOCE) pathway on TFR was explored based on gene silencing and gene overexpression techniques. The results showed that TFR significantly alleviated the histopathological damage of brains in MCAO rats after 3 days of admini-stration, reduced the contents of TNF-α, IL-1, and IL-6 in the serum, down-regulated the expression of ORAI1, STIM1, STIM2, and caspase-3 genes, and up-regulated the expression of PKB gene in brain tissues of MCAO rats. TFR significantly decreased OGD/R induced Ca~(2+) overload and apoptosis in PC12 cells. However, it induced TFR-like effect by ORAI1, STIM1 and STIM2 genes silencing. However, overexpression of these genes significantly blocked the effect of TFR in reducing Ca~(2+) overload and apoptosis in PC12 cells. In summary, in the early stage of focal cerebral ischemia-reperfusion injury and OGD/R-induced injury in PC12 cells TFR attenuates ischemic brain injury by inhibiting the STIM-ORAI-regulated SOCE pathway and reducing Ca~(2+) overload and inflammatory factor expression, and apoptosis.
Animals ; Male ; Rats ; Apoptosis ; Brain Ischemia/metabolism* ; Caspase 3 ; Interleukin-1 ; Interleukin-6 ; Rats, Sprague-Dawley ; Reperfusion Injury/metabolism* ; Tumor Necrosis Factor-alpha/genetics* ; Flavonoids/pharmacology* ; Rhododendron/chemistry*

OBJECTIVE: To investigate the effects of LASS2/TMSG1 gene overexpression on proliferation and apoptosis of human lung cancer A549 cells and explore the possible mechanism. METHODS: We examined LASS2/TMSG1 expression level in a previously constructed A549 cell line overexpressing LASS2/TMSG1 using Western blotting. The proliferation and apoptosis of the cells were detected using colony-forming assay, CCK-8 assay, Hoechst/PI double staining and flow cytometry. Fourteen nude mice were randomized into 2 groups (n=7) to receive subcutaneous injection of A549 cells with or without LASS2/TMSG1 overexpression on the back of the neck, and the cell proliferation in vivo was observed. The expression levels of p38 MAPK protein and p-p38 MAPK protein in the xenografts were detected with Western blotting. ELISA was used to detect the levels of ceramide and p38 MAPK protein in cultured A549 cell supernatants and the xenografts in nude mice. RESULTS: Compared with the negative control cells, A549 cells with LASS2/TMSG1 overexpression had significantly lowered proliferation ability in vitro with increased early apoptosis rate (P < 0.05), and showed obvious growth inhibition after inoculation in nude mice(P < 0.05). Western blotting showed that in both cultured A549 cells and the xenografts in nude mice, LASS2/TMSG1 gene overexpression significantly increased the expression levels of p38 MAPK protein and p-p38 MAPK protein (P < 0.05); the results of ELISA also revealed significantly increased levels of ceramide and p38 MAPK protein in the cell supernatant andxenografts as well (P < 0.05). CONCLUSION Overexpression of LASS2/TMSG1 gene can significantly inhibit the proliferation and promote early apoptosis of human lung cancer A549 cells both in vitro and in vivo possibly by upregulating the expressions of ceramide and p38 MAPK protein to activate a signal transduction cascade.
Animals ; Humans ; Mice ; A549 Cells ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Lung Neoplasms ; Membrane Proteins/metabolism* ; Mice, Nude ; p38 Mitogen-Activated Protein Kinases/metabolism* ; Signal Transduction ; Tumor Suppressor Proteins/metabolism*