Houpo Sanwutang， included in the Catalogue of Ancient Classical Prescriptions （Second Batch）， was first recorded in the Synopsis of Golden Chamber written by ZHANG Zhongjing from the Eastern Han dynasty and was modified by successive generations of medical experts. A total of 37 pieces of effective data involving 37 ancient Chinese medical books were retrieved from different databases. Through literature mining， statistical analysis， and data processing， combined with modern articles， this study employed bibliometrics to investigate the historical origin， composition， decoction methods， clinical application， and other key information. The results showed that the medicinal origin of Houpo Sanwutang was clearly documented in classic books. Based on the conversion of the measurements from the Han Dynasty， it is recommended that 110.4 g Magnolia Officinalis Cortex， 55.2 g Rhei Radix et Rhizoma， and 72 g Aurantii Fructus Immaturus should be taken. Magnolia Officinalis Cortex and Aurantii Fructus Immaturus should be decocted with 2 400 mL water first， and 1 000 mL should be taken from the decocted liquid. Following this， Rhei Radix et Rhizoma should be added for further decoction， and then 600 mL should be taken from the decocted liquid. A single dose of administration is 200 mL， and the medication can be stopped when patients restore smooth bowel movement. Houpo Sanwutang has the effect of moving Qi， relieving stuffiness and fullness， removing food stagnation， and regulating bowels. It can be used in treating abdominal distending pain， guarding， constipation， and other diseases with the pathogenesis of stagnated heat and stagnated Qi in the stomach. The above results provide reference for the future development and research of Houpo Sanwutang.

The liver performs multiple life-sustaining functions. Hepatic diseases, including hepatitis, cirrhosis, and hepatoma, pose significant health and economic burdens globally. Along with the advances in nanotechnology, mesoporous silica nanoparticles (MSNs) exhibiting diversiform size and shape, distinct morphological properties, and favorable physico-chemical features have become an ideal choice for drug delivery systems and inspire alternative thinking for the management of hepatic diseases. Initially, we introduce the physiological structure of the liver and highlight its intrinsic cell types and correlative functions. Next, we detail the synthesis methods and physicochemical properties of MSNs and their capacity for controlled drug loading and release. Particularly, we discuss the interactions between liver and MSNs with respect to the passive targeting mechanisms of MSNs within the liver by adjusting their particle size, pore diameter, surface charge, hydrophobicity/hydrophilicity, and surface functionalization. Subsequently, we emphasize the role of MSNs in regulating liver pathophysiology, exploring their value in addressing liver pathological states, such as tumors and inflammation, combined with multi-functional designs and intelligent modes to enhance drug targeting and minimize side effects. Lastly, we put forward the problems, challenges, opportunities, as well as clinical translational issues faced by MSNs in the management of liver diseases.

Objective Evaluation of Chinese-thyroid imaging reporting and data system(C-TIRADS)combined with contrast-enhanced ultrasound(CEUS)for the assessment of category 4 nodules in the setting of Hashimoto's thyroiditis.Methods Retrospective analysis of 120 C-TIRADS category 4 thyroid nodules from 79 patients with confirmed Hashimoto's thyroiditis who attended the Yiyang Central Hospital from June to December 2022.Thyroid nodules exhibiting one or more benign or malignant features that were suspicious on CEUS were treated as downgraded or upgraded one level.Using the final surgical pathology results as the gold standard,working characteristic(ROC)curves of subjects based on C-TIRADS grading before and after CEUS adjustment were plotted to compare diagnostic efficacy.Results The sensitivity,specificity,and accuracy of the CEUS-adjusted C-TIRADS were 93.0％,87.8％and 90.8％,respectively(P<0.05).The area under the ROC curve was 0.811 and 0.904,respectively(P<0.05).Conclusion C-TIRADS combined with CEUS has better diagnostic efficacy in evaluating category 4 nodules in Hashimoto's thyroiditis.

Hepatocellular carcinoma is the most common malignancy of the liver and poses serious health burdens on China and the whole world. However， most patients with hepatocellular carcinoma are already in the advanced stage at the time of diagnosis， with fewer opportunities for surgery and limited treatment options. In recent years， the advances in molecular targeted therapies have brought new hope for patients with advanced hepatocellular carcinoma. Among these therapies， lenvatinib is the second first-line drug after sorafenib approved by the US Food and Drug Administration for the treatment of advanced hepatocellular carcinoma， and it has attracted widespread attention for its powerful anti-tumor properties. However， the efficacy of lenvatinib is severely limited by its drug resistance. This article reviews the research advances in the molecular mechanisms of lenvatinib resistance in hepatocellular carcinoma and discusses possible ways to improve the efficacy of lenvatinib， so as to improve its efficacy.

Objective:To explore the advantages of minimally invasive internal fixation assisted by an orthopedic robot in the treatment of tibial plateau fractures of Schatzker types Ⅱ and Ⅲ that can be indirectly reduced.Methods:A retrospective study was conducted of the 18 patients who had been treated for tibial plateau fractures of Schatzker types Ⅱ and Ⅲ at Department of Orthopaedics, The Fourth Hospital of Wuhan from December 2019 to December 2021. They were 12 males and 6 females with an age of (45.2±9.6) years. All fractures were closed. Of them, 6 were complicated with an avulsion fracture at the insertion point of the anterior cruciate ligament, 1 with tear of the medial collateral ligament, and 8 with tear of the lateral meniscus. All patients were treated with minimally invasive internal fixation using the "fence" screw technique after indirect reduction assisted by an orthopedic surgical robot. Those combined with avulsion fracture of the anterior cruciate ligament and meniscus tear underwent one-stage arthroscopic surgery, while those combined with tear of the medial collateral ligament underwent one-stage open repair. The fracture reduction was evaluated according to the Rasmussen radiological scoring system, and the knee joint function evaluated using the American Hospital for Special Surgery (HSS) scoring system.Results:All the 18 patients were fully followed up for (10.6±1.9) months. The X-ray films immediately after surgery showed good fracture reduction. The fractures healed after (11.3±1.2) weeks. At 6 months after surgery, the Rasmussen knee score was (16.8±1.0) points, giving 5 excellent and 13 good cases; the HSS score was (93.2±3.0) points, giving 17 excellent and 1 good cases. By the last follow-up, no serious complications occurred, such as common peroneal nerve injury, popliteal vascular injury, postoperative infection, or internal fixation failure.Conclusion:Since minimally invasive internal fixation assisted by an orthopedic robot can lead to fine clinical efficacy for tibial plateau fractures of Schatzker types Ⅱ and Ⅲ, this technique can be widely applied in clinical practice.

AIM:To explore the expression and distribution of synaptic and extrasynaptic glutamate receptors under the action of amyloid β-protein 42 oligomers(Aβ42Os)in Alzheimer disease.METHODS:In vitro,primary neu-rons from neonatal mice were treated with different concentrations of Aβ42Os.In vivo,Aβ42Os were stereotaxically injected into the lateral ventricle of C57BL/6 mice.Western blot was used to detect the protein levels of metabotropic gultamate re-ceptor 5(mGluR5)and N-methyl-D-aspartate receptor(NMDAR)subunits(NR2A,NR2B and NR1)in mouse primary neurons and mice.Immunofluorescence staining was performed to observe the distribution of mGluR5 and NMDAR.Addi-tionally,Western blot was employed to examine the expression of mGluR5 downstream phosphatidylinositol 3-kinase(PI3K)/protein kinase B(PKB/AKT)signaling pathway-related proteins,calcium signaling pathway-related proteins and synapse-related proteins in mouse hippocampal tissues.RESULTS:(1)High concentrations of Aβ42Os increased mGluR5 expression in mouse primary neurons,but reduced the expression of NR2A,NR2B and NR1(P<0.01).Treatment of pri-mary neurons with high concentration of Aβ42Os resulted in aggregation of mGluR5 on the membrane surface,and re-duced the expression of NR2A,NR2B and NR1 on the membrane surface.(2)High concentration of Aβ42Os increased the expression of synaptic mGluR5 in mouse hippocampal tissues(P<0.01),but reduced the expression of synaptic NR2A(P<0.05)and NR2B(P<0.01)and increased the expression of extrasynaptic NR2B(P<0.01).High concentration of Aβ42Os inhibited the expression of PI3K and the phosphorylation of AKT and extracellular signal-regulated kinase(ERK),and overactivated calcium/calmodulin-dependent protein kinase IIα(CaMKIIα).High concentration of Aβ42 decreased the expression of postsynaptic density protein 95,spinophilin,synaptophysin and microtubule-associated protein 2(P<0.01).CONCLUSION:(1)High concentrations of Aβ42Os increase mGluR5 expression and decrease NR2A,NR2B and NR1 expression in synapse,along with an increase in extrasynaptic NR2B.(2)High concentrations of Aβ42Os inhibit the PI3K/AKT and ERK signaling pathways,overactivated the CaMKIIα pathway,and destroyed the synaptic structures.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective:The aim of our study is to develop an LC-MS/MS method using isotope internal standard for the determination of vancomycin in human blood serum and to validate its clinical value.Method:We conducted a methodological evaluation study using serum samples from 221 hospitalized patients (142 males and 79 females; mean age (59.31±15.32) years) who received treatments of vancomycin at the Sir Run Run Shaw Hospital of Zhejiang University between March 2021 and June 2022. In addition, thirty clinical residual serum samples from healthy individuals (15 males and 15 females; mean age (35.65±9.86) years) undergoing physical examination were used for methodological evaluation. The method was established using AB Sciex Triple Quad 4500 MD liquid chromatography-tandem mass spectrometer and chromatographic separation was carried out using a Phenyl-Hexyl column with gradient elution. The mobile phase was composed of 0.1% formic acid in water and methanol; the column temperature was 40℃; Vancomycin-[d12] TFA salt was used as the internal standard (IS). The sensitivity, specificity, linearity, accuracy, imprecision, matrix effect, and carry-over of the method were evaluated.Results:The detection limit of vancomycin was 0.2 mg/L and the lowest limit of quantification was 0.5 mg/L. It showed good linearity ( R2=0.998 4) in the 1 to 50 mg/L concentration range. Accuracy (recovery rate 87.45%-112.69%), intra-day and inter-day imprecision ( CV 4.91%-7.69%), internal standard standardized matrix factor (90.22%-104.29%). Carryover pollution was negligible. Of the 221 patients, the mean trough concentrations of vancomycin in serum was (13.15±8.56) mg/L. Conclusion:The LC-MS/MS method for the detection of serum vancomycin established in our laboratory meets the requirements of the reference method, and can be used for the monitoring of clinical therapeutic drugs.

【Objective】 Dyslipidemia has shown to be associated with cardiovascular, metabolic and renal diseases. This study aimed to investigate the association between residual cholesterol and the risk of subclinical renal damage (SRD). 【Methods】 A total of 2 342 participants were recruited from the previously established Hanzhong Adolescent Hypertension Study cohort. According to estimated glomerular filtration rate(eGFR) and urinary albumin-to-creatine ratio(uACR), the subjects were divided into SRD group and non-SRD group. The associations of residual cholesterol with eGFR, uACR, and the risk of SRD were analyzed by multiple linear and Logistic regression analyses. 【Results】 Residual cholesterol was positively correlated with uACR(r=0.081, P<0.001) but negatively correlated with eGFR (r=-0.091, P<0.001). Multiple linear regression analysis revealed that residual cholesterol was an influencing factor of uACR (β=0.075, P<0.001) and eGFR (β=-0.027, P<0.001) after adjustment for gender, age, smoke, alcohol, exercise, BMI, hypertension, diabetes and serum uric acid. In addition, Logistic regression analysis revealed that residual cholesterol was significantly associated with the risk of SRD independently of potential confounders [OR(95% CI)=1.387 (1.113-1.728), P<0.001]. Further subgroup analysis showed that residual cholesterol was significantly associated with the risk of SRD in women but not in men. 【Conclusion】 Residual cholesterol is a contributing factor in the risk of subclinical renal damage with gender-specific association.

【Objective】 4-like protein with down-regulated expression and development in neural precursor cells (NEDD4L) plays an important role in blood pressure (BP) regulation and sodium homeostasis by regulating epithelial sodium channel protein. In this study, we aimed to explore the relationship of NEDD4L gene polymorphisms with BP responses to sodium and potassium intake. 【Methods】 In 2004, 514 subjects from 124 families in Meixian County, Shaanxi Province, were recruited to establish a salt-sensitive hypertension study cohort. All the subjects received a 3-day baseline survey, a 7-day low-salt diet, a 7-day high-salt diet, and finally a 7-day high-salt and potassium supplementation. Their BP was measured and peripheral blood samples were collected at different intervention periods. The 14 gene polymorphisms of NEDD4L gene were genotyped and analyzed by MassARRAY platform. 【Results】 BP decreased on a low-salt diet, and significantly increased on a high-salt diet, and decreased again after potassium supplementation. NEDD4L SNPs rs74408486 were significantly associated with systolic BP, diastolic BP and mean arterial pressure responses to the low-salt diet. SNPs rs292449 and rs2288775 were significantly associated with pulse pressure response to the high-salt diet. In addition, SNPs rs563283 and rs292449 were significantly associated with diastolic BP, mean arterial pressure, and pulse pressure responses to high-salt and potassium supplementation diet. 【Conclusion】 NEDD4L gene polymorphisms were significantly associated with BP responses to sodium and potassium intake, suggesting that NEDD4L gene may be involved in the development of salt sensitivity and potassium sensitivity.