BACKGROUND:Studies have reported that alendronate intake significantly increases bone mineral density in patients with osteoporosis. OBJECTIVE:To analyze and compare the changes in metabolites before and after alendronate intervention in ovariectomized rats by chromatography-mass spectrometry,and to further explore the specific mechanism and target of alendronate in the treatment of osteoporosis. METHODS:A total of 36 female Sprague-Dawley rats were randomly divided into model group,alendronate sodium group and sham operation group.The osteoporosis model was established by ovariectomy in the first two groups.Four weeks after modeling,the rats in the alendronate group were intragastrically given alendronate sodium,while those in the sham operation group and model group were given equal volume of normal saline.After 12 weeks of continuous gavage,the metabolites of the lumbar spine were analyzed by chromatography-mass spectrometry,and the common differential metabolites were obtained,which were analyzed by bioinformatics such as Kyoto Gene and Genome Encyclopedia pathway. RESULTS AND CONCLUSION:Totally 17 different metabolites were obtained in the three groups.The enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes showed that alendronate sodium could regulate unsaturated fatty acid biosynthesis,linoleic acid metabolism and other pathways to protect ovariectomized rats.These results indicate that alendronate sodium may exert its anti-osteoporosis effect by interfering with unsaturated fatty acid bioanabolism and linoleic acid metabolism,so as to achieve the purpose of preventing osteoporosis

Objective To analyze the nonlinear relationship between hypothermic machine perfusion (HMP) parameters and delayed graft function (DGF) and optimize the construction of a predictive model for DGF. Methods The data of 923 recipients who underwent kidney transplantation from deceased donors were retrospectively analyzed. According to the occurrence of DGF, the recipients were divided into DGF group (n=823) and non-DGF group (n=100). Donor data, HMP parameters and recipient data were analyzed for both groups. The nonlinear relationship between HMP parameters and the occurrence of DGF was explored based on restricted cubic splines (RCS). Over-sampling, under-sampling and balanced sampling were used to address the imbalance in the proportion of DGF to construct logistic regression predictive models. The area under the curve (AUC) of each model was compared in the validation set, and a nomogram model was constructed. Results Donor BMI, cold ischemia time of the donor kidney, and HMP parameters (initial and final pressures, resistance, and perfusion time) were significantly different between the DGF and non-DGF groups (all P<0.05). The RCS analysis revealed a threshold-like nonlinear relationship between HMP parameters and the risk of DGF. Among the models constructed using different sampling methods, the balanced sampling model had the highest AUC. Using this model, a nomogram was constructed to stratify recipients based on risk scores. Recipients in the high-risk group had higher serum creatinine levels at 1, 6, and 12 months after kidney transplantation compared to those in the low-risk group (all P<0.05). Conclusions There is a nonlinear relationship between HMP parameters and the risk of DGF, and the threshold is helpful for organ quality assessment and monitoring of graft function after transplantation. The predictive model for DGF constructed on the base of balanced sampling algorithms helps perioperative decision-making and postoperative graft function monitoring of kidney transplantation.

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.

OBJECTIVE To analyze the influencing factors of voriconazole trough concentration and adverse drug reactions （ADR） in renal transplant recipients. METHODS Data from inpatients who received voriconazole and therapeutic drug monitoring in our hospital between January 2022 and August 2023 were retrospectively analyzed. Patients were divided into renal transplant group and non-renal transplant group based on transplantation status. A 1∶1 propensity score matching （PSM） method was used to balance differences in baselines between the two groups. Voriconazole trough concentrations， target attainment rate， clinical efficacy， and ADR were compared between the two groups. Multiple linear regression （backward） was used to analyze the factors influencing voriconazole trough concentrations in the renal transplant group. Univariate analysis and binary Logistic regression were used to identify independent risk factors for ADR in the renal transplant group. RESULTS After PSM， 48 patients were included in each group. There were no statistically significant differences in the mean voriconazole trough concentration， target attainment rate or efficacy rate between the two groups （P＞0.05）. The total incidence of ADR was significantly higher in the renal transplant group than in the non-renal transplant group （P＜0.05）. Multiple linear regression analysis showed that age， average daily dose， pulmonary infection， total bilirubin during medication， day-1 loading dose， use of the original drug， concomitant immunosuppressant use， and the occurrence of ADR were factors influencing voriconazole trough concentration in renal transplant patients （P＜0.05）. Binary Logistic regression analysis showed that abnormal direct bilirubin during medication [OR＝7.747， 95%CI （1.334， 45.005）， P＝0.023] was an independent risk factor for ADR in renal transplant patients receiving voriconazole. CONCLUSIONS Age， average daily dose， pulmonary infection， use of the original drug， day-1 loading dose， total bilirubin during medication， concomitant immunosuppressant use， and the occurrence of ADR are the factors influencing voriconazole trough concentration in renal transplant patients. Furthermore， patients with abnormal direct bilirubin during medication are more susceptible to ADR.

According to the World Health Organization's world report on hearing, nearly 2.5 billion people worldwide will suffer from hearing loss by 2050, which may contribute to a severe impact on individual life quality and national economies. Sensorineural hearing loss (SNHL) occurs commonly as a result of noise exposure, aging, and ototoxic drugs, and is pathologically characterized by the impairment of mechanosensory hair cells of the inner ear, which is mainly triggered by reactive oxygen species accumulation, inflammation, and mitochondrial dysfunction. Though recent advances have been made in understanding the ability of cochlear repair and regeneration, there are still no effective therapeutic drugs for SNHL. Chinese herbal medicine which is widely distributed and easily accessible in China has demonstrated a unique curative effect against SNHL with higher safety and lower cost compared with Western medicine. Herein we present trends in research for Chinese herbal medicine for the treatment of SNHL, and elucidate their molecular mechanisms of action, to pave the way for further research and development of novel effective drugs in this field.

Abstract: Inflammatory bowel disease (IBD), whose pathogenesis remains elusive, is a group of autoimmune diseases characterized by chronic, progressive, and lifelong inflammation of the digestive tract. The pathogenesis of IBD remains elusive. Although a number of drugs have been developed to treat IBD, their effects are merely anti-inflammatory. In addition, current treatments for IBD are easily susceptible to resistance in clinical practice. Mesenchymal stem cells (MSCs) have been reported to have the ability to migrate to the site of inflammation, with potent immunoregulatory effects, and to rebalance the immune microenvironment and restore the integrity of the epithelial barrier with significant value of application, particularly for patients who are refractory to classic medicines. In this paper, we reviewed the clinical applications, mechanisms and engineerable properties of MSC products and their exosomes to provide some reference for the use of MSCs and their exosomes in the treatment of IBD.

Objective To study the relationship between detachment and puncture site and chest wall thickness after preoperative positioning of peripheral lung nodules by CT-guided Hookwire puncture.Methods From July 2017 to December 2021,190 patients in our hospital underwent thoracoscopic surgery for peripheral lung nodules.All patients underwent preoperative CT-guided HOOKWIRE puncture mapping,recording the puncture site,whether the needle had fallen off,chest wall thickness,and the interval between the end of the puncture and the start of the surgery,logistic regression analysis,and receiver operating characteristic(ROC)curve analysis to explore the risk factors affecting needle fall off.Results Clinical data were collected for 190 patients,including 119 males and 71 females,age 22 to 78(58.1±10.2)years.There were 31 cases of shedding,with a shedding rate of 16.3％.Among them,31 cases were detached in the medial aspect of the subscapular horn line,15 cases were detached,with detachment rate being 48.4％;67 cases were detached in the medial axillary line,10 cases were detached,with detachment rate being 14.9％;65 cases were detached in the medial axillary line of the midclavicular line,5 cases were detached,with detachment rate being 7.6％;27 cases were detached in the medial axillary line,1 case was detached,with detachment rate being 3.7％;the detachment rate was highest in the subscapular horn line,with statistical significance(P＜0.05)compared with other locations;the tissue thickness of the thoracic wall was(49.38±6.28)mm,but the tissue thickness of the thoracic wall was(36.36±7.77)mm,with statistical significance(P＜0.05).The interval between puncture and operation was 73 to 98 min,with an average one of(81.99±4.48)min.Conclusions The detachment of the positioning needle is related to the thickness of the chest wall,and the proportion of detachment is significantly higher in the chest back,especially in the subscapular angle,before surgical treatment of peripheral lung nodules.In cases of peripheral pulmonary nodules with surface projections medial to the inferior scapular horn line,other methods of localization should be preferably considered.

This study， anchored in the traditional Chinese medicine （TCM） syndrome differentiation and treatment principles alongside the clinical characteristics of sepsis in Western medicine， extensively gathers and meticulously dissects the latest research findings on sepsis animal models from both Chinese and international sources. Adhering strictly to TCM syndrome diagnostic criteria for sepsis， the study conducts a thorough evaluation of various animal models across multiple dimensions， including clinical manifestations， pathological changes， and biomarker expressions， so as to reflect the degree of resemblance these models have to human sepsis TCM syndromes. The results reveal that the colon stent implantation model exhibits a higher degree of congruence with both TCM and Western medicine standards， particularly aligning with the diagnosis of the "Fu-Qi obstruction syndrome". Conversely， the extraperitoneal sepsis model shows a higher degree of congruence with TCM， fitting more closely with the diagnosis of "acute deficiency syndrome" and emphasizing the core pathogenesis of Qi deficiency in sepsis. These findings not only augment the diversity of sepsis animal models but also highlight the necessity and potential of integrated TCM and western medicine research. Current sepsis animal models predominantly focus on western pathophysiological mechanisms， with limited direct incorporation of TCM syndrome differentiation elements. This underscores the need， in future study designs， to actively explore integrating TCM syndrome classification and intervention principles into model development. This could be achieved by manipulating model-inducing factors and observing more TCM-specific symptoms and signs among other strategies， so as to establish sepsis models that more closely resemble clinical reality and incorporate both TCM and western medical perspectives.

In March 2020, the outflow of age limited videos from ICU in Spain inspired us to rethink whether there is age discrimination in the allocation of scarce medical resources. This paper frist reflected on the problem of age discrimination caused by this phenomenon from four moral intuitions: the sacred view of life, the quality of life and values, public health ethics and Chinese culture, and then examined whether it is illegal from the legal level, finally pointed out the negative impact on the society, and put forward that taking age as the standard for the allocation of scarce medical resources is not suitable for China’s national conditions.

ObjectiveTo observe the effect of Buyang Huanwutang in treating diabetic peripheral neuropathy （DPN） by inhibiting pyroptosis through AMP-activated protein kinase （AMPK）/UNC-51-like kinase 1 （ULK1） mitophagy pathway. MethodSixty male SPF SD rats （6-7 weeks old） were used in animal experiments and numbered according to their body mass. They were then randomly divided into four groups by computer： normal group， model group， α-lipoic acid group（60 mg·kg^-1）， and Buyang Huanwutang group（15 g·kg^-1）， with 15 rats in each group. The diabetic model was established by injection of streptozocin （STZ）. After successful modeling， the α-lipoic acid group and the Buyang Huanwutang group were given corresponding drugs， and the normal group and the model group were given normal saline. Sensory nerve conduction velocity （SNCV） and paw withdrawal threshold （PWT） were measured at the end of administration for 12 weeks. Immunohistochemistry and Western blot were used to detect the expression of phosphorylated AMP activated protein kinase （p-AMPK）， phosphorylated UNC-51-like kinase 1 （p-ULK1）， protein involved in microtubule-associated protein 1 light chain 3 （LC3）， selective autophagy receptors （p62/SQSTM1）， Beclin1， NOD receptor protein structure domain-related proteins 3 （NLRP3）， Caspase-1 （Caspase-1）， and interleukin-1 beta （IL-1β） in dorsal root ganglia （DRG）. Immunofluorescence was used to detect the expression of the N-terminal gasdermin D （N-GSDMD）. ResultCompared with those in the normal group， rats in the model group had increased fasting blood glucose （P<0.01） and significantly reduced SNCV， PWT （P<0.01）， LC3Ⅱ/LC3Ⅰ， Beclin1， p-AMPK/AMPK， and p-ULK1/ULK1 （P<0.01）. In addition， p62， NLRP3， N-GSDMD/GSDMD， IL-1β， and cleaved Caspase-1/Caspase-1 were significantly increased （P<0.01）. Compared with those in the model group， SNCV and PWT were increased （P<0.01） in each administration group， and LC3Ⅱ/LC3Ⅰ， Beclin1， p-AMPK/AMPK， and p-ULK1/ULK1 were significantly increased （P<0.05， P<0.01）. p62， N-GSDMD/GSDMD， cleaved Caspase-1/Caspase-1， NLRP3， and IL-1β decreased （P<0.05， P<0.01）. Compared with the α-lipoic acid group， the Buyang Huanwutang group had significantly increased SNCV， PWT （P<0.05）， LC3Ⅱ/LC3Ⅰ， and p-ULK1/ULK1 （P<0.05） and significantly decreased NLRP3 and N-GSDMD/GSDMD （P<0.05）. ConclusionBuyang Huanwutang regulates mitophagy and inhibits pyroptosis through the AMPK/ULK1 pathway to prevent and treat DPN， and its therapeutic effect may be better than α-lipoic acid.