Severe pneumonia is one of the most common and critical respiratory diseases in clinical practice. It is characterized by rapid progression， difficult treatment， high mortality， and many complications， posing a significant threat to the life and health of patients. The pathogenesis of severe pneumonia is highly complex， and studies have shown that its occurrence and development are closely related to multiple signaling pathways. Currently， the treatment of severe pneumonia mainly focuses on anti-infection， mechanical ventilation， and glucocorticoids， but clinical outcomes are often not ideal. Therefore， finding safe and effective alternative therapies is particularly important. In recent years， with the deepening of research into traditional Chinese medicine （TCM）， it has gained widespread attention in the treatment of severe pneumonia. This paper reviewed the relationship between severe pneumonia and relevant signaling pathways in recent years and how TCM regulated these pathways in the treatment of severe pneumonia. It was found that TCM could regulate the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB）， Janus kinase （JAK）/signal transducer and activator of transcription （STAT）， phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR）， NOD-like receptor protein 3 （NLRP3）， and nuclear factor E₂-related factor 2 （Nrf2） signaling pathways， playing a role in reducing the inflammatory response， inhibiting cell apoptosis and pyroptosis， improving oxidative stress， and other effects in the treatment of severe pneumonia. Among these pathways， it was found that all of them regulated inflammation to treat severe pneumonia. Therefore， reducing inflammation is the core mechanism by which Chinese medicine treats severe pneumonia. This review provides direction for the clinical treatment of severe pneumonia and offers a scientific basis for the research and development of new drugs.

Ulcerative colitis （UC）， which is characterized by a complex and multifactorial etiology， remains one of the challenging disorders in the international field of digestive system diseases. In recent years， rectal administration preparations have made rapid progress in UC therapeutic applications. This study systematically reviews the dosage forms， mechanisms of action， and clinical applications of rectally-administered preparations for the treatment of UC. It is found that suppositories are the most commonly used dosage forms for rectal administration. The newer suppositories have the advantages of high bioavailability and good stability. Enemas can retain the drug in the intestine as much as possible to achieve the effects of diluting intestinal toxins， cleansing the bowel， and reducing inflammation. Gels can achieve a drug-sustained-release effect and effectively improve intestinal mucosal damage. The mechanism of action of this type of preparation is mainly to inhibit inflammatory cell infiltration， regulate intestinal microbial homeostasis， and increase the expression of tight-junction proteins， so as to play anti-inflammatory， regulate the intestinal bacterial flora， repair the intestinal mucosa， and other efficacies. The diversity of rectal administration forms provides a wide range of choices for the clinical treatment of UC， such as Mesalazine suppositories， Lianshao enemas， and temperature- sensitive gels loaded with drugs for UC.

OBJECTIVE To investigate the efficacy and safety of ropivacaine combined with oxycodone for the analgesia of iliac fascia nerve block in patients undergoing hip replacement. METHODS Sixty-six patients who underwent hip replacement at the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture from October 2023 to April 2024 were selected and randomly divided into observation group and control group， with 33 cases in each group. Before induction of anesthesia， ultrasound-guided iliac fascial nerve block was performed. Patients in the observation group were treated with 0.33% ropivacaine+0.1 mg/kg oxycodone injection mixture 30 mL， and patients in the control group were treated with 0.33% ropivacaine injection 30 mL. The time of first postoperative rescue analgesia， 24 h postoperative analgesic drug consumption， sensory block and motor block effective and maintenance time， satisfaction degree， numerical rating scale （NRS） pain score， Ramsay sedation score， muscle strength score， heart rate （HR）， mean arterial pressure （MAP）， oxygen saturation（SpO2）， sleep score， anxiety score， and the occurrence of adverse reactions in the two groups were all recorded. RESULTS Compared with the control group， the first rescue analgesia time after operation was significantly prolonged in the observation group， and 24 h postoperative analgesic drug consumption after operation decreased； the effective time of sensory block was significantly shortened， and the maintenance time of sensory block was significantly prolonged， and the satisfaction score was higher； the NRS pain score after iliac fascia nerve block was lower， HR and MAP were lower， and the anxiety score and sleep score 24 and 48 h after operation were lower （P＜0.05）. In terms of safety， patients in both groups had adverse reactions after operation， such as hypertension， nausea， vomiting， and dizziness， but there was no significant difference in the incidence of adverse reactions between the two groups （P＞0.05）. CONCLUSIONS Oxycodone combined with ropivacaine shows good efficacy and safety for iliac fascial nerve block analgesia in patients undergoing hip replacement， can significantly prolong the analgesic time of ropivacaine， reduce postoperative analgesic drug consumption， improve the sleep quality of patients， and promote the rapid recovery of patients.

With the main pathological features of glomerulosclerosis and interstitial fibrosis， renal fibrosis is a key pathological process causing chronic kidney disease to progress to end-stage disease. As a cellular autophagic process， mitochondrial autophagy plays a crucial role in maintaining mitochondrial mass and functional stability. Mitochondrial dysfunction is considered to be one of the key factors driving the progression of fibrosis. Phosphatase and tension protein homologue （PTEN） induce various signalling pathways such as putative kinase 1/parkin， Nip3-like protein X/Bcl-2 interacting protein 3， and FUN14 structural domain-containing protein 1 to activate mitochondrial autophagy to participate in the regulation of fibrogenic factors， amelioration of oxidative stress， and inhibition of inflammatory response and apoptosis， which in turn effectively slows down the progression of renal fibrosis. Studies have shown that traditional Chinese medicine monomers and compound preparations， including phenolics， terpenoids， ketones， and alkaloids， can regulate mitochondrial autophagy-related signalling pathways and achieve significant clinical efficacy in intervening in the progression of renal fibrosis for the treatment of chronic kidney disease. This paper summarized the mechanism of mitochondrial autophagy and the research progress of traditional Chinese medicine intervention in renal fibrosis to provide new ideas for the study of the mechanism of traditional Chinese medicine in treating renal fibrosis.

With the main pathological features of glomerulosclerosis and interstitial fibrosis， renal fibrosis is a key pathological process causing chronic kidney disease to progress to end-stage disease. As a cellular autophagic process， mitochondrial autophagy plays a crucial role in maintaining mitochondrial mass and functional stability. Mitochondrial dysfunction is considered to be one of the key factors driving the progression of fibrosis. Phosphatase and tension protein homologue （PTEN） induce various signalling pathways such as putative kinase 1/parkin， Nip3-like protein X/Bcl-2 interacting protein 3， and FUN14 structural domain-containing protein 1 to activate mitochondrial autophagy to participate in the regulation of fibrogenic factors， amelioration of oxidative stress， and inhibition of inflammatory response and apoptosis， which in turn effectively slows down the progression of renal fibrosis. Studies have shown that traditional Chinese medicine monomers and compound preparations， including phenolics， terpenoids， ketones， and alkaloids， can regulate mitochondrial autophagy-related signalling pathways and achieve significant clinical efficacy in intervening in the progression of renal fibrosis for the treatment of chronic kidney disease. This paper summarized the mechanism of mitochondrial autophagy and the research progress of traditional Chinese medicine intervention in renal fibrosis to provide new ideas for the study of the mechanism of traditional Chinese medicine in treating renal fibrosis.

OBJECTIVE To investigate the antidepressant mechanism of Shugan hewei tang （SGHWT） based on the metabolomics of prefrontal cortex （PFC）-nucleus accumbens （NAc）-ventral tegmental area （VTA） neural circuit. METHODS Male SD rats were randomly divided into blank group， model group， SGHWT low-， medium- and high-dose groups [3.67， 7.34， 14.68 g/（kg·d）， by raw material]， and fluoxetine group [1.58 mg/（kg·d）， positive control]， with 12 rats in each group. Except for the blank group， the depression model was established by chronic unpredictable mild stress combined with individual cage housing in the remaining groups， and the corresponding drug solution or normal saline was administered via gavage during modeling， once a day， for 6 consecutive weeks. After the last administration， the body weight， sucrose preference rate， total moving distance， frequency into the center and immobility time of rats in each group were detected. Samples of PFC， NAc and VTA areas of rats in the blank group， model group， SGHWT medium-dose group and fluoxetine positive control groups were collected，and their histomorphological features were observed， and non-targeted metabolomics analysis （except for fluoxetine group）were performed and validated. RESULTS Compared with model group， the cytolysis， structural damage and other pathological damages in three brain regions of rats were significantly alleviated in each drug group， while their body weight， sucrose preference rate， total moving distance and frequency into the center were all significantly higher or longer （P＜0.05）， and immobility time was significantly shorter （P＜0.05）. The results of non-targeted metabolomics showed that a total of 78 endogenous differential metabolites were identified， with 40， 35 and 24 in the PFC， NAc and VTA regions respectively， mainly involved in amino acid， lipid and sphingolipid metabolism. The results of metabolic pathway enrichment analysis showed that SGHWT affected the neural circuits of depressed rats by regulating sphingolipid metabolism， alanine， aspartic acid and glutamic acid metabolism， saturated fatty acid biosynthesis， among which alanine， aspartic acid and glutamic acid metabolism was predominantly involved. Validation experiments showed that SGHWT significantly increased the phosphorylation levels of protein kinase B （Akt） and mammalian target of rapamycin （mTOR）， and decreased the protein expression of N-methyl-D-aspartic acid receptor 1 （NMDAR1） in the NAc region of rats. CONCLUSIONS SGHWT significantly improves the depression-like behavior and attenuates pathological damage of PFC-NAc-VTA neural circuit of model rats， the mechanism of which is associated with inhibiting NMDAR1 expression and activating the Akt/mTOR signaling pathway.

To investigate the genetic relatedness between carbapenem-resistant Klebsiella pneumoniae(CRKP) strains isolated from intestinal colonization and subsequent bloodstream infections.

OBJECTIVE To evaluate the cost-effectiveness of tafolecimab in patients with hypercholesterolemia， and provide support for optimizing management strategies for hypercholesterolemia and healthcare resource allocation. METHODS From the perspective of the Chinese healthcare system， an 11-state mutually exclusive Markov cohort model was developed to simulate disease progression and prognosis in the target population. The model cycle was set to one year， with a 30-year time horizon. Transition probabilities between health states were derived from the CREDIT series of clinical trials， while health utility values and medical cost parameters were sourced from the statistical yearbook and published literature. Quality-adjusted life years （QALYs） were used as the measure of health outcomes. Cost-effectiveness analysis was employed to calculate the incremental cost- effectiveness ratio （ICER） for three dosing regimens of tafolecimab [150 mg every 2 weeks （q2w）， 450 mg every 4 weeks （q4w）， and 600 mg every 6 weeks （q6w）] in combination with statins compared with control therapy （statins）. Using 1-3 times the per capita gross domestic product （GDP） of China in 2024 as willingness-to-pay threshold（WTP）， with a discount rate of 5%. Model robustness was assessed through one-way sensitivity analysis， probabilistic sensitivity analysis， and scenario analysis. RESULTS The 150 mg q2w regimen of tafolecimab yielded an ICER of 235 827.73 yuan/QALY， which was below the WTP （287 100 yuan/ QALY）， indicating that the regimen was cost-effective. In contrast， the ICERs for the 450 mg q4w and 600 mg q6w regimens were 329 498.24 and 318 630.51 yuan/QALY， respec-tively， both exceeding the WTP and thus not cost-effective.One-way sensitivity analysis identified the discount rate as a key influencing factor. Probabilistic sensitivity analysis showed that under the WTP set in this study， the probabilities of cost-effectiveness for the 450 mg q4w and 600 mg q6w regimens were 15.3% and 22.4%， respectively， while the 150 mg q2w regimen had an 85.2% probability of being cost-effective. The situational analysis revealed that， over a simulated time horizon of 5 to 30 years， the ICER of tafolecimab was progressively reduced compared with the control regimen. When the price of tafolecimab was lowered by more than 20%， all three dosing regimens were demonstrated to be cost-effective.CONCLUSIONS Under the current Chinese healthcare system， compared with statin monotherapy， tafolecimab （150 mg q2w） combination improves health outcomes in patients with hypercholesterolemia， and is cost-effective given the current WTP.

ObjectiveTo explore the protective effect and mechanism of Yangxin Dingji capsules on isoproterenol （ISO）-induced ventricular arrhythmia in SD rat cardiomyocytes based on the transforming growth factor-β activated kinase 1 （TAK1）-mitogen-activated protein kinase kinase 3 （MKK3）-p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway. MethodFifty male SPF-grade SD rats were randomly divided into a normal group， a model group， a propranolol group， a low-dose Chinese medicine group， and a high-dose Chinese medicine group. The ventricular arrhythmia model was constructed using the ISO "6+1" method. The propranolol group received propranolol at 0.015 g·kg^-1·d^-1. The Chinese medicine groups received Yangxin Dingji capsules at doses of 0.5、 2 g·kg^-1·d^-1， respectively. The normal and model groups were given an equal volume of 0.9% NaCl solution. Electrocardiogram （ECG） changes in SD rats were recorded using the BL-420F biological function experimental system. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in the heart. Serum levels of cardiac troponin I （cTnI）， creatine kinase-MB （CK-MB）， interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and transforming growth factor-β₁ （TGF-β₁） were measured using enzyme-linked immunosorbent assay （ELISA）. The mRNA expression of IL-1β and TNF-α was assessed using real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. Reactive oxygen species （ROS） expression was detected using immunofluorescence. Protein expression levels of TAK1， phosphorylated TAK1 （p-TAK1）， MKK3， phosphorylated MKK3 （p-MKK3）， p38 MAPK， phosphorylated p38 MAPK （p-p38 MAPK）， nuclear factor-κB （NF-κB）， phosphorylated NF-κB （p-NF-κB）， IL-1β， and TNF-α were measured using Western blot or immunohistochemistry. ResultCompared with normal group， the model group showed significant ventricular arrhythmia in ECG， with an increased arrhythmia score （P<0.01）. Pathological damage to myocardial tissue was evident， and serum levels of cTnI， CK-MB， IL-1β， TNF-α， and TGF-β₁ were elevated （P<0.01）. The mRNA and protein expression of IL-1β and TNF-α in myocardial tissue was also increased （P<0.01）. ROS level and protein expression of p-TAK1， p-MKK3， p-p38 MAPK， and p-NF-κB were elevated in myocardial tissue （P<0.01）. In the propranolol and Chinese medicine groups， the incidence of sustained ventricular tachycardia （SVT） and arrhythmia scores were significantly reduced compared to model group （P<0.05， P<0.01）. Pathological damage to cardiomyocytes was alleviated， and levels of myocardial injury markers and inflammatory factors in serum and myocardial tissue were decreased. The ROS level in myocardial tissue was also reduced （P<0.01）， with a noticeable reduction in related molecules in the p38 MAPK pathway （P<0.05， P<0.01）. ConclusionThe expression of p38 MAPK pathway molecules was up-regulated in myocardial tissue of ISO-induced ventricular arrhythmia rats. Yangxin Dingji capsules may inhibit cardiac inflammation damage by regulating the expression of related molecules in the p38 MAPK pathway， thereby exerting a protective effect on myocardial cells， with TAK1 being a potential target.

Objective To analyze the influencing factors of survival of patients with airway stenosis requiring clinical interventions after lung transplantation. Methods Clinical data of 66 patients with airway stenosis requiring clinical interventions after lung transplantation were retrospectively analyzed. Univariate and multivariate Cox’s regression models were adopted to analyze the influencing factors of survival of all patients with airway stenosis and those with early airway stenosis. Kaplan-Meier method was used to calculate the overall survival and delineate the survival curve. Results For 66 patients with airway stenosis, the median airway stenosis-free time was 72 (52,102) d, 27% (18/66) for central airway stenosis and 73% (48/66) for distal airway stenosis. Postoperative mechanical ventilation time [hazard ratio (HR) 1.037, 95% confidence interval (CI) 1.005-1.070, P=0.024] and type of surgery (HR 0.400, 95%CI 0.177-0.903, P=0.027) were correlated with the survival of patients with airway stenosis after lung transplantation. The longer the postoperative mechanical ventilation time, the higher the risk of mortality of the recipients. The overall survival of airway stenosis recipients undergoing bilateral lung transplantation was better than that of their counterparts after single lung transplantation. Subgroup analysis showed that grade 3 primary graft dysfunction (PGD) (HR 4.577, 95%CI 1.439-14.555, P=0.010) and immunosuppressive drugs (HR 0.079, 95%CI 0.022-0.287, P<0.001) were associated with the survival of patients with early airway stenosis after lung transplantation. The overall survival of patients with early airway stenosis after lung transplantation without grade 3 PGD was better compared with that of those with grade 3 PGD. The overall survival of patients with early airway stenosis after lung transplantation treated with tacrolimus was superior to that of their counterparts treated with cyclosporine. Conclusions Long postoperative mechanical ventilation time, single lung transplantation, grade 3 PGD and use of cyclosporine may affect the survival of patients with airway stenosis after lung transplantation.