Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

Objective To explore the expression characteristics of BAIAP2L1 in cervical cancer (CC) and its regulatory role in tumor cell metastasis. Methods The correlation between BAIAP2L1 expression and clinical prognosis was analyzed by using a public database. GO pathway enrichment and clinicopathological correlation analyses were conducted by employing R language. The effect of BAIAP2L1 knockdown on CC cell proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) were further investigated through gene silencing approaches. Results BAIAP2L1 expression was significantly upregulated in CC tissues (P_adj <0.001) and it was identified as an independent risk factor for patient mortality (HR=2.808, P=0.03). Elevated BAIAP2L1 levels showed significant correlations with poor overall survival, advanced T/N stage, recurrence, and metastasis (all P<0.05). Functional enrichment analysis revealed its involvement in tumor metastasis-related pathways. The knockdown of BAIAP2L1 significantly attenuated CC cell proliferation, invasion, and migration and suppressed key EMT processes (all P<0.05). Conclusion BAIAP2L1 is overexpressed in CC tissues and associated with patient prognosis and metastasis. The targeted inhibition of BAIAP2L1 can effectively curb tumor progression.

OBJECTIVE To explore the effects of levosimendan on cardiac function， hemodynamics and prognosis of patients with septic shock complicated with myocardial depression， and evaluate the safety of levosimendan. METHODS Patients with septic shock complicated with myocardial depression who were admitted to the Department of Critical Care Medicine of Chongqing University Three Gorges Hospital from April 2021 to August 2023， underwent adequate fluid resuscitation， had a mean arterial pressure （MAP） ≥65 mmHg， and received pulse indicator continuous cardiac output （PiCCO） monitoring were enrolled. The patients were randomly divided into dobutamine group and levosimendan group according to a random number table， with 20 patients in each group. Both groups received intravenous infusion of Norepinephrine bitartrate injection at a dose of 0.1-2.0 μg/（kg·min）. On this basis， the dobutamine group additionally received intravenous infusion of Dobutamine hydrochloride injection at a dose of 5- 10 μg/（kg·min） for 3 to 7 days， while the levosimendan group additionally received intravenous infusion of Levosimendan injection at a dose of 0.1-0.2 μg/（kg·min） for 24 hours. Heart rate （HR） and hemodynamic parameters [systolic blood pressure， diastolic blood pressure， MAP， central venous pressure （CVP）]， PiCCO monitoring parameters [cardiac function index （CFI）， cardiac index （CI）， stroke volume index （SVI）， extravascular lung water index， global end-diastolic volume index， pulmonary vascular permeability index （PVPI）， global ejection fraction （GEF）， systemic vascular resistance index， left ventricular contractility index]， and prognosis indicators [death within 3 days after administration， mechanical ventilation time，intensive care unit （ICU） stay time， 28-day mortality rate] were compared between the two groups before treatment and at 24 and 72 hours after treatment. Adverse reactions were E-mail：recorded for both groups. RESULTS Compared with before treatment in the same group， CFI， CI and GEF at 24 hours after treatment， CI and GEF at 72 hours after treatment in the dobutamine group， as well as SVI at 24 hours after treatment and SVI and GEF at 72 hours after treatment in the levosimendan group were significantly increased； PVPI at 72 hours after treatment in the dobutamine group was significantly decreased （P＜0.05）. Compared with the dobutamine group during the same period， patients in the levosimendan group had significantly lower HR and significantly higher CVP at 24 hours after treatment （P＜0.05）. Within 3 days after administration， there were no deaths in either group； there were no statistically significant differences in mechanical ventilation time， ICU stay time， 28-day mortality rate， or the incidence of adverse reactions between the two groups （P＞0.05）. CONCLUSIONS For patients with septic shock complicated with myocardial depression who have undergone adequate fluid resuscitation and have a MAP of ≥65 mmHg， levosimendan is comparable to dobutamine in improving cardiac function and hemodynamic parameters， without affecting patients’ prognosis or increasing the risk of adverse reactions such as hypotension.

OBJECTIVE To improve the quality evaluation method of Platycodonis Radix, to study the differences in the quality of three-years-old Platycodonis Radix under different harvesting periods, and to determine the optimal harvesting period of Platycodonis Radix. METHODS The leachate, ash, moisture, refractive index and the content of six saponins were used as the quality evaluation indexes. The differences between the herbs of Platycodonis Radix at different harvesting periods were characterized with the help of mathematical and statistical methods. And link the entropy weight method, gray correlation analysis and TOPSIS method were combined to obtain the statistical analysis of the relevant indexes and the quality ranking information of the herbs in different harvesting periods. RESULTS There were significant differences between the quality evaluation indexes of three-years-old Platycodonis Radix at different harvesting periods. The added multi-indicator testing had improved the quality evaluation system of Platycodonis Radix and enhanced the "Drug properties-Effectiveness" linkage of the herbs. And the results of the comprehensive quality evaluation model showed that the herbs harvested around October 21 (Frost’s Descent) were ranked best in terms of comprehensive index. CONCLUSION In order to ensure the quality of Platycodonis Radix, the best harvesting period for three-years-old Platycodonis Radix is determined around the "Frost’s Descent" season, taking into account the characteristics of the herbs' appearance and the material basis of herbs.

Ferroptosis is closely associated with the progression of various diseases.There are a series of anti-ferroptosis systems in the cell,the main function of which is to eliminate lipid peroxides and inhibit the occurrence of ferropto-sis.Ubiquitination is a crucial type of post-translational protein modification which can influence the degradation,intracellular localization,or function of substrate proteins.Ubiquitination modification plays an important role in regulating key proteins in-volved in ferroptosis pathways,such as SLC7A11,GPX4,FSP1,iron metabolism-related proteins,and other critical proteins in ferroptosis pathways.This review aims to summarize the research progress on ubiquitination modification of these key proteins in ferroptosis pathways,thereby elucidating the specific role of ubiquitination in ferroptosis pathways.

Objective:To investigate the alterations in soft tissue morphology and thickness in the mid-face region of patients with cleft lip and palate (UCLP) secondary to maxillofacial deformity following Le Fort I osteotomy.Methods:A total of 22 patients (16 males and 6 females aged from 17 to 28 years with an average of 20 years) diagnosed with cleft lip and palate secondary to maxillofacial deformity were collected from the Wuhan University Hospital of Stomatology from July 2012 to August 2020. All patients underwent Le Fort I osteotomy. CBCT scans were obtained at T0 (3 days before surgery), T1 (7 days after surgery), and T2 (1 year after surgery). The Dolphin11.95 software and 3D Slicer software were utilized to measure and analyze the soft tissue near the mid-face osteotomy line. Differences in soft tissue thickness before and after surgery were compared.Results:Before and after the operation, the soft tissue thickness at P3, P5, P6, and P8 on the affected side was thicker than that on the healthy side, and the difference was statistically significant, with a P-value of <0.05. At P5, P6, P7, P8, and P9 below the osteotomy line at T2-T0, the degree of postoperative thinning on the affected side was more apparent than that on the healthy side, and there was statistical significance at P6 ( P<0.05). The postoperative soft tissue asymmetry in the Ck region was improved compared with the preoperative one. The preoperative average protruding of the affected side was 0.63 compared with the healthy side, and the postoperative value was 0.17. The preoperative and postoperative Mann-Whitney U tests showed significantly statistical difference. Conclusions:After Le Fort I osteotomy, the facial asymmetry of patients with unilateral cleft lip and palate secondary to maxillofacial deformity is improved. However, there is still a difference in the soft tissue thickness between the healthy side and the affected side, and the change in soft tissue thickness on the affected side is more significant than that on the healthy side.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling exert essential regulatory function in microbial-and onco-immunology through the induction of cytokines, primarily type I interferons. Recently, the aberrant and deranged signaling of the cGAS-STING axis is closely implicated in multiple sterile inflammatory diseases, including heart failure, myocardial infarction, cardiac hypertrophy, nonalcoholic fatty liver diseases, aortic aneurysm and dissection, obesity, etc. This is because of the massive loads of damage-associated molecular patterns (mitochondrial DNA, DNA in extracellular vesicles) liberated from recurrent injury to metabolic cellular organelles and tissues, which are sensed by the pathway. Also, the cGAS-STING pathway crosstalk with essential intracellular homeostasis processes like apoptosis, autophagy, and regulate cellular metabolism. Targeting derailed STING signaling has become necessary for chronic inflammatory diseases. Meanwhile, excessive type I interferons signaling impact on cardiovascular and metabolic health remain entirely elusive. In this review, we summarize the intimate connection between the cGAS-STING pathway and cardiovascular and metabolic disorders. We also discuss some potential small molecule inhibitors for the pathway. This review provides insight to stimulate interest in and support future research into understanding this signaling axis in cardiovascular and metabolic tissues and diseases.

Objective:To explore the efficacy of tracheotomy and nasal intubation in airways management in treatment of patients with respiratory failure caused by severe tetanus.Methods:A respective case series study was conducted to analyze the data of 92 patients with respiratory failure caused by severe tetanus admitted to Jiangxi Chest Hospital from January 2012 to December 2019. There were 60 males and 32 females, aged 23-81 years [(47.5±14.1)years]. Overall 43 patients underwent tracheotomy (tracheotomy group), and 49 patients underwent nasal intubation (nasal intubation group). The blood gas related indexes (PaO 2, PaCO 2), catheter retention time, incidence of complications such as airway bleeding, nasosinusitis, catheter blockage and ventilator-associated pneumonia (VAP), and clinical outcome were compared between the two groups. Results:After mechanical ventilation, the PaO 2 and PaCO 2 in both groups were significantly improved ( P<0.01), with no significant difference between groups ( P>0.05). Both groups were similar regarding the catheter indwelling time, catheter blockage, airway bleeding and nasosinusitis ( P>0.05). The incidences of VAP and catheter blockage after extubation in tracheotomy group [12%(5/43), 12%(5/43)] were significantly different from those in nasal intubation group [0%(0/49), 31%(15/49)] ( P<0.05). There were 3 deaths in each group, with the mortality rate of 7% (3/43) in tracheotomy group and of 6% (3/49) in nasal intubation group ( P>0.05). Both groups of live tetanus patients were cured. After 3-month follow-up, the tetanus was cured in the two groups. Conclusions:The tracheotomy and transnasal tracheal intubation are optional for severe tetanus patients with respiratory failure. The former has airway and tissue trauma, but it is convenient for mechanical ventilation management, especially indicated for patients with severe convulsions, angular arch reflexes, poor sedation, and continuous application of muscle relaxants. Nasal intubation is relatively non-invasive, simple and fast method, but the prevention and monitoring of VAP requires higher requirements.

Objective:To study the combined use of endoscopic balloon dilation with endoscopic biliary brushings in diagnosis of bile duct strictures.Methods:A prospective single center study was conducted at the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology. All patients with suspected malignant bile duct strictures shown on CT or MRI imaging from January 2018 to January 2020 were reviewed. All patients gave informed consent to the endascopic retrograde cholangiopancreatography procedures. Their clinical and follow-up data were analyzed. All patients underwent endoscopic balloon dilation of bile duct strictures. Before and after balloon dilation, biliary brush cytology was performed, and the results were used to classify the patients into the control group and the experimental group. Pathological examination of the brush cytology samples was carried out by a single chief pathologist. Presence of cancer cells or significant heterogeneous cells indicated a positive brush cytology test. Negative patients who still highly consider cholangiocarcinoma and agree to surgery and whose gross specimen is confirmed to be malignant after surgery should be considered as false negative by brush examination; it is difficult to judge that patients with cholangiocarcinoma have progress after 2 months of follow-up should be considered as false negative by brush examination. Any progression of disease indicated that the brush test was wrong and the test was again classified as false negative. Only when there was no progression of strictures was the possibility of a benign biliary stricture being considered. The advantage test (McNemar test) was used to analyze the difference between the two diagnostic methods.Results:Of 39 patients who were included in this study, there were 26 males and 13 females, with an age of (68.0 ± 5.2) years. Cholangiocarcinoma was diagnosed by histopathology, surgery or at 2 months follow-up in 35 patients. In the control group, 17 patients had a positive brush test (sensitivity rate was 48.6%, 17/35). In the experimental group, 26 patients had a positive brush test (sensitivity rate was 74.2%, 26/35). In addition, 2 patients in the control group had a positive brush test, while in the experimental group, a negative brush test. A total of 28 patients were positive in the two groups. The sensitivity rate of the brush test was 80.0% (28/35). There were significant differences between the two groups ( P<0.05). Conclusion:Endoscopic balloon dilation combined with endoscopic biliary brushings improved the sensitivity of pathological diagnosis of cholangiocarcinoma, and endoscopic biliary brushings before and after balloon dilation improved the sensitivity of diagnosis.