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 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.

Six patients with factor Ⅴ deficiency were admitted in Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2006 to December 2022. All 6 patients presented with symptoms of coagulation dysfunction, 4 patients had recurrent nose bleeding, gingival bleeding, skin ecchymosis as the main manifestations, 1 patient had lower abdominal pain and ovarian active bleeding, and 1 patient had heavy menstruation. The prothrombin time and activated partial thromboplastin time were significantly prolonged, the factor Ⅴ level was significantly lower than normal, and the thrombin time was basically normal in all patients. Four patients received non-surgical treatment and transfusion of fresh frozen plasma; the bleeding symptoms were significantly relieved during hospitalization, and no aggravation of bleeding symptoms was found during follow-up. One patient with active ovarian hemorrhage underwent emergency surgical suture to stop bleeding, and fresh frozen plasma and prothrombin complex were given perioperatively; and no more bleeding occurred during follow-up. One patients with excessive menstruation underwent curettage plus hysteroscopic endometrial ablation, and the amount of menstruation was significantly reduced. It is suggested that the bleeding symptoms of coagulation factor Ⅴ deficiency vary in severity, which can be effectively alleviated by infusion of the fresh frozen plasma in most cases.

Objective: To investigate the effect of dexmedetomidine on stress response and immune balance in patients with acute respiratory distress syndrome(ARDS) undergoing mechanical ventilation. Methods: From March 2016 to September 2018, 90 ARDS patients with mechanical ventilation in Chongqing Three Gorges Center Hospital were randomly divided into dexmedetomidine group(D group, 30 cases), propofol group(P group, 30 cases), midazolam group(M group, 30 cases) by random number table method.Another 30 healthy workers in our hospital were selected as normal control group(C group). In M, P and D groups, the sedative drugs were infused by micro-pump on the basis of analgesic treatment(fentanyl citrate). The heart rate(HR), mean arterial pressure(MAP), Murray score, acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) score, plasma norepinephrine(NS), plasma cortisol(Cor), and blood T lymphocyte subsets(CD₄⁺, CD₈⁺, CD₄⁺/CD₈⁺) were observed in all patients at T0(the beginning of sedation), T1 (6h after sedation), T2 (24h after sedation), T3(48h after sedation). The levels of NS and Cor in plasma and blood T lymphocyte subsets(CD₄⁺, CD₈⁺, CD₄⁺/CD₈⁺) in C group were measured at 8∶00 a. m.the next day. Results: The plasma NS and Cor at T0 in M, P and D group were higher than those in C group (all P<0.05), while the levels of CD₄⁺ were lower than those in C group(all P<0.05). Compared with T0, the plasma NS and Cor decreased at T3 in M, P and D group (all P<0.05). The plasma Cor at T3 in P group was lower than that in M group[(475.77±49.69)μg/L vs.(502.33±60.92)μg/L](t=-26.57, P<0.05). The plasma NS and Cor at T3 in D group were lower than those in M group[(20.64±4.70)ng/L vs.(25.29±4.03)ng/L, (442.83±66.59)μg/L vs.(502.33±60.92)μg/L](t=-4.51, -59.50, all P<0.05), and were lower than those of P group[(20.64±4.70)ng/L vs.(23.60±4.49)ng/L, (442.83±66.59)μg/L vs.(475.77±49.69)μg/L](t=-2.96, -32.93, all P<0.05). Compared with T0, the level of CD₄⁺ decreased at T1, T2 and T3(except T3 in D group) in M, P and D group (all P<0.05), and the level of CD₈⁺ decreased at T1, T2 and T3 in M and P group (all P<0.05), but those in D group at T1, T2 and T3 were not significantly decreased(all P>0.05). The levels of CD₈⁺ at T2 and T3 in P and D groups were higher than that of M group (all P<0.05). The level of CD₄⁺/CD₈⁺ at T3 in D group were higher than that in M and P group[(1.46±0.30) vs.(1.26±0.33), (1.46±0.30) vs.(1.32±0.34)](t=0.21, 0.15, all P<0.05). Conclusion Sedation with dexmedetomidine or propofol can alleviate stress response and improve immune function in ARDS patients undergoing mechanical ventilation, and dexmedetomidine is better than propofol.

Acute respiratory distress syndrome(ARDS) is a common critical syndrome with high morbidity and mortality.The treatments include respiratory support and drug therapy.In this paper, the latest clinical advances in the treatment of ARDS with glucocorticoids, statins, antioxidants, recombinant human activated protein C, sedatives and muscle relaxants, exogenous alveolar surfactants, mesenchymal stem cells, and vasodilators are reviewed.

Objective To analyze the gonadal hormone and seminal plasma of patients with abnormal semen liquefaction and investigate the influence mechanism in order to provide guidance for the diagnosis and treatment. Methods 152 men of childbearing age were divided into two groups according to the liquefaction time (cut?off point: 60 minutes). Routine semen parameters,gonadal hormone and seminal plasma were tested and compared between the above groups. T?test was applied to compare individual gland function (pH value,neutralα?glycosidase,fructopyranose,seminal plasma zinc and citric acid) and gonadal hormone (FSH,LH,PRL,T and E2). Logistic regression analysis was adopted to probe the influencing factors for abnormal semen liquefaction. Results Seminal pH value (7.47 ± 0.13 vs. 7.32 ± 0.18),citric acid(51.12 ± 12.95 vs. 83.11 ± 33.46)and FSH (4.40 ± 1.03 vs. 4.85 ± 1.50)levels were significant different between the two groups (P < 0.05),but the other indexes showed no significant difference. Correlation regression analysis showed that semen liquefaction capacity has correlative relationship with seminal plasma fructose (OR=2.644),citric acid (OR=0.922),serum T (OR=1.029) and E2,while no correlative relationship with other indexes. Conclusions Correlation between two glands (seminal vesicle and prostate) and balance in the two hormones (T and E2) influence the liquefaction time. Specific causes should be distinguished before diagnosis.

To study alkaloid constituents in Corydalis decumbens,thirteen compounds were isolated from 95％ ethanol extracts of Corydalis decumbens (Thunb) Pers.by silica gel,RP-C1s,Sephadex LH-20 column chromatographer,recry stallization,thin-layer chromatography and HPLC.Their structures were elucidated on the basis of spectral data combined with physiochemical properties as tetrahydropalmatine (1),oxyhydrastinine (2),doryanine (3),palmatine (4),bicuculline (5),canadine (6),tetrahydrocoptisine(7),corydaldine (8),epicorynoxidine (9),N-methylcorydaldine (10),(+)-corlumine (11),N-methyl-6,7-dimethoxyisoquinolone (12) and oxysanguinarine (13).Compounds 2,3,6,7,and 9-13 were isolated from this plant for the first time.In addition,compounds 2,3,and 9-13 were obtained firstly from this genus.Pharmacological experiments showed that tetrahydropalmatine (1) might have analgesic or sedative effects,and the bicuculline (5) could probably induce epilepsy.

Objective To compare the effect of kidney-tonifying blood-activating recipe (KBR) and Aescuven Forte Tablets ( AFT) in improving the sperm quality of varicocele-induced male sterility, thus to optimize the therapeutic therapy for varicocele-induced male sterility. Methods A total of 102 varicocele-induced male sterility with abnormal sperm parameters after conservative treatment were randomized into KBR group (N=53) and AFT group ( N=49) . KBR group was given KBR plus natural vitamin E and AFT group was given AFT plus natural vitamin E, and the treatment lasted for 8 continuous weeks. Before and after treatment, the quality of seminal fluid was analyzed, sperm quantization parameters such as total number of sperm (TNS) , total number of progressive motility sperm ( TNPS) , total number of normal form sperm ( TNNS) and total number of nor mal form and progressive motility sperm ( TNNPS) were observed, and the improvement rate of sperm quantization parameter was compared. Results (1) Before treatment, the differences of TNS, TNPS, TNNS and TNNPS were insignificant between the two groups ( P>0.05) . After treatment, TNNS was not improved in AFT group ( P>0.05) , but TNS, TNPS, TNNPS were much improved in both groups ( P<0.01 compared with those before treatment) . The improvement of KBR group was superior to that of AFT group ( P<0.05) . ( 2) The improvement rate for TNS, TNPS, TNNS, TNNPS was 90.57%, 79.25%, 67.92%, 77.36%in KBR group, and was 75.51%, 73.47%, 28.57%, 61.22% in AFT group respectively. The improvement rate for TNS and TNNS in KBR group was superior to that in AFT group ( P<0.05 or P<0.01) . Conclusion Varicocele-induced male sterility patients usually have the syndrome of kidney deficiency and blood stasis, so KBR, which has the function of tonifying kidney and activating blood, has synergistic action on the effect of AFT in improving sperm quality of varicocele-induced male sterility patients.

Objective: To observe the clinical efficacy of acupoint injection at Neiguan (PC 6) plus acupuncture in treating insomnia due to heart-kidney disharmony.
Methods: A hundred patients with insomnia due to heart-kidney disharmony were randomized into an observation group and a control group. Fifty-three cases in the observation group were intervened by acupoint injection at Neiguan (PC 6) plus acupuncture; while 54 cases in the control group were intervened by acupuncture alone. The Pittsburgh sleep quality index (PSQI) was evaluated before and after intervention, and the therapeutic efficacies of the two groups were compared.
Results: Acupoint injection at Neiguan (PC 6) plus acupuncture produced significantly higher efficacies in improving sleep quality, shortening sleep latency, and enhancing sleep efficiency than acupuncture alone (P<0.05).
Conclusion: The two groups both can improve the condition of insomnia; acupoint injection at Neiguan (PC 6) has significant advantages, manifested by a higher therapeutic efficacy for insomnia due to heart-kidney disharmony, higher safety evaluation, efficiency, and less adverse events, thus proper for clinical application.