Acute liver injury (ALI) serves as a critical precursor and major etiological factor in the progression and ultimate manifestation of various hepatic disorders. The prevention and treatment of ALI is still a serious global challenge. Given the limited therapeutic options for ALI, exploring novel targeted therapeutic agents becomes imperative. The potential therapeutic efficacy of inhibiting RIPK2 is highlighted, as it may provide significant benefits by attenuating the MAPK pathway and NF-κB signaling. Herein, we propose a CMD-OPT model, a two-stage molecular optimization tool for the rapid discovery of RIPK2 inhibitors with optimal properties. Compound RP20, which targets the ATP binding site, demonstrated excellent kinase specificity, ideal oral pharmacokinetics, and superior therapeutic effects in a model of APAP-induced ALI, positioning RP20 as a promising preclinical candidate. This marks the first application of RIPK2 inhibitors in ALI treatment, opening a novel therapeutic pathway for clinical applications. These results highlight the efficacy of the CMD-OPT model in producing lead compounds from known active molecules, showcasing its significant potential in drug discovery.

Objective:To investigate the effect of etomidate combined with transversus abdominis plane block (TAPB) on serum inflammatory factors and immune function indexes in patients after total hysterectomy.Methods:The study included 86 patients who underwent transabdominal total hysterectomy from Jan. 2020 to Jan. 2023. They were divided into group A (44 cases) and group B (42 cases) according to the random number table method. Group A received general anesthesia (propofol for anesthesia maintenance) + TAPB anesthesia, and group B received general anesthesia (propofol combined with etomidate for anesthesia maintenance) + TAPB anesthesia. The changes of heart rate (HR) and mean arterial pressure (MAP) at different time points were observed in the two groups. The serum related factors [interleukin-6 (IL-6) , tumor necrosis factor-α (TNF-α) ] and immune function indexes (T lymphocyte subsets CD3 +, CD4 +, CD4 +/CD8 +) were compared between the two groups before anesthesia and 24 h after operation. The complications of the two groups after anesthesia were counted. Results:HR and MAP of the two groups were gradually increased at T1 and T2 compared with those at T0, and gradually decreased at T3 and T4 compared with those at T2. The serum levels of IL-6 and TNF-α in the two groups at 24 h after operation were higher than those before anesthesia. The levels of IL-6 and TNF-α in group B were (261.17±33.67) ng/L and (12.37±2.57) ng/L, lower than those in group A (287.89±45.71) ng/L and (16.46±3.78) ng/L ( P<0.05) . The levels of CD3 +, CD4 + and CD4 +/CD8 + in the two groups were lower than those before anesthesia. The levels of CD3 +, CD4 + and CD4 +/CD8 + in group B were (65.26±4.67) %, (27.83±2.59) % and (1.48±0.35) , higher than those in group A (62.17±3.85) %, (26.25±2.16) % and (1.32±0.21) ( P<0.05) . There was no significant difference in the total incidence of complications after anesthesia between the two groups (13.64% in group A and 7.21% in group B) ( P>0.05) . Conclusions:The application of etomidate combined with TAPB anesthesia in total abdominal hysterectomy can inhibit the inflammatory response caused by surgical trauma, maintain the stability of postoperative immune function,without increasing the impact on hemodynamics of patients, or the incidence of complications.

Objective:To improve the prognosis stratification, especially early mortality(EM), of elderly patients with newly diagnosed multiple myeloma(NDMM).Methods:In this retrospective study, univariate and multivariate Cox regression analysis were conducted to identify the independent prognostic factors associated with overall survival(OS)and the chi-square test and multivariate Logistic analysis were used to identify the prognostic factors associated with EM in 223 elderly patients(age≥65 years)with NDMM from three centers in the country.Results:Increased NT-pro-BNP(≥300 pg/ml), ECOG-PS≥2 and stage Ⅲ R-ISS were identified as three independent adverse prognostic factors of OS.The rates of EM3, EM6, EM12 and EM24 were 12.1%, 20.1%, 32.2% and 60%, respectively.The most common cause for EM6(particularly EM3)was disease-related complications resulting from ineligibility for treatment due to poor physical performance, severe organ dysfunction or treatment discontinuation due to treatment intolerance, while the most common cause for EM12(particularly EM24)was disease progression or relapse mainly as a result of inadequate treatment.R-ISS staging failed to predict EM, while decreased eGFR, ECOG-PS≥2, and increased NT-pro-BNP were able to estimate the risk of EM, with increased NT-pro-BNP as a common independent factor for EM12( P=0.03)and EM24( P=0.015). Conclusions:R-ISS staging, which primarily reflects MM biology, cannot predict EM.However, factors such as NT-pro-BNP, eGFR and ECOG-PS associated with frailty and impairment of organ functions can be used to estimate the risk of EM, among which NT-pro-BNP may be the most important independent factor for EM.Therefore, incorporation of these frailty-related biomarkers into R-ISS staging may be able to more precisely estimate the prognosis and particularly early death of elderly patients with NDMM.

AIM: To investigate the effect of an effective component total sterone (TSR) of Echinops latifolius Tausch, the main component of a Chinese patent medicine Cuiru Keli (national drug standard WS3-413 (Z-085)-2003 (Z), on lactation and its possible mechanism. METHODS: After mating between male and female SD rats, 60 female rats were randomly divided into normal control group, model group, TSR low-dose and high-dose groups and prolactin granule positive control group, with 12 female rats in each group and 8 newborn rats in each nest. In addition to the normal control group, the rats in each group were intraperitoneally injected with levodopa 2 mg/kg once a day for 7 days from the second day of delivery. The rats in the normal control group were given normal saline by gavage once a day for 14 days. From the beginning of self-sufficiency, the single lactation of the female rats was measured every day until the 14th day, and then the female rats in each group were killed. Pathological HE staining was used to observe the morphological changes of mammary gland tissue in each group. ELISA was used to detect the levels of serum prolactin (PRL) and 5-hydroxytryptamine (5-HT). Immunohistochemistry was used to detect the distribution of PRL in mammary gland tissue of each group. Furthermore, Real-time qPCR was used to detect the expression of milk protein, milk fat related genes β-casein, FAS, ACC and the expression of canonical Wnt signaling pathway related genes β-catenin, c-Myc, CCND1, SFRP4, DNMT1, MeCP2 in mammary gland of each group. RESULTS: Both low and high dose TSR could significantly increase the single lactation volume, improve the pathological morphology of mammary gland, and increase the serum levels of PRL and 5-HT. TSR increased the distribution of PRL and up-regulated the expression of milk protein, milk fat related genes β-casein, FAS, ACC and canonical Wnt signaling pathway related genes β-catenin, c-Myc, CCND1, SFRP4, DNMT1, MeCP2.CONCLUSION: TSR can significantly promote lactation in lactation deficient rats, and its mechanism may be related to promoting the release of PRL and 5-HT in serum, increasing the distribution of PRL in mammary gland, up-regulating the milk protein and milk fat related genes and activating the canonical Wnt signal.

Nasopharyngeal carcinoma (NPC) is a common malignant tumor in China. Radiotherapy is the first-line treatment. After appropriate radiotherapy, about 5%-15% patients experience recurrence. In view of the poor efficacy and high incidence of severe late toxicities associated with re-irradiation, salvage surgery by the transnasal endoscopic approach is recommended for recurrent NPC (rNPC). Compared with re-irradiation, endoscopic surgery can better prolong survival, improve the quality of life, and reduce complications and medical expenses of patients with rNPC. However, the complexity of the nasopharyngeal skull base enhances the difficulty and risk of surgery. Expanding the boundary of surgical resection remains a clinical challenge for otolaryngologists. In this regard, to help more advanced patients with rNPC, the surgical innovative system of NPC needs to be established by multi-disciplinary cooperation, involving skull base anatomy-based investigation, appropriate administration of the internal carotid artery (ICA), repair of skull base defect, and establishment of various types of endoscopic endonasal nasopharyngectomy.

Classlearning plays an important role in clinical study.The quality of problem design affects the efficiency of classroom teaching.However,there are many defectsIn teachers' problem design.According to the training objectives and the learning characteristics of clinical medicine,the article focuses on the angle of basic medical classroom.First of all,from the three aspects of knowledge,skills and comprehensive quality,this paper expounds the significance of the efficient problem design to achieve the training goal ofclinical specialty.Then,this paper studies the shortcomings in the current problem design.Finally,this paper puts forwardfeasible suggestion for improving the efficiency of problem design in clinical basic medical classroomfrom the following four aspects:the construction of reasonable knowledge structure,simulation of clinical diagnosis,critical thinking and questions from students to teachers.

Wearable devices are used in the new design of the maternal health care system to detect electrocardiogram and oxygen saturation signal while smart terminals are used to achieve assessments and input maternal clinical information. All the results combined with biochemical analysis from hospital are uploaded to cloud server by mobile Internet. Machine learning algorithms are used for data mining of all information of subjects. This system can achieve the assessment and care of maternal physical health as well as mental health. Moreover, the system can send the results and health guidance to smart terminals.
Algorithms ; Clothing ; Electrocardiography ; Equipment Design ; Female ; Humans ; Internet ; Machine Learning ; Maternal Health ; Monitoring, Ambulatory ; instrumentation ; Telemedicine ; instrumentation

Objective To evaluate the efficacy of dexmedetomidine mixed with ropivacaine for transversus abdominis plane (TAP) block combined with general anesthesia in the patients undergoing gynecological laparoscopy.Methods Ninety American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients, aged 20-50 yr, with body mass index of 18-24 kg/m2, scheduled for elective gynecological laparoscopic ovarian cyst resection under general anesthesia, were randomly divided into 3 groups (n =30 each) using a random number table: general anesthesia group (group G) , general anesthesia + ropivacaine for TAP block group (group G+R), and general anesthesia + dexanedetomidine mixed with ropivacaine for TAP block group (group G+DR).After the end of anesthesia induction, ultrasound-guided left-sided unilateral TAP block was performed in G+R and G+DR groups.In G+R and G+DR groups, 20 ml of 0.375％ ropivacaine and 20 ml of 0.375％ ropivacaine mixed with 1 μg/kg dexmedetomidine were injected, respectively.After induction of general anesthesia, the laryngeal mask airway (LMA) was inserted, and the patients were mechanically ventilated in the 3 groups.Anesthesia was maintenaned with iv infusion of remifentanil 0.2 μg · kg-1 · min-1 and propofol 4-8 mg · kg-1 · h-1.Narcotrend index was maintained at 37-46.Only group G received postoperative intravenous analgesia.The occurrence of TAP block-related adverse events was recorded.The emergence time, time for recovery of spontaneous breathing, time for removal of LMA, and Steward score at 5 min after removal of LMA were recorded.The occurrence of postoperative nausea and vomiting, and respiratory depression was recorded.Results Compared with G and G+R groups,the emergence time, time for recovery of spontaneous breathing, and time for removal of LMA were significantly shortened (P＜0.05 or 0.01) , and no significant change was found in Steward score in group G+DR (P＞0.05).There was no significant difference in the above parameters between group G and group G+R (P＞0.05).Compared with group G, the incidence of postoperative nausea and vomiting was significantly decreased in G+R and G+DR groups (P＜0.05).VAS score was maintained ≤ 3 after operation in the 3 groups.No TAP block-related adverse events were found in G+R and G+DR groups.Conclusion Dexmedetomidine mixed with ropivacaine provides faster recovery from anesthesia, and avoids postoperative hyperalgesia when used for TAP block combined with general anesthesia in the patients undergoing gynecological laparoscopy.

Objective To study the effectiveness of valsartan on the insulin resistance and high-sensitivity C-reactive protein(hs-CRP) of patients with essential hypertension.Methods One hundred and thirty patients with essential hypertension were randomly divided into two groups,the control group (n =65 cases) and the treatment group (n =65 cases).The patients in the control group were treated through amlodipine,while the patients in the treatment group were treated valsartan.They were all treated for six months.The insulin resistance(IR) and hs-CRP were compared.Results The systolic blood pressure and diastolic blood pressure were decreased after treatment in both groups (t =6.3706,6.4418,7.0519,7.2577,all P ＜ 0.01).There wasn't a significant difference between two groups (P ＞0.05).The IR and hs-CRP were decreased in both groups (t =6.3478,1.9977,4.0581,12.0722,all P ＜ 0.01).There was a significant difference between two groups (t =7.6049,4.6893,all P ＜ 0.05).Conclusion Valsartan can improve the insulin resistance and hs-CRP,which weren't dependent on lowing blood pressure.

Objective To optimize the formula ratio of matrix and the preparation process of Xuanshe Painkillers Cataplasm. Methods The optimal matrix prescription of Xuanshe Painkillers Cataplasm was optimized by uniform design,and the optimal preparation process was determined at the same time. The viscosity and the appearance of the Xuanshe Painkillers Cataplasm (film residue,uniformity,ductility,skin adhesive ability of the plaster)are used as indexes. Results The preparation process of Xuanshe Painkillers Cataplasm is good,and through the analysis of experimental data,the optimal ratio of the matrix is NP-700∶aluminum hydroxide ∶glycerol ∶0.1% tartrate solution=3∶0.3∶25∶5. Conclusion The Preparation process is good and the optimal matrix has moderate viscosity,no film residue,and with better uniformity,ductility and skin adhesive ability.