ObjectiveTo investigate the mechanisms of Runmu Dihuang decoction （RMDHD） in treating perimenopausal dry eye with liver-kidney Yin deficiency syndrome based on the silent information regulator 3 （SIRT3）/hypoxia-inducible factor-1α （HIF-1α）/nuclear factor-κB （NF-κB） signaling pathway. MethodsSixty female Sprague-Dawley rats were randomly divided into six groups （n=10 per group）： Sham operation group， model group， sodium hyaluronate eye drop group， and low-， medium-， and high-dose RMDHD groups （5.625， 11.25， 22.50 g·kg^-1）. Except for the sham operation group， all rats underwent bilateral ovariectomy and were administered 0.1% benzalkonium chloride eye drops combined with long-term chronic irritation to establish a perimenopausal dry eye model with liver-kidney Yin deficiency syndrome. Drug administration began in the 11th week after modeling and continued for 21 days. General conditions， screen-grip test scores， tear secretion volume， tear film breakup time （TFBUT）， and corneal fluorescein staining were recorded. Serum levels of reactive oxygen species （ROS）， follicle-stimulating hormone （FSH）， estradiol （E₂）， and progesterone （PROG） were measured by enzyme-linked immunosorbent assay （ELISA）. Pathological changes in the lacrimal glands， corneas， and uteri were observed using hematoxylin-eosin （HE） staining. Protein expression levels of SIRT3， HIF-1α， phosphorylated NF-κB p65 （p-NF-κB p65）， and total NF-κB p65 in the lacrimal glands were detected by Western blot. The expression of inflammatory cytokines interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in the lacrimal glands was assessed by immunohistochemistry （IHC）. ResultsAfter model establishment， no significant differences were observed among the groups except the sham operation group. Compared with the sham operation group， the other groups exhibited slowed movement， dull responses， increased irritability， reduced body weight， elevated rectal temperature， decreased screen-grip test scores， reduced tear secretion， and significantly shortened TFBUT （P<0.05）. After treatment， compared with the model group， the sodium hyaluronate eye drop group and all RMDHD groups showed improved general conditions， significantly increased tear secretion （P<0.05）， prolonged TFBUT （P<0.05）， and elevated screen-grip test scores （P<0.05）. Serum ROS and FSH levels were significantly decreased， while E₂ and PROG levels were significantly increased （P<0.05）. Pathological damage to the cornea， lacrimal glands， and uterus was ameliorated. In addition， protein expression levels of SIRT3 and HIF-1α in the lacrimal glands were significantly upregulated （P<0.05）， whereas the expression of p-NF-κB p65， IL-1β， and TNF-α was significantly downregulated （P<0.05）. ConclusionRMDHD increases tear secretion and TFBUT， improves lacrimal gland and corneal injury， and alleviates dry eye symptoms in a perimenopausal dry eye rat model with liver-kidney Yin deficiency syndrome. The underlying mechanism may be related to regulation of the SIRT3/HIF-1α/NF-κB signaling pathway， inhibition of oxidative stress and inflammatory responses， and reduction of ocular surface tissue damage.

Objectives: . The necessity to develop a method for prognostication and to identify novel biomarkers for personalized medicine in patients with head and neck squamous cell carcinoma (HNSCC) cannot be overstated. Recently, pathomics, which relies on quantitative analysis of medical imaging, has come to the forefront. CXCL8, an essential inflammatory cytokine, has been shown to correlate with overall survival (OS). This study examined the relationship between CXCL8 mRNA expression and pathomics features and aimed to explore the biological underpinnings of CXCL8. Methods: . Clinical information and transcripts per million mRNA sequencing data were obtained from The Cancer Genome Atlas (TCGA)-HNSCC dataset. We identified correlations between CXCL8 mRNA expression and patient survival rates using a Kaplan-Meier survival curve. A retrospective analysis of 313 samples diagnosed with HNSCC in the TCGA database was conducted. Pathomics features were extracted from hematoxylin and eosin–stained images, and then the minimum redundancy maximum relevance, with recursive feature elimination (mRMR-RFE) method was applied, followed by screening with the logistic regression algorithm. Results: . Kaplan-Meier curves indicated that high expression of CXCL8 was significantly associated with decreased OS. The logistic regression pathomics model incorporated 16 radiomics features identified by the mRMR-RFE method in the training set and demonstrated strong performance in the testing set. Calibration plots showed that the probability of high gene expression predicted by the pathomics model was in good agreement with actual observations, suggesting the model’s high clinical applicability. Conclusion . The pathomics model of CXCL8 mRNA expression serves as an effective tool for predicting prognosis in patients with HNSCC and can aid in clinical decision-making. Elevated levels of CXCL8 expression may lead to reduced DNA damage and are associated with a pro-inflammatory tumor microenvironment, offering a potential therapeutic target.

OBJECTIVE To evaluate the efficacy of immune checkpoint inhibitors （ICIs） in the treatment of non-small cell lung cancer （NSCLC） with different KRAS genotypes. METHODS Retrieved from PubMed， the Cochrane Library， Web of Science， Embase， CNKI， Wanfang data and VIP， randomized controlled trials （RCTs） about ICIs alone， combined use of various ICIs or ICIs combined with traditional chemotherapy （trial group） versus traditional chemotherapy （control group） for NSCLC were collected from the inception of the databases to April 1， 2023. After screening literature， extracting data and evaluating quality， meta-analysis， sensitivity analysis and publication bias analysis were conducted by using RevMan 5.4 software. RESULTS A total of 7 RCTs involving 5 980 patients were included. The results of the meta-analysis showed that overall survival （OS） [HR＝ 0.79， 95%CI （0.72， 0.87）， P＜0.000 01] and progression-free survival （PFS） [HR＝0.63， 95%CI （0.50， 0.80）， P＝0.000 2] of trial group were significantly longer than those of control group； furthermore， the OS of KRAS mutant type [HR＝0.63， 95%CI （0.53， 0.75）， P＜0.000 01] and KRAS wild type [HR＝0.87， 95%CI （0.78， 0.98）， P＝0.02]， PFS of KRAS mutant type [HR＝ 0.58， 95%CI （0.43， 0.78）， P＝0.000 3] and KRAS wild type [HR＝0.68， 95%CI （0.47， 0.99）， P＝0.04] in the trial group were all significantly longer than in the control group. Subgroup analysis by different treatment regimens showed that the OS of KRAS mutant type patients receiving first- and second-line treatment regimens， using ICIs alone and those receiving ICIs combined with traditional chemotherapy as well as PFS of KRAS mutant type and wild type patients receiving first-line treatment regimens in the trial group were all significantly longer than in the control group （P＜0.05）. Sensitivity analysis results indicated that the findings of this study were robust. Publication bias results showed that the possibility of publication bias in this study was small. CONCLUSIONS ICIs show significant efficacy in NSCLC patients， and NSCLC patients benefit equally regardless of whether KRAS mutations occur.

OBJECTIVE To systematically evaluate the efficacy and safety of immune checkpoint inhibitors （ICIs） in the treatment of metastatic colorectal cancer （mCRC）， so as to provide evidence-based reference for clinical practice. METHODS PubMed， the Cochrane Library， Web of Science， Embase， CNKI， Wanfang and VIP databases were searched to collect randomized controlled trials （RCT） of ICIs （trial group） versus traditional chemotherapy or optimal supportive treatment （control group） in the treatment of mCRC from the establishment of the database to June 1， 2022. After literature screening and data extraction， Cochrane Systematic Review Manual 5.1.0 was used to evaluate the quality of the included literature， and RevMan 5.4 software was used for meta-analysis and sensitivity analysis. RESULTS A total of 4 RCTs were included， involving 833 patients. Meta-analysis showed that the overall survival （OS） [HR＝0.77， 95%CI （0.64， 0.94）， P＝0.01] and progression-free survival （PFS） [HR＝0.67， 95%CI （0.57， 0.79）， P＜0.000 01] were significantly higher in trial group than control group； the difference was not statistically significant when comparing the incidence of grade 3 and above adverse events in the two groups [RR＝1.22， 95%CI （0.77， 1.94）， P＝0.39]. Subgroup analysis by mutation pattern showed that patients with mismatch repair proficiency and low levels of microsatellite instability （pMMR-MSS） mCRC patients in trial group had significantly higher PFS than control group （P＜0.05）. The results of sensitivity analysis showed that the results were robust. CONCLUSIONS Compared with traditional chemotherapy or optimal supportive treatment， ICIs can prolong the OS and PFS of mCRC patients， and maybe has more advantages in pMMR-MSS mCRC patients； the safety of ICIs is equivalent to that of traditional chemotherapy or optimal supportive treatment.

The morbidity and mortality of gastric cancer are high, while the overall therapeutic effect is poor without satisfactory. Clinical obstacles, such as low early-diagnosis rate, tumor heterogeneity, lack of accurate classification and precise treatment, therapeutic resistance, recurrence and metastasis, are the key point issues to the lower efficacy in treatment of gastric cancer. In order to solve these clinical problems, it is necessary to devote more energy to the basic research of gastric cancer, including tumor genomics; gene editing; tumor microenvironment; inflammation, aging and tumor; cell differentiation disorders; autophagy and cell death; metabolic disorders; immunotherapy and drug development. This paper will summarize the clinical obstacles in the treatment of gastric cancer, and describe the directions of basic research on these clinical problems in future, so as to provide notions for the translational research of gastric cancer.

Objective:For severe skin defects which are deep to dermis, engineered skin with epidermis and dermis (bilayered) is required. Based on the success of engineering epidermis with GT/PCL electrospun membranes, our study was to investigate whether this membrane could be also used for engineering bilayered skin graft.Methods:From 2013 to 2019, we first prepared three GT/PCL electrospun membranes with different proportion (70∶30; 50∶50; 30∶70) in our laboratory; the biocompatibility of the membrane was evaluated in vitro by seeding fibroblasts or keratinocytes on the membranes. Then the outcome of GT/PCL membranes repairing skin defects in the nude mouse was investigated.Results:Cell attachment and proliferation were significantly improved with increase of gelatin. Histological analyses showed that bilayered skin engineered with GT/PCL (70∶30) group could form relatively better structure after 3 weeks of cultivation in vitro. Further in vivo transplantation studies revealed that scaffolds were not degraded in all three groups, indicating that these materials were not suitable for engineering bilayered skin although they had good biocompatibility.Conclusions:The higher gelatin membranes possess better biocompatibility. Further in vivo transplantation studies reveal that bilayered skin engineered with GT/PCL membranes is able to repair skin defects in the nude mouse.

Bruton tyrosine kinase (BTK) is a key mediator of B-cell receptor signalling cascade and an effective target for treating mantle cell lymphoma (MCL). BTK inhibitors play a critical role in the treatment of MCL. Here we introduced the mechanism of action of BTKI in the treatment of MCL. Though generally well prescribed, Ibrutinib, as the first BTKI, still has limitations of toxicity and resistance. New BTK inhibitors, such as zanubrutinib, acalabrutinib and orelabrutinib, are designed to improve on the safety and efficacy as first-generation BTK inhibitors. Comparing the similarities and differences of the two generations of BTKI in structure and function provides a basis for better clinical application of BTKI. On November 15, 2019, FDA approved zanubrutinib for marketing for patients with adult mantle cell lymphoma. Compared with Ibrutinib, zanubrutinib was found with higher target selectivity, longer-lasting inhibition, fewer adverse reactions, and better patient benefit. Zanubrutinib provides a viable treatment option for patients with r/r MCL. At the same time, it is also actively carrying out clinical researches on the treatment of other B-cell lymphomas. It is a very promising targeted drug.

OBJECTIVE： To evaluate the medication of elderly inpatients receiving multiple medication， to evaluate the effects of pharmaceutical care provided by clinical pharmacists， and to provide reference for clinical drug use of elderly patients. METHODS： The elderly inpatients receiving multiple medication were selected from Beijing Friendship Hospital Affiliated to Capital Medical University during Oct. 2018 to Feb. 2019. The process of pharmaceutical care for elderly inpatients was established and developed through the CGA team of the elderly. PCNE classification system was used to analyze drug-related problems； Bayliff tool was used to evaluate the harmfulness of drug-related problems； Morisky questionnaire was used to analyze medication compliance. Drug use was followed up 3 months after discharge to evaluate the effect of clinical pharmacist’s intervention. RESULTS： A total of 71 elderly inpatients with multiple medication were included， 73.24％ of them （52 patients） suffered from 54 drug-related problems， 32 of which were related to therapeutic effects （59.26％）， 13 （24.07％） drug adverse events （possible）， 9 unnecessary drug therapy problems （16.67％）. There were 69 causes of pharmaceutical related problems， of which 58 （84.06％） were doctor’s orders. The main causes were drug selection （36.23％）， drug dosage （24.64％） and drug dosage form （20.29％）. Totally 143 interventions were conducted by clinical pharmacists， including 102 successful interventions， with success rate of 71.33％. The highest acceptance of intervention was adverse drug events reporting（100％）， followed by patient level （97.56％）， doctor level （65.12％） and drug level （52.83％）. Among 54 pharmaceutical-related problems， the most potential hazards were grade 1 hazards， involving 35 problems （64.81％）. The score of medication compliance in patients who received medication education from clinical pharmacists was （6.19±0.58）， which was significantly higher than （4.13±1.62） at the initial stage of admission （P＜0.05）. Follow-up results showed that 6 patients discontinued drugs by themselves， and 13 patients took drugs additionally by themselves. CONCLUSIONS： Drug related problems were common in elderly inpatients receiving multiple medication. Clinical pharmacists can establish a feasible pharmaceutical care process suitable for clinical needs according to the actual clinical situation. With the help of relevant evaluation tools such as relevant drug criteria， drug instructions and drug software， and at the same time， according to the physiological and pathological conditions of patients， they can cooperate with clinicians to select suitable therapeutic drugs for elderly patients to reduce the phenomenon of unreasonable medication and multiple medication， so as to improve the effectiveness and safety of drug use in the elderly.

Objective To analyze the relationship between tumor top,tumor neck,tumor rupture point of intraoperative aneurysm rupture (IAR) and the prognosis in patients with anterior circulation aneurysms (ACA) by craniotomy clipping.Methods Clinical materials of 123 patients with ACA (135 aneurysms) by craniotomy clipping were analyzed retrospectively,including 40 patients had IAR (41 aneurysms) during operation.The general informations of IAR patients were analyzed.Prognostic factors of IAR were analyzed by single and multiple factor analysis.Results The sex,age,history of hypertension,aneurysm diameter,the use of temporary blockage and blocking time,intraoperative blood loss showed no significant influences on the prognosis of patients with IAR (P ＞0.05),while preoperative Hunt-Hess classification and intraoperative rupture were the influencing factors for the prognosis of IAR patients (P ＜ 0.01).The preoperative Hunt-Hess classification and intraoperative rupture were the independent risk factors for the prognosis of IAR patients (P ＜0.01).Conclusion In craniotomy clipping,the different aneurysm rupture points can significantly affect the prognosis of patients with ACA,and aneurysm neck rupture is a main factor for poor prognosis of patients.

Objective To analyze the relationship between tumor top,tumor neck,tumor rupture point of intraoperative aneurysm rupture (IAR) and the prognosis in patients with anterior circulation aneurysms (ACA) by craniotomy clipping.Methods Clinical materials of 123 patients with ACA (135 aneurysms) by craniotomy clipping were analyzed retrospectively,including 40 patients had IAR (41 aneurysms) during operation.The general informations of IAR patients were analyzed.Prognostic factors of IAR were analyzed by single and multiple factor analysis.Results The sex,age,history of hypertension,aneurysm diameter,the use of temporary blockage and blocking time,intraoperative blood loss showed no significant influences on the prognosis of patients with IAR (P ＞0.05),while preoperative Hunt-Hess classification and intraoperative rupture were the influencing factors for the prognosis of IAR patients (P ＜ 0.01).The preoperative Hunt-Hess classification and intraoperative rupture were the independent risk factors for the prognosis of IAR patients (P ＜0.01).Conclusion In craniotomy clipping,the different aneurysm rupture points can significantly affect the prognosis of patients with ACA,and aneurysm neck rupture is a main factor for poor prognosis of patients.