Biliary tract carcinoma (BTC) is a highly aggressive malignancy,and the majority of patients present with advanced stage at first diagnosis which resulting in poor prognosis. Traditional chemotherapy and monotherapy have shown limited efficacy in treating BTC. However,with the continuous emergence of clinical research findings and updates to relevant guidelines,there have been some breakthroughs in systemic therapies for BTC. This paper analyzes domestic and international literature on neoadjuvant therapy and conversion therapy for BTC,aiming to provide a reference for clinical research. Overall,research on neoadjuvant therapy and conversion therapy remains in the preliminary exploration phase. Current evidence suggests that combination strategies involving immunotherapy and chemotherapy,with or without targeted therapy,have demonstrated promising clinical efficacy,offering new hope for neoadjuvant therapy and conversion therapy in BTC. Furthermore,the evolution of precision targeted therapies offers better opportunities for personalized treatment,and the combination of local interventions and systemic therapies demonstrates promising therapeutic potential. However,the optimal strategies and timing for surgery of neoadjuvant therapy and conversion therapy have not yet been standardized. Moreover,most studies lack precise designs to address the heterogeneity of BTC,new therapies have not yet reached the ideal stage of personalized treatment,further research is warranted to address these challenges.

Biliary tract carcinoma (BTC) is a highly aggressive malignancy,and the majority of patients present with advanced stage at first diagnosis which resulting in poor prognosis. Traditional chemotherapy and monotherapy have shown limited efficacy in treating BTC. However,with the continuous emergence of clinical research findings and updates to relevant guidelines,there have been some breakthroughs in systemic therapies for BTC. This paper analyzes domestic and international literature on neoadjuvant therapy and conversion therapy for BTC,aiming to provide a reference for clinical research. Overall,research on neoadjuvant therapy and conversion therapy remains in the preliminary exploration phase. Current evidence suggests that combination strategies involving immunotherapy and chemotherapy,with or without targeted therapy,have demonstrated promising clinical efficacy,offering new hope for neoadjuvant therapy and conversion therapy in BTC. Furthermore,the evolution of precision targeted therapies offers better opportunities for personalized treatment,and the combination of local interventions and systemic therapies demonstrates promising therapeutic potential. However,the optimal strategies and timing for surgery of neoadjuvant therapy and conversion therapy have not yet been standardized. Moreover,most studies lack precise designs to address the heterogeneity of BTC,new therapies have not yet reached the ideal stage of personalized treatment,further research is warranted to address these challenges.

Objective:To investigate the safety and efficacy of FOLFOX (5-fluorouracil + calcium folinate + oxaliplatin) hepatic arterial infusion chemotherapy (FOLFOX-HAIC) combined with immune and targeted therapy as triple combination therapy for patients with single China Liver Cancer Staging (CNLC) Ⅰb hepatocellular carcinoma.Methods:A total of 20 patients with single CNLC Ⅰb hepatocellular carcinoma who received FOLFOX-HAIC combined with immune and targeted therapy as triple combination therapy in the First Affiliated Hospital of Guangxi Medical University from October 2021 to August 2022 were included. The clinical data of all patients was retrospectively analyzed. There were 18 males and 2 females, with the age of (55.1±9.9) years. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and Modified Response Evaluation Criteria in Solid Tumors (mRECIST) were used to evaluate the efficacy of FOLFOX-HAIC combined with immune and targeted therapy, and the clinical safety of triple combination therapy was evaluated by common terminology criteria for adverse events 4.0.Results:According to RECIST 1.1, objective response rate of 20 patients was 70.0% (14/20) and disease control rate was 100.0% (20/20) after 2 cycles of treatment (one cycle of FOLFOX-HAIC plus programmed death-1 antibody). According to mRECIST, objective response rate was 90.0% (18/20) and the disease control rate was 100.0% (20/20) after 2 cycles of treatment. Following the treatment, 12 patients (60.0%) received liver tumor resection, and all of them achieved R 0 resection, 2 patients (10.0%) received radiotherapy, 3 patients (15.0%) stopped drug treatment for surgery, 2 patients (10.0%) refused surgery, and 1 patient (5.0%) died of multiple organ failure caused by immune hepatitis. According to pathological results, 3 patients (25.0%, 3/12) achieved pathological complete response, and 4 patients (33.3%, 4/12) achieved major pathological response. In the safety evaluation, the overall incidence of adverse events was 100.0% (20/20). Seven patients (35.0%) had grade 3 adverse events and 1 patient (5.0%) died of multiple organ failure due to immune hepatitis (grade 5). Grade 1-3 adverse events could be relieved after symptomatic treatment. Conclusion:The triple combination therapy of FOLFOX-HAIC combined with immune and targeted therapy is safe and has high objective response rate and disease control rate, which could be a new strategy for the neoadjuvant treatment of hepatocellular carcinoma.

Objective:To explore the effect of the combined effect of noise and heat on occupational hearing loss of workers by using Meta-analysis method.Methods:In August 2020, the Chinese and English literature on the relationship between exposure to noise and heat and occupational hearing loss published from January 2005 to August 2020 by CNKI, China Biomedical Literature Service System, Wanfang Data Knowledge Service Platform, VIP Official Database, Medline and PubMed Databases were searched, using noise, heat or hyperthermia, hearing as keywords. The selected data were analyzed by Stata 12.0 software, and the combined OR (95% CI) value included in the literature was calculated. Sensitivity analysis was used to explore the source of heterogeneity and analyze publication bias. Results:A total of 14 literatures (14 in Chinese, 0 in English) were included in the analysis, and 38654 subjects were included, including 6411 workers in the noise and heat combined effect group and 32243 workers in the noise alone group. The probability of hearing loss in the noise and heat combined effect group was 1.39 times higher than that in the noise alone group (95% CI: 1.14-1.69). The effect size OR was stable after sensitivity analysis, and there was no publication bias in the included literatures tested by Egger's and Begg's Method ( z=0.38, P=0.702, t=-0.74, P=0.476) . Conclusion:Simultaneous exposure to noise and heat may increase the risk of hearing loss for workers in noisy workplaces.

Objective:To explore the effect of the combined effect of noise and heat on occupational hearing loss of workers by using Meta-analysis method.Methods:In August 2020, the Chinese and English literature on the relationship between exposure to noise and heat and occupational hearing loss published from January 2005 to August 2020 by CNKI, China Biomedical Literature Service System, Wanfang Data Knowledge Service Platform, VIP Official Database, Medline and PubMed Databases were searched, using noise, heat or hyperthermia, hearing as keywords. The selected data were analyzed by Stata 12.0 software, and the combined OR (95% CI) value included in the literature was calculated. Sensitivity analysis was used to explore the source of heterogeneity and analyze publication bias. Results:A total of 14 literatures (14 in Chinese, 0 in English) were included in the analysis, and 38654 subjects were included, including 6411 workers in the noise and heat combined effect group and 32243 workers in the noise alone group. The probability of hearing loss in the noise and heat combined effect group was 1.39 times higher than that in the noise alone group (95% CI: 1.14-1.69). The effect size OR was stable after sensitivity analysis, and there was no publication bias in the included literatures tested by Egger's and Begg's Method ( z=0.38, P=0.702, t=-0.74, P=0.476) . Conclusion:Simultaneous exposure to noise and heat may increase the risk of hearing loss for workers in noisy workplaces.

To establish the experts consensus on the management of delirium in critically ill patients.A special committee was set up by 15 experts from the Chinese Critical Hypothermia-Sedation Therapy Study Group.Each statement was assessed based on the GRADE (Grading of Recommendations Assessment,Development,and Evaluation) principle.Then the Delphi method was adopted by 36 experts to reassess all the statements.(1) Delirium is not only a mental change,but also a clinical syndrome with multiple pathophysiological changes.(2) Delirium is a form of disturbance of consciousness and a manifestation of abnormal brain function.(3) Pain is a common cause of delirium in critically ill patients.Analgesia can reduce the occurrence and development of delirium.(4) Anxiety or depression are important factors for delirium in critically ill patients.(5) The correlation between sedative and analgesic drugs and delirium is uncertain.(6) Pay attention to the relationship between delirium and withdrawal reactions.(7) Pay attention to the relationship between delirium and drug dependence/ withdrawal reactions.(8) Sleep disruption can induce delirium.(9) We should be vigilant against potential risk factors for persistent or recurrent delirium.(10) Critically illness related delirium can affect the diagnosis and treatment of primary diseases,and can also be alleviated with the improvement of primary diseases.(11) Acute change of consciousness and attention deficit are necessary for delirium diagnosis.(12) The combined assessment of confusion assessment method for the intensive care unit and intensive care delirium screening checklist can improve the sensitivity of delirium,especially subclinical delirium.(13) Early identification and intervention of subclinical delirium can reduce its risk of clinical delirium.(14) Daily assessment is helpful for early detection of delirium.(15) Hopoactive delirium and mixed delirium are common and should be emphasized.(16) Delirium may be accompanied by changes in electroencephalogram.Bedside electroencephalogram monitoring should be used in the ICU if conditions warrant.(17) Pay attention to differential diagnosis of delirium and dementia/depression.(18) Pay attention to the role of rapid delirium screening method in delirium management.(19) Assessment of the severity of delirium is an essential part of the diagnosis of delirium.(20) The key to the management of delirium is etiological treatment.(21) Improving environmental factors and making patient comfort can help reduce delirium.(22) Early exercise can reduce the incidence of delirium and shorten the duration of delirium.(23) Communication with patients should be emphasized and strengthened.Family members participation can help reduce the incidence of delirium and promote the recovery of delirium.(24) Pay attention to the role of sleep management in the prevention and treatment of delirium.(25) Dexmedetomidine can shorten the duration of hyperactive delirium or prevent delirium.(26) When using antipsychotics to treat delirium,we should be alert to its effect on the heart rhythm.(27) Delirium management should pay attention to brain functional exercise.(28) Compared with non-critically illness related delirium,the relief of critically illness related delirium will not accomplished at one stroke.(29) Multiple management strategies such as ABCDEF,eCASH and ESCAPE are helpful to prevent and treat delirium and improve the prognosis of critically ill patients.(30) Shortening the duration of delirium can reduce the occurrence of long-term cognitive impairment.(31) Multidisciplinary cooperation and continuous quality improvement can improve delirium management.Consensus can promote delirium management in critically ill patients,optimize analgesia and sedation therapy,and even affect prognosis.

Objective To investigate the role of transient receptor potential melastatin 7 (TR PM7) in the protective role of sevoflurane preconditioning against hippocampal neuron injury caused by oxygen glucose deprivation (OGD).Methods Hippocampal neurons were harvested from postnatal day 1 SD rats,and randomly divided into 5 groups:control group (group C),sevoflurane group (group Sev),oxygen-glucose deprivation group (group OGD),sevoflurane+ OGD group (group SD) and sevoflurane+OGD+bradykinin group (group B).To build up the model of OGD,the neurons were cultured in a deoxygenated glucose-free medium and exposed to 95％ N2 and 5％％ CO2 in an anaerobic chamber equilibrated at 37℃ for 1.5 h,followed by replacement with glucose containing medium and return to a standard incubator for additional 24 h.The neurons in group C received no treatment.Group OGD was preconditioned with 2 ％ sevoflurane for 1 h.The neurons in group OGD were subjected to OGD.Group SD was preconditioned with 2％ sevoflurane for 1 h,followed by OGD at 24 h after the sevoflurane exposure.The neurons in group B was incubated in a medium supplemented with 200 μmol/L bradykinin (the selective agonist of TRPM7),followed sequen tially by the preconditioning of 2％ sevoflurane for 1 h and then OGD challenge.Twenty-four hours after re-oxygenation,The relative neuronal cell viability was determined by MTT assay,the neuronal apoptotic rate was analyzed by TUNEL assay,the protein expression of TRPM7 was detected by Western blot,the mRNA level of TRPM7 was estimated by real-time PCR,the neuronal release of IL-1β and TNF-α in the serum was measured by ELISA.Results Compared with group C,the mR NA and protein levels of TRPM7,the neuronal apoptotic rate,the mRNA and supernatant protein levels of IL-1β and TNFα were significantly up-regulated in group OGD (P＜0.05),whereas the cell viability was decreased (P＜0.05).Compared with group OGD,the mRNA and protein levels of TRPM7,the neuronal apoptotic rate,the mRNA and supernatant protein levels of IL1β and TNF-α were significantly down-regulated in group SD (P＜0.05),whereas the cell viability was increased (P＜0.05).Compared with group SD,the mRNA and protein levels of TRPM7,the neuronal apoptotic rate,the mRNA and supernatant protein levels of IL-1β and TNF-α were significantly up-regula ted in group B (P＜0.05),whereas the cell viability was decreased (P＜0.05).Conclusion Sevoflurane attenuates apoptosis and inflammatory responses induced by OGD via reduction of the overex pression of TRPM7 in the hippocampal neurons.

Objective To evaluate the effect of cardamonin on acute lung injury induced by hemorrhagic shock and resuscitation (HSR) in rats.Methods Thirty-two male Sprague-Dawley rats,aged 18-24 weeks,weighing 200-250 g,were divided into 4 groups (n =8 each) using a random number table:sham operation group (group Sham);group HSR;cardamonin group (group CA);cardamonin + adenosina A2A receptor antagonist ZM241385 group (group CZM).Bilateral common carotid arteries were only cannulated in group Sham.The left common carotid artery was cannulated for blood-letting until mean arterial pressure was reduced to 35-45 mmHg and maintained at this level for 30 min,and the animals were then resuscitated by infusion of shed blood and normal saline two-fold volume of shed blood to establish HSR model in HSR,CA and CZM groups.ZM241385 5 mg/kg was injected intraperitoneally at 30 min before blood-letting in group CZM,and cardamonin 75 mg/kg was injected intraperitoneally immediately after the beginning of resuscitation in CA and CZM groups.The rats were sacrificed at 2 h after completion of resuscitation,bronchoalveolar lavage fluid (BALF) was collected for determination of neutrophil count,and lungs were removed for microscopic examination of the pathological changes and for determination of wet/dry lung weight ratio (W/D ratio),contents of tumor necrosis factor-alpha (TNF-ct),interleukin-1 (IL-1β) and IL-6 (by enzyme-linked immunosorbent assay) and expression of adenosine A2A receptors in lung tissues (by Western blot).Results Compared with group Sham,the neutrophil count in BALF,W/D ratio and contents of TNF-α,IL-1β and IL-6 were significantly increased,the expression of adenosine A2A receptors was significantly down-regulated in group HSR,and the neutrophil count in BALF and contents of TNF-α and IL-6 were significantly increased (P＜0.05),and no significant changes were found in W/D ratio,content of IL-1β,and expression of adenosine A2A receptors in group CA (P＞0.05).Compared with group HSR,the neutrophil count in BALF,W/D ratio and contents of TNF-α,IL-1β and IL-6 were significantly decreased,the expression of adenosine A2A receptors was significantly up-regulated (P＜0.05),and the pathological changes were significantly attenuated in group CA,and no significant changes were found in the parameters mentioned above in group CZM (P＞0.05).Compared with group CA,the neutrophil count in BALF,W/D ratio and contents of TNF-α,IL-1β and IL-6 were significantly increased,the expression of adenosine A2A receptors was significantly down-regulated (P＜0.05),and the pathological changes were aggravated in group CZM.Conclusion Cardamonin can attenuate acute lung injury induced by HSR in rats,and activated adenosine A2A receptors and inhibited inflammatory responses are involved in the mechanism.

OBJECTIVE:To establish the method for the determination of tigecycline (TGC) in human plasma. METHODS:After precipitated by acetonitrile,the plasma sample was determined by LC-MS/MS. Using d9-TGC as internal standard,Kromasil C18 column was used with mobile phase consisted of water (containing 0.05% TFA)-acetonitrile (gradient elution) at flow rate of 0.6 ml/min,column temperature of 40 ℃. The ion transitions were performed under ESI positive MRM model at m/z 586.3→513.2 and m/z 595.3→514.3 for TGC and internal standard,respectively. RESULTS:The linear range of TGC was 25-2 000 ng/ml (r=0.999 8),and lowest quantification limit was 25 ng/ml;intra-day and inter-day RSD was 3.15%-7.23%,and relative error was-4.53%-10.48%. Plasma sample kept stable after 3 times of freezing and thawing cycle,at room temperature for 24 h,in automat-ic sample injector for 24 h and freezing for 42 d (RSD<15%). Plasma concentration of TGC was 0-438.0 ng/ml in one patient with pan-drug resistant bacteria infection(0-12 h after administration). CONCLUSIONS:The developed method is accurate,sensi-tive and specific,and can be used for plasma concentration determination of TGC and pharmacokinetic study.

OBJECTIVE:To investigate the role of clinical pharmacists in the therapy for acute exacerbation of chronic obstruc-tive pulmonary diseases (AECOPD) complicated with pulmonary infection. METHODS:Clinical pharmacists participated in the therapy for a case of acute exacerbation of AECOPD complicated with pulmonary infection. According to the patients’signs,assis-tant examination and disease condition,clinical pharmacists provided suggestions,i.e. Piperacillin sodium and sulbactam sodium for injection (4∶1) 5.0 g,ivgtt,q12 h,for anti-infective treatment;Bisacodyl enteric-coated tablet 5 mg,po,qd,for promoting defecation;Clostridium butyricum viable bacteria tablet 20 mg,po,tid,for regulating gastrointestinal flora;Pinaverium bromide tablet 50 mg,po,tid,for regulating gastrointestinal smooth muscle tension;Shexiang baoxin pills 22.5 mg,po,tid,instead of flu-id infusion for protecting heart,and isosorbide 5-mononitrate 20 mg,po,tid,for preventing angina pectoris;Cefminox capsule 100 mg,po,tid,for anti-infective treatment;fluconazol 0.4 g,ivgtt,qd,for antifungal treatment,and Bacillus licheniformis 500 mg,po, tid,for preventing alteration of intestinal flora. RESULTS:The physicians adopted clinical pharmacist’s suggestions. No ADR was found during treatment,and the patients transferred to ordinary ward after the disease condition had been controlled. CONCLU-SIONS:The participating of clinical pharmacists in pharmaceutical care can promote rational drug use in the clinic and guarantee the safety of drug use.