OBJECTIVE To study the pharmacokinetic characteristics of antidepressant active components from Jiaotai pills in healthy subjects. METHODS Eight healthy subjects （3 males and 5 females） were recruited and given a single oral dose of 8.55 g of Jiaotai pills. Venous blood samples were collected before administration （0 h） and at intervals from 0.25 to 36.0 hours post- administration. After treating the plasma samples with protein precipitation， the blood concentrations of the antidepressant active ingredients （coptisine， berberine， magnoflorine， and palmatine） in Jiaotai pills were determined using liquid chromatography- tandem mass spectrometry （LC-MS/MS） method. DAS 2.0 software was employed to calculate the pharmacokinetic parameters of healthy subjects [half-life （t1/2）， peak concentration （cmax）， time to peak concentration （tmax）， area under the concentration-time curve （AUC）， and mean residence time （MRT）] using a non-compartmental model. RESULTS After healthy subjects took Jiaotai pills， the drug-time curve of the four antidepressant active ingredients conforms to a two-compartment model and tmax values were similar， with all reaching peak blood concentrations within 2.00 to 4.00 hours post-administration. However， the t1/2 and MRT of coptisine and berberine were significantly longer than that of magnoflorine and palmatine. There were also significant differences in the AUC and cmax among the four antidepressant active ingredients， with magnoflorine exhibiting markedly higher AUC0-t and cmax compared to the other three components. CONCLUSIONS In this study，LC-MS/MS is used to analyze the pharmacokinetic characteristics of the antidepressant active ingredients from Jiaotai pills in healthy subjects， can provide valuable references for the clinical application of Jiaotai pills.

Objective To investigate the effect of ubiquitin-specific peptidase(USP)44 and nuclear receptor co-inhibitor 1(NCOR1)expression on prognosis in non-small cell lung cancer.Methods A total of 98 pa-tients with non-small cell lung cancer admitted to a hospital from May 2019 to May 2021 were selected as the study objects,and non-small cell lung cancer tissues and adjacent tissues were collected to detect the expres-sion levels of USP44 and NCOR1 in these tissues by immunohistochemical staining.The relationship between USP44 and NCOR1 expression and pathological features of non-small cell lung cancer patients was analyzed,and the prognostic factors of non-small cell lung cancer patients were analyzed by multivariate Cox regression.Results The positive expression rates of USP44 and NCOR1 in non-small cell lung cancer tissues were higher than those in adjacent tissues,the difference was statistically significant(P<0.05).The positive expression rates of USP44 and NCOR1 in patients with medium-low differentiation,lymph node metastasis,clinical stageⅢ to Ⅳ,and pleural metastasis were higher than those in patients with highly differentiated,no lymph node metastasis,clinical stage Ⅰ to Ⅱ,and no pleural metastasis,and the difference was statistically significant(P<0.05).The 3-year overall survival rate of USP44 and NCOR1 negative non-small cell lung cancer patients was higher than that of USP44 and NCOR1 positive non-small cell lung cancer patients,and the difference was statistically significant(all P<0.05).Multivariate Cox regression analysis showed that pleural metastasis,USP44 positive and NCOR1 positive were prognostic factors in non-small cell lung cancer patients(P<0.05).Conclusion The expression of USP44 and NCOR1 in patients with non-small cell lung cancer can be used as biomarkers for prognosis assessment,and provide evidence for progression assessment and clinical de-cision making of non-small cell lung cancer.

Objective:To investigate the correlation between pre- and post-treatment changing trends in peripheral blood inflammatory markers and efficacy and their predictive value for prognosis in non-small cell lung cancer (NSCLC) patients treated with the first-line immunotherapy plus chemotherapy.Methods:The clinical data of NSCLC patients admitted to the Department of Radiation and Chemotherapy for Lung Oncology, Zhongnan Hospital of Wuhan University from October 2018 to May 2023 were retrospectively analyzed. The χ2 test was used to analyze the correlation between the changing trend of peripheral blood inflammatory markers and the efficacy of immunotherapy plus chemotherapy. The influencing factors of objective response rate (ORR) were assessed using binary logistic regression analysis. Kaplan-Meier survival curve and Cox proportional hazards model were used to analyze the prognostic value of the changing trend of peripheral blood inflammation markers on patients' prognosis. Results:A total of 102 NSCLC patients treated with first-line immunotherapy plus chemotherapy were included. The proportion of patients with bone metastases was higher in the lymphocyte to monocyte ratio (LMR) decreased group ( n=50) than that in the increased group ( n=52) ( χ2=4.28, P=0.039), whereas the pathological type of patients in the platelet to lymphocyte ratio (PLR) decreased group ( n=51) was more common in squamous carcinoma compared to patients in the increased group ( n=51) ( χ2=18.99, P<0.001), and a higher proportion of patients in the prognostic nutritional index (PNI) decreased group ( n=46) was female than that in the increased group ( n=56) ( χ2=4.29, P=0.038), with statistically significant differences. The 2-cycle objective response rate (ORR) of patients in the LMR increased and decreased groups was 63.5% (33/52) and 44.0% (22/50) ( χ2=3.89, P=0.049), the 2-cycle ORR of patients in the neutrophil to lymphocyte ratio (NLR) increased ( n=24) and decreased ( n=78) groups was 29.2% (7/24) and 61.5% (48/78) ( χ2=7.74, P=0.005), and the 2-cycle ORR for patients in the systemic immune inflammatory index (SII) increased group ( n=27) and decreased group ( n=75) was 33.3% (9/27) and 61.3% (46/75) ( χ2=6.26, P=0.012), with statistically significant differences. Multivariate analysis showed that the changing trend of inflammatory markers in peripheral blood were not related to ORR. The Kaplan-Meier survival curve indicated that patients in the group with SII decreased had longer median progression-free survival (PFS) (not reached vs. 7.1 months, χ2=9.35, P=0.002) and median overall survival (OS) (not reached vs. 16.6 months, χ2=11.08, P<0.001) than those in the SII increased group, and patients in the NLR decreased group had longer median OS (not reached vs. 22.2 months, χ2=4.56, P=0.033) than that in the NLR increased group. Univariate analysis suggested that both brain and bone metastasis ( HR=4.04, 95% CI: 1.23-13.35, P=0.022), increased SII ( HR=2.83, 95% CI: 1.41-5.66, P=0.003) were found to be significant factors affecting the PFS of NSCLC patients, both brain and bone metastasis ( HR=3.47, 95% CI: 1.05-11.45, P=0.041), increased NLR ( HR=2.17, 95% CI: 1.05-4.51, P=0.037) and increased SII ( HR=3.12, 95% CI: 1.54-6.30, P=0.002) were found to be significant factors affecting the OS of NSCLC patients. Multivariate analysis demonstrated that both brain and bone metastasis ( HR=4.32, 95% CI: 1.30-14.40, P=0.017) and increased SII ( HR=2.89, 95% CI: 1.44-5.81, P=0.003) were independent risk factors for PFS in NSCLC patients, both brain and bone metastasis ( HR=3.76, 95% CI: 1.13-12.50, P=0.031) and increased SII ( HR=3.47, 95% CI: 1.28-9.41, P=0.014) remained independent risk factors for OS in patients with NSCLC. Conclusion:The changing trend of peripheral blood inflammatory markers of NSCLC patients cannot independently predict the efficacy of 2-cycle immunotherapy plus chemotherapy. Both brain and bone metastasis, as well as the changing trend of SII can be used as important indicators to predict PFS and OS in advanced NSCLC patients treated with first-line immunotherapy plus chemotherapy. The simultaneous occurrence of brain and bone metastasis and SII increased suggest poor prognosis of NSCLC patients.

Objective:To summarize the repair experience and clinical characteristics of cleft lip and palate in Tibet.Methods:From August 2020 to August 2021, patients with cleft lip and palate treated during the period of corresponding author aid to Tibet were included. The American Association of Anesthesiologists (ASA) was used to assess the anesthesia risk before operation. For the cleft lip repair, Millard rotation advancement technique and reconstruction of nasal-labial muscle tension lines group were used. Modified Von Langenbeck technique was adopted for cleft palate repair. The amount of blood loss and short-term postoperative complications such as hematoma, infection, wound dehiscence, flap circulation disorder and palatal fistula were counted. The Likert five-point scale was used to evaluate the surgical satisfaction of patients with cleft lip and the audiometric evaluation method was used to assess the improvement of cleft palate speech. The data were statistically analyzed by SPSS 20.0 software. The measurement data were expressed by Mean±SD. P<0.05 was considered statistically significant. Results:A total of 46 patients were included, including 26 males and 20 females, aged from 2 to 57 years, with a median of 32 years. There were 36 patients with cleft lip or secondary deformities after cleft lip surgery and 10 patients with cleft palate. Among the 46 cases, ASA Ⅰ was 39, and ASA Ⅱ, ASA Ⅲ were 5 and 2, respectively. There were 5 patients with congenital heart disease, including 2 cases of patent ductus arteriosus and 3 cases of patent foramen ovale. Pulmonary hypertension was found in 8 cases. The average blood loss during the repair of cleft lip and cleft palate was 30 ml and 50 ml, respectively. No postoperative complications such as hematoma, infection, wound dehiscence and palatal fistula occurred. The patients were followed up for 6 to 24 weeks, with an average of 8 weeks. The crista philtra point on the affected side of the patients with cleft lip was fully lowered and was basically symmetrical with the healthy side. The bilateral nostril symmetry was significantly improved compared with that before surgery, and the nasal columella was in the middle. The cleft palate was all closed and the mobility of soft palate was improved. All patients were satisfied with the surgical results, with an average satisfaction score of 4.5. The mean preoperative speech score of patients undergoing cleft palate repair was 1.4 ± 0.5 and the postoperative was 4.3 ± 0.5 ( t=16.16, P<0.001). Conclusion:Compared with the plain area, patients with cleft lip and palate in Tibet have the characteristics such as delayed treatment, the complex of deformity and often combined with other congenital organ malformation. In order to get good result and higher satisfaction rate, it is recommended to use classical surgical technique for the above deformity repair. It is also important to carefully evaluate the risk of general anesthesia.

Objective:To summarize the repair experience and clinical characteristics of cleft lip and palate in Tibet.Methods:From August 2020 to August 2021, patients with cleft lip and palate treated during the period of corresponding author aid to Tibet were included. The American Association of Anesthesiologists (ASA) was used to assess the anesthesia risk before operation. For the cleft lip repair, Millard rotation advancement technique and reconstruction of nasal-labial muscle tension lines group were used. Modified Von Langenbeck technique was adopted for cleft palate repair. The amount of blood loss and short-term postoperative complications such as hematoma, infection, wound dehiscence, flap circulation disorder and palatal fistula were counted. The Likert five-point scale was used to evaluate the surgical satisfaction of patients with cleft lip and the audiometric evaluation method was used to assess the improvement of cleft palate speech. The data were statistically analyzed by SPSS 20.0 software. The measurement data were expressed by Mean±SD. P<0.05 was considered statistically significant. Results:A total of 46 patients were included, including 26 males and 20 females, aged from 2 to 57 years, with a median of 32 years. There were 36 patients with cleft lip or secondary deformities after cleft lip surgery and 10 patients with cleft palate. Among the 46 cases, ASA Ⅰ was 39, and ASA Ⅱ, ASA Ⅲ were 5 and 2, respectively. There were 5 patients with congenital heart disease, including 2 cases of patent ductus arteriosus and 3 cases of patent foramen ovale. Pulmonary hypertension was found in 8 cases. The average blood loss during the repair of cleft lip and cleft palate was 30 ml and 50 ml, respectively. No postoperative complications such as hematoma, infection, wound dehiscence and palatal fistula occurred. The patients were followed up for 6 to 24 weeks, with an average of 8 weeks. The crista philtra point on the affected side of the patients with cleft lip was fully lowered and was basically symmetrical with the healthy side. The bilateral nostril symmetry was significantly improved compared with that before surgery, and the nasal columella was in the middle. The cleft palate was all closed and the mobility of soft palate was improved. All patients were satisfied with the surgical results, with an average satisfaction score of 4.5. The mean preoperative speech score of patients undergoing cleft palate repair was 1.4 ± 0.5 and the postoperative was 4.3 ± 0.5 ( t=16.16, P<0.001). Conclusion:Compared with the plain area, patients with cleft lip and palate in Tibet have the characteristics such as delayed treatment, the complex of deformity and often combined with other congenital organ malformation. In order to get good result and higher satisfaction rate, it is recommended to use classical surgical technique for the above deformity repair. It is also important to carefully evaluate the risk of general anesthesia.

Objective To analyze the clinical characteristics of Hashimoto's disease(HD) accompanying with thyroid cancer,and to explore the experience of diagnosis and treatment.Methods Clinical data of 41 cases of HD accompanying with thyroid cancer were retrospectively analyzed.The patients were diagnosed by postoperative paraffin pathological examination from Jan.2002 to July 2011.Results 10 cases of HD,37cases of thyroid cancer,and 8 cases HD accompanying with thyroid cancer were diagnosed before operation.The rate of preoperative diagnosis was only 19.51％.All patients underwent surgical treatment,including 22 cases total thyroidectomy,14 cases subtotal thyroidectomy,and 5 cases lesion side lobe resection.24 cases underwent ipsilateral neck dissection,and 4 cases underwent bilateral neck dissection (ipsilateral radical resection,contralateral selective resection).Postoperative paraffin pathological examination proved that there were 39 cases of HD accompanying with thyroid cancer,1 case of focal cancer and 1 case of B-cell lymphoma of mucosa-associated thyroid.All patients were followed up.Conclusions The preoperative diagnosis rate of HD accompanying with thyroid cancer is low and great attention should be paid to its diagnosis.For HD patients,if carcinoma can not be excluded,surgical exploration is recommended.Appropriate surgical method should be chosen according to intraoperative frozen section results.Postoperative thyroid hormone treatment is usually taken.

Objective To study the epidemiological and clinical features of primary hyperthyroidism complicated with thyroid cancer.Methods Clinical data of 30 cases of hyperthyroidism complicated with thyroid cancer(hyperparathyroidism group)were retrospectively analyzed.They were chosen from the 365 cases of primary hyperparathyroidism treated by operation from Jan.2002 to Jun.2011.At the same time,30 cases of thyroid cancer without hyperparathyroidism were randomly taken out as the control group.Results The incidence of thyroid cancer in primary hyperparathyroidism was 8.22％ (30/365).The median course,preoperative diagnostic rate of thyroid cancer,and lymph nodes metastasis rate for hyperparathyroidism group and control group was 875.00 vs 120.00 days(z =-2.501,P ＜0.05),40.0％ (12/30) vs 66.7％ (20/30) (x2 =4.286,P ＜0.05),and 20.0％ (6/30) vs 46.7％ (14/30) (x2 =4.800,P ＜ 0.05) respectively.All patients were followed up with the average of 4.5 years,ranging from 1 month to 9 yeas and a half.1 case(3.3％)in hyperparathyroidism group recurred hyperthyroidism 5 years after surgery.1 case(3.3％)recurred thyroid cancer 1 year after surgery and received operation again,and 1 case(3.3％)died half a year after operation from respiratory failure caused by lung metastasis of thyroid cancer in the control group.Conclusions Hyperthyroidism complicated with thyroid cancer has the characteristics of high incidence rate of thyroid cancer in the hyperthyroidism patients,long course,high preoperative misdiagnosis rate,low lymph node metastasis rate,favorable prognosis and so on.