OBJECTIVE To predict the possible impact of pembrolizumab（PEM） as a first-line drug after being included in the national medical insurance system in the treatment of advanced or metastatic non-small cell lung cancer based on real-world data from the perspective of the national medical insurance payer， to provide a basis for the decision-making of the medical insurance department. METHODS A budget impact analysis model was constructed to compare the impact of pembrolizumab not included in medical insurance and included in medical insurance on medical insurance fund expenditure in the next five years（ 2024- 2028） with 2023 as the baseline year. The target population was the patients with EGFR gene mutation-negative and anaplastic lymphoma kinase （ALK）-negative locally advanced or metastatic non-small cell lung cancer； estimated cost mainly included the cost of drugs， the cost of adverse reaction treatment， the cost of examination， the cost of admission and monitoring， etc； equipment ratio of PEM in 183 hospitals of Guangdong province from 2020 to 2022 was used as the market share. Univariate sensitivity analysis was used to test the robustness of the basic analysis results. RESULTS When PEM was not included in the medical insurance， the medical insurance reimbursement amount of the target population from 2024 to 2028 was 4 933 623.5 thousand yuan-5 151 198.3 thousand yuan， respectively. If PEM was included in the medical insurance， the above data were 11 871 972.2 thousand yuan-14 540 571.0 thousand yuan， respectively； the increase in medical insurance reimbursement under the two scenarios was 6 720 773.9 thousand yuan-9 606 947.5 thousand yuan， respectively. The proportion of medical insurance reimbursement to the medical insurance expenditure of the year after PEM was included in medical insurance was 0.298 0%， 0.262 1%， 0.228 8%， 0.208 2%， and 0.185 7%， respectively. The increase in medical insurance reimbursement accounted for 1.084 0%， 0.995 7%， 0.888 6%， 0.886 3%， and 0.861 6% of the increase in the expenditure of the medical insurance fund in the current year， all of which showed a decreasing trend year by year. CONCLUSIONS If PEM is included in medical insurance， due to its high unit price， the medical expenditure will increase accordingly， which will have a great impact on the medical insurance fund expenditure. However， when the drug is used in patients with EGFR mutation-negative and ALK-negative locally advanced or metastatic non-small cell lung cancer， the proportion of the medical insurance reimbursement amount in the current year’s medical insurance fund expenditure and the proportion of the increase in medical insurance reimbursement in the current year’s increase in medical insurance fund expenditure are decreasing year by year.

Objective:To investigate the clinical efficacy and safety of heat-clearing and spleen-invigorating method in the treatment of Helicobacter pylori (Hp) initial treatment failure population.Methods:The clinical data of 155 patients with initial Hp failure in our hospital from January 2021 to December 2022 were retrospectively analyzed. According to the treatment plan, they were divided into TCM group (66 cases) and Western medicine group (89 cases). Python 3.70 was used for bias score matching (PSM) to obtain samples with balanced covariates between groups. Finally 66 pair of cases were successfully matched according to the propensity score and the 1:1 matching principle.The TCM group was given Yiqing Capsule + Jianpi Pills (4 weeks) as a course of treatment. The Western medicine group was given four anti-Hp remedial regimen, 2 weeks for 1 course. 2 groups were treated for 1 course. Hp was detected by 14C breath test and its clearance rate was calculated. The overall symptoms of functional dyspepsia (FD) were evaluated from four aspects: postprandial fullness, early satiety, middle and upper abdominal pain, and middle and upper abdominal burning sensation. The adverse reactions during treatment were observed and the clinical efficacy was evaluated. Results:After treatment, the Hp clearance rate was 75.76% (50/66) in the TCM group and 83.33% (55/66) in the Western medicine group, which was significantly improved compared with that before treatment, without statistical significance ( χ2=1.16, P=0.281). After treatment, the scores of fullness and discomfort after meal [1 (0,2) vs. (2,4), Z=-6.85], early satiety [2 (0,2) vs. 4 (4, 6), Z=-8.02], middle and upper abdominal pain [2 (2, 4) vs. 4 (4, 6), Z=-4.48] in the TCM group were lower than those in Western medicine group ( P<0.01). The total effective rate was 75.76% (50/66) in the TCM group and 69.70% (46/66) in the Western medicine group, without statistical significance ( χ2=2.00, P=0.573). No adverse reactions occurred in the 2 groups during treatment. Conclusion:In terms of heat-clearing and spleen-invigorating method for Hp initially failed patients, its Hp clearance rate and clinical total effective rate are comparable to Western medicine, and can effectively improve the clinical symptoms of patients with Hp initial treatment failure.

Objective:To investigate the correlation between levels of fibroblast growth factor-23 (FGF-23) and monocyte chemoattractant protein-1 (MCP-1) and glucocorticoids-induced osteoporosis (GIOP) in children.Methods:From May. 2018 to May. 2022, 80 children with glucocorticoid osteoporosis admitted to our hospital were selected as the study subjects, and the control group was 62 children who received glucocorticoid therapy but had normal bone mass. General data were collected and bone density and bone metabolism were measured, including type 1 collagen carboxy-terminal peptide (CTX-1), type 1 procollagen amino-terminal peptide (PINP), and osteocalcin (OC). The levels of MCP-1and FGF-23 in the serum of the two groups were detected, and univariate and multivariate analysis was performed using prism software to analyze the risk factors affecting GIOP.Results:There was no significant difference in general data between the two groups (both P>0.05). The levels of FGF-23 (264.81±24.61) and MCP-1 (194.16±15.76) in serum of GIOP children were significantly higher than those in the control group (207.97±9.91; 179.00±18.34) ( t=17.13, P < 0.001; t=5.29, P < 0.001) ; Compared with those of the control group (0.88±1.08; 23.98±2.45; 8.36±3.71; 4.56±2.21), bone mineral density (0.44±0.29), PINP (16.29±3.97) and OC (6.74±3.22) levels were decreased, and CTX-1 level was increased (6.62±1.11) ( t=3.58, P<0.05; t=13.40, P<0.05; t=2.78, P<0.05; t=7.25, P<0.05) of the study group. Multivariate Logistic regression model showed that FGF-23 ( OR=1.161, 95% CI: 1.080-1.341, P<0.05), MCP-1 ( OR=1.179, 95% CI: 1.044-1.448, P<0.05) and CTX-1 ( OR=3.018, 95% CI: 1.526-10.510, P<0.05) were independent clinical risk factors for GIOP in children (all P<0.05). PINP ( OR=0.453, 95% CI: 0.169-0.740, P<0.05) was a protective factor affecting GIOP in children. Conclusion:FGF-23 and MCP-1 were independent risk factors for GIOP in children.

Objective:To screen the candidate genes in a patient with Kabuki syndrome (KS), providing basis for genetic counseling, prenatal screening, prenatal diagnosis and facilitating early treatment.Methods:This study included a 16-year-old female KS patient born of non-consanguineous Chinese parents who presented to Department of Orthognathic & Cleft Lip and Palate Plastic Surgery, School and Hospital of Stomatology, Wuhan University. Genomic DNA was extracted from the peripheral blood of the subjects and analyzed by whole-exome sequencing (WES). Sanger sequencing was performed to validate the mutation in the candidate gene. The conformational and physicochemical changes of the mutant were analyzed by Alphafold2, Antheprot and DOG.2.0.1, respectively. Distribution of KMT2D mutations in patients with KS was analyzed based on the Human Gene Mutation DatabaseResults:The proband manifested a typical KS facial gestalt, congenital cleft palate, fifth finger deformity, hypodontia, renal hypoplasia and hydronephrosis. Two de novo mutations c.[1166A>C; 1167dupC] (NM_003482) in cis on the same allele in the KMT2D gene were identified by WES and confirmed by allele-specific PCR. Bioinformatics analysis showed that three more α-helixes were added, and a (β-) turn and a (β-) sheet were reduced in KMT2D p. Y389S, p.V390Rfs*26 compared with the wild type. Meanwhile, the interceptive mutant-KMT2D protein p.V390Rfs*26 lost all four domains (FYRN domain, FYRC domain, SET domain, and PostSET domain), which may cause functional disabilities. Conclusions:Our study is the first to identify two novel and de novo KMT2D mutations in cis on the same allele in a KS patient and extends the KMT2D mutation spectrum of KS, providing evidence for genetic susceptibility counseling, prenatal screening and diagnosis, and early treatment of KS.

AIM: To study chronopharmacokinetics of helicid and its metabolites. METHODS: An HPLC-MS method for simultaneous determination of helicid and its three phase I metabolites were established and validated. At 8:00, 14:00 and 0:00, the rats were given helicid 50 mg/kg by gavage, respectively. Blood samples were collected from ophthalmic venous plexus. Then plasma concentration was measured. Pharmacokinetic behaviors of the original drug and its metabolites after administration at different time points were calculated and compared. RESULTS: This established HPLC-MS/MS method was successfully applied to simultaneous determination of helicid and its three metabolites in rat plasma after intragastric administration. Using AUC

AIM: To investigate the absorption of helicid in different segments of intestine based on rat everted intestine sac model. METHODS: To establish a high-performance liquid chromatography method for simultaneous determination of helicid and its metabolite. Krebs-ringer solution containing helicid was added to everted intestine sacs of different segments (duodenum, Jejunum, ileum and colon). Drug concentration in sacs was determined at different time points (5, 10, 15, 30, 45, 60, 75, 90 min). Adsorptions of helicid in four intestinal segments were compared. RESULTS: This high-performance liquid chromatography was successfully applied to the simultaneous determination of helicid and its metabolite. Absorption of helicid was rapid and time-dependent. The absorption and metabolism of helicid in duodenum segment were higher than these in other segments. CONCLUSION: The duodenum segment is the main site of segmental absorption and metabolism of helicid. This is the first report on intestinal segment metabolism of helicid.

Objective:To discuss the safety and feasibility for the use of 3D uniportal VATS sleeve resection.Methods:Totally 32 patients with central lung cancer received 3D uniportal VATS sleeve resection(group A) from June 2017 to May 2020 at Shanghai Chest Hospital. Meanwhile, 63 patients received conventional VATS sleeve resection(group B). The clinicopathological and perioperative outcome data were retrospectively collected and analyzed.Results:The baseline clinicopathological characteristics between these two groups were statistically similar. Compared with group B, the mean operative time[(174.19±73.69)min vs.(212.46±50.02)min, P=0.004] and blood loss[(73.13±42.70)ml vs.(130.48±133.72)ml, P=0.020] of group A were decreased, harvested lymph node stations was increased(7.63±1.59 vs. 6.76±1.70, P=0.018). Lymph nodes dissected showed no statistical difference(1.31±1.58 vs 1.21±1.96, P=0.803). There was no intraoperative death in both groups. Inspiringly, group A possessed lower rate of conversion to thoracotomy(0 vs. 36.5%, P=0.000), shorter chest drainage durations[(4.88±1.15)days vs.(6.81±3.8)days, P=0.007]. Although there were no deaths during hospitalization in both groups, the incidence of postoperative complications in group A was significantly lower than that in group B(25.0% vs. 47.6%, P=0.046). It also presented more complicated operations including pulmonary artery plasty(25.0% vs. 6.3%, P=0.024) and carina plasty(12.5% vs. 1.6%, P=0.005) against group B. Conclusion:3D uniportal VATS was a safe and feasible technique for the surgical treatment of central lung cancer when conducting a thoracoscopic sleeve resection.

Objective To evaluate the efficacy and safety of ilaprazole sodium for injection in the treatment of peptic ulcer bleeding.Methods It was designed as a multi-center,stratified randomized,double-blind,positive drug parallel controlled and non-inferiority study.From October 2014 to April 2015,at 40 hospitals,patients with peptic ulcer hemorrhage confirmed by gastroendoscopy were enrolled and divided into the ilaprazde sodium group (10 mg ilaprazole sodium for injection every 24 h,the first dose doubled) and the positive control group (40 mg of omeprazole sodium for injection every 12 h).The course of both treatment was 72 h.The hemostasis rate of overall group at 72 h,the clinical rebleeding rate at four to seven days,the blood transfusion rate,the incidence of switching to other treatments and the incidence of adverse reactions were compared between the two groups.A chi-square test or Fisher's exact probability method were performed for statistical analysis.Results A total of 533 patients with peptic ulcer bleeding were enrolled,355 patients in the ilaprazole sodium group and 178 patients in the positive control group.The hemostasis rates of ilaprazole sodium group and positive control group at 72 h were 97.69 ％ (339/347) and 97.14 ％ (170/175),respectively,and the difference was not statistically significant (P＞0.05).There were no rebleeding patients in both groups at four to seven days.The blood transfusion rates of ilaprazole sodium group and positive control group were 5.07 ％ (18/355) and 3.37 ％ (6/178).The incidence of switching to other treatments was 0.56％ (2/355) and 0.56％ (1/178),respectively,and the differences were not statistically significant (both P＞ 0.05).The incidence of adverse reactions in the ilaprazole sodium group was 3.94％ (14/355),which was lower than that of positive control group (8.43％,15/178).And the difference was statistically significant (Fisher's exact probability method,P=0.042).Conclusions The efficacy of ilaprazole sodium for injection in the treatment of peptic ulcer bleeding is similar to that of omeprazole sodium for injection.Moreover,the smaller the dose,the lower the frequency of administration and the better the safety.

Objective:To investigate the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in adenosqua-mous carcinoma (ASC) of the lung after resection. Methods:Clinical data of patients suffering from ASC and receiving EGFR-TKI treat-ment at one institution between January 2006 and December 2014 were retrospectively reviewed. Results:A total of 27 EGFR muta-tion-positive patients with ASC subjected to EGFR-TKI therapy were enrolled in this study. EGFR mutations included deletion in exon 19 in 15 cases and point mutation at codon 858 in exon 21 in 12 cases. Of the 27 ASC patients who received EGFR-TKI treatment, 9 exhibit-ed a partial response and 11 manifested a stable disease, and these patients accounted for a disease control rate of 74.1%(20/27). The median overall survival (OS), median progression-free survival, and median relapse OS of the EGFR mutation-positive patients who underwent TKI therapy were 39 months [95%confidence interval (CI)=25.6-52.4], 15 months (95%CI=12.9-17.1), and 19 months (95%CI=0.9-37.1), respectively. The 3-and 5-year survival rates of these patients after operation were 51.9%and 15.3%, respectively. Con-clusion:The survival of EGFR mutation-positive ASC patients treated with EGFR-TKIs was satisfactory. EGFR testing was recommended for ASCs and EGFR-TKI treatment was suitable for ASCs with EGFR-sensitizing mutation.

Objective:To investigate the prognostic factors and survival of patients with combined small cell lung cancer (C-SCLC) after they underwent complete resection. Methods:The clinical records of C-SCLC patients who were subjected to complete resection and systematic nodal dissection in one institution between January 2010 and December 2014 were retrospectively reviewed. Results:Sev-enty-eight patients with histologically diagnosed C-SCLC were identified. The most common combined component was large cell neuro-endocrine carcinoma (LCNEC) (n=42), followed by squamous cell carcinoma (SCC) (n=18), adenocarcinoma (AC) (n=10), and adenosqua-mous carcinoma (ASC) (n=8). The overall survival (OS) rate of the entire cohort was 39.1%. Multivariate analyses using Cox's propor-tional hazard models revealed that size [<3 cm vs.>3 cm;hazard ratio (HR)=0.406;95%confidence interval (CI)=0.202-0.816;P=0.011], performance status (<2 vs.>2;HR=0.113;95%CI=0.202-0.631;P=0.013), combined non-small cell lung cancer (NSCLC) components (LCNEC vs. non-LCNEC, HR=3.00;95%CI=0.096-0.483;P<0.001), stage Ⅲ A vs.Ⅰ;HR=0.195, 95%CI:0.063-0.602;P=0.004) and adju-vant therapy (yes vs. no, HR=0.402;95%CI=0.195-0.831;P=0.014) were significant prognostic factors of OS. Conclusion:The mixed NSCLC components within C-SCLC significantly influence survival. Adjuvant therapy is beneficial for patients with complete resection of C-SCLC.