Objective:To investigate the influence of ultrasonic monitoring of bladder filling levels on setup errors before fractionated radiotherapy for cervical cancer patients through a comparative analysis, and its effectiveness in improving clinical target volume (CTV) margins.Methods:A retrospective study was conducted on 1 284 error data of setup via cone beam CT (CBCT) and 6D setup error correction system from 172 cervical cancer patients treated in the Radiotherapy Department of Peking University Cancer Hospital from January 2019 to October 2023. These patients were classified into two groups: 87 (659 times of setup) with ultrasonic monitoring of bladder filling levels and 85 (625 times of setup) without ultrasonic monitoring. The setup errors, error distributions, and numbers of abnormal setups between the two groups were compared in the lateral (Lat), longitudinal (Lng), vertical (Vrt), pitch (Pitch), roll (Roll), and rotational (Rtn) dimensions. Moreover, the CTV to planning target volume(PTV) margin values in the three-dimensional direction were calculated for both groups to assess the clinical value of ultrasonic monitoring of bladder filling levels before fractionated radiotherapy.Results:Compared to the group without ultrasonic monitoring, the group with ultrasonic monitoring exhibited lower median values of setup errors in all six-dimensional directions and smaller upper and lower interquartile ranges ( Z = -10.86 to -6.34, P<0.05). The group with ultrasonic monitoring manifested more concentrated setup errors in various directions and statistically significantly reduced numbers of abnormal setups ( χ2=15.33, P<0.05). Moreover, CTV-PTV margins of the group with ultrasonic monitoring displayed reduced CTV-PTV margin values by 0.55, 1.52, and 1.26 mm in the Vrt, Lng, and Lat directions, respectively. Conclusions:Pre-radiotherapy ultrasonic monitoring of bladder filling levels in cervical cancer patients can significantly improve the repeatability of setup, thus notably reducing the incidence of abnormal setups. Theoretically, it can narrow the range from the CTV to the PTV, thereby minimizing radiation exposure to healthy tissues and ultimately enhancing radiotherapy precision for cervical cancer and reducing radiation damage.

Objective:To investigate the influence of ultrasonic monitoring of bladder filling levels on setup errors before fractionated radiotherapy for cervical cancer patients through a comparative analysis, and its effectiveness in improving clinical target volume (CTV) margins.Methods:A retrospective study was conducted on 1 284 error data of setup via cone beam CT (CBCT) and 6D setup error correction system from 172 cervical cancer patients treated in the Radiotherapy Department of Peking University Cancer Hospital from January 2019 to October 2023. These patients were classified into two groups: 87 (659 times of setup) with ultrasonic monitoring of bladder filling levels and 85 (625 times of setup) without ultrasonic monitoring. The setup errors, error distributions, and numbers of abnormal setups between the two groups were compared in the lateral (Lat), longitudinal (Lng), vertical (Vrt), pitch (Pitch), roll (Roll), and rotational (Rtn) dimensions. Moreover, the CTV to planning target volume(PTV) margin values in the three-dimensional direction were calculated for both groups to assess the clinical value of ultrasonic monitoring of bladder filling levels before fractionated radiotherapy.Results:Compared to the group without ultrasonic monitoring, the group with ultrasonic monitoring exhibited lower median values of setup errors in all six-dimensional directions and smaller upper and lower interquartile ranges ( Z = -10.86 to -6.34, P<0.05). The group with ultrasonic monitoring manifested more concentrated setup errors in various directions and statistically significantly reduced numbers of abnormal setups ( χ2=15.33, P<0.05). Moreover, CTV-PTV margins of the group with ultrasonic monitoring displayed reduced CTV-PTV margin values by 0.55, 1.52, and 1.26 mm in the Vrt, Lng, and Lat directions, respectively. Conclusions:Pre-radiotherapy ultrasonic monitoring of bladder filling levels in cervical cancer patients can significantly improve the repeatability of setup, thus notably reducing the incidence of abnormal setups. Theoretically, it can narrow the range from the CTV to the PTV, thereby minimizing radiation exposure to healthy tissues and ultimately enhancing radiotherapy precision for cervical cancer and reducing radiation damage.

Objective:To reassess the prognostic value of minimal residual disease (MRD) and IKZF1 gene deletions in adults with B-cell acute lymphoblastic leukemia (B-ALL) who received pediatric-specific chemotherapy regimens during the Nanfang Hospital PDT-ALL-2016 trial.Methods:We retrospectively analyzed the prognosis of 149 adult patients with B-ALL who were admitted to Nanfang Hospital from January 2016 to September 2020. Prognostic factors were identified using Cox regression models.Results:The complete remission rate was 93.2% in 149 patients, with a 5-year overall survival (OS) rate of (54.3±5.0) % and a cumulative incidence of relapse (CIR) of (47.5±5.2) %. The Cox regression analysis revealed that MRD positivity at day 45 (MRD 3) after induction therapy was independently associated with relapse risk ( HR=2.535, 95% CI 1.122-5.728, P=0.025). Deletion of IKZF1 gene was independently associated with mortality risk ( HR=1.869, 95% CI 1.034-3.379, P=0.039). Based on MRD 3 and IKZF1 gene status, we categorized adult patients with B-ALL into the low-risk (MRD 3-negative and IKZF1 gene deletion-negative) and high-risk (MRD 3-positive and/or IKZF1 gene wild type) groups. The 5-year OS and CIR rates were (45.5±6.0) % vs (69.4±8.6) % ( P<0.001) and (61.6±8.3) % vs (25.5±6.5) % ( P<0.001), respectively, in the high-risk and low-risk groups, respectively. The multivariate analysis showed that the high-risk group was an independent risk factor for OS ( HR=3.937, 95% CI 1.975-7.850, P<0.001) and CIR ( HR=4.037, 95% CI 2.095-7.778, P<0.001) . Conclusion:The combined use of MRD and IKZF1 gene in prognostic stratification can improve clinical outcome prediction in adult patients with B-ALL, helping to guide their treatment.

Background:The burden of Crohn's disease(CD)is rising globally,and the efficacy and safety of ustekinumab(UST)in treatment of CD need to be further verified.Aims:To assess the short-term efficacy and safety of UST in CD patients.Methods:A single-center retrospective observational study was conducted in the First Affiliated Hospital of Kunming Medical University.The clinical data of CD patients treated with UST from January 2020 to December 2023 were analyzed retrospectively.The clinical activity and endoscopic severity of the disease were assessed using Crohn's disease activity index(CDAI)and simple endoscopic score for Crohn's disease(SES-CD),respectively.The primary outcomes were clinical response(CDAI score decreased≥70 points,or CDAI score decreased<70 points but the total score<150)and clinical remission(CDAI score<150),while the secondary outcomes included endoscopic response(SES-CD decreased≥50%),endoscopic remission(SES-CD≤2),changes of inflammatory and nutritional indicators,and the adverse events.Results:Twenty-seven CD patients were included,of which,16 were males,and 11 were females,with median disease duration of 3.00 years.After treatment with UST,the median CDAI score decreased from 213.00(178.83,302.98)at baseline to 129.83(89.67,151.33)at week 16/20 and 95.07(67.45,178.34)at week 32(all P<0.017).The clinical response rate and remission rate at week 16/20 were 92.6%and 70.4%,respectively,and those at week 32 were 95.5%and 72.7%,respectively.When patients were stratified as biologic na?ve and exposure,or as with and without dose optimization,no significant differences were found in clinical response and remission rates among various subgroups.Seventeen patients reviewed endoscopy at week 16/20,the SES-CD decreased significantly from baseline(5.47±4.53 vs.9.88±4.58,P<0.05),with the endoscopic response rate and remission rate of 35.3%and 23.5%,respectively.C-reactive protein decreased significantly from baseline at week 16/20 and week 32 of treatment(all P<0.017),while the platelet count,hemoglobin,albumin and body mass index only showed insignificant improving trends.No serious adverse events were observed during the medication period.Conclusions:UST can improve the clinical symptoms,endoscopic manifestations,and systemic inflammation effectively in CD patients in short-term follow-up,and represents a good safety profile.

Background:The burden of Crohn's disease(CD)is rising globally,and the efficacy and safety of ustekinumab(UST)in treatment of CD need to be further verified.Aims:To assess the short-term efficacy and safety of UST in CD patients.Methods:A single-center retrospective observational study was conducted in the First Affiliated Hospital of Kunming Medical University.The clinical data of CD patients treated with UST from January 2020 to December 2023 were analyzed retrospectively.The clinical activity and endoscopic severity of the disease were assessed using Crohn's disease activity index(CDAI)and simple endoscopic score for Crohn's disease(SES-CD),respectively.The primary outcomes were clinical response(CDAI score decreased≥70 points,or CDAI score decreased<70 points but the total score<150)and clinical remission(CDAI score<150),while the secondary outcomes included endoscopic response(SES-CD decreased≥50%),endoscopic remission(SES-CD≤2),changes of inflammatory and nutritional indicators,and the adverse events.Results:Twenty-seven CD patients were included,of which,16 were males,and 11 were females,with median disease duration of 3.00 years.After treatment with UST,the median CDAI score decreased from 213.00(178.83,302.98)at baseline to 129.83(89.67,151.33)at week 16/20 and 95.07(67.45,178.34)at week 32(all P<0.017).The clinical response rate and remission rate at week 16/20 were 92.6%and 70.4%,respectively,and those at week 32 were 95.5%and 72.7%,respectively.When patients were stratified as biologic na?ve and exposure,or as with and without dose optimization,no significant differences were found in clinical response and remission rates among various subgroups.Seventeen patients reviewed endoscopy at week 16/20,the SES-CD decreased significantly from baseline(5.47±4.53 vs.9.88±4.58,P<0.05),with the endoscopic response rate and remission rate of 35.3%and 23.5%,respectively.C-reactive protein decreased significantly from baseline at week 16/20 and week 32 of treatment(all P<0.017),while the platelet count,hemoglobin,albumin and body mass index only showed insignificant improving trends.No serious adverse events were observed during the medication period.Conclusions:UST can improve the clinical symptoms,endoscopic manifestations,and systemic inflammation effectively in CD patients in short-term follow-up,and represents a good safety profile.

Wutou-Gancao herb-pair is extensively used to attenuate the toxicity and enhance the efficacy of aconite. In this study, potential synergic mechanism of the herb pair was investigated by utilizing multiple ap-proaches. In silico and in vitro Caco-2 cell models were applied to study the potential binding mode of bioactive ingredients existing in liquorice with P-glycoprotein (P-gp), as well as the inhibition effects on P-gp. Additionally, anti-inflammatory activity of aconitine (AC) combined with active ingredients of liquorice, as well as pharmacokinetic patterns of AC after co-administration was investigated. Anti-inflammatory effect of AC (1 mg/kg) in rats was enhanced in combination with bioactive ingredients of liquorice (10 mg/kg). In the meanwhile, the exposure of AC in vivo was altered, in terms of Cmax and AUC. For instance, the Cmax and AUC were increased to 1.9 and 1.3 folds, respectively, when used in combination with liquiritigenin. The in silico study revealed the potential binding mode with outward facing conformation of P-gp. The resulting data obtained from transport of rhodamine-123 (Rh-123) across Caco-2 cell monolayer further indicated that the function of P-gp was inhibited by chemicals in liquorice. The synergic effect was therefore proposed to be attributed to inhibition of P-gp by liquorice since AC has been demonstrated to be the substrate of P-gp. The resuls revealed that potential synergic mechanism of Wutou-Gancao herb-pair by inhibiting function of key efflux transporter P-gp to enhance the exposure of AC in systematic circulation, and further the anti-inflammatory effect, which helps clarify the compatibility rationale of these two herbs.

Objective:To investigate the acute and long-term toxicity of GJ-4 extracted from Gardenia jasminoides J.Ellis, and to provide safety basis for its development as a new drug for the treatment of dementia. Methods:In the acute toxicity experiment, 30 ICR mice were randomly divided into control group, gardenia extract 2.5 g/kg group and gardenia extract 5.0 g/kg group, 10 mice in each group. The mice in the 2.5 g/kg and 5.0 g/kg gardenia extract groups were administrated with GJ-4 suspension. The control group was given 0.5% sodium carboxymethyl cellulose (CMC-Na) by gavage. The mice were given continuous gavage for 7 days. The mortality, body weight and general condition of mice were recorded. The levels of ALT, ALP, BUN and creatinine (CRE) in serum were measured by automatic biochemical detector. In the long-term toxicity experiment, 75 ICR mice were divided into control group and gardenia extract 100, 250, 500, 1 000 mg/kg group according to the random number table method, 15 mice in each group. The GJ-4 suspension of Gardenia extract 100, 250, 500 and 1 000 mg/kg were administrated to the stomach respectively in the gardenia extract 100, 250, 500 and 1 000 mg/kg groups, and 0.5% CMC-Na of the same volume was administrated to the stomach in the control group once a day for 30 days. The mortality, weight and mental state of mice were recorded. The organ index and the levels of ALT, ALP and BUN in serum were observed.Results:In the acute toxicity experiment, the mental state and diet of mice in each group were good, and there was no death within 7 days. Compared with the control group, there was no significant differences in body weight, heart index, liver index and kidney index between the two groups ( P>0.05). Compared with the control group, the level of BUN (10.17 ± 0.82 mmol/L vs. 11.25 ± 0.47 mmol/L) in the gardenia extract 2.5 g/kg group significantly decreased ( P<0.05), and the level of ALP (116.0 ± 10.75 U/L vs. 148.0 ± 25.73 U/L) in the gardenia extract 5.0 g/kg group significantly decreased ( P<0.05). In the long-term toxicity experiment, the mice were in good mental state and had good diet, and no death occurred. Compared with the control group, there was no significant differences in body weight, heart index, kidney index, spleen index and serum ALT, ALP and BUN levels between the two groups ( P>0.05). The liver index (4.9 ± 0.56 vs. 4.38 ± 0.49) in the 250 mg/kg gardenia extract group significantly increased ( P<0.01), and the thymus index (0.09 ± 0.02 vs. 0.14 ± 0.04) significantly decreased ( P<0.05). Conclusions:The Gardenia jasminoides extract GJ-4 has no obvious toxicity in acute and long-term toxicity experiment, indicating that GJ-4 is safe.

Objective:To analyze pharmaceutical procurement model of hospital, and explore better pharmaceutical procurement model so as to suit the development of modern hospital.Methods: Combined with the current situation of pharmaceutical procurement in domestic medical organization in recent years to analyze the current problems that existed in pharmaceutical procurement of hospital management.Results: Aimed at the problems that existed in procurement management model in current hospital, the reasonable suggestions have been proposed, and these suggestions have provided reference and experience forpharmaceutical management and procurement in hospital.Conclusion: Pharmaceutical procurement is the material basis of pharmaceutical supply of pharmaceutical trading enterprise, and it is the start point of pharmaceutical circulation and distribution, and it also is the first important step. Especially, aimed at the institutional reform of separating pharmacy from clinic in Beijing, the normalization of pharmaceutical procurement management will be very important effect in working practice.

Objective To study the inhibitory effects ofberberine on human organic cation transporter (OCTs) including OCT1,OCT2,OCT3,OCTN1 and OCTN2.Methods Using animal cell transgenic method mediated by transporter Lipo 3000,the drug transporters over expression cell lines S2-OCT1,S2-OCT2,S2-OCT3,S2-OCTN1 and S2-OCTN2 were obtained by selective medium culture.The OCTs evaluation model was established by detecting the trans-membrane transport of radioactive substrate in vitro.Wild type (WT) cells were used as control group,activity of OCTs was verified by adding its inhibitor.The inhibition of berberine on the transporters was investigated in vitro.The IC50 of inhibitory effect of berberine on various drug transporters was also calculated.Result The transport activity of transporter cell lines was increased by more than 5 times compared to the WT cell line respectively,what's more,their transport activity decreased significantly by their corresponding inhibitor.The ICs0 of berberine to OCT1,OCT2,OCT3,OCTN1 and OCTN2 were respectively 7.63,6.80,2.25,4.66 and 210.34 μmol/L.Conclusion Berberine significant inhibition to OCT1,OCT2,OCT3,OCTN1 and OCTN2.The inhibition on OCT1,OCT2,OCT3,OCTN1 is stronger compared to OCTN2.

Objective To study the inhibition of berberine on organ anion transporters (OATs) and its bidirectional trans-membrane transport.Method The transgene cell lines of the organ anion transporters including OAT1,OAT2,OAT3,OAT4,OAT7,and URAT1 were constructed and selected by animal cell transgenic method mediated by transporter Lipo 3000.Wild type (WT) cells were used as control group,and activity of OATs was verified by adding their radiolabeled substrates and inhibitors.The inhibition of 100 μmol/L berberine on the transporters was investigated in vitro.The IC50 of berberine on URAT1 was also determined.The bidirectional transport of berberine was studied through the Caco-2 model.Result The results showed that 100 μmol/L berberine inhibited the activity of OAT1,OAT2,OAT3,OAT4,OAT7 and URAT1 to (70.48±4.23)％,(69.13±1.28)％,(72.12±3.28)％,(79.77±6.49)％,(69.51 ±5.99)％ and (38.4 ± 2.67)％ respectively,the IC50 of berberine to URAT 1 was 13.19 μmol/L,the Papp (A-B) of 50 μmol/L and 100 μmol/L berberine were separately 0.28 × 10-6 and 0.40 × 10-6 cm/s,and the effiux rates were separately 3.18 and 3.15.Conclusion Berberine shows a stronger inhibition to URAT1 compared to OAT1,OAT2,OAT3,OAT4 and OAT7.Berberine may be the substrate of some effiux transporters.This study provides theoretical basis for explaining the low bioavailability ofberberine and forecasting the possible drug-drug interaction.