Objective To observe the pharmacokinetic effect of amoxicillin and clavulanate potassium tablets on amoxicillin in Chinese healthy subjects under fasting and high fat and high calorie diet.Methods 71 healthy subjects were given a single dose of amoxicillin potassium clavulanate tablets(0.375 g)on fasting or high fat diet,and venous blood samples were collected at different time points.The concentrations of amoxicillin in human plasma were determined by HPLC-MS/MS method,and the pharmacokinetic parameters were calculated by non-atrioventricular model using PhoenixWinNonlin 8.0 software.Results The main pharmacokinetic parameters of amoxicillin potassium clavulanate tablets after fasting and high fat diet were(5 105.00±1 444.00),(4 593.00±1 327.00)ng·mL-1,and postprandial-fasting ratio 89.40％,90％confidence interval(79.55％-100.19％);t1/2 were(1.52±0.16),(1.39±0.22)h;AUC0-t were(12 969.00±1 841.00),(11 577.00±1 663.00)ng·mL-1·h,and postdietary/fasting ratio 89.20％,90％confidence interval(83.92％-94.28％);AUC0-∞ were(13 024.00±1 846.00),(11 532.00±1 545.00)ng·mL-1·h,and postprandial-fasting ratio 88.60％,90％confidence interval(83.48％-93.50％).The median Tmax(range)were 1.63(0.75,3.00)and 2.50(0.75,6.00)h,respectively,and the Tmax of postprandial medication was delayed(P＜0.01).Conclusion Compared with fasting condition,amoxicillin Tmax was significantly delayed after high fat diet,while Cmax,AUC0-t and AUC0-∞ were not significantly changed,indicating that food could delay the absorption of amoxicillin,but did not affect the degree of absorption.

Objective To observe the improvement of motor dysfunction and serum levels of C-reactive protein(CRP),blood glucose and blood lipid in post-stroke patients treated with scalp acupuncture at different needle retention time.Methods A total of 120 patients with motor dysfunction after stroke were randomly divided into control group,observation group 1 and observation group 2,with 40 cases in each group.The patients in the 3 groups were treated with scalp acupuncture,body acupuncture and routine rehabilitation exercise,once a day and 6 times a week,lasting for 2 weeks.The control group was given scalp acupuncture with retaining of needles for 30 minutes,the observation group 1 was given scalp acupuncture with retaining of needles for one hour,and the observation group 2 was given scalp acupuncture with retaining of needles for 2 hours.Before and after treatment,the 3 groups were observed in the changes of the scale scores of National Institutes of Health Stroke Scale(NIHSS),Fugl-Meyer Assessment(FM A),Berg Balance Scale(BBS)and modified Barthel Index(MBI),and the levels of laboratory indicators of peripheral blood CRP,fasting plasma glucose(FPG),total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C).After treatment,the clinical safety of the three groups was evaluated.Results(1)After treatment,the scale scores of NIHSS in the three groups were lower(P＜0.01)and the scale scores FMA,BBS and MBI were higher than those before treatment(P＜0.05 or P＜0.01).The comparison of post-treatment scale scores showed that the differences among the three groups were statistically significant(P＜0.01).The intergroup comparison showed that the decrease of NIHSS score and the increase of FMA,BBS and MBI scores in the observation group 2 were significantly superior to those in the control group and the observation group 1(P＜0.01);the improvement of FMA score in the observation group 1 was significantly superior to that in the control group(P＜0.01),while the improvement of NIHSS,BBS and MBI scores tended to be superior to that in the control group without statistically significant differences(P＞0.05).The results indicated that the curative effect of scalp acupuncture plus exercise regimen was positively correlated with the duration of needle retention for scalp acupuncture.(2)After treatment,the laboratory indicator levels of CRP and FPG in the peripheral blood of the three groups,the levels of TG and LDL-C in the two observation groups and the level of HDL-C in the observation group 2 were improved compared with those before treatment(P＜0.05 or P＜0.01).Statistically significant differences were presented in the post-treatment levels of CRP and TG in peripheral blood among the three groups(P＜0.05 or P＜0.01).The intergroup comparison showed that the improvement of CRP and TG levels in the observation group 2 was significantly superior to that in the control group,and the improvement of CRP level in the observation group 2 was significantly superior to that in the observation group 1,the differences being statistically significant(P＜0.05 or P＜0.01).The TC level in the three groups after treatment did not differ from that before treatment,and there was no significant difference in TC level after treatment among the three groups either(P＞0.05).(3)During the treatment,no adverse reactions such as fainting,needle breaking and hematoma occurred in the three groups,the vital signs of the patients were stable,and there were no obvious abnormal changes in pulse,blood pressure and respiratory rate.Conclusion Scalp acupuncture can effectively improve the motor function of post-stroke patients in a pasitive time-effect relationship with the needle retention,and better the curative effect can be achieved by retaining of the needle for 2 h.

Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.

Objective:To analyze clinical characteristics and high-frequency ultrasound features of localized scleroderma, and to construct and validate a non-invasive prediction model for staging of skin lesions based on the high-frequency ultrasound features.Methods:Patients with localized scleroderma were retrospectively collected from the Department of Dermatology and Venereology, Second Xiangya Hospital of Central South University from February 1, 2021 to February 28, 2023, and clinical data as well as high-frequency ultrasound and pathologic features of 85 lesions from these patients were analyzed. Lesions were divided into modeling cohort and validation cohort according to the chronological order of patient enrollment. The univariate analysis and multivariable logistic regression models were used to analyze the independent influential factors in the staging of localized scleroderma lesions in the modeling cohort, construct the regression equation, and to build a nomogram prediction model. The Bootstrap validation method was used for internal validation, and the predictive performance of the nomogram model in the modeling cohort and validation cohort was further evaluated by the calibration curve and receiver operating characteristic (ROC) curve.Results:In the modeling cohort, 60 patients with localized scleroderma, including 16 males and 44 females, were enrolled, with the age [ M ( Q1, Q3) ] being 22.0 (10.0, 39.2) years, and there were 28 lesions in the oedematous phase and 32 lesions in the fibrotic and atrophic phase; in the validation cohort, 25 patients with localized scleroderma, including 8 males and 17 females, were enrolled, with the age being 18.0 (7.0, 30.0) years, and there were 9 lesions in the oedematous phase and 16 lesions in the fibrotic and atrophic phase. Univariate analysis in the modeling cohort showed no significant differences in the age and gender of patients or the location of lesions between the oedematous phase group and the fibrotic and atrophic phase group (all P > 0.05) ; compared with the oedematous phase group, the fibrotic and atrophic phase group showed an increased proportion of patients with disease duration ≥ 2 years (20/32 cases vs. 10/28 cases, χ2 = 4.29, P = 0.038), decreased thicknesses of the subcutaneous fat layer in skin lesions (1.4 [0.0, 26.0] mm vs. 1.8 [0.1, 14.3] mm, Z = -2.14, P = 0.032), increased decrements in the subcutaneous fat layer thickness in the lesional sites compared with non-lesional control sites (1.8 [0.5, 11.0] vs. 0.3 [-1.9, 8.0] mm, Z = -4.72, P < 0.001), increased ratios of the lesional elasticity values to control elasticity values (2.9 [1.8, 6.9] vs. 1.8 [1.1, 5.9], Z = -4.34, P < 0.001), and increased ultrasound-based lesional activity scores (5.0 [3.0, 8.0] points vs. 3.0 [0.0, 5.0] points, Z = -4.76, P < 0.001). Multivariable logistic stepwise regression analysis showed that the disease duration ≥ 2 years ( P = 0.032), increased ratios of the lesional elasticity values to control elasticity values ( P = 0.019), increased ultrasound-based lesional activity scores ( P = 0.013), and increased decrements in the subcutaneous fat layer thickness in the lesions compared with the controls ( P = 0.013) helped to confirm localized scleroderma lesions in the fibrotic and atrophic phase. Based on the results of regression analysis, a total of 4 factors were included in the nomogram prediction model, including the disease duration, the decrement in the subcutaneous fat layer thickness in lesions compared with controls, the ratio of the lesional elasticity values to control elasticity values, and the ultrasound-based lesional activity score; additionally, the constructed logistic regression model formula for predicting the probability (p) of skin lesions in fibrotic and atrophic phase was "ln (p/[1 - p]) = -9.595 + 2.204 × the disease duration + 0.784 × the decrement in the subcutaneous fat layer thickness in the lesions compared with the controls (mm) + 0.887 × the ratio of the lesional elasticity values to control elasticity values + 1.374 × the ultrasound-based lesional activity score". The calibration curve showed a good predictive performance of the model through the Bootstrap validation method, and the ROC curve demonstrated good discrimination and accuracy (modeling cohort: area under the curve = 0.936, 95% CI: 0.879 - 0.994; validation cohort: area under the curve = 0.889, 95% CI: 0.748 - 1.000) . Conclusions:High-frequency ultrasound could provide essential details for staging the localized scleroderma lesions. Based on the disease duration, subcutaneous fat layer thickness, skin elasticity values, and ultrasound-based lesional activity scores, the constructed prediction model could predict the stages of localized scleroderma lesions with excellent discrimination, accuracy, and predictive performance.

Objective Exploring the occurrence and clinical characteristics of adverse drug reactions caused by the treatment of malignant hematological diseases in children with pegaspargase,in order to provide reference for safe drug use in clinical practice.Methods Summarize and organize 24 cases of adverse reactions related to pegaspargase reported in the pediatric hematology ward of our hospital from January 2016 to June 2023 for analysis and re evaluation.The basic information,severity of adverse drug reaction(ADR),dosage,route of administration,clinical manifestations,occurrence time and outcome of ADR were analyzed statistically.Results Among the 24 ADR reports,there were 15 males(62.50％)and 9 females(37.50％).The age ranged from 2 to 15 years,with an average age of(7.79±4.68)years.There were 16 children under 10 years old(66.67％).The primary disease is acute lymphocytic leukemia(87.50％).The administration mode of 24 patients was intramuscular injection,and the dosage was 1200-3 750 U.A total of 30 AD Rs occurred in 24 patients,10 of which were serious ADRs.The most common organ involved in ADR was gastrointestinal system damage(8 cases,27.59％),followed by systemic(6 cases,20.69％)and skin and Subcutaneous tissue(5 cases,17.24％).The shortest occurrence time of ADR is 5 minutes after medication,and the longest is 56 days after medication.Conclusion Clinical attention should be paid to the occurrence characteristics of asparaginase ADR.After medication,patients need to be monitored for safety over a long period of time,closely monitoring their clinical symptoms and related test indicators,especially in young children,to reduce the damage caused by ADR to patients.

The name， origin， place of origin， medicinal parts， harvesting and processing of lotus are verified by consulting ancient Chinese herbal medicines and medical books， combined with modern literature， providing a basis for the development of famous classical formulas containing lotus. According to textual research， the original base of lotus is Nelumbo nucifera since ancient times， rhizome （Nelumbinis Rhizomatis Nodus）， leaf （Nelumbinis Folium）， seed （Nelumbinis Semen）， embryo （Nelumbinis Plumula）， receptacle （Nelumbinis Receptaculum）， stamen （Nelumbinis Stamen） and other medicinal parts of N. nucifera can be used as medicine and have different clinical effects. Nelumbinis Semen was originally produced in Henan， and then gradually expanded to Jiangnan. Today， it can be cultivated and planted throughout the country， with Fujian， Hunan， and Jiangxi as the authentic production areas. After combing the medicinal parts of N. nucifera and the historical evolution of its processing， it is suggested that the dried and mature fruits of N. nucifera taking in autumn and removing the shell and Nelumbinis Plumula should be used in Qingxin Lianziyin. Nelumbinis Folium in Erdongtang should be harvested in summer and autumn， and the raw products was used as medicine and processed in accordance with the provision of the 2020 edition of Chinese Pharmacopoeia.

Based on the ancient literature of all dynasties， this article makes a systematic textual research on the name， origin， producing area， quality， harvesting and processing of Zisu （Perillae） in the famous classical formulas， so as to clarify the information of the drug in different historical periods and provide a reference for the development and utilization of the related formulas. The main origin of Perillae in the ancient literature was Perilla frutescens var. frutescens （purple leaf type）， followed by P. frutescens var. acuta （purple leaf type）， but not Baisu. Modern chemical composition studies also show that there are obvious differences between Perillae and Baisu， which provides a scientific basis for distinguishing them. Although they are often treated as a species in plant classification， P. frutescens var. frutescens （purple leaf type） is recommended in the development of famous classical formulas， and Baisu should be avoided. Perillae is widely distributed， but its producing area did not record in most of the literature in the past dynasties， or the producing area is described as everywhere today. In the period of the Southern and Northern dynasties， the medicinal parts of Perillae included stems， leaves and seeds， and doctors in the Ming dynasty began to pay attention to the differentiation of different medicinal parts. The harvesting and processing methods of Perillae in the past dynasties are close to that of today. Perillae Fructus is mostly stir-fried and ground into medicine， Perillae Folium and Perillae Caulis are mainly simple cleansing. In production， we can refer to the 2020 edition of Chinese Pharmacopoeia.

Through consulting the ancient herbal and medical books， combined with the field investigation， the name， origin， collection and processing of Dendrobium medicinal materials were researched， which provided a basis for the development of famous classical formulas containing this kind of herbs. Due to the wide distribution of D. officinale， the Dendrobium species represented by D. officinale and D. huoshanense， which are short， fleshy and rich in mucus， should be the most mainstream of Dendrobium medicinal materials in previous dynasties. Compared with Shihu， Muhu with loose texture， long and hollow is born on trees. According to the characteristic description， it should be D. nobile， D. fimbriatum and so on， of which D. nobile was the mainstream. The Chinese meaning of Jinchai was confused in the past dynasties， so it was not suitable to be treated as a plant name. The production areas of Dendrobium medicinal materials in the past dynasties have changed with the discovery of varieties， artificial cultivation and other factors. Lu'an， Anhui province， was the earliest recorded in the Han and Wei dynasties. Since the Tang and Song dynasties， it had been extended to Guangdong and Guangxi， and it was considered that "Dendrobii Caulis in Guangnan was the best". In the Ming dynasty， Sichuan and Zhejiang products were highly praised， and in the Qing dynasty， Huoshan products were highly praised. Dendrobium medicinal materials had been used as medicine by stems in all dynasties. The medicinal materials were divided into fresh products and dry products. The fresh products can be used immediately after removing the sediment from the roots. The dry products need further processing， most of them used wine as auxiliary materials for steaming， simmer to paste or decoction into medicine. D. officinale and D. huoshanense have special processing specifications since the middle of Qing dynasty， that is， "Fengdou". According to the research results， in Ganluyin， the effect of Dendrobium medicinal materials is mainly heat clearing， and D. nobile with bitter taste can be selected. The main effect of Dendrobium medicinal materials in Dihuang Yinzi is tonic， D. officinale or D. huoshanense can be selected.

In this study， name， origin， producing areas， harvesting time and processing methods of ancient Alismatis Rhizoma were systematically researched by consulting the literature of ancient herbs， medical and prescription books， so as to provide a basis for the development of famous classical formula containing this herb. According to textual research， the main base of ancient Alismatis Rhizoma was Alisma plantago-aquatica and A. orientale. A. canaliculatum and A. gramineum and other genera were sometimes used as the source of Alismatis Rhizoma， there was a confusion of medicinal varieties. The earliest producing area of Alismatis Rhizoma was in today's Henan province， and later Hanzhong， Shaanxi province， became the high-quality producing area of Alismatis Rhizoma. Since the Ming dynasty， its production area expanded to Fujian. In the Qing dynasty， Jian'ou in Fujian was the authentic production area of Alismatis Rhizoma. In the period of the Republic of China， Sichuan and Jiangxi were added to the production areas of Alismatis Rhizoma. Based on the research results， it is suggested that the dried tubers of A. orientale from Fujian and Jiangxi or A. plantago-aquatica from Sichuan should be used in the famous classical formulas. In ancient times， Alismatis Rhizoma was processed by wine， but most of the standards and specifications in modern times are no longer included the processing specifications of Alismatis Rhizoma with wine. Although salt-processed Alismatis Rhizoma is commonly used in modern times， it didn't become one of the main processing methods until the Qing dynasty. According to the relevant national documents， it is suggested that Alismatis Rhizoma without clear processing requirements in famous classical formulas should be used as raw products， and the formulas with processing requirements should be selected as processed products such as salt and wine according to the meaning of the formulas.

By consulting the ancient herbal and medical books， combined with modern literature， the name， origin， geoherbalism， harvesting and processing changes of Bambusae Caulis in Taenias in famous classical formulas were sorted out. According to the research， ancient doctors only approved three kinds of bamboo medicinal materials， namely， Jinzhu （䈽竹）， Kuzhu （苦竹） and Danzhu （淡竹）， and took bamboo leaves， made Bambusae Caulis in Taenias and Zhuli （竹沥） for medicine. Bamboo medicinal materials with different origins have different properties， tastes and effects， after clinical optimization， it is gradually considered that Danzhu is the best source of Bambusae Caulis in Taenias and Zhuli. According to the morphological description of the original plants and the attached drawings， it is considered that the Danzhu in ancient Chinese materia medica should be Phyllostachys nigra var. henonis， which has been included in the 2020 edition of Chinese Pharmacopoeia as one of the genuine sources of Bambusae Caulis in Taenias. Therefore， It is suggested that P. nigra var. henonis can be added as the source of Bambusae Caulis in Taenias in famous classical formulas， and the medicinal part is the dry middle layer of its stem. Ginger-processed can increase the anti emetic effect of Bambusae Caulis in Taenias， and the three formulas involving Bambusae Caulis in Taenias from The Catalogue of Ancient Famous Classical Formulas （The First Batch） all contain ginger， and the processing method of Bambusae Caulis in Taenias is not marked in the original formula， so it is suggested to use raw products in the three formulas of Jupi Zhurutang， Wendantang and Zhurutang.