Stability study of umbilical cord mesenchymal stem cells formulation in large-scale production / 药学学报

Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.

ZHANG Yunling's Experience in the Treatment of Amyotrophic Lateral Sclerosis from Emphasis on both Spleen and Kidney / 中医杂志

This paper summarized Professor ZHANG Yunling's experience in the treatment of amyotrophic lateral sclerosis （ALS） from emphasis on both spleen and kidney. It is considered that the characteristic of ALS manifested as overlap of atrophy-flaccidity disease and convulsive disease， and the core pathogenesis are the deficiency of spleen and kidney and the inner pathogenic qi. ZHANG advocated that ALS should be treated from tonifying both the spleen and kidney， as strong spleen and kidney led the latent pathogen at peace. Usually applied Huangqi （Astragalus mongholicus）， Baizhu （Atractylodes macrocephala） combined with Taizishen （Pseudostellaria heterophylla）， fried Yiyiren （Coix lacryma-jobi）， Doukou （Myristica fragrans） and Sharen （Wurfbainia villosa） to tonify the middle and replenish qi， ascend lucidity and descend turbidity to invigorate the spleen； Roucongrong （Cistanche deserticola）， Tusizi （Cuscuta chinensis） combined with Shanyao （Dioscorea oppositifolia）， Shanzhuyu （Cornus officinalis） and prepared Dihuang （Rehmannia glutinosa） are used to support the fire and nourish the water， so as to replenish the spleen. The empirical formula regarded invigorateing the spleen and replenishing the kidney as the core therapeutic principle throughout the treatment of the whole process， which aimed at extinguishing inner wind and pacifying latent pathogen when treating the root.

Herbal Textural Research on Treatment of Headache Based on Syndrome Differentiation / 中国实验方剂学杂志

ObjectiveTo summarize the thinking of treatment of headache based on syndrome differentiation by reviewing the literature of materia medica in the past dynasties， so as to guide the clinical practice. MethodAll the literature of materia medica in the Chinese Medical Dictionary， involving 76 works from Han to Qing Dynasties， were searched， and the information of the herbs for treating headache was extracted. According to Chinese Materia Medica （11th Edition） and Pharmacopoeia of the People's Republic of China （2020 Edition）， the nature， taste， and meridian tropism of the selected herbs were statistically analyzed， and the syndrome elements of headache were classified and counted. In addition， the contents of syndrome differentiation and treatment of headache by different herbs were extracted. ResultFrom the 76 monographs of materia medica in the past dynasties， 114 herbs for treating headache were selected. The herbs mainly had cold or warm nature， pungent or bitter taste， and tropism to the lung and live meridians. The syndrome elements of headache treated by the herbs mainly included wind attack， fire disturbance， turbid obstruction， stagnation， cold coagulation， and healthy Qi deficiency. ConclusionHeadache is mainly treated with the herbs with the effects of dispelling pathogenic wind， clearing heat and purging fire， eliminating phlegm and resolving dampness， regulating Qi movement and activating blood， warming Yang and dispelling cold， and tonifying deficiency and reinforcing healthy Qi， and the herbs are often used in combinations. Headache is treated following the principles of dispelling wind and pathogen， regulating Qi and blood， and tonifying deficiency and purging excess， which is in line with the laws of obstruction and nutrient deficiency causing pain.

Clinical application of Ivor-Lewis procedure under uniportal video-assisted thoracoscopy for esophageal cancer / 中华胸心血管外科杂志

Objective:To investigate the safety and feasibility of Ivor-Lewis procedure under uniportal video-assisted thoracoscopy(VATS) for esophageal cancer and Siewert type I esophago-gastric junction carcinoma.Methods:The patients with middle-lower segment esophageal cancer or Siewert type I esophago-gastric junction carcinoma received minimally invasive esophagectomy between October 2020 and June 2021, and the clinical data was collected and analyzed.Results:26 patients received Ivor-Lewis procedure underwent uniportal VATS, while 45 patients underwent McKeown surgery under multiport VATS. The average operation time of patients in the two groups were(265±110)min and (235±94)min, and the average intraoperative blood loss were(80±57)ml and(105±60)ml. The mean number of lymph nodes removed in the surgery were (19.3±2.9) and 18.6±2.7 respectively in two groups, and the mean length of hospital stay was(7.5±3.5)days and(8.3±2.7)days. The incidence of perioperative complications were not significantly different in two groups. The VAS score of patients received Ivor-Lewis procedure underwent uniportal VATS was lower than that of patients received McKeown surgery in ostoperative day 1, day 3, day 7 and 1 month. The difference was statistically significant in two groups( P<0.05). Conclusion:The Ivor-Lewis procedure under uniportal VATS for esophageal cancer and Siewert type I esophago-gastric junction carcinoma has the advantage of less postoperative pain, and the procedure is feasible in clinical practice.

Current status of surgery for portal hypertension in China: a national multi-center survey analysis / 中华器官移植杂志

Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.

Investigation of arterial stiffness and its influencing factors in prediabetic population / 中华超声影像学杂志

Objective:To explore the level of arterial stiffness and its influencing factors in prediabetic population.Methods:From June 2021 to June 2022, 207 prediabetes patients were prospectively and randomly recruited from the physical examination center and outpatient clinic of Tangdu Hospital of Air Force Military Medical University to be the prediabetic group and 130 healthy volunteers at the same time with the same gender and age as the healthy controls. The carotid-femoral pulse wave velocity (PWV), brachial-radial PWV, and femoral-ankle PWV were measured by an automatic ultrasonic arterial stiffness measurement technology. The common carotid artery wall intima-media thickness (IMT) and left heart function were routinely evaluated. A questionnaire was designed to investigate the subjects′ smoking, drinking, diet, staying up late, exercise and other living habits. Comparison between groups and multivariate linear regression analysis were used to analyze the relevant data.Results:The carotid-femoral PWV and common carotid artery wall IMT in prediabetic group were significantly higher than those in healthy controls [(7.10±2.00)m/s vs (6.26±1.14)m/s, (0.57±0.11)mm vs (0.51±0.08)mm; both P<0.001], but there were no significant differences in the brachial-radial PWV and femoral-ankle PWV between the two groups (both P>0.05). Multivariate linear regression analysis showed that prediabetes was an independent influencing factor in carotid-femoral PWV after adjusting for confounding factors ( P<0.001), in addition, age ( P<0.001), diastolic blood pressure ( P<0.001), staying up late ( P=0.011) and low density lipoprotein cholesterol ( P=0.022) were also the independent influencing factors of carotid-femoral PWV. Conclusions:Compared with healthy people, the stiffness of aorta is significantly increased in prediabetic people, but there is no significant change in the stiffness of peripheral arteries. Prediabetes, age, diastolic blood pressure, staying up late and low density lipoprotein cholesterol are independent influencing factors of carotid-femoral PWV.

Analysis of incidence and influencing factors of congenital heart disease in perinatal infants in Henan province / 新乡医学院学报

Objective To analyze the incidence, trend and influencing factors of congenital heart disease(CHD) in perinatal infants in Henan province. Methods From 2011 to 2020,1 356 838 perinatal infants born from 28 weeks of pregnancy to 7 days after delivery were selected from 37 national birth defect monitoring points in Henan province as the research subjects, and the incidence of CHD in perinatal infants from different regions, fetal sex and maternal age were compared. The Joinpiont regression model was established to analyze the temporal change trend of the incidence rate of CHD in perinatal infants in Henan province from 2011 to 2020; the annual percentage change (APC) represented the internal trend of each segment, and the average annual percentage change (AAPC) represented the overall change trend. The trend of gap in incidence rate of CHD in different regions, mother's age and perinatal sex was compared by the Joinpiont parallel test. Results From 2011 to 2020,19 004 cases of perinatal infants with CHD were detected in Henan province, with a total incidence of 140.06/10 000; the incidence of CHD in perinatal infants showed an increasing trend year by year (AAPC=43.3% ,P<0.05) From 2011 to 2020, the incidence of CHD in urban perinatal infants in Henan province was significantly higher than that in rural areas, the incidence of CHD in male perinatal infants was significantly higher than that in female perinatal infants，and the incidence of CHD in perinatal infants in older mothers was significantly higher than that in younger mothers (X2=7 259.160,5 415.473,499.520; P<0.05). From 2011 to 2020,the incidence of CHD in perinatal infants in urban and rural areas of Henan province showed an increasing trend year by year (AAPC=42.5% ,44.5% ;P<0.05); the difference between urban and rural areas in the incidence of CHD in perinatal infants was increasing year by year(P<0.05). From 2011 to 2020,the incidence of CHD in male perinatal and famale perinatal infants in Henan province showed an increasing trend year by year(AAPC=44.3%，42.7% ;P<0.05). From 2011 to 2020, the incidence of CHD in perinatal infants of non-elderly and elderly pregnant women in Henan province showed an increasing trend year by year (AAPC=42.9% ,42.7% ;P<0.05).the difference between the elderly arid non-elderly pregnant women in the incidence of CHD In perinatal infants was increasing year by year (P<0.05). Conclusion From 2011 to 2020 ,the incidence of CHD in perinatal infants in Henan province showed an upward trend, and the regional distribution, fetal sex and maternal age were related to the incidence of perinatal CHD.

Perioperative efficacy analysis of robotic surgical system assisted anatomic and non-anatomic hepatectomy / 中华消化外科杂志

Objective:To investigate the perioperative efficacy of robot surgical system assisted anatomic and non-anatomic hepatectomy.Methods:The propensity score matching and retrospective cohort study was conducted. The clinical data of 103 patients who underwent robot surgical system assisted hepatectomy in Sir Run Run Shaw Hospital, Affiliated with the Zhejiang University School of Medicine from March 2016 to December 2021 were collected. There were 54 males and 49 females, aged 56(range, 44?64)years. Of the 103 patients, 55 cases undergoing robot surgical system assisted anatomic hepatectomy were divided into the anatomic group, and 48 cases undergoing robot surgical system assisted non-anatomic hepatectomy were divided into the non-anatomic group. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) intraoperative conditions; (3) perioperative complications. Propensity score matching was done by the 1:1 nearest neighbor matching method. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were expressed as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the rank sum test. Results:(1) Propensity score matching and compari-son of general data of patients between the two groups after matching. Of the 103 patients, 94 cases were successfully matched, including 47 cases in the anatomic group and 47 cases in the non-anatomic group. The elimination of preoperative body mass index, preoperative platelet and preoperative albumin confounding bias ensured comparability between the two groups after propensity score matching. (2) Intraoperative conditions. After propensity score matching, the operation time and volume of intraoperative blood loss were 175(range, 120?240)minutes and 50(range, 50?100)mL in patients of the anatomic group, versus 155(range, 105?190)minutes and 100(range, 50?200)mL in patients of the non-anatomic group, showing significant differences in the above indicators between the two groups ( Z=1.97, 2.49, P<0.05). (3) Perioperative complications. After propensity score matching, cases with pleural fluid and/or ascites, case with biliary fistula, case with thrombosis, case with peritoneal infection, case with incision infection were 11, 1, 2, 4, 1 in patients of the anatomic group, versus 12, 0, 4, 1, 0 in patients of the non-anatomic group, showing no significant difference in the above indicators between the two groups ( P>0.05). Cases with complications classified as grade Ⅰ, grade Ⅱ, grade Ⅲ, grade Ⅳ of the Clavien-Dindo classification were 33, 14, 0, 0 in patients of the anatomic group, versus 28, 14, 3, 2 in patients of the non-anatomic group, showing no significant difference in the above indicators between the two groups ( Z=?1.38, P>0.05). Conclusions:Robotic surgical system assisted anatomic and non-anatomic hepatectomy are safe and feasible for clinical application. Compared with robot surgical system assisted non-anatomic hepatectomy, patients under-going robot surgical system assisted anatomic hepatectomy have long operation time and less volume of intraoperative blood loss.

Safety of minimally invasive liver resection for resectable hepatocellular carcinoma complica-ted with portal hypertension: a multicenter study / 中华消化外科杂志

Objective:To investigate the safety of minimally invasive liver resection for resectable hepatocellular carcinoma (HCC) complicated with portal hypertension.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 807 patients with resectable HCC who underwent minimally invasive liver resection in 8 medical centers, including Sir Run Run Shaw Hospital, Affiliated with the Zhejiang University School of Medicine et al, from June 2011 to November 2022 were collected. There were 670 males and 137 females, aged 58(50,66)years. Of the 807 patients, 173 cases with portal hypertension were divided into the portal hypertension group, and 634 cases without portal hypertension were divided into the non-portal hypertension group. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) intraoperative and post-operative situations; (3) subgroup analysis. Propensity score matching was done by the 1:1 nearest neighbor matching method, with the caliper setting as 0.001. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was constructed using the non-parameter rank sun test. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of the 807 patients, 268 cases were successfully matched, including 134 cases in the portal hypertension group and 134 cases in the non-portal hypertension group. The elimination of the tumor diameter and robot-assisted surgery confounding bias ensured comparability between the two groups after propensity score matching. (2) Intraoperative and postoperative situations. The occlusion time of porta hepatis, cases with intraoperative blood transfusion, cases with postoperative complication, cases with complication >Ⅱ grade of Clavien-Dindo classification, cases of Clavien-Dindo classification as Ⅰ grade, Ⅱ grade, Ⅲ grade, Ⅳ grade, cases with liver related complication were 27.0(15.0,43.0)minutes, 33, 55, 15, 13, 29, 14, 1, 37 in the portal hypertension group, versus 35.0(22.0,60.0)minutes, 17, 25, 5, 14, 9, 4, 1, 13 in the non-portal hypertension group, showing significant differences in the above indicators between the two groups ( Z=-2.15, χ2=6.30, 16.39, 4.38, 20.72, 14.16, P<0.05). (3) Subgroup analysis. Results of subgroups analysis showed that in cases with major live resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 243.5(174.6,296.3)minutes, 200.0(150.0,600.0)mL, 7.5(6.0,13.0)days in the portal hypertension group, versus 270.0(180.0,314.5)minutes, 200.0 (75.0,450.0)mL, 7.0(5.5,10.0)days in the non-portal hypertension group, showing no significant difference in the above indicators between the two groups ( Z=-0.54, -1.73, -0.92, P>0.05). In cases with non-major live resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 170.0(120.0,227.5)minutes, 100.0(50.0,200.0)mL, 8.0(5.0,10.0)days in the portal hypertension group, versus 170.0(120.0,227.5)minutes, 100.0(50.0,200.0)mL, 7.0(5.5,9.0)days in the non-portal hypertension group, showing no significant difference in the above indicators between the two groups ( Z=-1.39, -0.10, 1.05, P>0.05). In cases with anatomical liver resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 210.0(150.0,285.0)minutes, 150.0(50.0,200.0)mL, 8.0(6.0,9.3)days in the portal hypertension group, versus 225.5(146.3,306.8)minutes, 100.0(50.0,250.0)mL, 7.0(6.0,9.0)days in the non-portal hypertension group, showing no significant difference in the above indica-tors between the two groups ( Z=-0.75, -0.26, -0.91, P>0.05). In cases with non-anatomical liver resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 173.5(120.0,231.5)minutes, 175.0(50.0,300.0)mL, 7.0(5.0,11.0)days in the portal hyper-tension group, versus 186.0(123.0,262.5)minutes, 100.0(50.0,200.0)mL, 7.0(5.0,9.5)days in the non-portal hypertension group, showing no significant difference in the above indicators between the two groups ( Z=-0.97, -1.12, -0.98, P>0.05). Conclusion:Minimally invasive liver resection or even major liver resection is safe and feasible for screened HCC patients complicated with portal hyper-tension, but attention should be paid to the prevention and treatment of postoperative complications.

Study on medication law of TCM compounds with national patents for treatment of vascular dementia / 国际中医中药杂志

Objective:To explore the prescription and medication law of Traditional Chinese Medicine (TCM) compounds in the treatment of vascular dementia (VD) based on patent database.Methods:TCM compounds with patents about VD were retrieved from Chinese patent announcement website of the State Intellectual Property Office and CNKI. The retrieval time was from the establishment to the databases to 31 st, March 2022. The frequency, clusteringand association analysis were carried out with the help of TCM inheritance auxiliary platform (V2.5). The medication law was analyzed. Results:154 TCM compound patents for the treatment of vascular dementia were screened, involving 227 kinds of Chinese materia medica. Among them, Acori Tatarinowii Rhizoma (44 times, 28.57%) was used more frequently, and the common medicinal pair was Salviea Miltiorrhizae Radix et Rhizoma- Acori Tatarinowii Rhizoma (17 times, 11.03%). The medicinal property was mainly warm, the taste was mainly sweet, and the meridian was mainly liver meridian. Those with high confidence based on association rules were " Corni Fructus -Acori Tatarinowii Rhizoma" (0.90), " Corni Fructus -Rehmannize Radix et Praeparata" (0.90). Based on the complex network, it was concluded that the core drugs were 14 groups such as " Rehmannize Radix et Praeparata- Cistanches Herba- Corni Fructus". The new prescriptions extracted by entropy cluster analysis included 7 groups such as " Rehmannize Radix et Praeparata, Cistanches Herba, Corni Fructus and Asparagi Radix". Conclusion:The treatment of VD by TCM compounds with national patents is mainly based on tonifying deficiency, promoting blood circulation and removing blood stasis, eliminating phlegm and dampness, expelling wind and dredging collaterals, opening orifices and resuscitation, which can provide reference for clinical practice and new drug research and development.

Study on the Medication Rule of the National Patent of Traditional Chinese Medicine Compound Formula in the Treatment of Depression / 中医杂志

ObjectiveTo explore the medication rules of traditional Chinese medicine compounds for depression in the National Patent Database using data mining， and to provide ideas for the clinical treatment and the development of new drugs for depression. MethodsThe patent data of traditional Chinese medicine compounds for the treatment of depression were searched from inception to July 1st， 2022 on the Patent Publication Announcement website of China National Intellectual Property Administration. The selected traditional Chinese medicine compounds were analyzed by using the data mining section of the ancient and modern medical record cloud platform （V2.3.5） for drug frequency， and based on this， the nature， flavor， channel entry and function of the medicinals were analyzed. Representative high-frequency herbal combinations were obtained through correlation analysis， while the classification of Chinese medicine compounds for depression was analyzed by cluster analysis， and the core combinations of herbs for the treatment of depression were screened out using complex network analysis. ResultsA total of 325 Chinese medicine compounds were included， involving 452 herbs， with a total frequency of 3532 times. The top 10 mostly used herbs were Yujin （Radix Curcumae， 122 times）， Chaihu （Radix Bupleuri， 122 times）， Baishao （Radix Paeoniae Alba， 109 times）， Suanzaoren （Spina Date Seed， 95 times）， Fuling （Poria， 94 times）， Danggui （Radix Angelicae Sinensis， 94 times）， Yuanzhi （Radix Polygalae， 84 times）， Baizhu （Rhizoma Atractylodis Macrocephalae， 72 times）， Shichangpu （Rhizoma Acori Graminei， 71 times）， and Danshen （Salvia Miltiorrhiza， 61 times）. The natures of the herbs were mainly warm （998 times）， neutral （944 times）， slightly cold （596 times） and cold （497 times）； the flavors were mainly sweet （1648 times）， acrid （1392 times）， and bitter （1337 times）； the channels of entry were mainly liver （1695 times）， heart （1521 times）， spleen （1326 times） and lung （1268 times）. The medicinals with the function of soothing liver to relieve constraint， moistening the intestines to promote defecation， calming the heart and the mind， moving qi to relieve constraint were used more frequently. The high frequency herbal combinations by association analysis included “Chaihu （Radix Bupleuri）→ Baishao （Radix Paeoniae Alba）”， “Danggui （Radix Angelicae Sinensis）→Chaihu （Radix Bupleuri）” and “Baishao （Radix Paeoniae Alba）→ Yujin （Radix Curcumae）”. The 22 high frequency medicinals used more than 40 times could be clustered into six categories. Complex network analysis found the core herbal combination for the treatment of depression was the formula of Chaihu （Radix Bupleuri）， Yujin （Radix Curcumae）， Baishao （Radix Paeoniae Alba）， Danggui （Radix Angelicae Sinensis）， Fuling （Poria）， Suanzaoren （Spina Date Seed）， and Xiangfu （Cyperi Rhizoma）. ConclusionTraditional Chinese medicine compounds for the treatment of depression is mainly based on the pathogenesis of constraint， stasis and deficiency， focusing on the liver， heart， spleen and lung， commonly using medicinals with the function of soothing liver to relieve constraint， fortifying spleen and nourishing heart， regulating qi and invigorating blood， and moistening the intestines to promote defecation， which can provide a reference for the clinical treatment and new drug research and development for depression.

Clinical Application of Supplementing Essence and Boosting Marrow Method in the Treatment of Encephalopathy Based on the Marrow Sea Theory / 中医杂志

As the guiding theory for the diagnosis and treatment of encephalopathy in traditional Chinese medicine （TCM）， The marrow sea theory has important theoretical connotation and clinical value. This paper summarized the clinical research literature on the differentiation and treatment of common encephalopathy based on the marrow sea theory published in recent years， analyzed the treatment method and effects from eight aspects in terms of stroke， dizziness， insomnia， headache， constraint syndrome， dementia， tremor syndrome， and atrophy syndrome， and discussed the possible mechanism based on the relevant basic research. It is believed that marrow sea depletion is the common pathogenesis of encephalopathy in TCM. Guided by the method of supplementing essence and boosting marrow， the corresponding formulas and medicinals are recommended in accordance with differentiated syndromes， which can effectively improve the symptoms of the disease， delay the progression， increase the daily life ability of the patients， and improve the quality of life. Based on the marrow sea theory， the method of supplementing essence and boosting marrow， rectifying healthy qi and dispelling pathogen can be used to highlight the advantages of TCM and provide ideas for the diagnosis and treatment of encephalopathy in TCM.

Improvement effect of diterpene ginkgolides on acute tMCAO rats and chronic tMCAO rats / 药学学报

To study the cognitive effects of diterpene ginkgolides (DG), transient middle cerebral artery occlusion (tMCAO)-induced rats were established. tMCAO-rats induced by suture method were divided into sham operation group, solvent control group, NBP group, DG group. The animal experiments in the present study were performed in accordance with the Ethical Guidelines of the Laboratory Animal Welfare Ethical Committee of Peking Union Medical College (00000646, 00000635). The effects of DG on tMCAO rats were evaluated by neurological severity score, cerebral infarction volume measurement, step-down and Morris water maze test. In the acute tMCAO rat model, 100 mg·kg-1 DG improved the neural score and infarction volume. In the chronic tMCAO rat model, DG 100 mg·kg-1 significantly improved the survival rate of tMCAO-induced rats. The Morris water maze results showed 100 mg·kg-1 DG decreased the latency of tMCAO-induced rats to find the platform, while the effect was weaker than the NBP. However, DG 30 mg·kg-1 did not show a significant effect. In conclusion, DG exerted a therapeutic effect on transient middle cerebral artery occlusion.

Activation of p38 MAPK and its effect on the expression of Bax and Bcl-2 after cerebral ischemia-reperfusion in hyperlipidemia rats / 解剖学报

Objective To detecte the expressions of phosphorylated p38 MAPK (p-p38 MAPK), Bax and Bcl-2 in the cerebral cortex of hyperlipidemia rats after cerebral ischemia-reperfusion (I/R) injury and the effect of SB203580 on the expressions of p-p38 MAPK, Bax and Bcl-2, to explore the effect of p38 MAPK activation on the expressions of Bax and Bcl-2 in hyperlipidemia cerebral I/R injury. Methods After the hyperlipidemia model was established, the rats were randomly divided into 3 groups: sham operation group, operation group (I/R) and SB203580 treatment group (SB+I/R), with 10 rats in each group. The focal cerebral I/R model in hyperlipemia rats was established with thread embolism of the left middle cerebral artery. The neurobehavioral score was used to observe the symptoms of neurobehavioral injury. The 2, 3, 5-triphenyltetrazolium chloride (TTC) staining was used to detect the volume of cerebral infarction, and the TUNEL staining was used to observe apoptotic cells. The relative expression levels of p-p38 MAPK, Bax and Bcl-2 were analyzed by immunohistochemistry. Results Compared with the sham group, the infarct volume, apoptosis index and neurobehavioral score of rats in the I/R group increased significantly, and the expressions of p-p38 MAPK and Bax increased significantly, and the expression of Bcl-2 decreased significantly (P<0. 05). Compared with the I/R group, rats in the SB+I/R group had less brain damage, the infarct volume and the apoptosis index were significantly reduced, the expressions of p-p38 MAPK reduced significantly, Bax expression decreased while Bcl-2 expression increased. The differences were statistically significant (P<0. 05). Neurobehavioral scores were lower in SB+I/R group than in I/R group, but the difference was not statistically significant. Conclusion In the process of cerebral I/R injury in hyperlipidemiarats, activation of p38 MAPK can regulate the expression of Bax and Bcl-2.

Polyinosinic-polycytidylic acid affecting the expressions of Bcl-2 and Bax after cerebral ischemia-reperfusion in hyperlipidemic rats and its neuroprotective effect / 解剖学报

Objective To observe the effect of polyinosinic-polycytidylic acid ( Poly-IC ) treatment on the expressions of Bcl-2 and Bax after cerebral ischemia-reperfusion ( I / R ) injury in fryperlipidemia rats, and to detect the cerebral infarction, blood-brain barrier permeability and behavioral injury symptoms, to explore the neuroprotective effect of Poly-IC treatment on cerebral I /R injury in fryperlipidemia rats. Methods Hyperlipidemia rats were randomly divided into cerebral I /R group, Poly-IC pretreatment group, Poly-IC post-treatment group and sham operation group, 20 rats in each group. Neurobehavioral performance of rats in each group was recorded according to neurobehavioral score of 0-4 points. Blood-brain barrier permeability of rats in each group was detected by Evans blue staining. TTC staining was used to observe the cerebral infarction in each group. Apoptotic cells in the cerebral cortex of rats in each group was observed by TUNEL staining. The relative expression levels of Bcl-2 and Bax were determined by Western blotting. Results Compared with the sham group, the symptoms of neurobehavioral damage in the I/R group were serious and the score increased significantly (P<0. 05). The scores of Poly-IC pretreatment and post-treatment groups were significantly lower than that of I/R group (P<0. 05). Evans blue staining result showed that the blood-brain barrier permeability of the I/R group was significantly higher than that of the sham group (P<0. 05) , and Poly-IC pretreatment or post-treatment could significantly reduce the blood-brain barrier permeability ( P < 0. 05 ) . No infarct was observed in the sham group with uniform red staining, while white infarct was observed in the brain tissue of the I/R group. Compared with the I/R group, the volume of infarct in both Poly-IC pretreatment and post-treatment groups reduced significantly (P<0. 05). The apoptosis index in cerebral cortex of rats in I/R group was significantly higher than that in sham group ( P < 0 .05 ) , while the apoptosis index in Poly-IC pretreatment or post-treatment group was significantly lower than that in I/R group(P<0. 05 ) . The result of Western blotting showed that, compared with the sham group, the expression of Bax in the I/R group was significantly increased(P<0. 05) , the expression of Bcl-2 was significantly decreased(P<0. 05). Compared with the I/R group, the expression of Bax in the Poly-IC pretreatment or post-treatment group reduced significantly ( P < 0. 05 ) , the expression of Bcl-2 increased significantly(P<0. 05). Conclusion Poly-IC pretreatment or post-treatment can improve the symptoms of neurobehavioral injury, reduce the damage of blood-brain barrier, reduce the volume of cerebral infarction, decrease the apoptosis index of nerve cells, play a neuroprotective effect on cerebral ischemia reperfusion injury in rats with hyperlipidemia, and this protective effect may be related to the change of Bcl-2 and Bax expression levels.

Thought of Treatment of Orifices Based on Correspondence Between Drugs and Symptoms in Chinese Herbal Classics in Past Dynasties / 中国实验方剂学杂志

ObjectiveTo discuss the thought of treatment of orifices in the Chinese herbal classics in the past dynasties based on the correspondence between drugs and symptoms to guide the clinical treatment based on syndrome differentiation. MethodAll the literature data of Chinese herbal classics were retrieved from the database of the Chinese Medical Dictionary， involving 76 works of Chinese herbal classics and covering representative works from the Han dynasty to the Ming and Qing dynasties. The information on Chines herbal drugs for the treatment of orifices was collected and sorted out. According to Chinese Materia Medica （11th Edition） and Pharmacopoeia of the People's Republic of China （2020 Edition）， the nature， flavor， and meridian tropism of the selected Chinese herbal drugs were statistically analyzed. The pathogenesis elements in the treatment of orifices were classified and counted， and the contents of syndrome differentiation and treatment in various Chinese herbal classics were extracted. ResultIn 76 Chinese herbal classics in the past dynasties， 93 Chinese herbal drugs for the treatment of orifices were selected. The nature of drugs was mainly warm， followed by cold and mild. The flavor was mainly pungent， followed by bitter and sweet. In terms of meridian tropism， drugs mainly acted on the lung meridian， followed by stomach， heart， liver， spleen， and kidney meridians. The pathogenesis elements of orifices could be divided into six categories， i.e.， wind invasion， turbid obstruction and Qi stagnation， water and dampness stagnation， blood stasis and collaterals blockage， heat and toxin damage， deficiency of vital Qi and cold coagulation. ConclusionOrifices are mainly treated with drugs effective in dispelling wind and pathogenic factors， resolving turbidity and removing stagnation， inducing diuresis and eliminating dampness， promoting blood circulation and dredging collaterals， clearing heat and purging fire， tonifying deficiency and dispelling cold， which are used in combination. Eliminating pathogenic factors and dredging， tonifying deficiency and purging excess are the main characteristics of treatment of orifices based on syndrome differentiation， which is in line with the physiological dysfunction state of orifices in losing the function， evil Qi blockage and healthy Qi deficiency.

Treatment of rheumatoid arthritis by injection of sinomenine solid lipid nanoparticles under a fluorescence endoscopic laser confocal microscope / 中国中药杂志

A fluorescence endoscopic laser confocal microscope(FELCM) was used to direct the injection of sinomenine solid lipid nanoparticles(Sin-SLN) into the joint, and the in vitro effectiveness of Sin-SLN in the treatment of rheumatoid arthritis(RA) was evaluated. Sin-SLN was prepared with the emulsion evaporation-low temperature curing method. The Sin-SLN prepared under the optimal conditions showed the encapsulation efficiency of 64.79%±3.12%, the drug loading of 3.84%±0.28%, the average particle size of(215.27±4.21) nm, and the Zeta potential of(-32.67±0.84) mV. Moreover, the Sin-SLN demonstrated good stability after sto-rage for 30 days. The rabbit model of RA was established by the subcutaneous injection of ovalbumin and complete Freund's adjuvant. Five groups were designed, including a control group, a model group, a Sin(1.5 mg·kg~(-1)) group, a Sin-SLN(1.5 mg·kg~(-1)) group, and a dexamethasone(positive drug, 1.0 mg·kg~(-1), ig) group. The control group and the model group only received puncture treatment without drug injection. After drug administration, the local skin temperature and knee joint diameter were monitored every day. The knee joint diameter and the local skin temperature were lower in the drug administration groups than in the model group(P<0.05, P<0.01). FELCM recorded the morphological alterations of the cartilage of knee joint. The Sin-SLN group showed compact tissue structure and smooth surface of the cartilage. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the serum le-vels of interleukin-1(IL-1) and tumor necrosis factor-α(TNF-α). The findings revealed that the Sin-SLN group had lower IL-1 and TNF-α levels than the model group(P<0.05, P<0.01). Hematoxylin-eosin(HE) staining was employed to reveal the pathological changes of the synovial tissue, which were significantly mitigated in the Sin-SLN group. The prepared Sin-SLN had uniform particle size and high stability. Through joint injection administration, a drug reservoir was formed. Sin-SLN effectively alleviate joint swelling and cartilage damage of rabbit, down-regulated the expression of inflammatory cytokines, and inhibited the epithelial proliferation and inflammatory cell infiltration of the synovial tissue, demonstrating the efficacy in treating RA.

Literature analysis of sunitinib-induced nephrotic syndrome / 中国药房

OBJECTIVE To analyze the clinical characteristics of nephrotic syndrome induced by sunitinib， and to provide reference for clinical rational drug use. METHODS Retrieved from CNKI， VIP， Wanfang data， PubMed， Web of Science and Medline， case report about sunitinib-induced nephrotic syndrome were collected from the inception to Oct. 30th， 2022. Those case reports were analyzed statistically in terms of gender， age， primary disease， drug use， clinical manifestations， treatment and outcome. RESULTS A total of 15 pieces of literature were collected and 17 patients were involved， including 10 males and 7 females. The average age of patients was （59.35±15.72） years. Among 17 patients， there were 10 patients with renal cell carcinoma and 7 patients with gastrointestinal stromal tumor， all of whom received evidence-based medication； the dosage of sunitinib in 15 cases was recorded， and all of them were within the recommended range of the instructions； 9 patients received combined therapy； the time from sunitinib application to the occurrence of nephrotic syndrome was 21 days-52 months， of which 11 cases were ≤2 years. The clinical manifestations in 13 patients were described， including edema， oliguria， foamy urine， weight gain， fatigue， dyspnea on exertion， etc. Eight patients had other adverse reactions induced by sunitinib before suffering from nephrotic syndrome， including new hypertension or worsening of original hypertension， and hand-foot syndrome. Renal biopsy mainly manifested as thrombotic microangiopathy， focal segmental glomerular sclerosis and immune complex glomerulonephritis. Sunitinib withdrawal or dosage reduction was adopted in all patients， and they were given symptomatic treatment such as glucocorticoids and antihypertensive agents. Symptoms of 16 patients were improved， and renal function of one patient deteriorated and hemodialysis was started. Sunitinib was re-challenged in 6 patients， elevated creatinine and substantial proteinuria recurred in 5 patients. CONCLUSIONS In clinical use of sunitinib， it is advisable to periodically monitor renal function. In case of deterioration of renal function， albuminuria， edema， etc.， relevant examinations should be implemented in time， and symptomatic intervention should be taken as soon as possible. Besides， we should be alert to the recurrence of nephrotic syndrome after sunitinib rechallenge.

Screening of quantitative preparation quality markers of Zhibao Sanbian Wan / 药学学报

On the basis of the qualitative preparation quality markers of Zhibao Sanbian Wan (ZBSBW), we screened out the quantitative markers and evaluated the content consistency of ZBSBW. A method capable of simultaneously determining 34 compounds in ZBSBW was established based on HPLC-MS/MS, and 16 batches of ZBSBW were simultaneously analyzed by this method. Furthermore, we explored a general strategy for analyzing the component migration in preparation, plasma, brain tissue and cerebrospinal fluid. The methodological investigation was confirmed by linear range, recovery (85.10%-105.07%), precision (RSD: 1.37%-4.58%), stability, and repeatability (3.00%-12.45%), the established method was suitable for the detection and quantification of the compounds in ZBSBW. The contents of compounds in ZBSBW were all lower than 1 mg·g-1, and the contents and daily dose of nystose were the highest, followed by echinacoside, paeoniflorin, osthole and paeonol. The results of systematic clustering showed that the contents were consistent for ordinary preparations of ZBSBW. The principal component analysis showed that the components of berberine, ginsenoside Re, ginsenoside Rg1, pinoresinol diglucoside and tenuifolin had large variation, which contributed significantly to the grouping. The contents of echinacoside, verbascoside, polygalaxanthone Ⅲ, β-ecdysterone, osthole, alisol B 23-acetate, liquiritin and glycyrrhizic acid were stable from batch to batch. The animal experiment results showed that osthole, paeonol and liquiritin in ZBSBW could be absorbed into the blood and enter the brain tissue by passing through the blood-brain barrier. All animal studies were reviewed and approved by the Institutional Animal Care and Use Committee at Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences (No. 2020B071). The above compounds contributed the quantitative preparation quality markers of ZBSBW. In conclusion, the HPLC-MS/MS method established in this study was sensitive, accurate and rapid, and could be used for simultaneous quantification of 34 compounds and content consistency evaluation of multiple batches of preparations in ZBSBW. The result provided a methodological basis for the screening of quantitative preparation quality markers and material basis research of ZBSBW.

Volatile Oil of Linderae Radix Induces Apoptosis and Autophagy of Gastric Cancer AGS Cells via AMPK/mTOR Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effects of the volatile oil of Linderae Radix on the apoptosis and autophagy of human gastric cancer cell line AGS， and to explore the regulatory role of adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signaling pathway in this process. MethodThe volatile oil of Linderae Radix was extracted by steam distillation， and the effect of the volatile oil on the viability of AGS cells was detected by thiazolyl tetrazolium （MTT） colorimetry. The optimal intervention dose and time were determined according to the half maximal inhibitory concentration （IC50） for subsequent research. The blank， low， medium， and high-dose volatile oil （0， 15， 30， 60 mg·L-1） groups and the positive drug cyclophosphamide （CTX， 350 mg·L-1） group were designed. AGS cells were treated with different doses of volatile oil for 48 h. The changes in cell proliferation， cycle， and migration were measured by colony formation assay， flow cytometry， and cell scratch test， respectively. Hematoxylin-eosin （HE） staining was employed to observe the changes of cell morphology， Annexin-V/propidium iodide （PI） double staining to measure the apoptosis， and acridine orange （AO） staining to measure the autophagy level of the cells. Western blotting was employed to determine the expression of the autophagy effectors Beclin-1， p62， microtubule-associated protein 1-light chain 3 （LC3）， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved Caspase-3， cleaved poly ADP-ribose polymerase （PARP）， adenosine monophosphate-activated protein kinase （AMPK）， phosphorylated AMPK （p-AMPK）， mTOR， and phosphorylated mTOR （p-mTOR）. ResultCompared with the blank group， 24 h and 48 h of intervention with the volatile oil of Linderae Radix inhibited the viability of AGS cells in a concentration- and time-dependent manner （P<0.05， P<0.01）. Compared with the blank group， the volatile oil decreased the cell proliferation and migration （P<0.05， P<0.01） and blocked the AGS cell cycle in G2/M phase （P<0.05， P<0.01） in a concentration-dependent manner. The cells treated with the volatile oil became spherical and smaller， with the formation of apoptotic bodies and increased apoptosis rate （P<0.05， P<0.01）. As the dose of the volatile oil increased， the number of autophagosomes increased and the red fluorescence gradually enhanced， indicating the elevated level of autophagy. Compared with the blank group， different doses of volatile oil up-regulated the protein levels of Beclin-1， LC3 Ⅱ/LC3 Ⅰ， cleaved Caspase-3， cleaved PARP， Bax/Bcl-2， and AMPK （P<0.05， P<0.01） and down-regulated the protein levels of p62 and p-mTOR （P<0.05， P<0.01）. ConclusionThe volatile oil of Linderae Radix induces the apoptosis and exerts the autophagy-mediated growth inhibition of AGS cells by regulating the AMPK/mTOR signaling pathway.