Establishment of a novel co-cultured liver cancer model based on tumor microenvironment / 中华肿瘤杂志

Objective: To construct a new co-cultured liver cancer research model composed of activated hepatic stellate cells (aHSC) and liver cancer cells, explore the efficacy difference between it and traditional model, so as to establish a liver cancer research model in vitro and in vivo that can reflect the real clinical efficacy. Methods: A new co-culture model of liver cancer consisting of aHSC and liver cancer cells was constructed. The differences in efficacy between the new co-culture model and the traditional single cell model were compared by cytotoxicity test, cell migration test, drug retention test and in vivo tumor inhibition test. Western blot was used to detect the drug-resistant protein P-gp and epithelial-mesenchymal transition-related proteins. Masson staining was used to observe the deposition of collagen fibers in tumor tissues of tumor-bearing mice. CD31 immunohistochemical staining was used to observe the microvessel density in tumor tissues of tumor-bearing mice. Results: The cytotoxicity of single cell model and co-culture model was dose-dependent. With the increase of curcumin (CUR) concentration, the cell viability decreased, but the cell viability of single cell model decreased faster than that of co-culture model. When the concentration of CUR was 10 μg/ml, the cell viability of the co-culture model was 62.3% and the migration rate was (28.05±3.68)%, which were higher than those of the single cell model [38.5% and (14.91±5.92)%, both P<0.05]. Western blot analysis showed that the expressions of P-gp and vimentin were up-regulated in the co-culture model, which were 1.55 and 2.04 fold changes of the single cell model, respectively. The expression of E-cadherin was down-regulated, and the expression level of E-cadherin in the single cell model was 1.17 fold changes of the co-culture model. Drug retention experiment showed that the co-culture model could promote drug efflux and reduce drug retention. In vivo tumor inhibition experiment showed that the m-HSC+ H22 co-transplantation model had faster tumor growth and larger tumor volume than those of the H22 single cell transplantation model. After CUR treatment, the tumor growths of m-HSC+ H22 co-transplantation model and H22 single cell transplantation model were inhibited. Masson staining showed that the deposition of collagen fibers in tumor tissues of m-HSC+ H22 co-transplantation model mice was more than that of H22 single cell transplantation model. CD31 immunohistochemical staining showed that the microvessel density in tumor tissue of m-HSC+ H22 co-transplantation model was higher than that of H22 single cell transplantation model. Conclusions: The aHSC+ liver cancer cell co-culture model has strong proliferation and metastasis ability and is easy to be resistant to drugs. It is a new type of liver cancer treatment research model superior to the traditional single cell model.

Correlation analysis between post-stroke depression and serum bilirubin and high-sensitivity C-reactive protein / 中国基层医药

Objective:To analyze the influential factors of post-stroke depression and investigate the effects of changes in serum bilirubin and high-sensitivity C-reactive protein on post-stroke depression.Methods:A total of 199 patients with stroke admitted to Qinghai Provincial People's Hospital from December 2019 to December 2020 were included in this study. These patients were divided into the Xining urban group (2 000-3 000 meters above sea level; n = 165) and the Xining prefecture and county group (over 3 000 meters above sea level; n = 34) according to their long-term residence. They were also divided into the post-stroke depression group ( n = 56, including 45 patients in the Xining urban group and 11 patients in the Xining prefecture and county group) and non-post-stroke depression group ( n = 143, including 120 patients in the Xining urban group and 23 patients in the Xining prefecture and county group). Related scales were used to evaluate neurologic deficits and the degree of depression in the two groups. Serum levels of total bilirubin, direct bilirubin, and high-sensitivity C-reactive protein were measured in each group. Neurologic deficits and the degree of depression were correlated with serum levels of total bilirubin, direct bilirubin, and high-sensitivity C-reactive protein. Results:Serum levels of total bilirubin, direct bilirubin, and high-sensitivity C-reactive protein in the post-stroke depression group were (19.95 ± 7.22) mmol/L, (3.98 ± 1.49) mmol/L, and (1.40 ± 2.29) mg/L, respectively, which were significantly higher than (16.20 ± 7.61) mmol/L, (3.19 ± 1.62) mmol/L, and (0.63 ± 1.33) mg/L in the non-post-stroke depression group ( t = 3.17, 3.18, 2.35, all P < 0.05). There was a significant difference in serum level of high-sensitivity C-reactive protein between stroke patients with mild and moderate depression and stroke patients with severe depression ( t = 2.48, P < 0.05). Conclusion:Serum levels of bilirubin and high-sensitivity C-reactive protein play an important role in the pathogenesis of post-stroke depression and there is a significant correlation between the two.

Effects of acupoint application therapy with Chinese medicine combined with tiotropium bromide inhalation on quality of life in patients with stable chronic obstructive pulmonary disease / 中国基层医药

Objective:To investigate the effects of acupoint application therapy with Chinese medicine combined with tiotropium bromide inhalation on quality of life in patients with stable chronic obstructive pulmonary disease (COPD).Methods:A total of 109 patients with stable COPD admitted to People's Hospital of Gaomi from March 2019 to May 2020 were included in this study. They were randomly divided into a control group ( n = 54) and an observation group ( n = 55). Both groups were given tiotropium bromide powder inhalation and acupoint application therapy ( Dazhui, Shenque, Feishu, Pishu, Shenshu and Zusanli). Chinese medicine ointment was applied in the observation group, but not in the control group. All patients were treated for 6 consecutive months. Before and after treatment, pulmonary function indicators [forced expiratory volume in the first second (FEV 1), the percentage of expiratory volume in the first second (FEV 1%), forced vital capacity (FVC), FEV 1/FVC], modified Medical Research Council (mMRC) dyspnea scale score, and the Saint George's Respiratory Questionnaire (SGRQ) score were compared between the two groups before and after treatment to evaluate therapeutic efficacy and quality of life. Results:Before and after treatment, there were no significant differences in FEV 1, FEV 1% and FEV 1/FVC between the two groups (all P > 0.05). After treatment, mMRC score and SGRQ total score in the observation group were (1.91 ± 0.27) points and (38.54 ± 8.18) points, respectively, which were significantly lower than (2.43 ± 0.33) points and (43.12 ± 7.86) points in the control group ( t = 4.93, 4.47, both P < 0.05). The number of exacerbations and the number of hospitalizations were (0.42 ± 0.09) times/6 months and (0.27 ± 0.05) times/6 months in the observation group and they were (0.69 ± 0.17) times/6 months and (0.47 ± 0.13) times/6 months in the control group. There were significant differences in these indices between the two groups ( t = 3.90, 3.85, P < 0.05). Conclusion:Acupoint application therapy with Chinese medicine combined with tiotropium bromide inhalation has a good therapeutic effect on stable COPD. The combined therapy can reduce the number of acute attacks and improve patient's quality of life. This study is scientific and innovative.

Hospital Centralized Monitoring of Post-market Clinical Safety of Naoxintong Capsules in 7 345 Patients / 中国实验方剂学杂志

ObjectiveTo evaluate the clinical safety of Naoxintong （NXT） capsules after marketing， find out the potential risk factors of the drug as soon as possible， and reveal the incidence， nature， and clinical manifestations of the adverse events （ADE） and adverse reactions （ADR） of NXT capsules， so as to provide a basis for safe use of the drug in clinical practice. MethodA prospective， large-sample， multi-center observational cohort study was conducted to monitor all the 7 345 inpatients and outpatients orally taking NXT in 14 hospitals in China from January to December in 2018， with at least one follow-up. The demographic characteristics， disease type， NXT medication， ADR occurrence， characteristics， and prognosis of the patients were collected. SPSS 23.0 was used for single-factor and multivariate logistic regression to predict the influencing factors of ADR. ResultThe male and female patients accounted for similar proportions. There were 5 081 patients （79.40%） aged ≥60 years and 3 153 patients （49.27%） with body mass index （BMI） exceeding the normal standard. There were 344 （5.38%） patients with a history of allergy to medicines and food， 9 （0.14%） patients with a family history of allergy， and 52 （0.81%） patients with a history of allergic diseases. The ADRs associated with NXT occurred in 22 patients， with the incidence of 0.34%. The clinical manifestations of ADR appeared in 31 cases， involving 10 organs/systems， of which gastrointestinal system damage was the most common （17， 54.84%）. All ADRs were mild or moderate. Most ADRs （19， 86.36%） occurred within 4 weeks after administration. The patients with alleviated NXT-associated ADRs accounted for 81.82%. No indicators related to significant increases in ADR risks were found. ConclusionNXT is well tolerated in the general population. The hospital centralized monitoring for the clinical safety of oral Chinese patent drugs based on HIS data and Web tracking and follow-up system is an essential means for the post-market research on the safety of drugs.

Allergic reactions of COVID-19 vaccine based on mRNA-LNP and its pharmacokinetics in vivo / 药学学报

Vaccination has been proved to be the most effective strategy to prevent the Corona Virus Disease 2019 (COVID-19). The mRNA vaccine based on nano drug delivery system (NDDS) - lipid nanoparticles (LNP) has been widely used because of its high effectiveness and safety. Although there have been reports of severe allergic reactions caused by mRNA-LNP vaccines, the mechanism and components of anaphylaxis have not been completely clarified yet. This review focuses on two mRNA-LNP vaccines, BNT162b2 and mRNA-1273. After summarizing the structural characteristics, potential allergens, possible allergic reaction mechanism, and pharmacokinetics of mRNA and LNP in vivo, this article then reviews the evaluation methods for patients with allergic history, as well as the regulations of different countries and regions on people who should not be vaccinated, in order to promote more safe injection of vaccines. LNP has become a recognized highly customizable nucleic acid delivery vector, which not only shows its value in mRNA vaccines, but also has great potential in treating rare diseases, cancers and other broad fields in the future. At the moment when mRNA-LNP vaccines open a new era of nano medicine, it is expected to provide some inspiration for safety research in the process of research, development and evaluation of more nano delivery drugs, and promote more nano drugs successfully to market.

The mechanism of "Trichosanthis Fructus-Allii Macrostemonis Bulbus" on phlegm and blood stasis syndrome-related cardiovascular diseases based on network pharmacology and experimental verification / 药学学报

This study aimed to investigate the mechanism of "Trichosanthis Fructus-Allii Macrostemonis Bulbus" (GX) on phlegm and blood stasis syndrome (PBSS) rats combining the methods of network pharmacology and experimental verification. Animal experiment ethical requirements were approved by the Ethical Committee Experimental Animal Center of Anhui University of Chinese Medicine (grant number: AHUCM-rats-2021070). Based on the HPLC-Q-TOF-MS analysis and database, 69 chemical constituents of GX and 163 targets of GX for the treatment of phlegm and blood stasis-related cardiovascular diseases were obtained. Then, key targets such as serine/threonine kinase 1 (Akt1), tumor necrosis factor (TNF), interleukin 6 (IL6), vascular endothelial growth factor A (VEGFA), cellular tumor antigen p53 (Tp53) were screened. Pathway analysis showed that the targets of GX in the treatment of phlegm and blood stasis-relate cardiovascular diseases were mainly involved in PI3K/Akt signaling pathway, sphingolipid metabolism, platelet activation, hypoxia inducible factor-1 (HIF-1), ras-proximate-1 (rap1) and other signaling pathways. In addition, molecular docking analysis showed that apigenin, cucurbitacin D, linolenic acid and kaempferol and other key components had potential binding ability with Akt1, TNF, IL6, VEGFA and Tp53. In the animal experiments, compared to the phlegm and blood stasis syndrome group, GX could significantly improve the traditional Chinese medicine syndrome score, blood lipid, vascular endothelial structure disorders and reduce serum endothelin-1 (ET-1) level, increase serum nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) levels, which could restore aortic endothelial function. In addition, the expression of intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in aorta could be significantly reduced, which could improve the vascular endothelial injury of aorta. Western blot revealed that GX could significantly decrease the phosphorylation levels of phosphoinositide 3-kinase (PI3K) and Akt in aorta. This study revealed the mechanism of GX in treatment of phlegm and blood stasis-relate cardiovascular diseases is consistent with the characteristics of multiple ingredients, multiple targets and multiple pathways. In addition, this study also clarified that the reversal of pathological of phlegm and blood stasis syndrome rats may be related to GX inhibiting PI3K/Akt signaling pathway, which could improve vascular inflammation and vascular endothelial function injury.

Cystic echinococcosis misdiagnosed as hepatic cyst: a case report / 中国血吸虫病防治杂志

This case report presents the diagnosis and treatment of a case of cystic echinococcosis misdiagnosed as hepatic cyst. The case had anaphylactic shock caused by extravasation of cyst fluid during extraction of hepatic cyst and suffered from postoperative recurrence of echinococcosis. This case report may provide insights into diagnosis and treatment of cystic echinococcosis among healthcare workers in non-endemic areas.

Clinicopathological features and prognostic analysis of 44 patients with polyomavirus nephropathy after kidney transplantation / 器官移植

Objective To analyze the clinicopathological features and prognosis of polyomavirus nephropathy (PyVN) after kidney transplantation. Methods Clinical data of 44 patients who were diagnosed with PyVN after kidney transplantation were retrospectively analyzed. The causes of puncture and the time of pathological diagnosis were analyzed. Histological grading was carried out according to Banff 2018 classification. Clinical data and pathological characteristics of patients at all grades were statistically compared. BK viral DNA loads in the blood and urine were measured and renal allograft function were assessed. Clinical prognosis of all patients was compared among different groups and the risk factors affecting clinical prognosis were also analyzed. Results The time interval between pathological diagnosis of PyVN and kidney transplantation was 16(8, 29) months, and the increase of serum creatinine level was the main cause for puncture. Among 44 patients, 19 cases were classified as grade ⅠPyVN, 21 cases of grade Ⅱ PyVN and 4 cases of grade Ⅲ PyVN, respectively. Under optical microscope, there was no significant difference in the positive rate of virus inclusion bodies among different groups (P=0.148). Inflammatory cell infiltration, interstitial fibrosis and polyomavirus load in grade Ⅱ PyVN patients were all more or higher than those in grade Ⅰ counterparts. Inflammatory cell infiltration and polyomavirus load in grade Ⅲ patients were more or higher than those in grade Ⅰ counterparts. Polyomavirus load in grade Ⅲ patients was more or higher than that in grade Ⅱ counterparts. The differences were statistically significant (all P < 0.05/3). Upon diagnosis, BK viral DNA load was detected in the blood and urine of 39 patients. Among them, 38 patients were positive for BK virus in the urine and 30 patients were positive for BK virus in the blood. The serum creatinine level upon diagnosis was higher compared with that at postoperative 1 month. The serum creatinine level at the final follow-up was significantly higher than that upon diagnosis. The differences were statistically significant (P < 0.001, P=0.049). There was no significant difference in the serum creatinine level among patients with different grades of PyVN at postoperative 1 month (P=0.554). The serum creatinine level of patients with grade Ⅱ PyVN upon diagnosis was significantly higher than that of those with grade Ⅰ PyVN (P=0.007). The 1-, 3- and 5-year cumulative survival rates of renal allografts were 95%, 69% and 62%, respectively. The survival rates of renal allografts significantly differed among patients with different grades of PyVN. The higher the grade, the lower the survival rate (P=0.014). Univariate and multivariate Cox's regression analyses prompted that intrarenal polyomavirus load and serum creatinine level upon diagnosis were the independent risk factors for renal allograft dysfunction (all P < 0.05). Conclusions PyVN mainly occurs within 2 years after kidney transplantation. Clinical manifestations mainly consist of increased serum creatinine level, BK viremia and BK viruria. Postoperative routine monitoring of BK virus contributes to early diagnosis and protection of renal allografts. Banff 2018 classification may effectively predict the prognosis of renal allografts.

Intelligent diagnostic model of keratoconus based on deep learning algorithm / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To establish an intelligent diagnostic model of keratoconus for small-diameter corneas by data mining and analysis of patients' clinical data.METHODS: Diagnostic study. A total of 830 patients(830 eyes)were collected, including 338 male(338 eyes)and 492 female(492 eyes), with an average age of 14-36(23.19±5.71)years. Among them, 731 patients(731 eyes)had undergone corneal refractive surgery at Chongqing Nanping Aier Eye Hospital from January 2020 to March 2022, and 99 patients had a diagnosed keratoconus from January 2015 to March 2022. Corneal diameter ≤11.1 mm was measured by Pentacam in all patients. Two cornea specialists classified patients' data into normal corneas, suspect keratoconus, and keratoconus groups based on the Belin/Ambrósio enhanced ectasia display(BAD)system in Pentacam. The data of 665 patients were randomly selected as the training set and the other 165 patients as the validation set by computer random sampling method. Seven parametric corneal features were extracted by convolutional neural networks(CNN), and the models were built by Residual Network(ResNet), Vision Transformer(ViT), and CNN+Transformer, respectively. The diagnostic accuracy of models was verified by cross-entropy loss and cross-validation method. In addition, sensitivity and specificity were evaluated using receiver operating characteristic curve.RESULTS: The accuracy of ResNet, ViT, and CNN+Transfermer for the diagnosis of normal cornea and suspect keratoconus was 85.57%, 86.11%, and 86.54% respectively, and the area under the receiver operating characteristic curve(AUC)was 0.823, 0.830 and 0.842 respectively. The accuracy of models for the diagnosis of suspect keratoconus and keratoconus was 97.22%, 95.83%, and 98.61%, respectively, and the AUC was 0.951, 0.939, and 0.988 respectively.CONCLUSION: For corneas ≤11.1 mm in diameter, the data model established by CNN+Transformer has a high accuracy rate for classifying keratoconus, which provides real and effective guidance for early screening.

Equity and efficiency of resource allocation for management and treatment of severe mental disorders in Shanghai in 2020 / 公共卫生与预防医学

Objective To analyze the equity and efficiency of resource allocation for management and treatment of severe mental disorders in Shanghai in 2020, and to provide a foundation for making relevant policies. Methods Data on resource allocation for the management and treatment of severe mental disorders in 17 district-level mental health institutions in 2020 were collected. The Gini coefficient was used to evaluate the equity of resource allocation by population and geographic area, and data envelopment analysis was carried out to analyze the equity of resource allocation. Results The Gini coefficients of special funds, psychiatric medical staff and actual open beds according to population were 0.24, 0.25 and 0.27, respectively. The Gini coefficients according to area were 0.54, 0.62 and 0.64, respectively. The average efficiency of resource allocation was 0.865. There were 5 institutions where DEA was effective, accounting for 29.41%. There were 12 institutions where DEA was non-effective, accounting for 70.59%. Conclusion The equity of resources allocation for the management and treatment of severe mental disorders according to population is good, but the equity of allocation based on geographic area is not high. The efficiency of resource allocation needs to be further improved. It is suggested that the resource allocation should be optimized to promote the fairness and efficiency of resource allocation for the management and treatment of severe mental disorders.

Features of Henle fiber layer by spectral domain optical coherence tomography in central serous chorioretinopathy / 中华实验眼科杂志

Objective:To observe the features of Henle fiber layer (HFL) in eyes with central serous chorioretinopathy (CSC) using spectral domain optical coherence tomography (SD-OCT).Methods:A cross-sectional study was conducted.Thirty-five CSC patients (35 eyes) treated in the Third People's Hospital of Qingdao from January 2017 to November 2021 were enrolled.The subjects included 23 males (23 eyes) and 12 females (12 eyes), aged 24 to 60 years old, with an average age of (41.14±8.19) years, and had a CSC duration ranged from 1 day to 6 months.SD-OCT was performed on all eyes with a line scan through the central fovea horizontally.The features of HFL over subretinal fluid (SRF) area were analyzed and summarized.The study protocol adhered to the Declaration of Helsinki and was approved by the Ethics Committee of the Third People's Hospital of Qingdao (No.2022Y0403001).Results:In 26 eyes with regular dome-shaped neurosensory retinal detachment, HFL appeared to be delimited type 1 in 25 eyes, accounting for 96.15%, delimited type 2 in 7 eyes, accounting for 26.92%, bright in 17 eyes, accounting for 65.38% over SRF area.In 21 eyes with CSC duration≤21 days, HFL all showed delimited type 1 and some presented bright or delimited type 2 at the same time.In 5 eyes with CSC duration>21 days, HFL all showed bright and some were delimited type 1 or delimited type 2 in the meantime.In 15 eyes with symmetrical nasal and temporal retinal detachment, HFL showed symmetrical reflectivity over SRF area in horizontal OCT images in 6 eyes, and showed brighter reflectivity over nasal SRF in nasal elevated OCT images in 3 eyes and over temporal SRF in temporal elevated OCT images in 6 eyes.In 11 eyes with asymmetrical nasal and temporal retinal detachment, HFL showed brighter reflectivity over temporal SRF with larger retinal detachment range on temporal side in horizontal OCT images in 3 eyes.Of the 4 eyes with nasal elevated OCT images, the retinal detachment range was larger on temporal side and HFL showed symmetrical reflectivity over SRF area in 3 eyes, and HFL was brighter over nasal SRF area with larger retinal detachment range on nasal side in 1 eye.Of the 4 eyes with temporal elevated OCT images, the retinal detachment range was larger on nasal side and HFL showed symmetrical reflectivity over SRF area in 3 eyes, and HFL was brighter over nasal SRF area with larger retinal detachment range and higher height on nasal side in 1 eye.In 9 eyes with irregular neurosensory retinal detachment, HFL appeared to be delimited type 1 in 7 eyes, accounting for 77.78%, delimited type 2 in 5 eyes, accounting for 55.56%, bright in 6 eyes, accounting for 66.67%, dark in 4 eyes, accounting for 44.44%, and indistinct in 2 eyes, accounting for 22.22%.The detached neurosensory retina was not smooth in 7 eyes, and the phenotypes of HFL changed with the directions of detached neurosensory retina.In 2 eyes with only low neurosensory retinal detachment, HFL reflectivity on the raised side was slightly weaker than that on the lowered side.Conclusions:HFL appears to be delimited type 1 and bright mostly over SRF area in CSC in SD-OCT images.The phenotypes of HFL vary regularly with the tilt directions of OCT images, CSC duration, and the symmetry, range, height, directional characteristics of detached neurosensory retina.

Effect of neoadjuvant chemotherapy on the safety of laparoscopic D 2 radical resection and prognosis of patients with locally advanced gastric cancer / 中华消化外科杂志

Objective:To investigate the effect of neoadjuvant chemotherapy on the safety of laparoscopic D 2 radical resection and prognosis of patients with locally advanced gastric cancer. Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 351 patients with locally advanced gastric cancer who underwent laparos-copic D 2 radical resection in the Second Affiliated Hospital of Air Force Medical University from December 2016 to December 2021 were collected. There were 256 males and 95 females, aged (58±9)years. Of the 351 patients, 124 cases undergoing neoadjuvant chemotherapy were divided into the neoadjuvant chemotherapy group, 227 patients undergoing postoperative adjuvant chemotherapy were divided into the adjuvant chemotherapy group. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) effect evaluation of neoadjuvant chemotherapy; (3) intraoperative and postoperative situations; (4) postoperative histopathological examinations; (5) follow-up. 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. Measure-ment data with skewed distribution were represented as M(range) or 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. The Kaplan-Meier method was used to draw survival curves, and the Log-Rank test was used for survival analysis. Results:(1) Propensity score matching conditions and comparison of general data of patients between the two groups of patients after matching. Of 351 patients, 154 cases were successfully matched, including 77 cases in the neoadjuvant chemotherapy group and 77 cases in the adjuvant chemotherapy group. The elimination of gender, age, preoperative body mass index, clinical T staging and clinical N staging confounding bias ensured comparability between the two groups after propensity score matching. (2) Effect evaluation of neoadjuvant chemotherapy. Of the 77 patients receiving neoadjuvant chemotherapy, none of patient achieved complete response, 26 patients achieved partial response, 46 patients showed stable disease, 5 patients had progression of disease, showing the objective response rate as 33.8%(26/77) and the disease control rate as 93.5%(72/77). There were 15 males and 11 females sensitive to neoadjuvant chemotherapy, while 46 males and 5 females not sensitive, showing a significant difference between them ( χ2=11.05, P<0.05). (3) Intra-operative and postoperative situations. The operation time, volume of intraoperative blood loss, cases with intraoperative blood transfusion, time to postoperative first flatus, time to postoperative first liquid food intake, duration of postoperative hospital stay, cases with postoperative immediate complications, cost of hospital stay were (308±71)minutes, 100(range, 20?600)mL, 5, 3.0(range, 2.0?10.0)days, 4.0(range, 2.0?12.0)days, 9.0(range, 4.0?31.0)days, 7, 7.96(7.37,8.58) ten thousand yuan in patients of the neoadjuvant chemotherapy group, versus (296±67)minutes, 100(range, 20?500)mL, 4, 3.5(range, 1.0?14.0)days, 4.0(range, 2.0?15.0)days, 8.0(range, 5.0?45.0)days, 11, 8.18(7.52,9.19) ten thousand yuan in patients of the adjuvant chemotherapy group, showing no signifi-cant difference in the above indicators between the two groups ( t=1.13, Z=?0.37, χ2=0.12, Z=?1.26, ?0.33, ?0.70, χ2=1.01, Z=?1.04, P>0.05). (4) Postoperative histopathological examinations. Results of postoperative histopatho-logical examinations showed that all 154 patients achieving R 0 resection. Cases with pathological T staging as stage T1, stage T2, stage T3, stage T4, cases with pathological N staging as stage N0, stage N1, stage N2, stage N3, number of positive lymph nodes, cases with human epidermal growth factor receptor 2 (negative, positive) were 3, 7, 5, 62, 27, 19, 19, 12, 1(range, 0?28), 59, 18 in patients of the neoadjuvant chemotherapy group, versus 0, 0, 2, 75, 17, 15, 21, 24, 3(range, 0?31), 44, 33 in patients of the adjuvant chemotherapy group, showing significant differences in the above indicators between the two groups ( Z=?3.39, ?2.55, ?3.12, χ2=6.60, P<0.05). (5) Follow-up. Of the 154 patients, 143 patients were followed up for 37(range, 5?69)months. The 3-year overall survival rate and 3-year disease-free survival rate was 72.1% and 70.0%, respectively, in patients of the neoadjuvant chemotherapy group, versus 74.8% and 76.6% in patients of the adjuvant chemo-therapy group, showing no significant difference in the above indicators between the two groups ( χ2=0.14, 0.60, P>0.05). Conclusions:Compared to postoperative adjuvant chemotherapy, neoadjuvant chemotherapy does not bring additional surgical risks, but can reduce the tumor stage of patients who underwent laparoscopic D 2 radical resection for locally advanced gastric cancer. However, it does not show any advantage in improving survival of patients.

Effect of self-made Bushen Jiangu Decoction combined with conventional western medicine therapy on the postoperative efficacy and bone transformation markers of osteoporotic vertebral compression fracture in the elderly / 国际中医中药杂志

Objective:To investigate the effect of self-made Bushen Jiangu Decoction on bone transformation markers in elderly patients with osteoporotic vertebral compression fracture after operation, and to evaluate the clinical efficacy.Methods:Prospective cohort study. A total of 92 patients with osteoporotic vertebral compression fracture after operation in Fangshan Hospital of Beijing University of Chinese Medicine from April 2020 to December 2021 who met the inclusion criteria were divided into 2 groups by random drawing method, with 46 in each group. The control group was treated with routine western medicine after operation, and the observation group was treated with self-made Bushen Jiangu Decoction on the basis of the control group. Both groups were treated for 3 months. TCM symptom scores were performed before and after treatment, and the prognosis of the patients was evaluated with the Chinese Osteoporosis Quality of Life (COQOL), VAS scale, and the Oswestry Dysfunction Index (ODI). The levels of amino terminal propeptide (PINP), cross-linked terminal peptide β special sequence (β-CTX) and bone morphogenetic protein 6 (BMP6) of type Ⅰ procollagen were determined by contrast chromogenic method with o-benzaldehyde. The adverse reactions during treatment were recorded and the clinical efficacy was evaluated.Results:The total effective rate was 95.7% (44/46) in the observation group and 82.6% (38/46) in the control group, and there was a significant difference between the two groups ( χ 2=4.04 , P=0.044). After treatment, the scores of fracture nonunion, pain in back and loin, chilliness and lassitude, and pallor in the observation group were significantly lower than those in the control group ( t values were 4.84, 4.09, 4.87, 4.14, respectively, P<0.01). The scores of COQOL, VAS and ODI in the observation group were significantly lower than those in the control group ( t values were 6.26, 10.57 and 6.15, respectively, P<0.01). The levels of PINP [(44.93±5.86)μg/L vs. (49.76±6.02)μg/L, t=3.90] and β-CTX [(0.49±0.17) μg/L vs. (0.68±0.20) μg/L, t=4.91] in observation group were significantly lower than those in the control group after treatment ( P<0.05). The level of BMP6 [(81.23±9.14) μg/L vs. (75.14±8.25) μg/L, t=3.36] in observation group was significantly higher than that of the control group ( P<0.05). During the treatment,the incidence of adverse reactions in the observation group was 13.0% (6/46), while that in the control group was 8.7% (4/46), and there was no significant difference between the two groups ( χ 2=0.45, P=0.503). Conclusion:The self-made Bushen Jiangu Decoction combined with conventional western medicine therapy can adjust the level of bone transformation markers in elderly patients with osteoporotic vertebral compression fractures, improve the lumbar function and quality of life, and improve the clinical efficacy.

Thoracic SMARCA4-deficient undifferentiated tumor-pathological diagnosis and combined immune checkpoint inhibitor treatment / 北京大学学报(医学版)

We explored clinicopathological features and treatment strategies for thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT). Thoracic SMARCA4-UT is a new entity recently acknowledged in the 2021 edition of World Health Organization Classification of Thoracic Tumors, and doctors are relatively unfamiliar with its diagnosis, treatment, and prognosis. Taking a case of SMARCA4-UT treated in Peking University First Hospital as an example, this multi-disciplinary discussion covered several hot issues on diagnosing and treating thoracic SMARCA4-UT, including histological features, immu- nohistochemical and molecular phenotype, immune checkpoint inhibitor (ICI) therapy, and pathological assessment of neoadjuvant therapy response. The patient was an older man with a long history of smoking and was admitted due to a rapidly progressing solid tumor in the lower lobe of the right lung. Histologically, tumor cells were epithelioid, undifferentiated, diffusely positive for CD34, and partially positive for SALL4.The expression of BRG1 protein encoded by SMARCA4 gene was lost in all of tumor cells, and next-generation sequencing(NGS)confirmed SMARCA4 gene mutation (c.2196T>G, p.Y732Ter). The pathological diagnosis reached as thoracic SMARCA4-UT, and the preoperative TNM stage was T1N2M0 (ⅢA). Tumor proportion score (TPS) detected by immunohistochemistry of programmed cell death 1-ligand 1 (PD-L1, clone SP263) was 2%. Tumor mutation burden (TMB) detected by NGS of 1 021 genes was 16. 3/Mb. Microsatellite detection showed the tumor was microsatellite stable (MSS). Neo-adjuvant therapy was implemented with the combined regimen of chemotherapy and ICI. Right lower lobectomy was performed through thoracoscopy after the two weeks' neoadjuvant. The pathologic assessment of lung tumor specimens after neoadjuvant therapy revealed a complete pathological response (CPR). The post-neoadjuvant tumor TNM stage was ypT0N0M0. Then, five cycles of adjuvant therapy were completed. Until October 2022, neither tumor recurrence nor metastasis was detected, and minimal residual disease (MRD) detection was negative. At present, it is believed that if BRG1 immunohistochemical staining is negative, regardless of whether SMARCA4 gene mutation is detected, it should be classified as SMARCA4-deficient tumors. SMARCA4-deficient tumors include a variety of carcinomas and sarcomas. The essential criteria for diagnosing SMARCA4-UT includes loss of BRG1 expression, speci-fic histological morphology, and exclude other common thoracic malignant tumors with SMARCA4-deficiency, such as squamous cell carcinoma, adenocarcinoma and large cell carcinoma. SMARCA4-UT is a very aggressive malignant tumor with a poor prognosis. It has almost no targeted therapy mutations, and little response to chemotherapy, but ICI is currently the only effective drug. The successful diagnosis and treatment for this case of SMARCA4-UT should enlighten significance for various kinds of SMARCA4-deficient tumors.

Application of endoscopic suturing instrument in laparoscopic gastrojejunostomy / 中华胃肠外科杂志

Objective: To investigate the safety and feasibility of using an endoscopic suturing instrument in laparoscopic gastrojejunostomy. Methods: A descriptive case series study was conducted to retrospectively analyze the clinical data of 5 patients with gastric cancer who underwent laparoscopic distal gastrectomy (Billroth II + Braun anastomosis) at Tangdu Hospital, Air Force Medical University from October 2022 to January 2023. The common opening was closed using an endoscopic suturing instrument. The indications were as follows: (1) patients aged between 18 and 80 years; (2) patients with gastric adenocarcinoma; (3) cTNM between I-III; (4) lower-third gastric cancer and radical gastrectomy is recommended; (5) no history of upper abdominal surgery (except for laparoscopic cholecystectomy). The surgery was performed as follows: A side-to-side gastrojejunostomy was performed with endoscopic linear cutter stapler. Then the common opening was closed with endoscopic suturing instrument. During suturing and closing the common opening, a vertical mattress suture was used to completely invert and close the mucosa-to-mucosa and serosa-to-serosa of the gastric and jejunum walls. After the first layer of suture was completed, the seromuscular layer was sutured from top to bottom to embed the common opening of stomach and jejunum. Results: Laparoscopic closure of the common gastrojejunal opening with endoscopic suturing instrument was successfully completed in all 5 patients. The operative time was (308.6±22.6) minutes, while the time of gastrojejunostomy was (15.4±3.1) minutes. The operative blood loss was (34.0±10.8) ml. No intraoperative or postoperative complications occurred in any of the patients. The first passage of gas occurred at (2.6±0.9) days, and the postoperative hospital stay was (7.0±1.9) days. Conclusion: The application of endoscopic suturing instrument in laparoscopic gastrojejunostomy is safe and feasible.

Research progress on the role of type II innate lymphoid cells in liver diseases / 中华肝脏病杂志

Type II innate lymphoid cell (ILC2) is a newly identified innate immunological cell that belongs to the lymphocyte lineage in cell morphology, resides in the body's mucosal tissues, and has the dual functions of innate and adaptive immunity to promote tissue remodeling and repair after injury. Additionally, it is involved in the occurrence and development of a variety of liver diseases and plays an important role in maintaining the immunological homeostasis of the liver region. This article reviews the differentiation, development, and biological functions of ILC2, with particular attention to the research progress in liver diseases.

Application and development of alveoloplasty in implant-supported full-arch fixed prosthesis / 中华口腔医学杂志

Implant-supported full-arch fixed prosthesis is hot in edentulous therapy currently. Appropriate contour of bone is the premise of good restoration outcome. Alveoloplasty is an important part during treatment procedure. Alveoloplasty can be used to obtain bone platform for implant insertion, create adequate prosthetic space, achieve good Aesthetic effect, and form appropriate soft tissue morphology. The design of alveoloplasty has evolved from traditional plaster models and cone beam CT to three-dimensional (3D) virtual patients. The surgical techniques of alveoloplasty have also undergone the evolution from free-hand to static guide or dynamic navigation. This article elaborates on the concept, purpose and significance of alveloplasty in implant supported full-arch fixed restoration, technology evolution and process to provide reference for clinical practice.

Fumarate hydratase deficient uterine leiomyoma: a clinicopathological and molecular analysis of 80 cases / 中华病理学杂志

Objective: To investigate the clinicopathologic and molecular characteristics of fumarate hydratase (FH) deficient uterine leiomyoma. Methods: Eighty cases of FH deficient uterine leiomyoma were diagnosed from April 2018 to September 2022 in Department of Pathology, Peking University Third Hospital. Sanger sequencing of FH gene exons (exon 1-10) were performed on tumor tissues and matched non-tumor tissues/peripheral blood for all cases. FH immunohistochemistry were performed in 74 cases; S-(2-succino)-cysteine (2SC) were also detected by immunohistochemistry in five cases. Results: Patients' age ranged from 18 to 54 (36.0±7.5) years, with more than 60% exhibiting clinical symptoms of multiple and large leiomyomas (the median diameter was 70 mm). More than four histologic features, including staghorn vasculature, alveolar-pattern edema, bizarre nuclei, oval nuclei arranged in chains, prominent eosinophilic nucleoli with perinucleolar haloes and eosinophilic intracytoplasmic globules were observed in 98.5% (67/68) patients. The immunohistochemical sensitivity of FH and 2SC were 97.3% and 100%, respectively. Based on the Sanger sequencing results, the cases were divided into germline variant group (31 cases), somatic variant group (29 cases) and no variant group (20 cases). Sixty-nine percent (20/29) of the patients with FH germline variation had clear family history. Conclusions: Clinical features, histological morphology, FH and 2SC immunohistochemistry and Sanger sequencing have their own significance and limitations in differential diagnosis of FH deficient uterine leiomyoma. In clinical practice, the above information should be fully integrated and studied for accurate pathologic diagnosis and selection of patients with FH germline variation.

Prognosis analysis of radical or modified radical hysterectomy and simple hysterectomy in patients with stage Ⅱ endometrial cancer / 中华妇产科杂志

Objective: To compare the prognosis and perioperative situation of patients with stage Ⅱ endometrial cancer (EC) between radical hysterectomy/modified radical hysterectomy (RH/mRH) and simple hysterectomy (SH). Methods: A total of 47 patients diagnosed EC with stage Ⅱ [International Federation of Gynecology and Obstetrics (FIGO) 2009] by postoperative pathology, from January 2006 to January 2021 in Peking University People's Hospital, were analyzed retrospectively. The patients were (54.4±10.7) years old, and the median follow-up time was 65 months (ranged 9-138 months). They were divided into RH/mRH group (n=14) and SH group (n=33) according to the scope of operation. Then the prognosis of patients between the groups were compared, and the independent prognostic factors of stage Ⅱ EC were explored. Results: (1) The proportions of patients with hypertension in RH/mRH group and SH group were 2/14 and 45% (15/33), the amounts of intraoperative blood loss were (702±392) and (438±298) ml, and the incidence of postoperative complications were 7/14 and 15% (5/33), respectively. There were significant differences (all P<0.05). (2) The median follow-up time of RH/mRH group and SH group were 72 vs 62 months, respectively (P=0.515). According to Kaplan-Meier analysis and log-rank method, the results showed that there were no significant difference in 5-year progression-free survival (PFS) rate (94.3% vs 84.0%; P=0.501), and 5-year overall survival rate (92.3% vs 92.9%; P=0.957) between the two groups. Cox survival analysis indicated that age, pathological type, serum cancer antigen 125 (CA125), and estrogen receptor (ER) status were associated with 5-year PFS rate (all P<0.05). But the scope of hysterectomy (RH/mRH and SH) did not affect the 5-year PFS rate of stage Ⅱ EC patients (P=0.508). And level of serum CA125 and ER status were independent prognostic factors for 5-year PFS rate (all P<0.05). Conclusions: This study could not find any survival benefit from RH/mRH for stage Ⅱ EC, but increases the incidence of postoperative complications. Therefore, the necessity of extending the scope of hysterectomy is questionable.

Melanogenesis of quality markers in Vernonia anthelmintica Injection based on UPLC-Q-TOF-MS combined network pharmacology / 中国中药杂志

This study aimed to evaluate the biological effect and mechanism of Vernonia anthelmintica Injection(VAI) on melanin accumulation. The in vivo depigmentation model was induced by propylthiouracil(PTU) in zebrafish, and the effect of VAI on melanin accumulation was evaluated based on the in vitro B16F10 cell model. The chemical composition of VAI was identified according to the high-performance liquid chromatography quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS). Network pharmaco-logy was applied to predict potential targets and pathways of VAI. A "VAI component-target-pathway" network was established, and the pharmacodynamic molecules were screened out based on the topological characteristics of the network. The binding of active molecules to key targets was verified by molecular docking. The results showed that VAI promoted tyrosinase activity and melanin production in B16F10 cells in a dose-and time-dependent manner and could restore the melanin in the body of the zebrafish model. Fifty-six compounds were identified from VAI, including flavonoids(15/56), terpenoids(10/56), phenolic acids(9/56), fatty acids(9/56), steroids(6/56), and others(7/56). Network pharmacological analysis screened four potential quality markers, including apigenin, chrysoeriol, syringaresinol, and butein, involving 61 targets and 65 pathways, and molecular docking verified their binding to TYR, NFE2L2, CASP3, MAPK1, MAPK8, and MAPK14. It was found that the mRNA expression of MITF, TYR, TYRP1, and DCT in B16F10 cells was promoted. By UPLC-Q-TOF-MS and network pharmacology, this study determined the material basis of VAI against vitiligo, screened apigenin, chrysoeriol, syringaresinol, and butein as the quality markers of VAI, and verified the efficacy and internal mechanism of melanogenesis, providing a basis for quality control and further clinical research.