Structurally novel HDAC inhibitors based on the trans-β-arylacryl tetrahydroisoquinoline scaffold: the design, synthesis, and anti-cancer activity / 药学学报

In this study, a series of 18 histone deacetylases inhibitors (HDACis), derived from our in-house anti-cancer trans-β-arylacryl 1,2,3,4-tetrahydroisoquinoline-based scaffold, were designed, synthesized, and antitumor evaluated. HDAC1 inhibitory activity assay showed that compounds 13d-13f and 13m-13o demonstrated attractive enzymatic activity with IC50 at single-digit nanomolar or subnanomolar level.In addition, 13o exerted superior anti-proliferative activity (A549, IC50 = 0.89 μmol·L-1; HCT116, IC50 = 0.49 μmol·L-1) to that of vorinostat (SAHA).Besides,13e, with the most potent HDAC1 enzymatic activity (IC50 = 3.8 nmol·L-1), also displayed attractive cellular activity (A549, IC50 = 1.74 μmol·L-1; HCT116, IC50 = 2.43 μmol·L-1). The Western blot analysis illustrated that 13e treatment increased the acetylation of H3 and α-tubulin in a dose-dependent manner in A549 cells. In summary, 13e and 13o deserve further functional investigation.

Advances in the study of new BCR-ABL kinase inhibitors / 药学学报

The oncogenic product of BCR-ABL is an abnormal tyrosine kinase that causes chronic myeloid leukemia (CML). With further research into the pathogenesis of CML, the discovery of compounds that selectively inhibit abnormal BCR-ABL tyrosine kinases is a research focus worthy of attention. The first three generations of BCR-ABL inhibitors are orthosteric inhibitors, which competitively block the binding of ABL protein tyrosine kinase to ATP and prevent it from activating downstream signals. The fourth-generation BCR-ABL inhibitors allosterically inhibit ABL protein tyrosine kinase by binding to the myristoyl pocket, providing greater selectivity and maintaining activity against drug-resistant mutations proteins. Novel drug design strategies such as proteolytic targeting chimera (PROTAC), covalent inhibitors and dual targeting inhibitors also provide new directions for the development of BCR-ABL kinase inhibitors. This paper reviews recent research advances on BCR-ABL kinase inhibitors and discusses drug design strategies for various novel BCR-ABL inhibitors.

Vascularization of intravitreal injection of Conbercept in the treatment of retinopathy of prematurity / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate retinal vascularization caused by the intravitreal injection of Conbercept in the treatment of a series of retinopathy of prematurity(ROP)cases in Type Ⅰ(threshold and pre-threshold period)and aggressive ROP(A-ROP).METHODS: The data of 34 ROP cases(67 eyes)treated by intravitreal injection of Conbercept(IVC)in the ophthalmology department of the Xiamen Children's Hospital from July 2017 to March 2020 were retrospectively analyzed. Reactivation, which refers to recurrence of acute phase features, occurred at any stage of the disease in the presence or absence of other diseases. RESULT: The average gestational age of the 34 children was 28.82±2.32wk. The average birth weight was 1155.18±398.22g. The lesion zone of 19 cases(37 eyes)was Zone Ⅰ. In 10 cases(20 eyes), the lesion was in Zone Ⅱ, and in 5 cases(10 eyes), the lesion was in the posterior Zone Ⅱ. The total effective rate of disease control in ROP children treated with once IVC was 73.1%(49/67), and the vascularization of Zone Ⅱ was completed. The patients showed variable changes in the vascularization in Zone Ⅲ. For the patients who received one treatment and did not reactivate, the average rate of Type Ⅰ vascularization of ROP was 9.11±2.49wk, and the A-ROP was 13.40±4.04wk. The rate of A-ROP vascularization in Zone Ⅱ was significantly longer compared to Type Ⅰ.CONCLUSION: IVC effectively completes vascularization in Zone Ⅱ.

Relationship between uric acid and coronary atherosclerotic heart disease in adults / 公共卫生与预防医学

Objective To analyze the correlation between uric acid and coronary atherosclerotic heart disease in adults. Methods A total of 186 patients with hyperuricemia from January 2020 to October 2021 were selected as the observation group and 186 subjects with normal blood uric acid were selected as the control group . The levels of uric acid, hs-CRP, MCP-1, IL-6, RANTES and adropin protein were measured . The SYNTAX score was used to assess the risk of coronary heart disease and the incidence rate of coronary heart disease was recorded. The correlation between uric acid and inflammatory indexes was analyzed by linear regression model . The relationship between serum uric acid level and coronary atherosclerotic heart was tested by spearman correlation test. Results The levels of hs-CRP, MCP-1, IL-6, RANTES and adropin protein in the observation group were higher than the control group significantly (P<0.05) . The syntax score of the observation group was higher than the control group significantly (P<0.05) .The incidence rate of coronary heart disease in the observation group was significantly higher than that in the control group, and the difference was statistically significant (P<0.05). The level of uric acid was significantly positively correlated with hs-CRP, MCP-1, IL-6, RANTES and adropin . There was positive correlation between serum uric acid and syntax score and the incidence of coronary atherosclerotic heart disease (P<0.05). Conclusion The increase of uric acid level can predict coronary atherosclerotic heart disease. Patients with hyperuricemia should actively carry out uric acid lowering treatment to prevent the risk of coronary atherosclerotic heart disease.

Analysis of influencing factors and regularity of inferior mediastinal lymph node metastasis in Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction / 中华消化外科杂志

Objective:To investigate the influencing factors and regularity of inferior mediastinal lymph node metastasis in Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction (AEG).Methods:The retrospective case-control study was conducted. The clinicopatho-logical data of 185 Siewert type Ⅱ and Ⅲ AEG patients in two medical centers (113 cases in Changzhi People's Hospital Affiliated to Changzhi Medical College and 72 cases in Heji Hospital Affiliated to Changzhi Medical College) from January 2017 to January 2022 were collected. There were 143 males and 42 females, aged (64±8)years. Patients underwent radical resection of AEG combined with inferior mediastinal lymph node dissection. Observation indicators: (1) clinicopathological charac-teristics of Siewert type Ⅱ and Ⅲ AEG patients; (2) analysis of influencing factors for inferior mediastinal lymph node metastasis in Siewert type Ⅱ and Ⅲ AEG; (3) regularity of inferior mediastinal lymph node metastasis in Siewert type Ⅱ and Ⅲ AEG. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were represented as absolute numbers or percentages, and comparsion between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the rank sum test. Univariate and multivariate analyses were conducted using the Logistic regression model. Results:(1) Clinicopathological characteristics of Siewert type Ⅱ and Ⅲ AEG patients. Pathologic staging as stage Ⅰ, Ⅱ, Ⅲ and Ⅳ, degree of tumor invasion as stage T1, T2, T3 and T4, length of esophageal invasion ≤1 cm, >1 cm and ≤2 cm, >2 cm and ≤3 cm, >3 cm and ≤4 cm were found in 30, 61, 75, 7, 3, 41, 79, 50, 101, 46, 18, 8 cases of the Siewert type Ⅱ and Ⅲ AEG patients without inferior mediastinal lymph node metastasis, respectively, versus 0, 2, 10, 0, 0, 0, 5, 7, 4, 3, 2, 3 cases of the Siewert type Ⅱ and Ⅲ AEG patients with inferior mediastinal lymph node metastasis, showing a significant differences between them ( Z=?2.21, ?2.49, ?2.22, P<0.05). (2) Analysis of influencing factors for inferior mediastinal lymph node metastasis in Siewert type Ⅱ and Ⅲ AEG. Results of univariate analysis showed that pathological staging, depth of tumor invasion and length of esophageal invasion were related factors affecting inferior mediastinal lymph node metastasis in Siewert type Ⅱ and Ⅲ AEG ( odds ratio=2.48, 3.26, 2.03, 95% confidence intervals as 1.02?6.01, 1.21?8.80, 1.18?3.51, P<0.05). Results of multivariate analysis showed that depth of tumor invasion and length of esophageal invasion were independent influening factors affecting inferior mediastinal lymph node metastasis in Siewert type Ⅱ and Ⅲ AEG ( odds ratio=4.01, 2.26, 95% confidence interval as 1.35?11.96, 1.26?4.06, P<0.05). The inferior mediastinal lymph node metastasis probability of AEG patients with the length of esophageal invasion >3 cm and ≤4 cm was 9.47 times that of AEG patients with the length of esophageal invasion ≤1 cm. (3) Regularity of inferior mediastinal lymph node metastasis in Siewert type Ⅱ and Ⅲ AEG. The number of inferior mediastinal lymph nodes including No.110, No.111 and No.112 dissected in 185 patients of Siewert type Ⅱ and Ⅲ AEG were 127, 50 and 27. The number of lymph nodes dissected and the number of metastatic lymph nodes in No.110 and No.111 of patients with length of esophageal invasion ≤1 cm, >1 cm and ≤2 cm, >2 cm and ≤3 cm, >3 cm and ≤4 cm were 69, 4, 42, 4, 4, 1, 12, 4 and 23, 0, 17, 0, 7, 2, 3, 0, respectively. There were significant differences in metastatic lymph nodes in No.110 and No.111 of patients with length of esophageal invasion ≤1 cm, >1 cm and ≤2 cm, >2 cm and ≤3 cm, >3 cm and ≤4 cm ( χ2=8.45, 7.30, P<0.05). Of the 185 patients of Siewert type Ⅱ and Ⅲ AEG, the ratio of cases with inferior mediastinal lymph nodes metastasis was 6.49%(12/185). The ratio of inferior mediastinal lymph nodes metastasis in cases with length of esophageal invasion ≤1 cm, >1 cm and ≤2 cm, >2 cm and ≤3 cm, >3 cm and ≤4 cm were 3.81%(4/105), 6.12%(3/49), 10.00%(2/20), 27.27%(3/11), respectively. The ratio of No.110 lymph nodes metastasis in cases with length of esophageal invasion ≤1 cm, >1 cm and ≤2 cm, >2 cm and ≤3 cm, >3 cm and ≤4 cm were 2.86%(3/105), 6.12%(3/49), 5.00%(1/20), 27.27%(3/11), respectively, showing a significant difference among them ( χ2=8.26, P<0.05). Conclusions:Depth of tumor invasion and length of esophageal invasion are independent influening factors affecting inferior mediastinal lymph node metastasis in Siewert type Ⅱ and Ⅲ AEG. The rate of inferior mediastinal lymph node metastasis increases with the increase of the length of esophageal invasion.

Short-term clinical efficacy of Kamikawa anastomosis and jejunal interposed double channel anastomosis in laparoscopic proximal gastrectomy / 中华消化外科杂志

Objective:To investigate the short-term clinical efficacy of Kamikawa anasto-mosis and jejunal interposed double channel anastomosis in laparoscopic proximal gastrectomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 68 patients with esophagogastric junctional tumors and upper gastric tumors who underwent laparoscopic proximal gastrectomy in two medical centers, including 63 cases in the Changzhi People's Hospital Affiliated to Changzhi Medical College and 5 cases in the Heji Hospital Affiliated to Changzhi Medical College, from March 2018 to December 2020 were collected. There were 57 males and 11 females, aged 62(range, 39?78)years. Of 68 patients, 35 patients undergoing Kamikawa anastomosis in laparoscopic proximal gastrectomy were allocated into Kamikawa group, and 33 patients under-going jejunal interposed double channel anastomosis in laparoscopic proximal gastrectomy were allocated into double channel group. Observation indicators: (1) intraoperative situations; (2) post-operative situations; (3) follow-up. The patients were followed up by outpatient examinations and telephone interview to detect the postoperative score of chew-wun wu special symptoms, post-operative reflux anastomotic esophagitis and anastomotic stenosis up to December 2021. Measure-ment data with normal distri-bution were represented as Mean±SD, and comparison between groups was performed by the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted by Mann-Whitney U test. Comparison of ordinal data was performed by nonparametric rank sum test. Count data were expressed as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability method. Results:(1) Intraoperative situations. All the 68 patients successfully under-went laparoscopic proximal gastrectomy combined with D 1+ lymph node dissection. The operation time and volume of intraoperative blood loss of the Kamikawa group were (5.15±0.31)hours and (89±11)mL, versus (4.21±0.11)hours and (142±20)mL of the double channel group, respectively, showing significant differences between the two groups ( t=2.81, ?2.34, P<0.05). The digestive tract reconstruction time and the number of lymph node dissection were (1.95±0.13)hours and 30.4±2.4 of the Kamikawa group, versus (1.69±0.76)hours and 28.0±2.4 of the double channel group, respectively, showing no significant difference between the two groups ( t=1.79, 0.73, P>0.05). (2) Postoperative situations. The time to postoperative first flatus, duration of drainage tube placement, duration of postoperative hospital stay were (3.03±0.12)days, (5.46±0.22)days, (13.00±0.50)days of the Kamikawa group, versus (4.42±0.21)days, (9.97±0.76)days, (16.46±0.92)days of the double channel group, showing significant differences in the above indicators between the two groups ( t=?5.80,?5.58, 3.40, P<0.05). Cases with or without drainage tube placement were 32 and 3 of the Kamikawa group, versus 33 and 0 of the double channel group, respectively, showing no significant difference between the two groups ( P>0.05). Cases with grade 1, grade 2, grade 3, grade 4 complica-tions of Clavien-Dindo classification were 31, 0, 4, 0 of the Kamikawa group, versus 27, 3, 1, 2 of the double channel group, respectively, showing a significant difference between the two groups ( Z=?6.28, P<0.05). Postoperative anastomotic stenous, reflux symptoms, anastomotic fistula, pancreatic fistula, pulmonary infection were found in 4, 2, 0, 0, 0 case of the Kamikawa group and 0, 1, 3, 1, 2 cases of the double channel group, respectively. There was no significant difference in the above indicators between the two groups ( P>0.05). There was no complication of incisional infection, abdominal hemorrhage, lymphatic fistula or gastroparesis in either group. Of the 4 patients with perioperative anastomotic stenosis in the Kamikawa group, 2 cases were improved after once gastroscopic balloon dilatation, 2 cases were improved after 4 times of gastro-scopic balloon dilatation. (3) Follow-up. All the 68 patients were followed up at postoperative 3, 6, 12 months. The scores of chew-wun wu special symptoms scale at postopertaive 12 months of the Kamikawa group and double channel group were 16.8±0.7 and 14.6±0.7, respectively, showing a significant difference between the two groups ( t=2.20, P<0.05). There were 2 cases of grade B reflux esophagitis and 1 case of grade B reflux esophagitis, respectively, showing no significant difference between the two groups ( P>0.05). There was no anastomotic stenosis occurred in either group. Conclusions:Laparos-copic proximal gastrectomy with Kamikawa anastomosis or jejunal interposed double channel anastomosis is safe and feasible for esophagogastric junction tumors and upper gastric tumors. The Kamikawa anastomosis has less volume of intraoperative blood loss, shorter time to postoperative first flatus, duration of drainage tube placement and postoperative hospital stay, higher quality of postoperative lfe.

Training status of operating room nurses of robotic-assisted surgery system in China: a cross-sectional survey / 中国实用护理杂志

Objective:To investigate the training status of robotic-assisted surgery nurses in hospitals with robotic-assisted surgery system in China, and to provide reference for the training and management of robotic-assisted surgery nurses.Methods:From August to December in 2021, hospitals with robotic-assisted surgery system in China were surveyed by a self-designed questionnaire distributed online.Results:The participants in the survey of 111 hospitals in 30 provinces, cities, autonomous regions and municipalities directly under the central government, nurses cooperated with robotic-assisted surgery exist the phenomenon of their own training was up to 96.40% (107/111) of hospital, 47.75% (53/111) of the hospital said the current training content also need to add other aspects of the course. Training duration of theoretical courses was 0-13 (2.86 ± 3.03) periods arranged by hospitals, and the training duration of practical courses was 1-60 (8.38 ± 9.91) d. 35.14% (39/111) of hospitals set up regular assessment after training, and the assessment cycle of them was 1-12 (4.08 ± 3.31) months. Many hospitals put forward suggestions on strengthening English training and attaching importance to team cooperation and so on.Conclusions:In our country, Robotic-assisted surgery nurses′ training has turned to that training themselves in operating rooms, the training time, form, content and other aspects have no uniform standard, strict admittance, standardization of specialist training , these are questions need to solve.

Modified transcricothyroid electrode recording method for monitoring recurrent laryngeal nerve function during thyroidectomy / 中华内分泌外科杂志

Objective:To study the safety, validity and practicability of the modified trans-cricothyroid needle electrode method for neurmonitoring during thyroidectomy.Methods:115 patients from the Department of Thyroid Surgery in Peking University Shenzhen Hospital scheduled for thyroid surgery were recruited into the group. Two paired needle electrodes were obliquely inserted into the cricothyroid membrane from the angle between the rectus cricothyroid muscle and the inferior margin of thyroid cartilage. The function of recurrent laryngeal nerve (RLN) was localized, exposed and evaluated by standard four-step method (V1-R1-R2-V2) . The vocal cord movement was evaluated by electronic laryngoscope before and after operation, and t-test was used to compare the difference of EMG signal amplitude before and after operation.Results:A total of 130 RLN from 115 patients were recorded effective electromyographic (EMG) signals, including 12 cases of giant goiter with tracheal compression stenosis; 13 cases had repeated adjustments of the position of tracheal intubation electrode during operation, but EMG signals were not satisfactory; 15 cases were with of accidental findings during operation and requiring neurmonitoring, but tracheal intubation electrodes were not used in advance. 75 cases were volunteers. The signals of 3 RLN were lost during operation. On the second day after operation, electronic laryngoscope showed that 2 cases had normal vocal cord movement and 1 case had vocal cord paralysis and no recovery for 6 months follow-up. The EMG signals of other 127 nerves were V1/R1=1857±1718μV/2347±2323μV, V2/R2=1924±1705μV/2450±2345μV. There was no significant difference in EMG signals between pre-operation and post-operation ( t=0.31/0.35, P=0.755/0.725) . The electronic laryngoscope showed normal vocal cord movement before and after operation. During the operation, 2 patients had a little bleeding at the needle electrode insertion point, which stopped after 5 minutes of compression. No electro-acupuncture breakage, infection or local hematoma occurred. Conclusions:The modified trans-cricothyroid needle electrode method had been proved to be safe and feasible for evaluating the function of recurrent laryngeal nerve in thyroid surgery. Besides of unaffected by tracheal conditions, it has good stability, simple implantation and low cost. In thyroid surgery, it can be used as a useful supplement to endotracheal intubation electrode.

Research progress of single cell sequencing technique in predicting the immunotherapeutic efficacy of lung cancer / 国际生物医学工程杂志

Globally, lung cancer is the leading cause of cancer death. Although survival rates for lung cancer patients have improved over the past few decades, the survival rates have not yet reached the levels of other common malignancies. In recent years, immune checkpoint inhibitors (ICIs) have shown great promise in clinical trials and have been rapidly incorporated into the standard of care for patients with advanced non-small cell lung cancer (NSCLC). However, many patients do not benefit from treatment. Our findings suggest that the heterogeneity of the tumor microenvironment (TME) is closely related to the efficacy of ICIs. Single-cell sequencing is a technology that can specifically analyze cell populations at the genome and transcriptome levels at the single-cell level. This article reviews the potential value of single-cell sequencing technology in predicting immune responses to lung cancer.

Study on dynamic changes of odor components in Cornus officinalis during processing by ultra -fast gas phase electronic nose / 中国药房

OBJECTIVE To establish the method for monitoring the dynamic changes of odor components in Cornus officinalis during processing . METHODS The decoction pieces of C. officinalis with different processing time were prepared by the wine steaming method . The dynamic changes of odor components were obtained by using ultra -fast gas electronic nose ；odor components were identified by comparing with AroChemBase database ；the dynamic changes of odor compounds were analyzed in combination with peak area ，and the chemical pattern recognition analysis were carried out . RESULTS A total of 12 common peaks of odor components were identified in the fingerprints of raw C. officinalis，and 21 in the fingerprints of decoction pieces of C. officinalis. Eight odor components with the high proportion of peak area during processing were ethanol ， isopropyl alcohol ， 2- methylpropylaldehyde，ethyl acetate ，2-methylbutanal，isoamyl alcohol ，2-hexanol and furfural ，among which ，the peak areas of ethanol，isoamyl alcohol and 2-hexanol showed a trend of first increasing and then decreasing ；at 24 h of processing ，their peak areas were still higher than those of raw products . The peak areas of ethyl acetate ，2-methylbutanal and furfural nearly increased with the increase of processing time . Variable importance in projection of above eight odor components were all greater than 1. CONCLUSIONS The method is established for monitoring the dynamic changes of odor components of C. officinalis during processing. Eight odor components such as ethanol can be used as monitoring indicators of C. officinalis dring processing .

The expression of collagen type Ⅰ alpha 2 chain in glioma and its influence on the migration and invasion of glioma / 中国医师进修杂志

Objective:To study the expression and clinical significance of collagen type Ⅰ alpha 2 chain (COL1A2) in glioma , and its effect on the migration and invasion of glioma cell lines.Methods:Through in-depth mining of the data related to COL1A2 in the Oncomine database, meta-analysis of its expression in different types of tumors, different grades and different molecular types of glioma, and then through the Chinese glioma genome map project (Chinese Glioma Genome Atlas, CGGA) database to explore the relationship between its expression level and the prognosis of glioma patients. The COL1A2 gene was functionally annotated by gene ontology (GO) and Pathway analysis. The annotation content includes cell components, biological processes, molecular functions and related signal pathways.Results:A total of 426 research results on COL1A2 in different types of tumors were collected in the Oncomine database, 114 of which were statistically different, 103 studies with increased COL1A2 expression, and 11 studies with decreased expression; the analysis shows there were 22 studies on high expression of COL1A2 in tumors, and no studies on low expression. Analysis of different grades of glioma and different molecular types of glioma Compared with the control group, COL1A2 was highly expressed in various types of glioma. Through the analysis of the gene chip data of the CGGA database, it was found that in glioblastoma, low expression levels of COL1A2 were significantly associated with an improved prognosis in patients with glioma ( P<0.05). Next, through GO and Pathway annotations, it was found that COL1A2 was involved in the biological processes of NAD metabolic salvage pathway, cell and cell signal transduction, circadian rhythm regulation and so on. Finally, through the construction of overexpression and knockdown cell lines in glioblastoma cell lines U87 and T98, scratch experiments and transwell cell function experiments confirmed that COL1A2 can significantly promote the migration and invasion of glioblastoma cell lines. Conclusions:Low expression levels of COL1A2 were significantly associated with improved prognosis in patients with glioma. Knockdown and overexpression of COL1A2 on glioblastoma cell lines U87 and T98 manifested that COL1A2 can promote glioblastoma cell lines migration and invasion ability. Based on the above results, COL1A2 may be used as an indicator for judging the prognosis of glioblastoma and as a potential biological target for therapy.

Rehabilitation nursing of hoarseness and dysphagia after resection of schwannoma in jugular foramen: a case report / 中国实用护理杂志

Objective:To summarize the combined rehabilitation nursing process of a case of voice and deglutition disorders following surgical removal of intra-and extracranial schwannoma in the jugular foramen area.Methods:A case of hoarseness and dysphagia after surgery for intracranial and extracranial schwannomas in the left jugular foramen region in Xuanwu Hospital, Capital Medical University in October 2020 was collected. Early step-wise voice training assisted by respiratory muscles and tongue muscle exercises was carried out, electronic laryngoscope-based breathing and swallowing methods, assessment of food and bite-size, maintenance of food consistency with the assistance of chewing times, and swallowing and ingestion guidance for the update of dietary methods were performed. The continuous rehabilitation training was provided throughout the process.Results:The grade of GRBAS scale decreased from G3 to G2 after training from home for 3 months following discharge; the voice handicap index of Chinese version reduced from 75 points to 52 points, and the average pronunciation time extended from 2.45 s to 5.32 s. The frequency of choking with food optimized from 0.4 to 0.5 times/min to no choking.Conclusions:Early rehabilitation training of voice and, swallowing and ingestion is a boon for the recovery of hoarseness and dysphagia after resection of schwannomas in the jugular foramen region.

Dose-enhanced immunochemotherapy followed by first-line autologous peripheral blood stem cell transplantation for young patients with high-risk aggressive B-cell lymphoma: an efficacy and prognostic factor analysis / 中华血液学杂志

Objective: This study aimed to determine the efficacy of dose-enhanced immunochemotherapy followed by autologous peripheral blood stem cell transplantation (ASCT) in young patients with newly diagnosed high-risk aggressive B-cell lymphoma. Methods: A retrospective study was conducted to examine the clinical and survival data of young patients with high-risk aggressive B-cell lymphoma who received dose-enhanced immunochemotherapy and ASCT as first-line treatment between January 2011 and December 2018 in Blood Diseases Hospital. Results: A total of 63 patients were included in the study. The median age range was 40 (14-63) years old. In terms of the induction therapy regimen, 52 cases received R-DA-EP (D) OCH, and the remaining 11 received R-HyperCVAD/R-MA. Sixteen (25.4% ) patients achieved partial response in the mid-term efficacy assessment, and ten of them were evaluated as complete response after transplantation. The median follow-up was 50 (8-112) months, and the 3-year progression-free survival (PFS) rate and overall survival (OS) rate were (83.9±4.7) % and (90.4±3.7) % , respectively. Univariate analysis demonstrated that age-adjusted international prognostic index ≥2 scores was a negative prognostic factor for OS (P=0.039) , and bone marrow involvement (BMI) was an adverse prognostic factor for OS (P<0.001) and PFS (P=0.001) . However, multivariate analysis confirmed that BMI was the only independent negative predictor of OS (P=0.016) and PFS (P=0.001) . Conclusions: The use of dose-enhanced immunochemotherapy in combination with ASCT as first-line therapy in the treatment of young, high-risk aggressive B-cell lymphoma results in good long-term outcomes, and BMI remains an adverse prognostic factor.

The NO inhibitory constituents from Illigera rhodantha / 药学学报

Sixteen compounds were isolated from the ethanol extract of Illigera rhodantha by silica gel, ODS, and Sephadex LH-20 column chromatographies. These compounds were identified as (2R,3R)-2,3-dihydroxy-2-methylbutane-1,4-diyldibenzoate (1), p-hydroxyphenethyl trans-ferulate (2), 4-O-benzoyl-2-C-methyl-D-erythritol (3), N-trans feruloyl-3-methyldopamine (4), tribulusamide A (5), cryptomeridiol (6), teuclatriol (7), oleanolic acid (8), icario A2 (9), vanillic acid (10), p-hydroxybenzoic acid (11), gallic acid (12), ethyl gallate (13), chrysophanol (14), D-1-O-methyl-inositol (15), and hexadecanoic acid (16) based on their spectral data and physico-chemical properties. Compound 1 is an undescribed compound, of which its absolute configurations were determined by Mosher and ROESY methods; all the compounds except 10, 11 and 14 were isolated from Illigera genus for the first time. Compared with the positive control indomethacin, compounds 4-6, 8 and 9 inhibited significantly against the NO production in LPS-induced RAW 264.7 cells.

Visualization analysis of microfluidics research status / 生物医学工程学杂志

Microfluidics is the science and technology to manipulate small amounts of fluids in micro/nano-scale space. Multiple modules could be integrated into microfluidic device, and due to its advantages of microminiaturization and controllability, microfluidics has drawn extensive attention since its birth. In this paper, the literature data related to microfluidics research from January 1, 2006 to December 31, 2021 were obtained from Web of Science Core Collection database. CiteSpace 5.8.R3 software was used for bibliometrics analysis, so as to explore the research progress and development trends of microfluidics research at home and abroad. Based on the analysis of 50 129 articles, it could be seen that microfluidics was a hot topic of global concern, and the United States had a certain degree of authority in this field. Massachusetts Institute of Technology and Harvard University not only had a high number of publications, but also had strong influence and extensive cooperation network. Combined with ultrasonic, surface modification and sensor technology, researchers constructed paper-based microfluidic, droplet microfluidic and digital microfluidic platforms, which were applied in the field of immediate diagnosis, nucleic acid and circulating tumor cell analysis of in vitro diagnosis and organ-on-a-chip. China was one of the countries with a high level of research in the field of microfluidics, while the industrialization of high-end products needed to be improved. As people's demand for disease risk prediction and health management increased, promoting microfluidic technological innovation and achievement transformation is of great significance to safeguard people's life and health.

Conbercept combined with trabeculectomy and retinal photocoagulation in the treatment of nevoascular glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To evaluate the effect and safety of conbercept combined with trabeculectomy and retinal photocoagulation in the treatment of nevoascular glaucoma.<p>METHODS: A retrospectively analysis study. The clinical data of 47 patients(47 eyes)with neovascular glaucoma admitted to Shaanxi Eye hospital from January 2018 to December 2020. The patients were followed up for 6mo to observe the changes of visual acuity and intraocular pressure and the occurrence of complications before and after treatment.<p>RESULTS: At 6mo after compound trabeculectomy, the visual acuity of this group of patients improved in 25 eyes(53%), among which 8 eyes without light perception before operation, visual acuity increased to 0.2 and 0.02 respectively, to hand motion/30cm in 2 eyes,restoring light perception from no light perception 2 eyes; The visual acuity remained unchanged in 19 eyes(40%)and decreased in 3 eyes(6%). 40 eyes of 40 cases did not use any intraocular pressure lowering drugs, the intraocular pressure <21mmHg and the complete success rate was 85% at the 6mo follow up post-operatively. The intraocular pressures were 15.6±6.2, 12.8±5.9, 14.7±5.3, 17.1±6.9, 18.3±6.7mmHg at 1, 7d, 1, 3 and 6mo after compound trabeculectomy, which were different from the intraocular pressure at admission(46.0±11.9mmHg)and intravitreal intraocular pressure(39.9±12.5mmHg)after 3d of intravitreal injection of conbercept were significantly different(<i>F</i>=106.65, <i>P</i><0.001). Hyphema occurred in 3 eyes after compound trabeculectomy, and completely absorbed within 3-7d after conservative drug treatment.<p>CONCLUSION: Intravitreal injection of conbercept combined with compound trabeculectomy and retinal photocoagulation is safe and effective in the treatment of neovascular glaucoma.

Co-delivery of Tim-3 mAb and sorafenib enhanced chemoimmunotherapy for hepatocellular carcinoma using "responsive shell-peeling" mesoporous silica nanoparticles / 药学学报

Chemoimmunotherapy has attracted much attention as an emerging therapy pattern for the treatment of cancers. Exploring effective drug combination schemes and reasonable delivery methods remained the key issue in current research. Herein, we designed sorafenib (SF) and anti-Tim-3 monoclonal antibody (Tim-3 mAb) co-loaded MMP2-responsive mesoporous silica nanoparticles (ST-MSNs) for combined chemoimmunotherapy of hepatocellular carcinoma (HCC). The shell of ST-MSNs was fabricated by Tim-3 mAb through matrix metalloproteinase 2 (MMP2) sensitive peptides as "gatekeepers" to prevent drug release during the blood circulation. In tumor microenvironment, the high levels of MMP2 caused the responsive shedding of Tim-3 mAb, leading to the triggerred release of SF and Tim-3 mAb. Then, SF could be delivered to tumor cells and Tim-3 mAb could be delivered to T cells, respectively. In vivo tumor inhibition study results demonstrated that ST-MSNs can significantly enhance synergistic antitumor activity compared with sequential administration of free SF solution and Tim-3 mAb solution. Meanwhile, the expression of antitumor cytokines IFN-γ, IL-12 and the percentage of CD3+CD4+ cells, CD3+CD8+ cells in tumors were upregulated after the administration of ST-MSNs, demonstrating good immunomodulatory ability. In addition, within the dosage range, the ST-MSNs had low cytotoxicity and hemolysis, and no obvious tissue toxicity was observed. All animal experiments were performed in line with national regulations and approved by the Animal Experiments Ethical Committee of Shandong University. In conclusion, this study provided a promising drug combination of chemoimmunotherapy with good application prospects for clinical HCC treatment, and exhibited a potential drug carrier for clinical chemoimmunotherapy.

Independent innovation research, development and transformation of precise bionic repair technology for oral prosthesis / 北京大学学报(医学版)

According to the fourth national oral health epidemiological survey report (2018), billions of teeth are lost or missing in China, inducing chewing dysfunction, which is necessary to build physiological function using restorations. Digital technology improves the efficiency and accuracy of oral restoration, with the application of three-dimensional scans, computer-aided design (CAD), computer-aided manufacturing (CAM), bionic material design and so on. However, the basic research and product development of digital technology in China lack international competitiveness, with related products basically relying on imports, including denture 3D design software, 3D oral printers, and digitally processed materials. To overcome these difficulties, from 2001, Yuchun Sun's team, from Peking University School and Hospital of Stomatology, developed a series of studies in artificial intelligence design and precision bionics manufacturing of complex oral prostheses. The research included artificial intelligence design technology for complex oral prostheses, 3D printing systems for oral medicine, biomimetic laminated zirconia materials and innovative application of digital prosthetics in clinical practice. The research from 2001 to 2007 was completed under the guidance of Prof. Peijun Lv and Prof. Yong Wang. Under the support of the National Natural Science Foundation of China, the National Science and Technology Support Program, National High-Tech R & D Program (863 Program) and Beijing Training Project for the Leading Talents in S & T, Yuchun Sun's team published over 200 papers in the relevant field, authorized 49 national invention patents and 1 U.S. invention patent and issued 2 national standards. It also developed 8 kinds of core technology products in digital oral prostheses and 3 kinds of clinical diagnosis and treatment programs, which significantly improved the design efficiency of complex oral prostheses, the fabrication accuracy of metal prostheses and the bionic performance of ceramic materials. Compared with similar international technologies, the program doubled the efficiency of bionic design and manufacturing accuracy and reduced the difficulty of diagnosis and cost of treatment and application by 50%, with the key indicators of those products reaching the international leading level. This program not only helped to realize precision, intelligence and efficiency during prostheses but also provided functional and aesthetic matches for patients after prostheses. The program was rewarded with the First Technical Innovation Prize of the Beijing Science and Technology Awards (2020), Gold Medal of Medical Research Group in the First Medical Science and Technology Innovation Competition of National Health Commission of the People's Republic of China (2020) and Best Creative Award in the First Translational Medical Innovation Competition of Capital (2017). This paper is a review of the current situation of artificial intelligence design and precision bionics manufacturing of complex oral prosthesis.

History and present situation of seromuscular flap anastomosis in proximal gastrectomy / 中华胃肠外科杂志

With the increasing detection rate of early upper gastric cancer and adenocarcinoma of esophagogastric junction, the safety of proximal gastrectomy with clear indications has been verified, and function-preserving proximal gastrectomy has been widely used. However, proximal gastrectomy destructs the normal anatomical structure of esophagogastric junction, resulting in severe postoperative gastroesophageal reflux symptoms and seriously affecting the quality of life. Among various anti-reflux surgery methods, reconstruction of "cardiac valve" has always been the focus of relevant scholars because its similarity with the mechanism of normal anti-reflux. After years of development, evolution and optimization, the designed seromuscular flap anastomosis includes tunnel muscle flap anastomosis, Hatafuku valvuloplasty, single muscle flap anastomosis and double muscle flap anastomosis. The double muscle flap anastomosis has become a research hotspot because it shows good anti-reflux effect in clinical application. This paper reviews the history, research status and hot issues of seromuscular flap anastomosis of esophageal remnant stomach at home and abroad.

Current status and progress in the standardized surgical management of specimens after radical gastric cancer surgery / 中华胃肠外科杂志

Standardized surgical management of postoperative specimens of gastric cancer is an important part of the standardized diagnosis and treatment of gastric cancer. It can reflect the accurate number and detailed distribution of lymph nodes in the specimen and lay the foundation for accurate and standardized pathological reports after surgery. Meanwhile, it can evaluate the scope of intraoperative lymph node dissection, the safety of cutting edge, and the standardization of surgery (principle of en-bloc dissection), which is an important means of surgical quality control. It also provides accurate research samples for further research and is an important way for young surgeons to train their clinical skills. The surgical management of postoperative specimens for gastric cancer needs to be standardized, including specimen processing personnel, processing flow, resection margin examination, lymph node sorting, measurement after specimen dissection, storage of biological specimens, documentation of recorded data, etc. The promotion of standardized surgical management of specimens after radical gastrectomy can promote the homogenization of gastric cancer surgical diagnosis and treatment in medical institutions and further promote the high-quality development of gastric cancer surgery in China.