OBJECTIVE： To discuss the selectivity of enatiomers of clinically used asymmetric drugs.METHODS： To exsamplify this issue in respect to pharmacokinetic characteristics,pharmacodynamic properties and clinical application of asymmetric drugs.RESULTS ＆ CONCLUSION： The enatiomers of asymmetric drugs assume complex pharmacokinetic and pharmacodynamic characteristics.Thorough study of enatiomers of asymmetric drugs will exert great influence on rational use of asymmetric drugs.

In order to further investigate the mechanisms of action of berberine (Ber), we assessed the effects of Ber on the mRNA expression of nitric oxide synthases (NOS) in rat corpus cavernosum. After incubation with Ber for 1 or 3 h respectively, the levels of NOS mRNA were examined by reverse transcription polymerase chain reaction (RT-PCR). Our results showed that there were iNOS and eNOS mRNA expressions in rat corpus cavernosum. Ber enhanced eNOS mRNA expression in rat penis, but exhibited no effect on the expression of iNOS mRNA (P > 0.05). The present study indicated that the relaxation of Ber involved the NO-cGMP signal transduction pathway. The enhancing effect of Ber on eNOS mRNA expression might associated with its relaxation of corpus cavernosum.
Berberine/*pharmacology ; Connective Tissue/physiopathology ; Nitric Oxide Synthase/*biosynthesis ; Nitric Oxide Synthase/genetics ; Nitric Oxide Synthase Type I/biosynthesis ; Nitric Oxide Synthase Type I/genetics ; Nitric Oxide Synthase Type III/biosynthesis ; Nitric Oxide Synthase Type III/genetics ; Penile Erection/*physiology ; Penis/*metabolism ; Penis/physiology ; RNA, Messenger/biosynthesis ; RNA, Messenger/genetics

To further investigate the mechanisms of action of icariin (ICA), we assessed the effects of ICA on the in vitro formation of cGMP and cAMP in isolated rabbit corpus cavernosum. Isolated segments of rabbit corpus cavernosum were exposed to increasing concentrations of ICA and the dose-dependent accumulation of cGMP and cAMP was determined in the tissues samples by means of 125I radioimmunoassay. Responses of the isolated tissues preparations to ICA were compared with those obtained with the reference compounds sildenafil (Sild). Furthermore, the effects of ICA on the mRNA expression of specific cGMP-binding phosphodiesterase type V (PDE5) in rat penis were also observed. After incubation with ICA for 6 h or 14 h respectively, the levels of PDE5 mRNA were examined by reverse transcriptase polymerase chain reaction (RT-PCR). The results showed that ICA increased cGMP concentrations directly (P < 0.05), but there was no significant effect on cAMP concentrations (P > 0.05). In the presence of sodium nitroprusside (SNP), a stimulatory agent of cGMP, both ICA and Sild increased cGMP concentrations with increasing dose (P < 0.01). Their EC50 was 4.62 (ICA) and 0.42 (Sild) micromol/L respectively. Under the same condition, ICA and Sild unaltered cAMP level significantly (P > 0.05). There were PDE5A1 and PDE5A2 mRNA expressions in rat corpus cavernosum with PDE5A2 being the dominant isoform. ICA could obviously inhibit these two isoforms mRNA expression in rat penis, and decrease PDE5A1 more pronouncedly (P < 0.01). The present study indicated that the aphrodisiac mechanisms of icariin involved the NO-cGMP signal transduction pathway, with increasing cGMP levels in the corpus cavernosum smooth muscle. The inhibitory effect of icariin on PDE5 mRNA expression, especially on PDE5A1, might account for its molecular mechanisms for its long-term activity.

In order to further investigate the mechanisms of action of berberine (Ber), we assessed the effects of Ber on the mRNA expression of nitric oxide synthases (NOS) in rat corpus cavernosum. After incubation with Ber for 1 or 3 h respectively, the levels of NOS mRNA were examined by reverse transcription polymerase chain reaction (RT-PCR). Our results showed that there were iNOS and eNOS mRNA expressions in rat corpus cavernosum. Ber enhanced eNOS mRNA expression in rat penis, but exhibited no effect on the expression of iNOS mRNA (P＞0.05). The present study indicated that the relaxation of Ber involved the NO-cGMP signal thansduction pathway. The enhancing effect of Ber on eNOS mRNA expression might associated with its relaxation of corpus cavernosum.

To further investigate the mechanisms of action of icariin (ICA), we assessed the effects of ICA on the in vitro formation of cGMP and cAMP in isolated rabbit corpus cavernosum. Isolated segments of rabbit corpus cavernosum were exposed to increasing concentrations of ICA and the dose-dependent accumulation of cGMP and cAMP was determined in the tissues samples by means of 125I radioimmunoassay. Responses of the isolated tissues preparations to ICA were compared with those obtained with the reference compounds sildenafil (Sild). Furthermore, the effects of ICA on the mRNA expression of specific cGMP-binding phosphodiesterase type V (PDE5) in rat penis were also observed. After incubation with ICA for 6 h or 14 h respectively, the levels of PDE5 mRNA were examined by reverse transcriptase polymerase chain reaction (RT-PCR). The results showed that ICA increased cGMP concentrations directly (P＜0.05), but there was no significant effect on cAMP concentrations (P＞0.05). In the presence of sodium nitroprusside (SNP), a stimulatory agent of cGMP,both ICA and Sild increased cGMP concentrations with increasing dose (P＜0.01). Their EC50 was 4.62 (ICA) and 0.42 (Sild) μmol/L respectively. Under the same condition, ICA and Sild unaltered cAMP level significantly (P＞0.05). There were PDE5A1 and PDE5A2 mRNA expressions in rat corpus cavernosum with PDE5A2 being the dominant isoform. ICA could obviously inhibit these two isoforms mRNA expression in rat penis, and decrease PDE5A1 more pronouncedly (P＜ 0.01). The present study indicated that the aphrodisiac mechanisms of icariin involved the NO-cGMP signal transduction pathway, with increasing cGMP levels in the corpus cavernosum smooth muscle. The inhibitory effect of icariin on PDE5 mRNA expression, especially on PDE5A1, might account for its molecular mechanisms for its long-term activity.

Objective:To investigate the safety and short-term efficacy of laparoscopic pro-ximal gastrectomy (LPG) for proximal gastric cancer and adenocarcinoma of esophagogastric junction.Methods:The retrospective cohort study was conducted. The clinicopathological data of 385 patients with proximal gastric cancer and adenocarcinoma of esophagogastric junction who underwent LPG in the 15 medical centers, including the First Affiliated Hospital of Xiamen University et al, from January 2014 to March 2022 were collected. There were 304 males and 81 females, aged (63±9)years. Of the 385 patients, 335 cases undergoing LPG were divided into the laparoscopic group and 50 cases undergoing open proximal gastrectomy were divided into the open group. Observation indicators: (1) intraoperative and postoperative situations; (2) follow-up; (3) stratified analysis. 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 represented as M(range), and comparison between groups was conducted using the Wilcoxon 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. Repeated measurement data were analyzed using the repeated ANOVA. Results:(1) Intraoperative and postoperative situations. The operation time, cases with reconstruction of digestive tract as esophagogastric anastomosis and esophageal-jejunal anastomosis, cases with postoperative pathological staging as stage 0?Ⅰ and stage Ⅱ?Ⅲ, duration of postoperative hospital stay, cases with postoperative early complications were (212±96)minutes, 270, 65, 177, 107, 10(range, 8?14)days, 40 in patients of the laparoscopic group, with 51 cases missing the data of postoperative pathological staging. The above indicators were (174±90)minutes, 39, 11, 22, 28, 10(range, 8?18)days, 10 in patients of the open group. There were significant differences in the opera-tion time and postoperative pathological staging between the two groups ( t=2.62, χ2=5.93, P<0.05), and there was no significant difference in the reconstruction of digestive tract, duration of post-operative hospital stay, postoperative early complications between the two groups ( χ2=0.19, Z=0.40, χ2=2.50, P>0.05). (2) Follow-up. Of the 385 patients,202 cases were followed up during the post-operative 12 months, including 187 cases in the laparoscopic group and 15 cases in the open group. Cases with reflux esophagitis, cases with esophageal anastomotic stenosis were 48, 11 in patients of the laparoscopic group, versus 5, 2 in patients of the open group, showing no significant difference in the above indicators between the two groups ( P>0.05). The body mass index (BMI), hemoglobin (Hb), albumin (Alb) at postoperative 6 months and 12 months were (21±3)kg/m 2, (130±15)g/L, (40±4)g/L and (21±3)kg/m 2, (132±14)g/L, (41±4)g/L in patients of the laparoscopic group, versus (21±3)kg/m 2, (121±19)g/L, (37±5)g/L and (21±3)kg/m 2, (125±21)g/L, (43±6)g/L in patients of the open group. There were significant differences in postoperative Hb between the two groups ( Fgroup=5.88, Ftime=5.49, Finteraction=19.95, P<0.05) and there were significant differences in time effect of postopera-tive BMI and Alb between the two groups ( Ftime=9.53, 49.88, P<0.05). (3) Stratified analysis. ① Incidence of postoperative of reflux esophagitis and esophageal anastomotic stenosis in patients with different reconstruction of digestive tract. Of the 202 patients, cases with reconstruction of digestive tract as esophagogastric anastomosis and esophageal-jejunal anastomosis were 168 and 34, respectively. The incidence rates of postoperative of reflux esophagitis were 26.79%(45/168)and 23.53%(8/34)in cases with reconstruction of digestive tract as esophagogastric anastomosis and esophageal-jejunal anastomosis, showing no significant difference between them ( χ2=0.16, P>0.05). Cases undergoing esophageal anastomotic stenosis were 13 in patients with reconstruction of diges-tive tract as esophagogastric anastomosis. ② The BMI, Hb, Alb in patients with different reconstruc-tion of digestive tract. The BMI, Hb, Alb were (24±3)kg/m 2, (135±20)g/L, (41±5)g/L in the 168 patients with reconstruction of digestive tract as esophagogastric anastomosis before the operation, versus (23±3)kg/m 2, (130±19)g/L, (40±4)g/L in the 34 patients with reconstruction of digestive tract as esophageal-jejunal anastomosis before the operation, showing no significant difference between them ( t=1.44, 1.77, 1.33, P>0.05). The BMI, Hb, Alb at postoperative 6 months and 12 months were (21±3)kg/m 2, (128±16)g/L, (39±4)g/L and (21±3)kg/m 2, (131±16)g/L, (41±4)g/L in the 168 patients with reconstruction of digestive tract as esophagogastric anastomosis, versus (20±4)kg/m 2, (133±13)g/L, (43±3)g/L and (21±3)kg/m 2, (135±12)g/L, (44±3)g/L in the 34 patients with reconstruction of digestive tract as esophageal-jejunal anastomosis. There were significant differences in the group effect and time effect of postoperative Alb between patients with different reconstruction of diges-tive tract ( Fgroup=15.82, Ftime=5.43, P<0.05), and there was also a significant difference in the time effect of postoperative BMI between them ( Ftime=4.22 , P<0.05). Conclusion:LPG can be used to the treatment of proximal gastric cancer and adenocarcinoma of esophagogastric junction, with a good safety and short-term efficacy.

OBJECTIVETo evaluate the clinicopathological features and prognostic factors of carcinoma in the remnant stomach (CRS).

METHODSClinicopathological data of 217 consecutive CRS patients from January 2000 to March 2017 at Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University were retrospectively analyzed. CRS was defined as the primary cancer arising from the remnant stomach following gastrectomy, regardless of the initial disease or operation, and at no special time interval. The clinicopathological features and treatment were compared between CRS after benign disease operation (CRS-B) group and CRS after gastric cancer operation (CRS-C) group, and factors influencing prognosis were analyzed using Cox regression model analysis.

RESULTSOf 217 patients, 189 were male and 28 were female with mean age of (60.9±11.2) years. The interval between the first and the second operations was (18.3±15.1) years. The CRS-B group comprised 108 patients and the CRS-C group comprised 109 patients. Compared to CRS-C group, CRS=B group had higher ratio of male [92.6% (100/108) vs. 81.7% (89/109), χ=5.779, P=0.016], longer interval [30(25-40) years vs. 4(1.5-8.0) years, Z=-1.685, P=0.000], longer tumor diameter [(5.9±3.2) cm vs. (3.9±2.4) cm, t=3.390, P=0.000] and later tumor stage [patients in stage I(, II(, III(, and IIII(: 6 (8.0%), 14 (18.7%), 41 (54.7%), and 14 (18.7%) vs. 16 (25.4%), 14 (22.2%), 21(33.3%), and 12(19.0%), respectively, Z=-2.018, P=0.044]. A total of 138 patients underwent surgery, including 118(85.5%) patients of curative resection and 20(14.5%) patients of palliative resection. The other 79 patients did not receive surgery due to extensive metastasis or miscellaneous reasons. Among 138 patients receiving surgery, 3 patients underwent endoscopic resection, 6 patients underwent minimally invasive surgery (laparoscopy or robot), and 129 patients underwent laparotomy. Forty-eight patients underwent surgery involving combined resection. The median postoperative hospital stay was 10(8-14) days. The incidence of postoperative complication was 23.2%(32/138). A total of 91 patients were followed up for 7-120 months, including 51 patients in CRS-B group and 40 in CRS-C group. The overall 1-, 3-, and 5-year survival rates of the 75 patients receiving curative resection were 80.7%, 55.1%, and 41.6%, respectively. The overall 1-, 3-, and 5-year survival rates were 73.5%, 48.3%, and 29.0% respectively in CRS-B group and 83.1%, 51.2%, and 32.5% respectively in CRS-C group. There was no significant difference between two groups (P=0.527). Multivariate analysis showed that age (RR=1.879, 95%CI: 1.015-3.479, P=0.045), radical procedure (RR=2.956, 95%CI: 1.421-6.150, P=0.004) and TNM stage (RR=1.570, 95%CI: 1.047-2.354, P=0.029) were independent prognostic factors for CRS.

CONCLUSIONSAs compared to the CRS-C group, the CRS-B group has higher percentage of male, longer interval, larger tumor diameter and later TNM stage. Radical resection indicates better prognosis.

Aged ; Female ; Gastrectomy ; Gastric Stump ; pathology ; surgery ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms ; pathology ; surgery ; Survival Rate

OBJECTIVE: To compare the effects of robotic and laparoscopic-assisted radical total gastrectomy on lymph node dissection and short-term outcomes in patients with Siewert type II adenocarcinoma of esophagogastric junction (AEG). METHODS: Inclusion criteria: the tumor center was located between 2 cm above and below the esophagogastric junction and was confirmed as adenocarcinoma by endoscopic biopsy. EXCLUSION CRITERIA: tumor with local invasion of the liver,spleen, pancreas or other organs; intraoperative finding of tumor dissemination or distant metastasis; patients undergoing palliative surgical treatment or preoperative neoadjuvant chemotherapy; patients with serious heart diseases, lung diseases, liver diseases, kidney diseases and other comorbidities; patients with multiple primary cancers;patients receiving emergency surgery. According to the above criteria, 82 patients with Siewert type II AEG who underwent gastrointestinal surgery at the Affiliated Hospital of Qingdao University from October 2014 to October 2018 were enrolled in the study. They were randomly divided into robotic surgery groups (41 cases) and laparoscopic group (41 cases) according to a computer-generated randomized allocation table. Both groups underwent radical total gastrectomy plus D2 lymph node dissection through the transabdominal esophageal hiatus approach. The intraoperative conditions and postoperative short-term outcomes were compared between two groups, including surgery time, intraoperative blood loss, length of esophagectomy, postoperative complications, postoperative gastrointestinal recovery time, length of hospital stay, postoperative unplanned reoperation rate and rehospitalization rate. Mean±SD is used for the measurement data that conforms to the normal distribution, and two independent sample t-tests are used to compare the two groups; the comparison of the count data is performed by the χ² test. RESULTS: There were 35 males (85.4%) with age of (62.3±10.0) years and body mass index of (24.4±3.2) kg/m² in the robotic surgery group. There were 37 males (90.2%) with age of (62.5±10.0) years and body mass index of (23.8±2.6) kg/m² in the laparoscopic group. No significant differences in the baseline data between two groups were found (all P>0.05). All the patients of both groups completed R0 resection successfully without conversion to laparotomy or perioperative death. Compared with the laparoscopic group, the robotic group had less intraoperative blood loss [(70.7±39.9) ml vs. (110.2±70.6) ml, t=3.118, P=0.003], longer resected esophagus [(3.0±0.7) cm vs. (1.9±0.5) cm, t=8.759, P<0.001], but longer setup time [(56.5±7.4) minutes vs. (36.0±6.6) minutes, t=4.241, P<0.001], and higher hospitalization costs [(122 317.31±57 789.33) yuan vs. (99 401.56±39 349.53) yuan, t=2.099, P=0.039], whose differences were statistically significant (all P<0.05). The total number of harvested lymph node in the robotic surgery group was 39.2±15.3,which was significantly higher than that in the laparoscopic group (33.0±12.1) (t=0.733, P=0.047). In the robotic group and the laparoscopic group, the mediastinal lymph node No.110 and No.111 were 3.6±1.2 vs. 1.5±1.0 and 3.7±2.0 vs. 1.8±1.1, respectively, with significant difference (t=10.138, P<0.001, t=8.227, P<0.001); axillary lymph node No.19 and No.20 were 2.3±1.2 vs. 1.1±0.9 and 2.0±1.0 vs. 1.0±0.1, respectively, with significant difference (t=7.082, P<0.001,t=8.672,P<0.001). There were no significant differences in the total number of abdominal lymph node and the number of lymph node in abdominal stations between two group (all P>0.05). The highest lymph node metastasis rate was approximately 20% and observed in No.1, No.2, No.3, and No.7, followed by No.8a, No.9, No.11p, and No.110 with around 5%. The lymph node metastasis rate in other stations (No.4sa, No.4sb, No.4d, No.5, No.6, No.11d, No.12a, No.19, No.20 and No.111) was less than 5%.There were no significant differences in postoperative complication rate, postoperative fever time, postoperative exhaust and defecation time, fluid diet time, and postoperative hospital stay (all P>0.05). There were 2 patients(4.9%) with unplanned reoperation and 1 patient (2.4%) with unplanned re-admission in the laparoscopic group,while 3 patients (7.3%)with unplanned reoperation and 2 patients (4.9%)with unplanned re-admission in the robotic surgery group, whose differences were also not statistically significant (χ²=0.240,P=0.675;χ²=0.346,P=1.000). CONCLUSION Robot-assisted radical total gastrectomy for Siewert II AEG is safe and feasible, which is characterized by more sophisticated operation, less blood loss and higher quality of lymph node dissection, especially for subphrenic and inferior mediastinal lymph nodes.
Adenocarcinoma ; classification ; pathology ; surgery ; Aged ; Esophageal Neoplasms ; classification ; pathology ; surgery ; Esophagectomy ; Esophagogastric Junction ; pathology ; surgery ; Female ; Gastrectomy ; Humans ; Laparoscopy ; Lymph Node Excision ; methods ; Male ; Middle Aged ; Retrospective Studies ; Robotic Surgical Procedures ; Stomach Neoplasms ; classification ; pathology ; surgery ; Treatment Outcome