The breakage pattern of unit particles during the production of oral solid dosage forms (OSD) is closely related to the quality of intermediate or final products. To accurately characterize the particles and study the evolution law of particle breakage, the Bonding model of the discrete element method (DEM) was used to investigate the breakage patterns of model parameters, particle shape and process conditions (loading mode and loading rate) on the dynamic breakage, force-time curve, breakage rate, maximum breakage size ratio and fracture strength of particles. The results showed that the particle breakage force was positively correlated with normal strength and bonded disk scale, negatively correlated with normal stiffness per unit area and tangential stiffness per unit area, and weakly correlated with tangential strength. The particle breakage rate was negatively correlated with the aspect ratio of the particles, and the maximum breakage size ratio was positively correlated with the aspect ratio of the particles; among the three loading modes, the breakage rate of compression breakage model was the largest, the breakage rate of shear breakage model was the second largest, and the breakage rate of wear breakage model was the smallest; the maximum breakage size ratio was positively correlated with the loading rate, the loading mode and the loading rate had no mutual influence on particle breakage rate, but had mutual influence on the maximum breakage size ratio. The research results will provide a theoretical basis for the shift of OSD from batch manufacturing to advanced manufacturing.

The quality difference of pharmaceutical excipients from different sources affects the molding properties of the powder, resulting in changes in the properties of the final product. In this study, the critical quality attributes of hydroxypropyl methylcellulose (HPMC) with different specifications from two manufacturers (manufacturer A and manufacturer B) were characterized including particle size, physical morphology, viscosity and powder physical quality attributes. Aminophylline, diclofenac sodium, and metformin hydrochloride were utilized as model drugs with different solubility to prepare sustained-release tablets, and the effect of HPMC from different sources on drug release of sustained-release tablets in vitro was investigated. The results showed that HPMC with the same viscosity specification from different sources had outstanding differences in the physicochemical properties (including particle size, physical morphology, viscosity, dimension, compressibility and powder flow), which could change the hardness and friability of the sustained-release tablets. The differences in the physicochemical properties of HPMC had different effects on the dissolution of different sustained-release tablets in vitro. It had no significant effect on the release of easily soluble aminophylline and metformin hydrochloride, but had a greater impact on the release of poorly soluble diclofenac sodium. Compared with manufacturer A, the sustained-release effect of matrix tablets prepared by HPMC from manufacturer B was more excellent. The results of this study will provide a theoretical reference on selecting the appropriate excipients for formulation design.

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.
Chemotherapy, Adjuvant ; Female ; Gastrectomy ; Humans ; Male ; Neoadjuvant Therapy ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/surgery*

In this study, physical fingerprint and multivariate statistical analysis was applied to characterize the quality consistency of different sources of carboxymethylcellulose sodium, and the visualization of R language was used to explore the intrinsic correlation on its performances, and we drew contour maps between independent variables and flowability of powder to find the design space. Through the physical fingerprint and multivariate statistical analysis, it was found that there were differences in the powder properties of carboxymethylcellulose sodium from different sources, and its moisture content, bulk density and tapped density have a great influence on the fluidity. The fillibility was positively correlated with flowability, both negatively correlated with compressibility by R intelligent visualization analysis, which was statistically significant (P < 0.01). When the angle of repose is 30° - 40°, the appropriate design space was found as 5.092 2% < moisture content < 7.006 7%, 0.560 2 g·cm^-3 < bulk density < 0.579 9 g·cm^-3, and 0.646 3 g·cm^-3 < tapped density < 0.816 5 g·cm^-3. The results show that it is scientific and feasible to evaluate the quality consistency of pharmaceutical excipients by using the physical fingerprint, multivariate statistical analysis and visualization methods, which provides new ideas for the production and quality evaluation of excipients and the development of generic prescriptions.

In this study, the texture analyzer acupuncture pressure sensor was used to objectively characterize the "herb soaking with exact amount of water" for moistening process of ginseng. The single factor rotation experiment was used to investigate the effects of puncture speed, puncture depth and puncture site on puncture force and work. According to ginseng processing method in Chinese Pharmacopoeia, ginseng medicinal materials with diameters of about 1 cm and 2 cm were selected, and puncture experiments were carried out at the set measurement time to determine the hardness, work and water absorption of the ginseng moistening process. The endpoint threshold for the ginseng softening process was determined and verified. To reflect the actual internal conditions of the ginseng softening process, the puncture depth was preferably 70%, and the puncture speed was 30 mm·min~(-1). In the ginseng moistening process, the softening hardness and the puncture work were in accordance with the first-order kinetic equation y=a×exp(-k×x). The 0 h initial hardness a of 1 cm and 2 cm ginseng herbs were 289.8 N and 1 227 N, and the rate constants K were 0.149 4 N·h~(-1) and 0.100 7 N·h~(-1), respectively. After the ginseng was completely softened, the force required for puncture was 10 N, which can be used as the standard for "drug penetration". At this time, the water absorption rate of ginseng was 70%-100%. The softening time of ginseng with a diameter of 1 cm was about 20-22 h, and the softening time of ginseng with a diameter of 2 cm was about 40-46 h. A needle-type pressure sensor was used to accurately determine the end point of the softening process of ginseng and reduce the loss of active ingredients. The study results provide reference for the softening process kinetics and the process intelligent monitoring of other dried roots and rhizomes.
Drugs, Chinese Herbal ; Panax ; Plant Roots ; Rhizome ; Technology, Pharmaceutical ; Water

Objective To understand the water quality of self-supply wells in four provinces of northern China (Heilongjiang, Beijing, Inner Mongolia and Tibet), so as to provide a reference for supervision and management of self-supply wells. Methods Water were sampled from 233 self-supply wells in four northern provinces of China according to standard examination methods for drinking water (GB/T 5750-2006). In total, The samples were tested for 27 kinds of water quality parameters involving sensory properties, chemistry, bacteriology and toxicology, and then evaluated. Results The total unqualified rate of water quality in self-supply well water in four northern provinces of China was 52.36%. The water quality varied greatly among provinces. As for Heilongjiang, the main unqualified indicators of self-supply wells water involved turbidity, visible to the naked eye, manganese, arsenic and nitrate. In relation to Beijing, these referred to the nitrate and microorganism. In case of Inner Mongolia province, these included sulfate and fluoride. With reference to Tibet, these were zinc and chloride. Conclusions To ensure the safety of drinking water for residents, the management, disinfection and purifying measures of self-supply wells should be strengthened basing on their regional differences and water quality characteristics.

Objective To find out about the sanitary conditions of drinking water along the border line of Inner Mongolia via safety evaluation of drinking water along the border line of Inner Mongolia.Methods 108 samples of drinking water along the border line of Inner Mongolia(70 samples of self-supply source water,21 ones of self-supply tap water and 17 ones of municipal tap water)were collected.Hygienic evaluation of sensory indexes, normal chemical indexes, toxicological indexes and microbiology indexes of water quality was performed according to hygienic standards for drinking water(GB 5749—2006).Results 58 samples were qualified with a total qualified rate of 53.7%.The unqualified rate of the total number of coliforms was the highest(20.4%),followed by fluoride(19.4%).As for deep wells, shallow wells and surface water,there was no statistically significant difference.Compared with municipal tap water,the unqualified rate of self-supply water(28.6%)was higher(17.7%).Conclusion The qualified rate along the border line of Inner Mongolia of drinking water is low.Treatment and disinfection facilities for drinking water,detection devices of water quality are needed.The cleaning and disinfection of storage tanks should be performed periodically in oder to prevent waterborne infectious diseases.

OBJECTIVETo investigate the correlation of patients with thrombosis or prothrombotic status with hyperhomocysteinemia (HHcy), activated protein C-resistance(APCR) and gene polymorphism of coagulation factor V.

METHODSThree hundred healthy voluteers were selected as controls, 223 cases of thrombosis (80 cases of cerebral infarction of CT, the MI of 82 cases of myocardial infarction, venous thrombosis of VTE 61 cases), 270 cases of patients with prothrombotic state (76 cases of pregnancy disease of PIH, 62 cases of chronic obstructive pulmonary disease (COPD), 60 cases of diabetes(DM) and 72 cases of cancer) were enrolled in this study. The plasma APCR and hyperhomocysteinemia were detected by APTT coagulation method and cycling enzyme method respectively, and restriction fragment length polymorphism(RFLP) were was used to detect the gene polymorphism of FV G1691-A, G1091-C and A1090-G in the patient and control groups.

RESULTSAPCR positive rate was 62.29% and 7.33%, and the positive hyperhomocysteinemia accounted for 68.42% and 10.00% respectively in the group of the patients with venous thrombosis and the normal control group. 3 cases of heterozygous FV gene mutations were found in the APCR-positive patients with venous thrombosis.

CONCLUSIONHHcy possitive rate of patients with venous thrombosis is signiticantly higher than that in control, the HHcy is one of the important causes resulting in thrombosis, the patients with venous thrombosis have proved to be with APCR, and the possitive APCR may be related with the coagulation factor V gene polymorphism.

?AlM: To compare the clinical effect between small-incision cataract surgery and phacoemulsification.
?METHODS: Totally 93 patients ( 124 eyes ) with age-related cataract who received treatment in Mar 2010 and Feb 2013 were dicided into 2 groups randomly. Forty-two patients ( 59 eyes ) in group small - incision cataract surgery ( SlCS ) were treated by SlCS, while other 51 patients ( 65 eyes ) in group Phaco were treated by phacoemulsification. And then, postoperative visual acuity, corneal astigmatism, surgically induced astigmatism ( SlA ) and intraoperative and postoperative complications were contrasted between groups.
?RESULTS: After 1d and 1wk of postoperation, there were 38 eyes ( 64. 4%) and 41 eyes ( 69. 5%) having a better visual acuity of 0. 5 in the SlCS group, while there were 29 eyes (44. 6%) and 32 eyes (49. 2%) in the Phaco group. The vision of SlCS group was better than that of Phcao group (χ2 = 4. 877, 5. 242, P < 0. 05 ). On postoperative 1 and 3mo, with acuity of 0. 5 or better, eye numbers showed no statistically significant differences between two groups (χ2 = 0. 005, 0. 085, P>0. 05). The average corneal astigmatism used analysis of repeatedly measuring designing variance: Comparing the corneal astigmatism in intra - groups at different times, it was statistically significant (F=25. 624, P<0. 05), and had a tendency to decrease with time. However, there was no statistical significance for corneal astigmatism between groups (F=0. 986, P>0. 05). The coneal astigmatism of each group was higher at 1wk after the surgery than that of preoperation, and the contrast had statistical sigenficence (t=2. 906, 2. 427, P<0. 05). The Phaco group with SlA was lower than the SlCS group at 1wk and 1mo after the surgery (t=-4. 628, 2. 770, P<005). lt had no statistical significance in SlA by comparing with the two groups at 3mo after the surgery (t=0. 754, P>0. 05). There were statistical differences in SlA at different time both by intra-group comparison and group comparison ( F=26. 37, P<0. 05, F = 14. 29, P<0. 05). The comparison of posterior capsule rupture, the postoperative corneal edema and anterior chamber pigment membrane reaction in two groups showed no statistical significance.
?CONCLUSlON: Our research shows that small-incision cataract surgery and phacoemulsification had similar effect in the treatment of cataract. Phacoemulsification is not the only surgery option for the best treatment effect. Small- incision cataract surgery can be popularized in basic- level hospitals, achieving the effect similar to phacoemulsification.

AIM:To observe the application efficiency of 5g/L indocyanine green ( ICG ) staining technique for continuous circular capsulorhexis ( CCC ) during phacoemulsification in white cataract.
METHODS:Ninety-eight patients (98 eyes) with white cataract were randomly divided into staining group ( 50 cases, 50 eyes) and control group (48 cases, 48 eyes). The control group didn't do anterior capsule staining. The staining group was injected to fill the anterior chamber, 5g/L ICG 0.1mL was applied on the central surface of the anterior capsule, using a 27G blunt needle through the side-port after 30s, and the redundant ICG was replaced by BSS, and continuous curvilinear capsulorhexis was accomplished using capsulorhexis forceps.
RESULTS: In staining group: after ICG staining, the capsule, which presented uniform light green and visualization of the anterior capsule was significantly improved. There are 48 eyes capsulorhexis success. The rate of success was 96%. Meanwhile, in control group, there was 29 eyes capsulorhexis success. The rate of success was 60%. The difference was statistically significant (P<0. 05). During follow-up, no dye particle and the complications of iritis or high intraocular pressure were found in the eyes of staining group. Anterior chamber inflammation, corneal opacity compared with control group, the difference was not statistically significant.
CONCLUSION:Indocyanine green staining increases the visibility of anterior capsule in over mature cataract, and it should be an effective and helpful method which can increase the success rate of capsulorehxis. At the same time, it can reduce the incidence of intraoperative complications. This will help beginners quickly grasp continuous curvilinear capsulorhexis, and shorten the learning curve.