Limitations and Innovative Application Methods of Surfactants for Solubilization of Poorly Water-Soluble Drugs.

Poor solubility of drugs leads to poor bioavailability and therapeutic efficiency. A large proportion of drugs that are not developed and marketed for use by patients are due to their extremely low solubility. Therefore, improving the solubility of poorly water-soluble drugs is one of the most important aspects of the field of drug research. With the continuous development of more and more formulation techniques and excipient applications, the solubility of poorly water-soluble drugs can be improved to a certain extent to obtain better pharmacokinetics and pharmacodynamics, including pH microenvironment regulation technology, inclusion complex, solid dispersion, nanotechnology, and application of surfactants. However, the most widely used among them is the application of surfactants. This technique can reduce the surface tension, improve wettability, and have a remarkable solubilizing ability after forming micelles. However, surfactants have also been found to possess certain limitations in solubilization. In this review, the factors affecting the solubilization of surfactants and limiting their application have been summarized from several aspects. These factors include drugs, additives, and media. Some ideas to solve these application limitations have also been put forward, which can lay a foundation for the wider application of surfactants in the future.

Surgical Technique and Efficacy Analysis of Extra-pseudocapsular Transnasal Transsphenoidal Surgery for Pituitary Microprolactinoma.

OBJECTIVE: To elucidate the role of transsphenoidal surgery in the treatment of pituitary microprolactinoma. METHODS: The clinical data of 107 prolactinoma cases treated by extra-pseudocapsular transnasal transsphenoidal surgery (ETTS) for different indications in our department since 2011 was retrospectively analyzed. RESULTS: The most common indication was the ineffectiveness of oral medication (41.1%), followed by the personal willingness of the patient (35.5%), and 20.6% of the patients were young women with clear tumor boundaries. The pseudocapsule was not observed in 63 cases (58.9%), incomplete pseudocapsule was observed in 26 cases (24.3%), and complete pseudocapsule in 18 cases (16.8%). A total of 97 patients (90.7%) obtained 1-year post-operation remission. According to the relative location of the adenoma and pituitary gland on the MRI scan, 46 patients were classified into a central type, 59 a lateral type, and 2 a supra-pituitary type. Two patients developed hypogonadism, one patient developed hypocortisolism, and one patient developed post-operative hypothyroidism. Two patients were administrated with hormone replacement treatment, and the treatment was stopped within one week. There was no permanent hypopituitarism. Further investigation demonstrated that the adenoma types could affect the remission rates of hyperprolactinemia and gross total resection rate in microprolactinoma. CONCLUSION: ETTS was an effective treatment for pituitary microprolactinomas. This could be the first choice for patients who presented enclosed adenoma on the MRI and were potentially curable in a preoperative evaluation. Maximal safe removal of the adenoma by ETTS with the aim to increase the sensitivity of the drugs was also recommended for patients with invasive dopamine agonist resistant prolactinomas and patients with difficulty in childbirth.

Extra-pseudocapsular Transnasal Transsphenoidal Resection of Pituitary Macroadenoma: Technique Note and Evaluation of Endocrine Function.

OBJECTIVE: In this study, we investigated the surgical technique and endocrine assessment of pituitary function of patients with macroadenoma treated by extra-pseudocapsular transnasal transsphenoidal surgery (ETTS). METHODS: Clinical data of 144 patients with pituitary macroadenomas in the same surgical group at the Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology were retrospectively analyzed from January 2019 to June 2021. Based on the results of the endocrinological evaluation and MRI examinations before and after surgery, the fluctuation of pituitary function and the extent of resection were analyzed. Multiple Logistic regression analysis was used to determine the predictors affecting postoperative tumor residual. RESULTS: Among the 144 patients with pituitary macroadenomas, 72 (50.0%) were female and 72 (50.0%) were male, the median age was 50 years, 26 (18.1%) had invasiveness grade 0, 46 (31.9%) had grade I, 57 (39.6%) had grade II, and 15 (10.4%) had grade III according to Lu's classification method. Based on observation during surgery, 37 cases (25.7%) had no pseudocapsule, 54 cases (37.5%) had incomplete pseudocapsule, and 53 cases (36.8%) had intact pseudocapsule. In addition, 91 (63.2%) patients had total resection, 39 (27.1%) had subtotal resection, and 14 (9.7%) had partial resection. As for anterior pituitary function, 13 of 19 hypothyroid patients had recovery after surgery, with a remission rate of 68.4%. Eighteen of the 26 decreased cortisol patients got back to normal, with a remission rate of 69.2%. A total of 27 of 51 patients with hypogonadism improved, with a remission rate of 52.9%. Univariate and multivariate analyses indicated that gender, tumor size, and invasiveness were predictors of postoperative residual in patients (P<0.05). CONCLUSION: The results showed that ETTS is an effective treatment modality for restoring the function of pituitary gland of the patients with macroadenomas. Tumor size and invasiveness are predictors of the extent of surgical resection and postoperative residual of macroadenomas.

Enhanced protective immunity against spring viremia of carp virus infection can be induced by recombinant subunit vaccine conjugated to single-walled carbon nanotubes.

As a successful prevention strategy for controlling the highly contagious and pathogenic disease of spring viremia of carp (SVC), DNA vaccines reported in recent years could trigger protective responses against SVC with the means of injection. However, there remains many concerns and uncertainties related to DNA vaccination as well as injection is labor intensive, costly and not suitable to vaccinate large numbers of fish. Therefore, more efficient and safe prophylactic measures should be urgently investigated. In this research, single-walled carbon nanotubes (SWCNTs) as the candidate SWCNTs-pET32a-G subunit vaccine carrier were administrated via bath (1, 5, 10, 20, 40 mg L-1) or injection (1, 4, 8, 12, 20 µg) in common carp juvenile, and the different immune treatments to induce immunoprotective effect were analyzed. The results showed that SWCNTs-pET32a-G could enter fish body after immersion for 10 h, furthermore, compared to control groups, antibody levels, the non-specific immune parameters (complement activity, superoxide dismutase activity and alkaline phosphatase activity), and immune-related genes (especially the TNF-α and IFNg2b) in vaccinated groups were significantly enhanced in fish immunized with SWCNTs-subunit vaccine. In addition, as a promising carrier, SWCNTs can increase the immune protective effect of naked subunit vaccine by ca. 16% in bath immunization group and by ca. 23% in injection group. This study suggests that SWCNTs-vaccine may represent a potentially efficient immersion vaccine against viral pathogens of fish in the future.

[Analysis of relationship between natural death of Oncomelania hupensis snails and water level in Eastern Dongting Lake district].

OBJECTIVE: To study the reasons of natural death of Oncomelania hupensis snails by comparing the differences of the indicator days covered with water (DCW) in snail marshland and non-snail marshland around the build of Three Gorges Dam in Eastern Dongting Lake areas. METHODS: Two marshlands were selected, one was a non-snail marshland (Qianliang Lake) and another was a snail marshland (Junshan Park). The measuring points were set through the mechanical sampling. The snails and elevation of the points were surveyed, and the data of the water levels from the hydrological station were collected, and then DCWs were calculated. RESULTS: From 1995 to 2013, DCWs of the marshland of natural death of snails were all more than that of the snail marshland (P < 0.01). In Qianliang Lake marshland, the difference between DCW before natural death and DCW from natural death until the dam was not significant (P = 0.23), while DCWs of the two stages both were more than that after the dam (P1 = 0.045, P2 = 0.002). Before the build of the dam, DCW of the Qianliang Lake marshland of natural death of snails was more than that after the build of the dam (P = 0.013), and there was the same situation in Junshan Park marshland (P = 0.005). The relationship between snail density and DCW was not significant in Junshan Park marshland (r(s) = 0.008, P = 0.914), and the reference range of DCW of all the measuring points was 76-251 days. CONCLUSION: In the eastern Dongting Lake district, the build of Three Gorges Dam and DCW may be not the direct factors affecting the natural death of snails and the latter may change the distribution of snails.

Three Gorges Dam: Impact of Water Level Changes on the Density of Schistosome-Transmitting Snail Oncomelania hupensis in Dongting Lake Area, China.

BACKGROUND: Schistosomiasis remains an important public health issue in China and worldwide. Oncomelania hupensis is the unique intermediate host of schistosoma japonicum, and its change influences the distribution of S. japonica. The Three Gorges Dam (TGD) has substantially changed the ecology and environment in the Dongting Lake region. This study investigated the impact of water level and elevation on the survival and habitat of the snails. METHODS: Data were collected for 16 bottomlands around 4 hydrological stations, which included water, density of living snails (form the Anxiang Station for Schistosomiasis Control) and elevation (from Google Earth). Based on the elevation, sixteen bottomlands were divided into 3 groups. ARIMA models were built to predict the density of living snails in different elevation areas. RESULTS: Before closure of TGD, 7 out of 9 years had a water level beyond the warning level at least once at Anxiang hydrological station, compared with only 3 out of 10 years after closure of TGD. There were two severe droughts that happened in 2006 and 2011, with much fewer number of flooding per year compared with other study years. Overall, there was a correlation between water level changing and density of living snails variation in all the elevations areas. The density of living snails in all elevations areas was decreasing after the TGD was built. The relationship between number of flooding per year and the density of living snails was more pronounced in the medium and high elevation areas; the density of living snails kept decreasing from 2003 to 2014. In low elevation area however, the density of living snails decreased after 2003 first and turned to increase after 2011. Our ARIMA prediction models indicated that the snails would not disappear in the Dongting Lake region in the next 7 years. In the low elevation area, the density of living snails would increase slightly, and then stabilize after the year 2017. In the medium elevation region, the change of the density of living snails would be more obvious and would increase till the year 2020. In the high elevation area, the density of living snails would remain stable after the year 2015. CONCLUSION: The TGD influenced water levels and reduced the risk of flooding and the density of living snails in the study region. Based on our prediction models, the density of living snails in all elevations tends to be stabilized. Control of S. japonica would continue to be an important task in the study area in the coming decade.

[Hemocyte morphology and classification in Oncomelania hupensis].

Hemocytes were collected from Oncomelania hupensis in Junshan, Hunan Province and Puge, Sichuan Province, respectively, and stained with Giemsa solution for light microscopic examination. The cells were classified morphologically. Five types of hemocytes were identified, viz., large acidophilic hyalinocytes, small acidophilic hyalinocytes, basophilic hyalinocytes, basophilic small granulocytes and basophilic large granulocytes. The proportion of small acidophilic hyalinocytes was the most abundant hemocyte [36.7% (229/624) in snails from Junshan and 31.7% (257/810) in snails from Puge], followed by basophilic hyalinocyte [23.1% (144/624) in Junshan and 24.4% (198/810) in Puge]. Basophilic large granulocyte was about 9.3% (58/624) in Junshan and 11.6% (94/810) in Puge. The length of large acidophilic hyalinocytes was the maximum and its nucleocytoplasmic ratio was minimum, followed by small acidophilic hyalinocytes. The length of basophilic cells was shorter and its nucleocytoplasmic ratio was smaller than those of acidophilic cells. There was no significant difference in cellular constituents of hemocytes and the morphological features of hyalinocytes between the snails from Junshan and Puge, while the length and nucleocytoplasmic ratio of granulocytes in Junshan snails were smaller than those of Puge ones.

[Contrastive analysis of environmental factors between Oncomelania hupensis snail marshland and snail natural death marshland in eastern Dongting Lake schistosomiasis endemic areas].

OBJECTIVE: To study the reasons of natural death of Oncomelania hupensis snails in marshland by comparing the differences of environmental factors between snail marshland and non-snail marshland in East Dongting Lake schistosomiasis endemic areas. METHODS: Two adjoining marshlands were selected, one was a snail marshland and another was a non-snail marshland. The measuring points were set by grid of "20 m x 20 m". The soil moisture, elevation, soil pH and temperature of the points were measured, and the snails of the points were surveyed. RESULTS: The elevation, soil pH and temperature of the snail natural death marshland were all lower than those of the snail marshland (P < 0.01). The soil moisture, elevation, soil pH and temperature of different snail densities in the snail marshland were different (P < 0.05). The soil moisture of the non-snail group was higher than that of other four groups (P < 0.01) and the soil moisture of the group with 0-11 snails per frame was lower than that of other four groups (P < 0.01). The elevation of the group with 0-11 snails per frame was lower than that of the group with 24-39 snails per frame and the group with more than 39 snails per frame (P < 0.05). The soil pH of the group without snails was higher than that of other four groups (P < 0.01) and the soil temperature of the group with 0-11 snails per frame was lower than that of the group with 24-39 snails per frame. The differences of soil moisture and elevation of different death snail densities were not significant, while the differences of soil pH and temperature were significant. The soil pH of the non-snail died group was higher than that of the 2-died, 3-died and more than 3-died groups (P < 0.05). The soil temperature of the non-snail died group was higher than that of other four groups (P < 0.05). CONCLUSION: The elevation, soil pH and soil temperature within the range of the research may be the factors affecting the snail natural death and the soil moisture, elevation, soil pH and soil temperature may be the factors affecting the distribution of snails.

Identification of optimum scopes of environmental factors for snails using spatial analysis techniques in Dongting Lake Region, China.

BACKGROUND: Owing to the harmfulness and seriousness of Schistosomiasis japonica in China, the control and prevention of S. japonica transmission are imperative. As the unique intermediate host of this disease, Oncomelania hupensis plays an important role in the transmission. It has been reported that the snail population in Qiangliang Lake district, Dongting Lake Region has been naturally declining and is slowly becoming extinct. Considering the changes of environmental factors that may cause this phenomenon, we try to explore the relationship between circumstance elements and snails, and then search for the possible optimum scopes of environmental factors for snails. METHODS: Moisture content of soil, pH, temperature of soil and elevation were collected by corresponding apparatus in the study sites. The LISA statistic and GWR model were used to analyze the association between factors and mean snail density, and the values in high-high clustered areas and low-low clustered areas were extracted to find out the possible optimum ranges of these elements for snails. RESULTS: A total of 8,589 snail specimens were collected from 397 sampling sites in the study field. Besides the mean snail density, three environmental factors including water content, pH and temperature had high spatial autocorrelation. The spatial clustering suggested that the possible optimum scopes of moisture content, pH, temperature of the soil and elevation were 58.70 to 68.93%, 6.80 to 7.80, 22.73 to 24.23°C and 23.50 to 25.97 m, respectively. Moreover, the GWR model showed that the possible optimum ranges of these four factors were 36.58 to 61.08%, 6.541 to 6.89, 24.30 to 25.70°C and 23.50 to 29.44 m, respectively. CONCLUSION: The results indicated the association between snails and environmental factors was not linear but U-shaped. Considering the results of two analysis methods, the possible optimum scopes of moisture content, pH, temperature of the soil and elevation were 58.70% to 68.93%, 6.6 to 7.0, 22.73°C to 24.23°C, and 23.5 m to 26.0 m, respectively. The findings in this research will help in making an effective strategy to control snails and provide a method to analyze other factors.

[Distribution of univalvia molluscs in area with natural decline of Oncomelania hupensis snails in Eastern Dongting Lake area].

OBJECTIVE: To understand the distribution of univalvia molluscs in Eastern Dongting lake area where the Oncomelania hupensis is extinct, so as to explore the causes of extinction and to provide the evidence for formulating schistosomiasis control strategy. METHODS: The univalvia molluscs of the Qianliang Lake district, Jianxin District and Junshan Park were investigated in August of 2013. All the collected snails were classified and identified. The data were analyzed by using the method of Shapiro-Wilk normality test and non-parametric test. The ecological biodiversity differences from each district were compared by the biodiversity indexes. RESULTS: The univalvia molluscs collected were from 6 species in 3 families in Gastropoda class, namely Oncomelania hupensis Gredler in Pomatiopsidae family, Parafossarulus striatulus, Alocinma longicornis, Parafossarulus sineasis, Bithynia fuchsisana in Bithyniidae family, and one genus provisioy nally named Radix in Lymaneidae family. In Junshan Park, a total of 4553 snails were collected, among which 1264 were Oncomelania snails. In Jianxin District, 336 univalvia molluscs were collected, and no Oncomelania snails were found. In Qianliang Lake district, there were only 7 Alocinma longicornis snails, 2 Parafossarulus sinensis snails and 1 Parafossarulus striatulus snail collected. There were significant differences among the distributions of the samples from the three districts (chi2 = 166.225, P < 0.01) .The Simpson's diversity indexes in Qianliang Lake area, Jianxin Dis- trict and Junshan Park were 0.4028, 0.7186 and 0.6788, respectively, and the Shannon-Wiener indexes of the 3 areas were 0.7215, 1.4313 and 1.1999, respectively. CONCLUSIONS: With the extinction of Oncomelania snails, the species and quantities of other snails become rare in Qianliang Lake area. Whether their causes are relevant is worth further studying.

[Evaluation of comprehensive measures with emphasis on schistosomiasis infectious source control at embankment level].

OBJECTIVE: To evaluate the effects of comprehensive measures with emphasis on schistosomiasis infectious source control at the embankment level. METHODS: The comprehensive measures with emphasis on schistosomiasis infectious source control were carried out, and the data of human and Oncomelania snail infection rates were collected and analyzed statistically at embankment levels. RESULTS: In Anbao Embankment, except the other comprehensive measures were performed, 2606 buffaloes were removed. The infection rates of residents reduced from 8.04% before the intervention to 0.7% after the intervention, and the infection rates of snails reduced from 0.56% to 0.05%. In Anli Embankment, 535 buffaloes were removed. In the third year after the intervention, the infection rates of residents reduced from 5.87% to 1.09%, and the infection rates of snails reduced from 0.17% to 0.07%. In Anzao Embankment, 62 buffaloes were removed. In the second year after the intervention, the infection rates of residents reduced from 2.67% to 0.39%, and the infection rates of snails reduced from 1.12% to 0.00%. In Anchang Embankment, the buffaloes were not removed. The human infection rates reduced from 1.76% before the intervention to 1.23% after the intervention. CONCLUSION: The comprehensive measures with emphasis on schistosomiasis infectious source control, especially the buffalo's removal, are effective in the control of schistosome infection rates of residents and snails.

[Short-term effect of black film covering on Oncomelania hupensis snail control in marshland and lake regions].

OBJECTIVE: To evaluate the short-term effect of the black film covering combined with niclosamide on Oncomelania hupensis snail control in marshland and lake regions. METHODS: A ditch with snails in Anxiang County was selected as the experimental sites. The ditch was divided into 3 groups: a film group, a niclosamide group, and a niclosamide and film group. The snails were surveyed before the test and 1, 3, 5, 7 days after the experiment. RESULTS: After the film covering, the highest temperature of the surface of soil was 63.7 degrees C on the first day, and the temperature higher than 40 degrees C lasted 4.34 hours. On the second day, the highest temperature was 52.3 degrees C, and the temperature higher than 40 degrees C lasted 4.96 hours. On the fourth day and fifth day, the temperature was lower than 30 degrees C, while the temperature was lower than 34 degrees C on the sixth day. On the seventh day of the experiment, the snail death rates of the film group, the niclosamide group, and the niclosamide and film group on the soil surface were 16.36%, 58.40% and 53.57%, respectively. On the seventh day, the snail death rates of the film group, and the niclosamide and film group under the soil were 20.00% and 40.00%, respectively, while no snails were found under the soil in the niclosamide group 3 days after the experiment. In mesh bags, the snail death rates of the film group, the niclosamide group, and the niclosamide and film group were 84.00%, 95.33% and 95.33%, respectively. CONCLUSION: The short-term effect of the black film covering on snail control is not obvious, and the black film covering does no promote the molluscicidal effect of niclosamide.

[Natural growth and decline of Oncomelania hupensis snails in marshland of Qianliang Lake District in Eastern Dongting Lake area, China].

OBJECTIVE: To understand the change trend of Oncomelania hupensis snails in the bottomland areas of Qian Liang Lake district in Eastern Dongting Lake area so as to provide the evidence for formulating a schistosomiasis control strategy. METHODS: The monitoring data of snails of Qianliang Lake district from 1988 to 2011 were collected retrospectively and analyzed by using the method of the trend Chi-square test. The correlations among the snail density indicators were analyzed. RESULTS: 1988 to 2011, the area of snails surveyed did not change and was 433.2 hm(2). The monitoring data showed that the change trend of the density of living snails and the schistosome infection rates of snails were not obvious (P > 0.05), but the mortality of snails showed a falling trend (P < 0.05); There were positive correlations between the average density of infected snails and the mortality of snails (r = 0.640, P < 0.05) , the infection rate of snails (r = 0.639, P < 0.05) , and the average density of living snails (r = 0.646, P < 0.05) , respectively. There was no correlation among other snail indicators. In 1999, only 7 snails were found, of them, only one snail was alive. The alive snails were not found after 2000. CONCLUSION: In the bottomland areas of Qianliang Lake district, the change trend of the density of alive snails were not obvious from 1988 to 1998, but the number of snails underwent a sharp drop in 1999 and snails have been not found till now.

[Snail habitats detection in the marshland of Eastern Dongting Lake Area, based on China-Brazil Earth Resources Satellite-02B CCD data].

OBJECTIVE: To detect the snail habitats from the marshland of Eastern Dongting Lake Area, using the Remote Sensing (RS) and Geographic Information System (GIS) technology based on the China-Brazil Earth Resources Satellite-02B (CBERS-02B) CCD images. METHODS: According to the two typical traits of snail habitats in marshland including "water in summer and land in winter" and "no grass, no snails", the "water in summer and land in winter" region and the vegetation coverage region were calculated by RS image processing respectively. The two regions mentioned above were then overlapped to confirm the snail habitats through comparing with the data from field survey under spatial overlapping of Arcgis as the last step. RESULTS: In Eastern Dongting Lake area, the "water in summer and land in winter" region and vegetation coverage region were predicted based on the formula normalized difference water index (NDWI) > 0.01 and normalized difference vegetation index (NDVI) > 0.36, respectively. The snail habitat was determined by theme overlay of the two regions said above. The agreement rate between the prediction and the geospatial data of field survey was 93.55%, which demonstrated the final results were credible and reliable. CONCLUSION: CBERS-02B image could be used to detect the snail habitats and to monitor the changes of them, so as to find out the characteristics of distribution and the trends of diffusion. The snail index (discriminant 1 and 2) seemed to be suitable for the detection of snail habitats in the marshland of Lake area and used for the programs of snail control.

Study on the reliability and validity of the Chinese Menopause Rating Scale (CMRS) / 中华流行病学杂志

Objective To evaluate the feasibility,reliability,validity and responsiveness of a Chinese Menopause Rating Scale (CMRS).Methods Cross-sectional survey and convenience sampling were adopted. Participants:women with menopause syndrome and those in menopause but without menopause syndrome were recruited.All participants were asked to complete the CMRS,Kupperman Index,WHOQOL-BREF and MENQOL.The Self-control observation design was adopted when the responsiveness was evaluated.Patients were treated with TCM for weeks.MRSTCM was evaluated before and after the treatment.Results (1) Feasibility:3343 participants including 2320 patients and 1023 menopause women,were surveyed in 8 different settings.The recovery rate of CMRS was 100%,with a response rate as 99.7%.The completion of the CMRS took 10.30 minutes on average.(2)Reliability:Cronbach's alpha of CMRS,soma dimension,psychology dimension and community dimension of CMRS were 0.93,0.87,0.89 and 0.73 respectively,with the correlation coefficient of split half of the CMRS.Soma dimension,psychology dimension and community dimension were 0.92,0.89,0.86 and 0.73 respectively and the test-retest correlation coefficient of MRSTCM,the soma dimension,psychology dimension and community dimension were as 0.88,0.91,0.85 and 0.77 respectively.(3) Validity:CMRS was established on the basis of connotation of menopause syndrome,and a series of steps were adopted to modify the scale.CMRS was applicable for patients with menopause syndrome.CMRS seemed to have had good content-related validity.The result of exploratory factor analysis was accorded with the theory frame of CMRS by and large.The correlations between CMRS and KI,CMRS and WHOQOLBREF,CMRS and MENQOL seemed good.The CMRS was able to discriminate between groups of people with or without menopausal syndrome and bad good discriminative validity.(4) Responsibility:The CMRS was measured based on 174 patients with menopausal syndrome before and after the TCM therapy.Our result showed that the CMRS having the ability to measure the clinically important differences.Conclusion CMRS was suitable for outcome assessment of menopausal syndrome.This primary research proved that the CMRS had good feasibility,reliability,validity as well as responsiveness.