In this study, we developed a novel liposome-silica hybrid nano-carrier for tumor combination therapy via oral route, using paclitaxel and cyclosporine as a model drug pair. Optimization of the preparation of the drug-loading formulation and characterization of its physicochemical parameters and drug release profile were performed in vitro. Then in vivo pharmacodynamics and pharmacokinetics studies were performed. The results showed that the obtained formulation has a small particle size (mean diameter of 100.2 +/- 15.2 nm), a homogeneous distribution [the polydispersity index was (0.251 +/- 0.018)] and high encapsulation efficiency (90.15 +/- 2.47) % and (80.64 +/- 3.52) % for paclitaxel and cyclosporine respectively with a mild and easy preparation process. A sequential drug release trend of cyclosporine prior to palictaxel was observed. The liposome-silica hybrid nano-carrier showed good biocompatibility in vivo and co-delivery of cyclosporine and paclitaxel significantly enhanced the oral absorption of paclitaxel with improved anti-tumor efficacy, suggesting a promising approach for multi-drug therapy against tumor and other serious diseases via oral route.

A new enhancement method is proposed based on the characteristics of fundus images in this paper. Firstly, top-hat transform is utilized to weaken the background. Secondly, contrast limited adaptive histogram equalization (CLAHE) is performed to improve the uneven illumination. Finally, two-dimensional matched filters are designed to further enhance the contrast between blood vessels and background. The algorithm was tested in DIARETDB0 databases and showed good applicability for both normal and pathological fundus images. A new no-reference image quality assessment method was used to evaluate the enhancement methods objectively. The results demonstrated that the proposed method could effectively weaken the background, increase contrast, enhance details in the fundus images and improve the image quality greatly.
Algorithms ; Contrast Media ; Fundus Oculi ; Humans ; Image Enhancement

Objective: To investigate the immune reconstitution of HIV/AIDS patients and its influencing factors after receiving antiviral therapy (ART) in Hangzhou City, so as to provide insights into improving the treatment effects and quality of life in HIV/AIDS patients. Methods: A retrospective cohort of HIV/AIDS patients who began antiviral treatment between January 1, 2016 and August 31, 2021 and had a baseline CD4+T lymphocyte (CD4) counts of less than 500 cells/μL or a baseline CD4/CD8+T lymphocyte (CD8) ratio of less than 0.8 in Hangzhou City was followed up until August 31, 2023. Demographic information, antiviral therapy in formation, CD4 counts, and CD4/CD8 were collected from the Chinese Disease Prevention and Control Information System. A good immune reconstitution was defined as having CD4≥500 cells/μL and CD4/CD8≥0.8. The immune reconstitution status of HIV/AIDS patients were analyzed, and factors affecting immune reconstitution were identified using a multivariable Cox proportional risk regression model. Results: A total of 3 349 HIV/AIDS patients were enrolled, with a median age at ART of 31 (interquartile range, 20) years. There were 3 075 males (91.82%), 1 600 cases with college education and above (47.78%) and 2 455 cases at WHO clinical stage Ⅰ-Ⅱ(73.31%). There were 1 368 cases with good immune reconstitution, accounting for 40.85%, and the proportion of HIV/AIDS patients with good immune reconstitution that began ART in 2016 was the highest, reaching 51.90%. Multivariable Cox proportional risk regression model identified WHO clinical stage (Ⅰ-Ⅱ, HR=2.529, 95%CI: 2.023-3.162), timely ART (HR=1.196, 95%CI: 1.027-1.394), initial treatment regimen (TDF+3TC+NVP/EFV, HR=2.185, 95%CI: 1.891-2.524; integrase inhibitors, HR=8.509, 95%CI: 6.706-10.795), baseline CD4/CD8 (≥0.1, HR: 1.600-4.515, 95%CI: 1.061-6.661), baseline hemoglobin (<90 mg/dL, HR=0.327, 95%CI: 0.121-0.880), hepatitis B infection (HR=0.619, 95%CI: 0.457-0.840) and hepatitis C infection (HR=0.308, 95%CI: 0.099-0.956) as factors affecting immune reconstitution in HIV/AIDS patients. Conclusion The immune reconstitution in HIV/AIDS patients after ART is associated with WHO clinical stage, timely ART, initial treatment regimen, baseline CD4/CD8, baseline hemoglobin and hepatitis B or C infection.

Objective To summarize the distribution of departments,conditions of diagnosis and treatment of the syphilis patients in the general hospitals,and thus to improve the level of diagnosis and treatment.Methods A retrospective analysis of epidemiology and clinical data of 282 cases with syphilis in recent 5 years were conducted. Results The ratio of male to female was about 1:1.9.Female showed a high incidence in the 21 -50 years old,aver-age (41.68 ±0.96)years old,but for male in the 41 -70 years old,average (53.25 ±1.59)years old.The cases combined with other infectious diseases accounted to 22.0 % (62/282).The cases from the department of obstetrics and gynecology were the most (106 cases),followed by surgery (86 cases)and internal medicine (49 cases).Only 23 cases showed the clinical manifestations of syphilis in the 79 cases,which must be treated.The test rate of TRUST was only 39.0% (110/282).Furthermore,it was very low for the rate of treatment and standard treatment. Conclusion Syphilis is the most in department of obstetrics and gynecology in general hospital,and it is also com-mon in the surgery and internal medicine.The most prominent problems are that the non-special doctors had weak awareness for definite diagnosis of syphilis,and the low rate of treatment and standard treatment.

Objective To prepare insulin-containing chitosan-thioglycollic acid conjugates microspheres and evaluate their hypoglycemic effect.Methods The insulin-containing chitosan-thioglycollic acid conjugates microspheres were prepared by the dry-in-oil method using the chitosan-thioglycollic acid conjugates which the content of thiol group was 983?mol?g-1.The hypoglycemic effect of the microsphere was evaluated by drug release test in vitro and hypoglycemic test on hyperglycemic rats.Results The insulin-containing chitosan-thioglycollic acid conjugates microspheres with an average diameter of 13?m were administered by intraduodenal and intraileal application,and gave visible decrease in plasma glucose level in 4h at a dose of 20IU?kg-1.The relative bioavailability of the latter compared to hypodermic injection was 29.9%.Couclusion The results showed that the bioavailability of oral insulin could be facilitated by insulin-containing chitosan-thioglycollic acid conjugates microspheres,and good biological availability was obtained when the microspheres were administered by intraileal application.

OBJECTIVETo compare the difference in the efficacy on cervical spondylotic radiculopathy (CSR) between acupuncture at the acupoints on the axillary nerve distribution and the regular selection of acupoints. Methods Eighty patients of cervical spondylotic radiculopathy were randomized into an observation group and a control group, 40 ca.ses in each one. In the observation group, Jianjing (GB 21), Jianzhen (SI 9), Jianliao (TE 14) , Jianyu (LI 15) , Quyuan (SI 13), Tianzong (SI 11) and the trigger points in the scalpular region were selected along the axillary nerve distribution. The Hegu needling was adopted at the trigger points and stimulated with electric apparatus, continuous wave, 1Hz. In the control group, Dazhui (GV 14), Tianzhu (BL 10), Houxi (SI 3), cervical Jiaji (EX-B 2) were selected and stimulated with the regular acupuncture. Electric stimulation was added at cervical Jiaii (EX-B 2), with continuous wave, 1Hz. The needles were retained for 30 min in the two groups, once every two days and 10 treatments made one session. The efficacy was assessed in one session of treatment. The 20-point scale of CSR developed by Japanese scholar, Tanaka Yasuhisa, and the visual analogue scale (VAS) were adopted to score the clinical symptoms and pain degree before and after treatment in the patients and assess the efficacy of the two groups.

RESULTSThe symptom scores and VAS scores after treatment were improved apparently as compared with those before treatment in the two groups (P<0. 05, P<0. 01), and the results in the observation group were better than those in the control group (both P<0. 05). The total effective rate in the observation group was 85. 0% (34/40), better than 71. 8% (28/39) in the control group (P<0. 05).

CONCLUSIONThe acupuncture at the acupoints on the axillary nerve distribution achieves the definite efficacy on CSR, better I than the regular acupuncture at cervical Jiaji (EX-B 2).

Acupuncture Therapy ; Adult ; Aged ; Axilla ; innervation ; Female ; Humans ; Male ; Middle Aged ; Pain Measurement ; Radiculopathy ; therapy ; Shoulder Pain ; therapy ; Spondylosis ; therapy ; Treatment Outcome

Objective To explore the relationship of protein kinase B1 ( PKB1 ) gene polymorphisms in PI3-K pathway of BDNF and event-related potentials in depression.Methods The design of case-control research was used ,and 91 major depressive patients and 65 normal controls who were made in age and gender matched with patients were measured auditory event-related potential P300 and contingent negative variation ( CNV ) in the day when two groups were collected.Polymerase chain reaction (PCR) and direct DNA sequencing technology were used to detect PKB1 gene polymorphisms.Three SNPs that named rs3001371 ,rs2494738 ,rs1130214 were selected from 3 representative BLOCK Districts of PKB1.Two independent samples t test was used to analysis P300 and CNV between two groups,and the same way to analysis the average level of P300 and CNV and PKB1 SNP genolatency of P2(P＜0.05) and lower amplitude of P3a(P＜0.01 ) ,P3b(P＜0.01 ) and P3 (P＜0.01 ) ;CNV had der had statistical difference (P＜ 0.05 )in PKB1 rs3001371 gene between C/C and C/T genotype combined which included C allele, and T/T genotype.The amplitude of P3a( (5.93 ± 2.35 ) μV, P3b(6.51 ± 3.00) μV, P3 (6.27±2.43) μV) were lower than TT Genotype ( (7.45 ±2.19)μV, (8.63 ±3.57)μV,(8.04 ±2.57)μV,respectively).The mean of CNV indicators were not found different in statistics among the rs3001371 genotypes.Conclusions PKB1 gene rs3001371 polymorphism is associated with the principal component of P300 amplitude in patients with Major depressive disorder which suggest that genetic factors may have a certain impact on cognitive function in the patients with Major depressive disorder.

In the face of escalating problems with pathogen control, the development of proper formulations of existing antibiotics is as important as the development of novel antibiotics. Daptomycin is a lipopeptide antibiotic with potent activity against Gram-positive bacteria. Currently, only injectable solution of daptomycin has been approved for clinical use. In the present study, the formulation of PEGylated liposomal daptomycin (PLD) was prepared and optimized, and its efficacy against methicillin-resistant Staphylococcus aureus (MRSA252) strains was investigated. The obtained PLD had a mean vesicle diameter of (111.5 +/- 15.4) nm and a mean percent drug loading of (5.81 +/- 0.19) % with high storage stability. Potent activity of PLD against MRSA was demonstrated in vitro with a more sustained effect than that of conventional liposomal daptomycin and daptomycin solution. In addition, intravenous administration of a single dose (equal to human use) of PLD significantly increased the survival of mice in a MRSA252 systemic infection model compared with other formulations. Drug distribution in the lung was significantly enhanced following administration of PLD, and no measurable tissue lesions or pathological changes were detected during PLD treatment. Taken together, PEGylated liposomes loaded with daptomycin may represent a promising approach to reduce MRSA252 infections, especially those involving bloodstream dissemination, such as hematogenous pulmonary infection.

Objective To understand whether or not artesunate (Art. ) combined with naphtho-quine (Nap. ) can delay the resistance of Plasmodium falciparum to Art. Methods In Group A, P. falciparum was cultured in culture medium and was stimulated by Art/Nap disconnectedly, and in Group B, stimulated by Art disconnectedly. When P. falciparum recovered to normal growth level, the changes of sensitivity (ID50) to the drugs were compared between the two groups after P. falciparum touched on the drug. Results In Group A, the times P. falciparum recovered to normal growth level were 24, 37 d respectively when it contacted the drugs in the first and second times; P. falciparum didn't recover to normal growth level in 90 d when it contacted the drugs in the third time. In Group B, the times P. falciparum recovered to normal growth level were 16. 7 d (15-20) on average. ID50(s) of Art/Nap were 2.42/37.81, 1. 70/26.30 nmol/L before and 65 d after contacting the drugs in Group A; ID50(s) of Art were 9. 60, 30. 61, 85.12 nmol/L before and 68 and 129 d after contacting the drug in Group B. Conclusion Artesunate-resistant P. falciparum can be cultured by touching artesunate at intervals in vitro; Artesunate combined with naph-thoquine may delay the resistance of P. falciparum to artesunate in vitro.

Objective To explore cost of standard operation procedure of primary public healthcare services.Methods Standard operation procedure of primary public healthcare services was put forward according to national basic public healthcare service standards (2011 edition) in 2012.Random sampling method was used to choose participants from two community sanitary service centers,two township heahhcare centers and one maternity and child heahhcare hospital.Service standard operation procedure was used to measure human cost and supportive cost of public healthcare services.Results Management of 10 thousand patients who had different diseases needed various numbers of medical staff (MS),such as health profile needed 3.4 MS,hypertension management needed 10.8 MS,diabetes management needed 10.6 MS,elderly people care needed 9.2 MS,child care needed 4.6 MS,maternal care needed 24.3 MS,psychosis management needed 13.3 MS,and planned immunity for children needed 4.6 MS.Besides,the people whole covered service projects need 2.4 MS per 100 thousand people.The research showed that managing 1 sample of different kind people needed different human cost,such as health profile needed 22.67 yuan,hypertension management needed 72.69 yuan,planned immunity for children needed 30.68 yuan,diabetes management needed 71.34 yuan,old people management needed 61.50 yuan,child care needed 30.88 yuan,maternal care needed 157.15 yuan,psychosis management needed 74.25 yuan.Besides,the people whole covered service projects needed 124.9 thousand yuan per 100 thousand people.Conclusion For primary public healthcare service project,it should be critical to modify manning regulation and labor costs.