The methyl group plays an important role in the rational drug design. Introducing methyl into small molecules has become an important strategy of lead compound optimization. The application of methyl in drug design is reviewed in this paper. Methyl can modulate the physicochemical, pharmacodynamic, and pharmacokinetic properties by ortho effect, inductive effect, and conformational effect. It also improves the metabolic stability as a soft metabolic point. In addition, introducing methyl into drug molecules can also be applied as a strategy in new uses of old drugs and generate me-too drugs.

Objective To study the effects of Bis(maltolato) oxovanadium(BMOV) on renal structure of spontaneously hypertensive rats(SHRs) and its mechanism.Methods Thirty-six SHRs were divided into three groups at random: blank group,Nifedipine group and BMOV group.The light microscope and electron microscope were used to examine the pathologic changes of the kidney in rats.Results The rat glomerular mesangial expansion was found and the lumen of glomeruler capillary nearly closed in bland group,while in BMOV group the pathological changes mentioned above were unobvious.Conclusion BMOV may have protective effects on kidney in SHRs.

Objective To analyze the outcomes of radiotherapy for 74 patients with intracranial ger-minoma. Methods Between 1990 and 2007,74 patients with intracranial germinoma(9 pathologically diag-nosed and 65 clinically diagnosed) were treated with radiotherapy in our hospital. The median age at diagno-sis was 15 (range 5-45) years. Radiation treatment fields varied among patients, including craniospinal irra-diation(CSI), whole brain irradiation, whole ventricular irradiation with primary tumor boost, and involved-field irradiation only to the primary tumor plus margin. The dose was 38.5 -50.0 Gy to the tumor,18-25 Gy to the whole brain/ventricular,and 21-25 Gy to the whole spinal cord in fractions of 1.6-2.0 Gy per day,5 fractions per week. Results The median follow-up time was 80(range 12-168) months and the fol-low-up rate was 97%. Fourteen patients had been followed up for over 10 years. The 1-,5- and 10-year o-verall survival rates were 99% ,96% and 93%. The corresponding disease free survival rates were 97%, 90% and 83%, respectively. Relapses occurred in 9 patients. For the 6 patients with in-field relapse, the dose to the tumor was 38.5-40.0 Gy in 3 patients, 41-45 Gy in 2 and 46-50 Gy in 1. Relapse in the spinal cord was found in 3 patients and none of them received spinal irradiation. Twenty-one patients re-quired hormonal replacement therapy because of radiation induced hypofunction of prehypophysis. Conclu-sions Radiotherapy alone is a curative treatment for intracranial germinoma. The proper dose should be de-termined by tumor numbers and the examination of cerebrospinal fluid.

Objective To study the efficacy,late complications and prognostic factors of postopera-tive radiotherapy for bladder cancer: Methods Between July 1995 and January 21307,109 patients with primary bladder cancer who had received adjuvant pelvic radiation therapy were retrospectively analyzed. The age ranged from 41 to 94 (median 68) years. There were 29 patients with T1 disease,60 with T2,17 with T3, 3 with T4, and 7 with positive lymph node. Three-dimensional radiotherapy was given with a median total dose of 49.2 Gy(39.3 -62.2 Gy) in conventional fractionation after surgery. Field-in-field intensity modu-lated radiotherapy was given to 57 patients. Results The total follow-up rate was 98% ,with a median fol-low up time of 36(2-144) months. The 1-,3- and 5-year local control rate was 63% ,47% and 42% ,respec-tively. The 1-,3- and 5-year overall survival rate was 80% ,48% and 37% ,respectively. Among the 109 pa-tients,33 died of tumor progression or metastasis,42 showed local recurrence,and 22 had lymph node metas-tasis. According to the RTOG criteria,grade 1,2,3 and 4 radiation related early urological side effects were 22% ,59% ,12% and 1% ,respectively;The corresponding late urological side effects were 29% ,28% ,2% and 1%, respectively. Two patients underwent whole bladder cystectomy due to the radiation related side effects. Conclusions Postoperative three-dimensional radiotherapy, achieving high response rate with tol-erable side effects, can be offered as an alternative option to the radical cystectomy in the bladder conserving treatment.

Objective To analyze the efficacy,late complications and prognostic factors of post-op-erative radiotherapy for cervical cancer. Methods From Nov. 1999 to Feb. 2005,114 patients with cervi-cal cancer received adjuvant pelvic radiotherapy after radical hysterectomy and pelvic lymphadenectomy. The median age was 42.5 (24 to 72) years old. According to the FIGO staging system,6,51,18,26 and 13 pa-tients had stage ⅠA, Ⅰb1, Ⅰb2, ⅡA and ⅡBdisease. The pathological type was squamous cell carcinoma,ade-nocarcinoma, squamous-adenocarcinoma and undifferentiated carcinoma in 92,19,2 and 1 patients, respec-tively. The whole-pelvic external beam irradiation of 50 Gy (40 to 60 Gy) was given with 6 MV or 15 MV X-ray beams using four-field box technique. Eighty-one patients received intravaginal brachytherapy of 16 Gy (4 -30 Gy in 1 -6 fractions) 4 weeks after the beginning of radiotherapy, with the referrence point being at 0.5 cm under the vaginal mucosa. Eighty-seven patients received preoperative and/or concurrent chemother-apy. The survival and independent prognostic factors were analyzed by Log-rank method and Cox model. Results The median follow-up time was 26.0 (5 - 75) months. The overall survival rate, disease-free sur-rival rate and local control rate were 93.1%, 88.1% and 94.6% at 2-year, and 75.7%, 62.3% and 85.6% at 5-year,respectively. The independent prognostic factors were lymph node metastasis and positive surgical margin for overall survival, positive surgical margin for local control, and stage, uterine body invasion and positive surgical margin for disease-free survival. Sixteen patients ( 14% ) had distant metastasis, and the most common sites were the lung,inguinal region,bone,liver and brain. According to RTOG grading sys-tem, the incidence of late gastrointestinal side effects of grade 1,2 and 3 was 11.4%, 11.4% and 3.5%. The corresponding genitourinary side effects were 14.0% ,6.1% and 0.9%, respectively. The incidence of leg lymphedema was 7 % . Conclusions Post - operative radiotherapy can achieve good local control in cervical cancer with acceptable late side effects. Distant metastasis is the main cause of death.

Objective To evaluate treatment results and prognostic factors of 47 patients withprimary urethral transitional cell carcinoma treated with post-operative adjuvant radiotherapy. Methods From October 1998 to October 2008, 47 patients with primary urethral transitional cell carcinoma received postoperative adjuvant radiotherapy. Thirty-one patients had stage T_3/T_4 disease, 7 had lymph node metastasis. Thirty-nine patients had G3 tumor, 13 had stump-positive. The median radiotherapy dose was 60 Gy (36-64 Gy). 81% patients (38/47) were treated with regional irradiation. Results The median follow-up time was 21 months (6 -88 months). The follow-up rate was 92%. The median overall survival time was 35 months (5 -88 months). The 2-and 5-year overall survival rates were 57% and 49%, respectively. In univariate analysis, the median overall survival time was better in patients with stage T_1 or T_2 compared with stage T_3 or T_4 tumor (42 months vs. 19 months,Χ~2 =7. 28,P=0. 007), with age of ≤65 years compared with >65 years (28 mouths vs 18 months,Χ~2 =8.23 ,P =0. 004). There was no significantdifference in the long term survival in patients with non-radical surgery compared with radical mastectomy (21 months vs. 20 months, Χ~2 = 0. 90, P = 0. 344). In multivariate analysis, the stage T_3 or T_4 (Χ~2 = 7. 89, P =0. 005), >65 years old (Χ~2 = 4.85, P = 0. 028), renal pelvis involvement (Χ~2= 5.65, P = 0. 018), and tumor located in the mid or inferior segment (Χ~2=6. 08 ,P =0. 014) were factors associated with poorer prognosis. Conclusions Postoperative adjuvant radiotherapy can improve the efficacy of patients with locally advanced urethral transitional cell carcinoma. Advanced T stage and > 65 years age are associated with poorer prognosis.

BACKGROUND: Percutaneous vertebroplasty for osteoporotic vertebral compression fractures has achieved very good results, but its long-term efficacy as well as impact on patients has been rarely reported so far.OBJECTIVE: To investigate the long-term effect of vertebroplasty with bone cement on osteoporotic vertebral compression fractures through a follow-up.METHODS: Thirty-four patients with osteoporotic vertebral compression fractures who had undergone percutaneous vertebroplasty were recruited. Visual analogue scale scoring was measured and compared as well as lesioned vertebral height and kyphosis angle shown on lateral X-ray examination prior to, 1 week and 6 years after percutaneous vertebroplasty.RESULTS AND CONCLUSION: The kyphosis angle was improved 1 week and 6 years after percutaneous vertebroplasty, and it changed insignificantly during the follow-up period. The vertebral height was also improved significantly after percutaneous vertebroplasty (P < 0.01); however, there was no obvious variation in the vertebral height at 1 week and 6 years after percutaneous vertebroplasty. The visual analogue scale exhibited an improvement after percutaneous vertebroplasty (P < 0.01); however, with time going by, the scoring on the visual analogue scale had an increased tend. All the parameters remained stable and had no large fluctuations. It is proved that the percutaneous vertebroplasty is effective and safe to treat osteoporotic vertebral compression fractures with an excellent long-term effect.

OBJECTIVE: To analyze the features of drowning victims with psychiatric disorders to support further investigation on such cases. METHODS: One hundred and five archives of drowning victims with psychiatric disorders from January 2010 to June 2014 in Harbor Public Security Subbureau, Shanghai Public Security Bureau were reviewed. The decedents' general information, autopsy findings, case investigation data and disease histories were statistically analyzed. RESULTS: Of the 105 cases, 104 were suicides. Most decedents were poorly educated. Most suicides occurred in warm climate, and the corpses were usually found within 2 days. Most decedents had no suicide history and notes, but had abnormal mental or behavior changes before suicide. Depression, depression status and schizophrenia were the main types of psychiatric disorders, and only 9 decedents had received regular therapies before their deaths. CONCLUSION Mental disorder is a high risk factor in the drowning victims. Guardians should be aware of psychotic abnormal behaviors, especially during warm climate seasons.
China/epidemiology* ; Depression/epidemiology* ; Depressive Disorder/epidemiology* ; Drowning/psychology* ; Female ; Humans ; Male ; Mental Disorders/psychology* ; Psychotic Disorders ; Retrospective Studies ; Risk Factors ; Schizophrenia ; Seasons ; Suicide/statistics & numerical data*

The methyl group plays an important role in the rational drug design. Introducing methyl into small molecules has become an important strategy of lead compound optimization. The application of methyl in drug design is reviewed in this paper. Methyl can modulate the physicochemical, pharmacodynamic, and pharmacokinetic properties by ortho effect, inductive effect, and conformational effect. It also improves the metabolic stability as a soft metabolic point. In addition, introducing methyl into drug molecules can also be applied as a strategy in new uses of old drugs and generate me-too drugs.
Drug Design ; Hydrophobic and Hydrophilic Interactions ; Lipid Metabolism ; Methylation ; Pharmaceutical Preparations ; chemical synthesis ; chemistry ; metabolism ; Solubility ; Stereoisomerism ; Structure-Activity Relationship

Delayed-Action Preparations ; Drug Carriers ; Drug Delivery Systems ; Lactic Acid ; Microspheres ; Nanotechnology ; Polyesters ; Polymers ; Technology, Pharmaceutical ; methods