Charged particle therapy offers a better effect and obvious dosimetric and biological advantages over conventional radiotherapy in tumor control.Charged particles form Bragg peak in the dose distribution in tissue, enable most of energy to be deposited in the target region, and thus enhance tumor control and reduce the damage to normal tissues surrounding the tumor.With the increasing demand for charged particle therapy and the advances in particle accelerator, particle therapy technology is developing rapidly.The core apparatus of particle therapy facility is particle accelerator, and the accelerator type, particle type, and implementation technique determine the performance and therapeutic effect of the facility.This article provides a detailed comparative analysis of various particle therapies.Statistical data show that proton therapy is dominant in particle therapy, and high construction difficulty, large facility size, and extremely high cost have limited the development of heavy ion therapy.Nowadays, there are still some technical problems regarding charged particle therapy, and more clinical trials are required.

Transient receptor potential vanilloid 1(TRPV1)is a nonselective cationic channel,and can be activt-ed by capsaicin,protons and heat.TRPV1 plays a critical role in the initiation of neural inflammatory response and the pathway of pain signal transduction.As a new analgesics,TRPV1 antagonists block pain behaviors in models of inflammatory,neuropathic,and cancer pain.A number of pharmaceutical companies developed a range of TRPV1 antagonists with various structures.It was found that various chemotypes of TRPV1 antagonists would cause an increase in body temperature(hyperthermia),which may become concerns for their development.This article summarizes the recent progress in TRPV1 antagonists development and the relevant hyperthermia.

Objective To evaluate the influence and significance of Pingyangmycin chemotherapy on the c-myc and Ras-P21 protein expression in penile cancer .Methods A total of 100 penile squamous cell carci-noma cases was retrospectively studied and divided into two groups .Data were obtained from 1995 to 2005 .In the chemotherapy group ,50 cases of patients were selected to perform preoperative chemotherapy before surgery .The patients were treated by Pingyangmycin .After 7 times of medication ,partial excision of penis plus improved ingui-nal lymph node dissection was performed .In the control group ,50 cases of patients were selected for partial exci-sion of penis plus improved inguinal lymph node dissection directly without any pre -operative chemotherapy .All pathology specimens were detected of c -myc and Ras-P21 protein expression by immunohistochemical staining assay.Theχ2 test was used for the statistical analysis .Results In chemotherapy group,the positive expression rates of c-myc and Ras-P21 were 30%,27%,respectively.However,in control group,the positive expression rate of c-myc,Ras-P21 were 52%,48%,respectively.By theχ2 test,the expressive differences of c -myc,Ras-P21 positive expression rate between chemotherapy group and control group were all significant (P<0.05). Conclusion The protein expressions of c -myc and Ras-P21 is significantly decreased in the tissue of Pingy-angmycin chemotherapy of penile cancer .

Objective To improve the diagnosis and treatment ot adrenocorticotropin-independent macornodular adrenal hyperplasia (AIMAH).Methods The clinical data of 17 cases with AIMAH from 2000 to 2011 were analyzed retrospectively,including 3 subclinical AIMAH,10 clinical AIMAH and 4 highrisk AIMAH patient,with common radiological characteristic of bilaterally enlarged adrenal glands with multiple nodules like ginger.The 3 cases of subclinical AIMAH patients presented with decreased serum ACTH,normal or slightly elevated plasma cortisol and urinary free cortisol level,no suppression following 1 mg overnight dexamethasone suppression test and absence of clinical signs of Cushing syndrome (CS).While clinical AIMAH and high-risk AIMAH presented with clinical signs of CS,elevated plasma cortisol and urinary free cortisol level,suppressed serum ACTH,loss of normal circadian rhythm in cortisol secretion and no suppression following the low-dose and high-dose overnight dexamethasone suppression test.Among the 4 cases of high-risk AIMAH,2 cases presented with osteoporosis,2 cases with hepatic dysfunction,3 cases with cardiopulmonary dysfunction,and 4 cases with severe hypertension.Three cases of subclinical AIMAH were treated with symptomatic treatment,10 cases of clinical AIMAH patients with surgical operation,4 cases of high-risk AIMAH patients with ketoconazole and surgical operation.Results Three subclinical AIMAH patients received symptomatic treatment and discharged from hospital with normal blood pressure and blood glucose.During the period of follow-up from 3 months to 3 years,endocrine results were normal.Seven clinical AIM AH patients underwent unilateral adrenal tumor resection plus ipsilateral partial adrenalectomy or total adrenalectomy.CS disappeared completely after 6 to 9 months.Two clinical AIMAH patients underwent simultaneous bilateral adrenalectomy.One case died of adrenal crisis after operation,and the other case presented with adrenal insufficiency but returned to normal after glucocorticoid replacement therapy,no Nelson's syndrome happened during the follow-up for 5 years.One clinical AIMAH patient undertook unilateral adrenalectomy twice by interval,followed by routine corticosteroid replacement therapy.Followed up for 10 years,no Nelson's syndrome happened.Four high-risk AIMAH patients received ketoconazole and then underwent right total adrenalectomy.Cortisol levels returned to normal after 1 to 2 months and during the follow-up for 1 to 3 years,the laboratory examinations maintained normal.Conclusions Different treatment methods should be adapted to different subtypes of AIMAH.For subclinical AIMAH,the principal treatment is symptomatic,and close follow-up with regular adrenal imaging and endocrine examination is required.Surgical operation should be performed when clinical symptoms of AIMAH appear.Medical management is essential for high-risk AIMAH to inhibit the production of cortisol at first.Once these patients could stand the stimulation caused by operation,the adrenal glands should be resected as soon as possible.The unilateral adrenalectomy is an effective treatment for clinical AIMAH.

ObjectiveTo investigate the diagnosis and treatment of adrenocorticotropin-independent macronodular adrenal hyperplasia (AIMAH). MethodsThe clinical data of 14 cases of AIMAH from August 1972 to July 2010 were retrospectively analyzed.The cases included 5 males and 9 females with a mean age of 45 (range 26 to 58 ) years.Ten patients demonstrated typical Cushing's syndrome (CS) and 4 patients presented with weight gain,hypertension or diabetes mellitus without any signs of CS.The circadian rhythm of serum cortisol was abnormal.Low and high dose dexamethasone suppression tests failed to suppress cortisol secretion.CT scan showed bilateral enlargement of the adrenal glands with multiple macronodules.All patients underwent open surgery,including 5 cases of unilateral adrenalectomy,6 cases of adrenalectomy combined with contralateral subtotal adrenalectomy and 3 cases of bilateral adrenalectomy.ResultsIt was established by pathological examination that all patients had bilateral adrenal macronodular or adenomatoid hyperplasia.During the mean follow-up of 69 months (range 12 to 120 months),the clinical symptoms of CS disappeared after surgery in all cases.The 5 patients who received unilateral adrenalectomy had urinary free cortisol and serum cortisol within normal ranges and no further enlargement of the contralateral gland was noticed.Among the 3 patients who received bilateral adrenalectomy,1 case died of adrenal crisis on day seven post-operation.The remaining 2 cases presented with adrenal insufficiency but returned to normal after glucocorticoid replacement therapy.Nelson's syndrome was not observed in the other patients.ConclusionsAIMAH has unique endocrinological and pathological features,presenting as an independent etiology of CS.Unilateral adrenalectomy appears to be an effective and safe alternative treatment for AIMAH and long-term remission can be achieved.Bilateral adrenalectomy or unilateral adrenalectomy combined with contralateral subtotal adrenalectomy may be performed if the symptoms have not improved or recurred after unilateral adrenalectomy.

Objective To improve the diagnosis and treatment of ACTH-independent macronodular adrenal hyperplasia(AIMAH).Methods A 51-year-old female patient with Cushing's syndrome caused by AIMAH was reported.Elevated early morning plasma cortisol levels,increased 24 h urinary free cortisol excretion,and loss of the normal circadian rhythm in cortisol secretion were presented.There was no suppression of cortisol secretion by administration of low-and high-dose overnight dexamethasone suppression test.Cardio-pulmonary function was very bad with the highest blood pressure reaching 300/120 mm Hg( 1 mm Hg=0.133 kPa).Initially,she was treated with mitotane(60 mg/d),but was not effective.After taking ketoconazole (800 mg/d)for 5 days,cardio-pulmonary function was not effectively improved with blood pressure only descending to 180/120 mm Hg.Orthopnoea appeared and Spo2fell once to 75％.The patient had to undergo right total adrenalectomy immediately.ResultsThe mass resected was 10 cm× 10 cm in size and weighted 67.5 g.Histological examination of the removed adrenal revealed nonpigmented macronodular cortical hyperplasia.The patient continued to take ketoconazole (400-800 mg/d)from the 6th day of the operation without steroid replacement therapy in that period.With normal cortisol levels( plasma cortisol at 8:00 was 18.65 μg/dl,24 h urinary free cortisol was 78.75 μmol),she left hospital after the general condition had been improved.During the following updated 10 months follow up,the indexes of her laboratory examination were maintained normal.ConclusionIndividualized therapy should be adopted for the patient with AIMAH.The medication is useful to suppress the adrenal gland cortisol production for those with progression of symptoms,very high blood pressure,hypokalemia and hypoproteinemia.Once the cardio-pulmonary function improves,the target organ should be resected as soon as possible.The supplement of cortisol is not appropriate during the perioperative period.The unilateral adrenalectomy is an effective treatment for AIMAH.

OBJECTIVETo establish the theories and methods to determine apparent solubility paraneters of multiple components for the Chinese materia medica (CMM) with HPLC fingerprint.

METHODThe mathematical functional expresses to determine the apparent solubility parameters for multiple constituents were established according to total quantum geometrical average retention time (TQGART) for HPLC fingerprint that characterized the entirety tendencies for all-over chromatographic peaks, validated by the aloe-emodin's solubility parameters which had been determined. The HPLC for the aloe-emodin's solubility parameters were carried out with an Alltech Apollo C18 as column, Acetone: Water as mobile phase, gradient elution,flow rate as 1.0 mL x min(-1), the detection wave-length as 430 nm and the temperature as 30 degrees C.

RESULTThe mathematical functional model between the TQGART of HPLC chromatographic fingerprint and the total quantum apparent solubility parameters was established and used to determine the aloe-emodin's mixture solubility parameter as 36.12 J(1/2) x cm(-3/2), nearly equal to 35.57, 36.07 J(1/2) x cm(-3/2) calculated by ration of peak area ratios and molecular fraction, respectively.

CONCLUSIONThe TQGART of HPLC fingerprint can be used to determine simultaneously the apparent or single intrinsic solubility parameters for total quantum or intrinsic solubility parameters for single in multiple constitute systems, by which theoretical and technologic platform to study the compatibility rule and dosage form reform of the single CMM will be established.

Objective To study the correlation between interleukin(IL)-21 and the recurrence of chronic hepatitis B(CHB)in hepatitis B e antigen(HBeAg)-positive patients after discontinuation of entecavir(ETV).Methods A total of 112 HBeAg-positive CHB patients treated with ETV were enrolled.Serum levels of IL-21 at week 0,12,24 and 52 after ETV discontinuation were detected.The Cox regression model was used to analyze the correlation between IL-21 and the recurrence after ETV discontinuation.The receiver operating characteristic(ROC)curve was applied to determine the predictive value of IL-21 for CHB recurrence after ETV discontinuation.The expression differences of IL-21 were compared between sustained viral response(SVR)group and viral relapse(VR)group.The t test and Chi-square test were used for statistical analysis.Results The serum levels of IL-21 in SVR group at week 0,12,24 and 52 after ETV withdrawal were(60.0 ± 10.8),(60.2 ± 14.7),(60.6 ± 19.5)and (61.2 ± 15.4)ng/L,respectively,which were all significantly higher than those in VR group(47.5 ± 10.7),(47.3 ± 12.9),(46.9 ± 12.2)and(46.4 ± 12.8)ng/L,respectively(t=6.153,4.926,4.382 and 5.515,respectively,all P< 0.01).The area under curve(AUC)was 0.811(95% CI:0.728 ~0.893,P<0.01)and the best cut-off value of serum IL-21 level was 49.8 ng/L.The recurrence rates of patients with serum IL-21 level ≥49.8 ng/L and <49.8 ng/L at time of ETV withdrawal was 25.4%(16/63)and 77.6%(38/49),respectively.The difference was statistically significant(χ2=30.027,P<0.01).The serum IL-21 level at the time of drug withdrawal(P= 0.005),serum hepatitis B surface antigen(HBsAg)level at the time of HBeAg seroconversion(P= 0.008)and age(P= 0.016)were factors associated with CHB recurrence after ETV withdrawal by multivariate Cox model analysis.The serum levels of ALT,HBV DNA,HBeAg and HBsAg in SVR group were significantly lower than those of VR group at week 12,24 and 52 after ETV withdrawal(t= -5.968,-7.691,-8.093; -3.047,-9.477,-28.900;-2.872,-10.424,-18.330;-4.633,-4.030 and -5.032,respectively;all P<0.01).Serum level of IL-21 was negatively correlated with HBsAg in SVR group after ETV withdrawal (r= -0.241,P<0.01),while positively correlated with HBsAg in VR group(r=0.286,P<0.01). Conclusions The serum IL-21 level at the time of drug withdrawal is associated with the recurrence after ETV discontinuation.IL-2l may play an important role as an immunomodulatory factor in maintaining virological responses in HBeAg-positive CHB patients after ETV withdrawal.

Objective: To explore the safety and effectiveness of left bundle branch area pacing (LBBAP) in children. Methods: Clinical data, pacing electrocardiogram and parameters of 6 patients (5 females and 1 male) who underwent permanent pacemaker implantation and LBBAP from January to June 2019 in the Department of Pediatric Cardiology of Anzhen Hospital were retrospectively analyzed. Results: The weight of the 6 patients aged between 9 and 14 years ranged from 26 to 48 kg. Five patients were diagnosed with third degree atrioventricular block, and 1 patient was diagnosed with cardiac dysfunction after right ventricular apical pacing. Cardiac function decreased in one patient and remained normal in the other five patients. Left ventricular end diastolic diameter (LVEDD) Z score was 1.85±0.65. V₁ lead showed changes like right bundle branch block in pacing electrocardiogram. No significant difference was found regarding QRS wave duration ((95±13) ms vs. (111±20) ms, t=-1.610, P>0.05) between preoperation and postoperation. Pacing threshold was (0.85±0.26) V. The sensing threshold was (15.0±4.3) mV and the impedance was (717±72) Ω. P potential was recorded in 3 cases. The earliest left ventricular local activation time was (56±5) ms and remained stable at different output voltages. Postoperative echocardiography revealed that the electrodes were located near the endocardium of the left ventricular septum. No complications such as myocardial perforation and electrode dislocation occurred during follow-up. The pacing threshold, sensing threshold and impedance were (0.60±0.09)V, (16.1±3.9)mV, (662±78)Ω respectively at 3 months after operation. The patient with low left ventricular ejection fraction (LVEF) recovered to normal on the 3 rd day after LBBAP (45% vs. 57%). The LVEDD Z score decreased to (1.1±0.3) at 3 months after operation and was significantly lower than that before operation (t=2.38, P<0.05). Conclusions LBBAP in children can achieve narrow QRS pacing andphysiological pacing with stablepacing parameters. It can improve left ventricular enlargement caused by long-term bradycardia, and cardiac dysfunction and cardiac enlargement caused by long-term right ventricular apical pacing quickly and effectively.LBBAP is safe and feasible for older children in the near future. However, the long term potential risks of LBBAP need further observation and study.

Objective To quantitatively assess the plan quality of conventional fractionated volumetric modulated arc therapy ( VMAT ) plans for liver cancer treatments using flattening filter-free (FFF) and flattening filter (FF) modes based on plan quality metric (PQM). Methods A total of ten patients with liver tumor were selected. The patients were planned in FF and FFF mode of 6 MV X-ray respectively. The dose distribution of the planning target volume ( PTV) and the organ at risk ( OAR) were evaluated, and the monitor units ( MUs) and the beam on time ( BoT) were compared. According to the clinical requirements, a PQM with 16 submetrics was defined to evaluate the plan quality of the two modes. Results The maximal dose of FFF plan was less than that of FF plan (t =3.828, P <0.05). The normalized volume of 5 Gy ( V5 ) and mean dose ( Dmean ) of the normal liver of FFF plan were lower than those of the FF plan (t=2.716, 3.007, P<0.05). The average MU of FFF plan [(574 ± 130) MU] was higher than that of FF plan [(518 ± 81) MU](t= -2. 782,P<0. 05), while the average BoT of FFF plan [(108 ±36)s] was significantly lower than that of FF plan [(160 ±29) s](t=6.767,P<0.05). The score of FFF plan was higher than that of FF plan (t= -2.746, P<0.05). Conclusions FFF mode can better protect the OAR at low dose levels. The MU of FFF mode plan were higher, but the beam on time was significantly lower than FF mode plan. With reference to the PQM evaluation criteria, the overall plan quality of the FFF mode was slightly higher.