Objective: To investigate the preparation of pulsatile release tablets, the release of the drug in vitro and the pharmacokinetics in vivo . Methods: Dil tiazem hydrochloride（DIL） was used as model drug. The pulsatile release tabl e ts were prepared by dry-coated method with carnauba wax, bee wax and hydrophil i c cellulose as coating materials. The effects of formulation and technology on t he release characteri stic of diltiazem hydrochloride was investigated. The mechanism of pulsatile rel ease of the drug was proved by erosion test. The pharmacokinetic study on four h uman subjects was done by means of HPLC measurement. Results: In vitro ， delayed-release ti me t 10 was 2.1　h, the maximum release time t rm 4.0　h and t he pulsed-releas e time t 10-90 1.7　h. In vivo ， delayed-release time t la g was 5.7　h, the p eak time 8.5　h and the pulsed-release time 2.6　h. Conclusion: The rele ase of drug from pulsatile-released tablets of diltiazem hydrochloride was in a pulsed way both in vitro and in vivo .

Objective:To explore the long-term efficacy of a modified unilateral cutaneous ureterostomy in bladder cancer patients receiving radical cystectomy.Methods:The medical data of 104 bladder cancer patients who underwent ureterostomy in our hospital from Janurary 2013 to December 2020 were retrospectively analyzed. The patients were divided into unilateral and bilateral group. The unilateral group contained 66 cases, with 53 males and 13 females, average age (71.8±9.8) years, body mass index (BMI)(23.3±3.2)kg/m 2. The bilateral group contained 38 cases, with 33 males and 5 females, average age (75.1±10.8) years; BMI (22.7±3.0)kg/m 2. There was no significant difference in the above characteristics between the two groups ( P>0.05). The pathology, survival status, long-term complications between the two groups were compared. Quality of life was assessed during follow-up using the European Core Questionnaire for Quality of Life in Cancer Patients (EORTC QLQ-C30). Results:The unilateral group contained 46(69.7%) muscle invasive bladder cancer (MIBC) cases, 15 (22.7%) cases with lymph node metastasis, 7 (10.6%) cases with distant metastasis. The bilateral group contained 24(63.2%) muscle invasive bladder cancer(MIBC) cases, 6 (15.8%) cases with lymph node metastasis, 2 (5.3%) cases with distant metastasis. There was no significant difference in disease specific survival between the two groups ( P>0.05). During the follow-up, the incidence of overall complication rate in the unilateral group was significantly lower than that in the bilateral group [43.9% (29/66) vs. 63.2% (24/38), P<0.001]. The incidence of pyelonephritis in unilateral group was significantly lower than that in the bilateral group [16.6%(11/66) vs. 42.1%(16/38), P=0.006]. There was no statistical significance in terms of quality of life before operation in the two groups. After operation, both physical function score[(54.9±7.1) vs.(49.2±6.7)] and emotional function score [(63.1±6.4) vs.(59.9±6.7)] in unilateral group were higher than that in bilateral group ( P<0.05). Conclusions:The modified unilateral cutaneous ureterostomy could achieve relatively low complication rate, and improve the quality of life to some extent compared with bilateral ureterostomy.

BACKGROUND:The displacement change parameters of the bone structure of the first metatarsal bone at the two-dimensional level of hallux valgus deformity are of great significance for clinical diagnosis and treatment,while the quantitative analysis of the three-dimensional deformity index may have some influences on the postoperative efficacy. OBJECTIVE:To explore the quantitative change of the three-dimensional deformity index of the first metatarsal bone after routine osteotomy and orthosis for hallux valgus deformity and to provide reference for clinical work. METHODS:100 patients with hallux valgus deformity(foot)in Hengshui People's Hospital from October 2020 to April 2023 were selected and all of them underwent conventional osteotomy and orthosis.Foot function was assessed by the American Orthopedic Foot and Ankle Society Ankle-Hindfoot Scale 6 months after surgery.Anterolateral X-rays of the foot in weight-bearing position and CT images in simulated weight-bearing position were taken before surgery and 6 months after surgery.The three-dimensional deformity indexes of the first metatarsal bone before and after surgery were quantitatively analyzed in patients with different ages,genders and therapeutic effects,including first-second intermetatarsal angle,hallux valgus angle,distal metatarsal articular angle,tibial sesamaid position,and first metatarsal rotation α angle.The value of the difference of three-dimensional deformity indexes of the first metatarsal bone before and after operation in evaluating the curative effect was analyzed. RESULTS AND CONCLUSION:(1)Six months after operation,the American Orthopedic Foot and Ankle Society score was 75-98(88.25±4.14)points,among which 56 cases were excellent,28 cases were good,14 cases were average,and 2 cases were poor.The excellent and good rate was 84%(84/100).(2)Compared with the preoperative results,first-second intermetatarsal angle,hallux valgus angle,distal metatarsal articular angle,tibial sesamaid position,and first metatarsal rotation α angle were significantly improved in patients of different ages and genders 6 months after surgery(P<0.05).First-second intermetatarsal angle,hallux valgus angle,distal metatarsal articular angle,tibial sesamaid position,and first metatarsal rotation α angle were all lower in patients with good curative effect 6 months after surgery than those with poor curative effect,and the difference before and after surgery was greater than those with poor curative effect(P<0.05).(3)The area under the curve of the difference evaluation of the first metatarsal three-dimensional deformity index before and after surgery was above 0.7,and the area under the curve of the combined evaluation of all indexes was the largest(0.902),which was significantly greater than the first metatarsal rotation α angle and distal metatarsal articular angle(P<0.05).(4)The quantitative analysis of the three-dimensional deformity index of the first metatarsal in patients with hallux valgus deformity is related to the postoperative effect,which has important guiding significance for improving the accuracy and comprehensiveness of preoperative evaluation and improving the treatment plan.

Objective To summary the pathological and clinical characteristics,treatments and prognosis of malignant renal perivascular epithelioid cell tumor (PEComa).Methods Between August 2013 and June 2017,8 cases of malignant renal PEComa were analysed respectively.Of all the patients,there were 4 males and 4 females,aged 27-65 years with the average of 46.3 years old.Three cases were detected in routine examination occasionally,three cases complained of intermittent back pain with fever,one presented with swollen and painful right hand and right foot,and one case presented with hematuria.CT or MRI examinations indicated the malignant lesions before the surgery.Clinical staging was performed with 2 cases of T1N0M0,1 case of T1 N0M1,2 cases of T2N0M0,1 case of T3M0M0,and 2 cases of T4N0M1.Three cases underwent radical nephrectomy,1 case underwent radical nephrectomy plus renal artery embolization,2 cases underwent partial nephrectomy,and 2 cases underwent nephrectomy plus inferior vena cava tumor thrombectomy.One case was treated with ifosfamide plus epirubicin after operation due to multiple distant metastases and 1 case was treated with oxaliplatin before the sugery because of excessive tumor diameter.None of the rest received any adjuvant therapy.Results Postoperative histopathological examination showed multiple nodules in reddish gray and yellow color,with soft texture and partial incomplete capsule.Microscopically,there were large atypical cell components,some of which were spindle shaped,with disordered cell arrangement,some of which were associated with a large amount of necrotic tissue,and abundant light eosinophil cytoplasm.Tissue components can be found thick-wall blood vessels,smooth muscle-like cells,and adipose tissue.Immunohistochemistry showed 4 cases were positive of HMB-45,4 of Melan-A,7 of SAM.Seven cases were negative of CK,6 of S-100 75％ (6/8) and Ki67 (10％-70％).Two cases died of multiple metastases (lung,bone,liver),1 case survived with tumor recurrence,with a follow-up from 14 to 60 months (mean 29 months).Conclusions Primary malignant renal PEComa is rare in practice with relative large diameter.The diagnosis depends on pathological findings,and radical nephrectomy is the first choice of treatment.It is easy to recur and metastasize after the operation.

Objective To investigate the effect of calcitriol on osteogenic differentiation of mesenchymal stem cells (MSCs) induced by bone morphogenetic protein 9 (BMP9). Methods The experiment was divided into four groups: control group, calcitriol group, BMP9 group and BMP9+calcitriol group. Quantitative PNPP method was used to detect alkaline phosphatase (ALP) activity. RT-PCR and Western blotting method analyzed expression of osteocalcin（OCN）and osteopontin (OPN). Alizarin red staining assessed the formation of mineralized nodules. In addition, the changes of cell morphology and elastic modulus during osteogenic differentiation were studied by atomic force microscope. ResultsCompared with control group, calcitriol alone had no significant effect on the osteogenic differentiation of MSCs, but calcitriol could enhanced expression of osteogenic markers and formation of mineralized nodules induced by BMP9. However, neither calcitriol nor BMP9 could affect elastic modulus of cells. The combined treatment of BMP9 and calcitol could enhance phosphorylation of AKT and β-catenin which were both important for osteogenesis. The pretreated PI3K inhibitor could inhibit phosphorylation of AKT and β-catenin as well as ALP activity in BMP9+calcitriol group. In addition, calcitriol did not affect the BMP/Smad signaling pathway induced by BMP9. Conclusions Calcitriol synergies with BMP9 could promote MSCs osteogenesis by activating the PI3K/AKT signaling pathway. The study about effects and mechanisms of different regulatory factors on osteogenic differentiation of MSCs is of great significance for the treatment of osteoporosis and the development of bone tissue engineering.

As a natural plant source of artemisinin,a first-line drug against malaria,Artemisia annua directly affects the extraction process of artemisinin and the source of artemisinin. At present,traditional breeding methods combined with tissue culture are often used to breed high-yield artemisinin-containing new varieties of A. annua. However,the breeding method has the disadvantages of low efficiency and continuous selection. In this study,heavy ion beam irradiation technology was used to observe the specific germplasm resources of A. annua,and the morphological characteristics,agronomic traits and artemisinin content were used as indicators to observe the selection materials and materials. The cultivated new varieties were compared with trials and regional trials. In addition,the new variety of A. annua was identified by SRAP molecular marker technology. The results showed that the new variety of A. annua, " Kehao No.1",had an average yield of 235. 0 kg of dry leaf per mu,which was more than 20% higher than that of the control. Especially,the average artemisinin content was 2. 0%,which was 45% higher than that of the control,and the " Kehao No.1" has high anti-white powder disease,high-yield and high-quality new varieties. Therefore,mutagenic breeding of heavy ion beam irradiation can significantly improve the yield and artemisinin content of the " Kehao No. 1" and it has a good promotion value.
Artemisia annua/genetics* ; Artemisinins/analysis* ; Heavy Ions ; Mutagenesis ; Phenotype ; Plant Breeding ; Plants, Medicinal/genetics*