OBJECTIVE:To establish a method for the dissolubility determination of Manidipine Hydrochloride tablet and eval-uate the quality consistency of generic and original preparation. METHODS:HPLC was performed on the column of Waters Sym-metry C18 column with mobile phase of potassium phosphate monobasic solution (potassium phosphate monobasic 6.8 g was well-mixed with water 1 000 ml,and pH was adjusted to 4.6 by potassium hydroxide solution)-acetonitrile (49∶51,V/V) at flow rate of 1.0 ml/min,detection wavelength was 228 nm,column temperature was 25℃,and the injection volume was 20μl. The dis-solution mediums were 0.1 mol/L hydrochloric acid solution,acetic acid-sodium acetate buffer solution(pH 4.0)and phosphate buf-fer solution [pH 6.8,adding into 0.5% sodium dodecyl sulfonate(SDS)],volume of dissolution medium was 900 ml and rotating rate was 50 r/min,and the dissolubility of Manidipine hydrochloride tablet generic and original preparation was investigated and the similarity of dissolution profile was evaluated by calculating similar factor (f2). RESULTS:The linear range of manidipine hydro-chloride was 0.625-20 μg/ml;RSDs of instrument precision and stability tests were lower than 2.0%;recoveries of 3 dissolution mediums were 92.86%-102.97%(RSD=1.9%,1.8% and 2.7%,n=9),respectively. The dissolubility of 3 batches of Manidipine hydrochloride tablet generic and original preparations was higher than 85% in 0.1 mol/L hydrochloric acid solution in 15 min;f2 was >50 in acetic acid-sodium acetate buffer solution (pH 4.0) and phosphate buffer solution (pH 6.8,adding into 0.5% SDS). CONCLUSIONS:The method is suitable for the dissolubility determination of Manidipine hydrochloride tablet;meanwhile,the dis-solution profile in vitro of Manidipine hydrochloride tablet generic and original preparations has similarities,so the quality consis-tency is good.

OBJECTIVE To establish a model for chlorpyrifos(CPF)whole-body dynamic inhalation exposure in SD rats and investigate the injury effects after acute exposure by CPF. METHODS By optimizing the aerosol parameters ,the animal acute dynamic inhalation exposure of CPF was established. Absorption sampling-gas phase detecting technology was used to monitor the concentration of CPF in the whole-body dynamic-inhalation exposure cabin by exploring the relationship between the concentration , particle size of CPF aerosol and the CPF inhalation time in the exposure cabin via a particle size detector. Using Bliss method,specific pathogen free SD male rats were allocated to the environment of CPF exposure at different lethal concentrations and time points. The symptoms and deaths of these SD male rats in different groups were recorded within the following 10 d. Based on the median lethal concentra?tion time(LCt50),the values of plasma cholinesterase(ChE)were checked at different time points after being exposed at different doses. RESULTS The mean concentrations of CPF aerosol at nine time points was 160.6 mg · m-3,the relative standard deviation value was 6.9%;the geometrical mean of aerosol particle size was 1.1 μm,and the geometric standard deviation was 1.8. The results met the technical requirements of Organization for Economic Cooperation and Development regarding acute inhalation exposure. Under these equipment conditions,the LCt50 of CPF acute inhalation of SD male rats was 1654.2 mg · m-3 · h,suggesting that plasma ChE inhibitory rate was higher with the increase in the exposing dose,and that there was a significant difference as compared with the controls(P<0.05). CONCLU?SION The model for whole-body dynamic-inhalation exposure of CPF is applicable to rats,which can serve as an experimental platform and technical support to inhalation vulnerability and the research on prevention and cure of organophosphate industrial products and nerve agents.

Objective To investigate the inhibitory effects of arsenic trioxide on salivary duct carcinoma cell colony and to explore a new approach to treat salivary duct carcinoma .Methods Human salivary duct carci-noma cancer cells were established .The effects of different concentrations (0.5、1、2、4μmol/L)and time(48,96 H) of arsenic trioxid on salivary duct carcinoma cell colony and the changes of the cell colony were observed with MTT assay and microscopic cell analysis .Results Human salivary duct carcinoma were significantly inhibited by Different concentrations of arsenic trioxide at different times points , and the relationship between the doses and time points are dependent ,cell atypia disappearing apoptosis appears apoptotic bodies .Conclusion Arsenic tri-oxide can significantly inhibit proliferation ,induce differentiation and promote apoptosis in the salivary duct carci-noma cells .

Objective To investigate the pathological changes and mechanism in the urethra by parturition-induced stress urinary incontinence.Methods Sprague Dawley female rats underwent vaginal balloon dilation for 4 hours immediately after delivery.One week later,the rats were anesthetized and both ovaries were excised.Then a rat model of stress urinary incontinence (SUI) was successfully established.One month after ovariectomy,conscious cystometry and Leak-Point Pressure (LPP) were measured by MP150.Histological examination and Western blotting were performed after functional assays.Results (1) 85％ of rats presented astress urinary incontinence in the model group.(2) The urethras in SUI rats had decreased muscles,and striated muscles showed fragmentized and disorganized.(3) Elastic fibers were long,well organized and tightly connected to the muscle bundles in sham group,while elastic fibers showed fragmentation and disorganization in the model group.(4) The protein expression of vascular endothelial growth factor (VEGF) and blood vessels were reduced in SUI rats as compared with the sham rats.Conclusions Muscle and elastic fibers in the urethra are disrupted in SUI rat.VEGF may play an important role in regulation of pathological changes in urethra.

Objective:To explore the factors related to functional recovery of the knee in patients with tibial plateau fracture complicated with intercondylar ridge fracture.Methods:Included in this retrospective study were 63 patients who had been treated at Emergency Center of Trauma, The Third Hospital of Hebei Medical University from January to June 2019 for tibial plateau fracture complicated with intercondylar ridge fracture. They were 43 males and 20 females, aged from 18 to 66 years (average, 43.9 years). According to our comprehensive classification of tibial plateau fractures, there were 27 simple ones (20 cases of type Ⅰ and 7 cases of type Ⅱ) and 36 complicated ones (16 cases of type Ⅲ, 17 cases of type Ⅳ, one of type Ⅴ and 2 cases of type Ⅵ). To screen out major influencing factors, a multiple linear regression model was used to analyze the 12 factors that might affect functional recovery of the knee by the Hospital for Special Surgery (HSS) scoring: age, gender, occupation, fracture type, way of medical payment, cause of injury, operation method, starting time for rehabilitation, postoperative brace installation, time from injury to operation, length of hospital stay, and presence or absence of a free intercondylar ridge fracture fragment.Results:The 63 patients were followed up for 6.0 to 7.1 months (average, 6.1 months). The HSS knee scores ranged from 45 to 100 points (average, 92.4 points). The HSS knee scores were significantly different between different fracture types ( P<0.05). The HSS scores were significantly higher for the patients without a free intercondylar ridge fracture fragment than for those with ( P<0.05). Multiple linear regression model analysis of the 5 variables with P<0.02 in the single factor analysis (age, fracture type, way of medical payment, hospital stay and presence or absence of a free intercondylar ridge fracture fragment) and HSS scores showed that only fracture type and presence or absence of a free intercondylar ridge fracture fragment had a significant impact on the knee function. Their regression equation was Y=125.591-7.790a-17.277b (Y indicates HSS score, a indicates fracture type and b indicates presence or absence of a free intercondylar ridge fracture fragment). Conclusions:The short-term prognosis for tibial plateau fractures of comprehensive types Ⅰ&Ⅱ (simple ones) may be better than that for tibial plateau fractures of comprehensive types Ⅲ, Ⅳ, Ⅴ&Ⅵ (complicated ones). For patients with a free intercondylar ridge fracture fragment on their lateral knee X-ray film, effective reduction and fixation is indicated but is not for those without.

With a deepened understanding of the pathophysiology and pathogenesis of thoracic malignancies, the treatment has been transited from traditional treatment on the basis of surgery, radiotherapy, and chemotherapy to individualized and precise targeted therapy and immunotherapy. As an antitumor immunotherapy, chimeric antigen receptor gene-modified T (CAR-T) cells have been approved by the FDA for the treatment of hematological malignancies in five CAR-T products. They have also achieved good therapeutic effects in solid tumors. However, significant challenges remain in the clinical application of CAR-T cell immunotherapy in thoracic malignancies. In this review, the latest research progress of CAR-T cell immunotherapy in the treatment of thoracic malignancies were summarized, including the basic characteristics of CAR-T cells, the popular target antigens, and the existing problems and challenges, to provide new ideas and strategies for clinical immunotherapy of thoracic malignancies.

Objective:To discuss the effect of simultaneous implantation of artificial cavernous body and urethral sphincter for severe erectile dysfunction and urinary incontinence after traumatic posterior urethral stricture.Methods:A retrospective analysis was performed on 3 patients with traumatic posterior urethral stricture admitted to the Southern Theater General Hospital from January 2021 to December 2022, aged 42, 32, 28 years old, all of whom suffered pelvic fracture and posterior urethral stricture after trauma. Patient 2 were missing left lower limb and patient 3 were missing right lower limb, all of whom had dysuria. Preoperative cystourethrography indicated posterior urethral stricture with a length of 2, 2, 3 cm, respectively. No erectile response and severe erectile dysfunction were reported in penile nocturnal erectile function tests. Posterior urethral stricture was cured by end-to-end anastomosis surgery. After urethral stricture was cured, the nighttime erectile function test indicated severe erectile dysfunction and diagnosed erectile dysfunction and urinary incontinence. After 3 months of continuous administration of sildenafil and/or tadalafil, the erectile dysfunction did not improve, and the score of the international erectile function test was 1, 2, 2 points. Severe erectile dysfunction. The urine could not be controlled, the number of urine pads per day was 6, 6, 8, respectively, and pelvic floor rehabilitation training was adopted for urinary incontinence. 6 months later, urodynamic examination indicated severe stress incontinence, and the urine pad test was 30g, 32g, and 82g per hour. Patients were fully informed of the surgical risks before surgery. Simultaneous implantation of artificial penile cavernous body and artificial urethral sphincter were performed after full preoperative preparation: General anesthesia, supine frog position with transverse incision in upper scrotum, the urethra was separated and the artificial urethral sphincter cuff was easily inserted into the upper scrotum. Then the left and right sides of the penis cavernous sinus were dilated and the length of the cavernous body was measured. Suitable artificial penis cavernous body was implanted, water sacs were placed in the posterior pubic space and the anterior vesical space, and the tubes were connected. The erectile switch was placed under the scrotum, and the incision was closed after repeated testing of urine control and normal erectile function.Results:Three cases were successfully completed. The simultaneous implantation time of artificial cavernous body and artificial urethral sphincter was 270, 260, 240 min, respectively. The catheter was removed 1 week after surgery, and the erection switch was trained 2 weeks after surgery, and full erection was achieved after 1 week. The urine control switch was activated 6 weeks after surgery, and urine control was normal without urine pad. Following up for 12 to 18 months, 2 cases had normal erections and urinary control, 1 case had urethral corrosion 2 months after surgery, the original artificial sphincter was removed completely and a new artificial urethral sphincter was implanted in the same period, the operation was successful, and the follow-up was 1 year, urine control and erectile function returned to normal.Conclusions:For the severe erectile dysfunction and severe urinary incontinence after traumatic posterior urethral stricture, simultaneous implantation of artificial penile cavernous body and artificial urethral sphincter could be alternative choice.

Objective:To explore the epidemiological characteristics of inpatients with tibial pilon fracture in The Third Hospital of Hebei Medical University from 2016 to 2019.Methods:The data of all the patients who had been hospitalized for pilon fracture from January 2016 to December 2019 in The Third Hospital of Hebei Medical University were collected using the medical image computer archiving and transmission system and the medical record query system. The patients' age, gender, occupation, residence, season, cause of injury, Rüedi-Allg?wer classification, and AO classification were analyzed.Results:A total of 234 inpatients with tibial pilon fracture were collected, including 179 males and 55 females, with a ratio of male to female of 3.3∶ 1. The prevalence age ranged from 41 to 50 years in male patients (31.3%, 56/179) and from 51 to 60 years in female patients (25.5%, 14/55). In the 234 patients, farmers (101 cases, 43.2%), rural area (166 cases, 70.9%) and spring season (77 cases, 32.9%) accounted for a higher proportion. The proportions of high-altitude falling (41.0%, 96/234) and high-energy injury (61.5%, 144/234) were the highest. Of the 234 patients by the Rüedi-Allg?wer classification, 23 (9.8%) had type Ⅰ fracture, 90 (38.5%) type Ⅱ fracture, and 121 (51.7%) type Ⅲ fracture, with type Ⅲ fracture prevalent in males (58.1%, 104/179) and type Ⅱ fracture prevalent in females (16.4%, 9/55). Of the 234 patients by the AO classification, 131 (56.0%) had type 43B fracture and 103 (44.0%) type 43C fracture, with a higher proportion of type 43B fractures in women (67.3%, 37/55) than in men (52.5%, 94/179). In type 43B fractures, type 43B3 (43.5%, 57/131) and type 43B3.3 (75.4%, 43/57) were the most common; in type 43C fractures, type 43C3 (74.8%, 77/103) and type 43C3.3 (51.9%, 40/77) were the most common.Conclusions:In the recent 4 years in The Third Hospital of Hebei Medical University, pilon fractures increased year by year and occurred more frequently in spring. They were more common in farmers and in the rural areas. They prevailed in the patients aged from 41 to 50 years. The Rüedi-Allg?wer type Ⅲ fractures and the AO type 43B fractures were the most common.

Objective To investigate the impact of various distribution of bone cement on the early clinical outcomes in osteoporotic vertebral compression fracture (OVCF) patients treated with percutaneous kyphoplasty (PKP).Methods A total of 312 patients (54 males and 258 females,mean age 69.37 years) who diagnosed as OVCF and received PKP treatment from January 2015 to July 2017 were enrolled in the present study.All subjects were divided into two groups according to different distribution of bone cement:the shaped "O" distribution (group O,113 cases),in which bone cement in the vertebral body presented whole crumb,no separation or loss of bone cement,and the shaped "H" distribution (group H,199 cases),in which bone cement in the vertebral body presented two briquettes,connected with or without a small amount of bone cement.Demographic data,surgical details,radiographic data,and clinical outcomes (at preoperatively,two-days and one-year follow-up) were compared between the two groups.Results There was no significant difference in bone mineral density (BMD),operation duration,blood loss,and occurrence of leakage of bone cement between two groups.In comparison with group O,group H was accompanied with higher volume of injected bone cement and higher proportion of bilateral approach (P＜0.05).Both groups achieved significant improvement of VAS scores after surgery,while the group H had a dramatical reduction of VAS scores at one-year follow-up compared with two-days follow-up (P＜0.05).In addition,group H had a better restoration of VAS scores at one-year follow-up than group O (P＜0.05),though no significant difference was observed at preoperative and two-days follow-up.Both groups achieved significant improvement of radiographic data after surgery (P＜0.05) with similar effects of correction.Conclusion Either shaped "H" or shaped"O" distribution of bone cement can obtain satisfied early clinical effects of PKP for the treatment of OVCF.Compared with shaped "O" distribution,shaped "H" distribution can achieve better pain relief at early follow-up.

Objective:To explore the influence of bromodomain-containing protein 4 (BRD4) inhibitor on wild-type Kras differentiated thyroid carcinoma (DTC) and its mechanism.Methods:The DTC cell line Kras WT TPC-1 was selected and the mutant Kras G12D TPC-1 cells were constructed. CCK-8 assay was used to detect the effect of BRD4 inhibitor JQ-1 on the proliferation activity of Kras WT TPC-1 cells. Kras WT TPC-1 cells were treated with 0.2 μmol/L JQ-1 (JQ-1 group), and a negative control group (NC group) was set. Transwell invasion assay and flow cytometry were used to detect the effect of JQ-1 on the invasion and apoptosis of Kras WT TPC-1 cells. The effect of JQ-1 on the expressions of BRD4, miR-106b-5p and P21, and the effect of P21 inhibitor UC2288 on the expressions of P21 and BRD4 were detected. Kras WT TPC-1 cells were divided into JQ-1+ NC-OE group, JQ-1+ p21-OE group (overexpression of p21) and JQ-1+ p21-OE+ miR-106b-5p mimic group (overexpression of p21 and miR-106b-5 at the same time), and the proliferation, invasion and apoptosis of cells in each group were detected. TPC-1 cells were divided into Kras WT group, Kras WT+ JQ-1 group, Kras G12D group and Kras G12D+ JQ-1 group, and the cell proliferation, invasion and apoptosis of each group were detected. Results:JQ-1 inhibited the proliferation activity of Kras WT TPC-1 cells in a dose-dependent and time-dependent manner. In the NC group and JQ-1 group, the numbers of cell invasion were 124.67±9.61 and 82.67±8.02, and the apoptosis rates were (5.91±0.34)% and (10.33±1.10)%, respectively, with statistically significant differences ( t=5.812, P=0.004; t=6.653, P=0.003). JQ-1 significantly inhibited the expressions of BRD4 and miR-106b-5p, and promoted the expression of P21 in Kras WT TPC-1 cells. UC2288 significantly inhibited P21 expression, but had no significant effect on BRD4 expression. In the JQ-1+ NC-OE group, JQ-1+ p21-OE group and JQ-1+ p21-OE+ miR-106b-5p mimic group, the proliferation activities at 24 h of Kras WT TPC-1 cells was 0.46±0.03, 0.35±0.04 and 0.44±0.03 ( F=8.720, P=0.017), and the proliferation activity of JQ-1+ p21-OE group was significantly lower than that of the JQ-1+ NC-OE group ( P<0.05). The numbers of cell invasion in the three groups were 83.00±9.17, 56.67±6.03 and 79.67±10.07 ( F=8.347, P=0.018), and the number of cell invasion in the JQ-1+ p21-OE group was significantly lower than that in the JQ-1+ NC-OE group ( P=0.009). The apoptosis rates of the three groups were (10.00±0.49)%, (15.39±1.14)% and (10.32±0.80)% ( F=37.764, P<0.001), and the apoptosis rate of the JQ-1+ p21-OE group was significantly higher than that in the JQ-1+ NC-OE group ( P<0.001). There were no significant differences in cell proliferation activity, invasion number and apoptosis rate between JQ-1+ p21-OE+ miR-106b-5p mimic group and JQ-1+ NC-OE group (all P>0.05). In Kras WT group, Kras WT+ JQ-1 group, Kras G12D group and Kras G12D+ JQ-1 group, the cell proliferation activities at 24 h were 0.50±0.05, 0.39±0.04, 0.68±0.08 and 0.64±0.05 ( F=17.776, P<0.001). Compared with the Kras WT group, cell proliferation activity in the Kras WT+ JQ-1 group was significantly decreased, while that in the Kras G12D group was significantly increased (both P<0.05). The numbers of cell invasion in the four groups were 129.33±11.50, 86.00±9.54, 161.67±13.01 and 146.33±13.20 ( F=22.598, P<0.001). Compared with the Kras WT group, the number of cell invasion in the Kras WT+ JQ-1 group was significantly decreased ( P=0.002), and that in the Kras G12D group was significantly increased ( P=0.010). The apoptosis rates in the four groups were (6.17±0.50)%, (10.42±0.73)%, (3.43±0.47)% and (3.41±0.32)% ( F=119.170, P<0.001). Compared with the Kras WT group, the apoptosis rate in the Kras WT+ JQ-1 group was significantly increased ( P<0.001), and that in the Kras G12D group was significantly decreased ( P<0.001). There were no significant differences in cell proliferation activity, invasion number and apoptosis rate between Kras G12D+ JQ-1 group and Kras G12D group (all P>0.05). Conclusion:BRD4 inhibitor can specifically inhibit the development of wild-type Kras DTC via regulating the molecular axis of BRD4/miR-106b-5p/P21, but has no significant effect on the proliferation, invasion and apoptosis of mutant Kras DTC tumor cells.