To meet the domestic clinical demand timely,the national health commission has released three batches of encourage generic drug catalogues,which plays a good guiding role in improving the supply level and accessibility of generic drugs.Based on literature investigation,the typical cases of novel pharmaceutical preparations were analyzed,and the pharmaceutical considerations were put forward in terms formulation,manufacturing process and quality control,aimed to provide scientific reference for research and development of such drugs.

To meet the domestic clinical demand timely,the national health commission has released three batches of encourage generic drug catalogues,which plays a good guiding role in improving the supply level and accessibility of generic drugs.Based on literature investigation,the typical cases of novel pharmaceutical preparations were analyzed,and the pharmaceutical considerations were put forward in terms formulation,manufacturing process and quality control,aimed to provide scientific reference for research and development of such drugs.

Aim To develop an UPLC-MS/MS method to determine the concentration of lorcaserin hydrochloride in beagle plasma, and study the pharmacokinetics of osmotic pump controlled-release tablets of lorcaserin hydrochloride. Methods A randomized crossover design was used, carbamazepine as the internal standard(IS), and plasma protein precipitation with acetonitrile. The chromatographic was Phenomenex Polar C18 column(100 mm×2. 1 mm, 3 μm), and acetonitrile - water(containing 10 mmol·L-1 ammonium acetate and 0.1% formic acid)(40:60, V/V)was mobile phase. Multiple reaction monitoring mode and electrospray positive ionization were used to detect lorcaserin hydrochloride. The MS/MS ion transitions were monitored at m/z 196.2→129.2 for lorcaserin hydrochloride and m/z 237→194.1 for carbamazepine, respectively. Results The linear range was 1 to 500 μg·L-1(r=0.999 2), the extraction recovery rate ranged from 87.70% to 89.70%, the precision RSD was 9.7%. The accuracy and matrix effect met the requirements, and the stability of lorcaserin hydrochloride was good in -20 ℃ refrigerator for 45 d, repeated freezing and thawing for three times, placed at room temperature for 24 h, and the disposed samples placed in automatsampler for 6 h were stable. The main pharmacokinetic parameters of the controlled-release tablet and immediate-release tablet were as follows:Tmax was(8.00±1.27)h and(1.00±0.13)h, Cmax was(70.56±3.73)μg·L-1 and(176.33±16.73)μg·L-1, and AUC0-t was(966.33±7.56)μg·h·L-1 and(973.05±69.09)μg·h·L-1, respectively. Conclusions The established UPLC-MS/MS method can be used to study the pharmacokinetics of lorcaserin hydrochloride in the plasma of beagle dogs, and osmotic pump controlled-release tablets has sustained release effect.

Objective: To verify the feasibility and accuracy of the transanal multipoint full-layer puncture biopsy (TMFP) technique in determining the residual status of cancer foci after neoadjuvant therapy (nCRT) in rectal cancer. Methods: Between April 2020 and November 2022, a total of 78 patients from the Beijing Chaoyang Hospital of Capital Medical University, the Beijing Friendship Hospital of Capital Medical University, the Qilu Hospital of Shandong University, the Zhongnan Hospital of Wuhan University with advanced rectal cancer received TMFP after nCRT participated in this prospective multicenter trial. There were 53 males and 25 females, aged (M(IQR)) 61 (13) years (range: 35 to 77 years). The tumor distance from the anal verge was 5 (3) cm (range: 2 to 10 cm). The waiting time between nCRT and TMFP was 73 (26) days (range: 33 to 330 days). 13-point transanal puncture was performed with a 16 G tissue biopsy needle with the residual lesion as the center. The specimens were submitted for independent examination and the complications of the puncture were recorded. The consistency of TMFP and radical operation specimen was compared. The consistency of TMPF with clinical remission rates for the diagnosis of complete pathological remission was compared by sensitivity, specificity, negative predictive value, positive predictive value and accuracy. Statistical analysis between groups was performed using the χ² analysis, and a paired χ² test was used to compare diagnostic validity. Results: Before TMFP, clinical complete response (cCR) was evaluated in 27 cases. Thirty-six cases received in vivo puncture, the number of punctures in each patient was 13 (8) (range: 4 to 20), 24 cases of tumor residue were found in the puncture specimens. The sensitivity to judgment (100% vs. 60%, χ²=17.500, P<0.01) and accuracy (88.5% vs. 74.4%, χ²=5.125, P=0.024) of TMFP for the pathologic complete response (pCR) were significantly higher than those of cCR. Implement TMFP based on cCR judgment, the accuracy increased from 74.4% to 92.6% (χ²=4.026, P=0.045). The accuracy of the in vivo puncture was 94.4%, which was 83.3% of the in vitro puncture (χ²=1.382, P=0.240). Overall, the accuracy of TMFP improved gradually with an increasing number of cases (χ²=7.112, P=0.029). Conclusion: TMFP is safe and feasible, which improves the sensitivity and accuracy of rectal cancer pCR determination after nCRT, provides a pathological basis for cCR determination, and contributes to the safe development of the watch and wait policy.

OBJECTIVE: To investigate the clinical features and outcome of neonatal acute respiratory distress syndrome (ARDS) in southwest Hubei, China. METHODS: According to the Montreux definition of neonatal ARDS, a retrospective clinical epidemiological investigation was performed on the medical data of neonates with ARDS who were admitted to Department of Neonatology/Pediatrics in 17 level 2 or level 3 hospitals in southwest Hubei from January to December, 2017. RESULTS: A total of 7 150 neonates were admitted to the 17 hospitals in southwest Hubei during 2017 and 66 (0.92%) were diagnosed with ARDS. Among the 66 neonates with ARDS, 23 (35%) had mild ARDS, 28 (42%) had moderate ARDS, and 15 (23%) had severe ARDS. The main primary diseases for neonatal ARDS were perinatal asphyxia in 23 neonates (35%), pneumonia in 18 neonates (27%), sepsis in 12 neonates (18%), and meconium aspiration syndrome in 10 neonates (15%). Among the 66 neonates with ARDS, 10 neonates (15%) were born to the mothers with an age of ≥35 years, 30 neonates (45%) suffered from intrauterine distress, 32 neonates (49%) had a 1-minute Apgar score of 0 to 7 points, 24 neonates (36%) had abnormal fetal heart monitoring results, and 21 neonates (32%) experienced meconium staining of amniotic fluid. Intraventricular hemorrhage was the most common comorbidity (12 neonates), followed by neonatal shock (9 neonates) and patent ductus arteriosus (8 neonates). All 66 neonates with ARDS were treated with mechanical ventilation in addition to the treatment for primary diseases. Among the 66 neonates with ARDS, 10 died, with a mortality rate of 15% (10/66), and 56 neonates were improved or cured, with a survival rate of 85% (56/66). CONCLUSIONS Neonatal ARDS in southwest Hubei is mostly mild or moderate. Perinatal asphyxia and infection may be the main causes of neonatal ARDS in this area. Intraventricular hemorrhage is the most common comorbidity. Neonates with ARDS tend to have a high survival rate after multimodality treatment.
China ; Female ; Humans ; Infant, Newborn ; Meconium Aspiration Syndrome ; Pregnancy ; Respiratory Distress Syndrome, Newborn ; Retrospective Studies

BACKGROUND: An artificial intelligence system of Faster Region-based Convolutional Neural Network (Faster R-CNN) is newly developed for the diagnosis of metastatic lymph node (LN) in rectal cancer patients. The primary objective of this study was to comprehensively verify its accuracy in clinical use. METHODS: Four hundred fourteen patients with rectal cancer discharged between January 2013 and March 2015 were collected from 6 clinical centers, and the magnetic resonance imaging data for pelvic metastatic LNs of each patient was identified by Faster R-CNN. Faster R-CNN based diagnoses were compared with radiologist based diagnoses and pathologist based diagnoses for methodological verification, using correlation analyses and consistency check. For clinical verification, the patients were retrospectively followed up by telephone for 36 months, with post-operative recurrence of rectal cancer as a clinical outcome; recurrence-free survivals of the patients were compared among different diagnostic groups, by methods of Kaplan-Meier and Cox hazards regression model. RESULTS: Significant correlations were observed between any 2 factors among the numbers of metastatic LNs separately diagnosed by radiologists, Faster R-CNN and pathologists, as evidenced by rradiologist-Faster R-CNN of 0.912, rPathologist-radiologist of 0.134, and rPathologist-Faster R-CNN of 0.448 respectively. The value of kappa coefficient in N staging between Faster R-CNN and pathologists was 0.573, and this value between radiologists and pathologists was 0.473. The 3 groups of Faster R-CNN, radiologists and pathologists showed no significant differences in the recurrence-free survival time for stage N0 and N1 patients, but significant differences were found for stage N2 patients. CONCLUSION: Faster R-CNN surpasses radiologists in the evaluation of pelvic metastatic LNs of rectal cancer, but is not on par with pathologists. TRIAL REGISTRATION www.chictr.org.cn (No. ChiCTR-DDD-17013842).
Adult ; Aged ; Aged, 80 and over ; Artificial Intelligence ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Neural Networks (Computer) ; Pathologists ; Radiologists ; Rectal Neoplasms ; diagnostic imaging ; mortality ; pathology

OBJECTIVE: To observe the clinical efficacy of " acupuncture" and oral estradiol and dydrogesterone tablets (femoston) on premature ovarian insufficiency of kidney deficiency. METHODS: A total of 50 patients with premature ovarian insufficiency of kidney deficiency were randomized into an observation group and a control group, 25 cases in each one.In the observation group, " acupuncture" was applied at Baihui (GV 20), Zhongwan (CV 12), Guanyuan (CV 4), Qihai (CV 6), Zhongji (CV 3), Yaoyangguan (GV 3), Yaoshu (GV 2), Mingmen (GV 4), etc. once every 2 days, 1 month as a course. In the control group, femoston was prescribed for oral administration, one tablet per time, once a day, 1 month as a course. Both of the two groups were given consecutive treatment for 3 courses. Before and after treatment, the clinical symptoms, menstrual improvement as well as the changes of estradiol (E), luteotrophic hormone (LH) and follicle-stimulating hormone (FSH) in serum were observed in the two groups. RESULTS: After treatment, the clinical symptoms and menstrual conditions were improved (<0.01), the levels of FSH and LH were significantly reduced (<0.01), and the levels of E were significantly increased in the two groups (<0.01). There were no significant difference in menstrual improvement rate and menstrual improvement time between the observation group and the control group (<0.05), the recurrence rate of menopause and clinical symptom score improvement in the observation group were superior to the control group (<0.05). In the observation group, the level of E in serum was lower and the levels of FSH and LH in serum were significantly lower than those in the control group (<0.05, <0.01). In the observation group, the rate of adverse reaction was 4.0% (1/25), which was lower than 36.0% (9/25) in the control group (<0.05). CONCLUSION " acupuncture" has better therapeutic effect for premature ovarian insufficiency of kidney deficiency. It is superior to femoston in improving clinical symptoms and recurrence rate of menopause as well as reducing the levels of FSH and LH.
Acupuncture Points ; Acupuncture Therapy ; Female ; Follicle Stimulating Hormone ; Humans ; Kidney Diseases ; therapy ; Primary Ovarian Insufficiency ; therapy

OBJECTIVE: To investigate the incidence of neonatal asphyxia and possible contributing factors for the development of severe asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture, China. METHODS: A total of 16 hospitals in Hubei Enshi Tujia and Miao Autonomous Prefecture were selected as research centers. A retrospective analysis was performed for the clinical data of 22 294 live births in these 16 hospitals from January to December, 2016 to investigate the incidence rate of neonatal asphyxia and possible contributing factors for the development of severe asphyxia. RESULTS: Of the 22 294 neonates born alive, 733 (3.29%) were diagnosed with neonatal asphyxia, among whom 627 had mild asphyxia and 106 had severe asphyxia. The neonates with low maternal education level, maternal anemia during pregnancy, chorioamnionitis, abnormal amniotic fluid, abnormal umbilical cord, placenta previa, placental abruption, Tujia Minority, preterm birth, and low birth weight had a higher incidence of severe asphyxia (P<0.05). CONCLUSIONS The incidence rate of neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture is higher. Low maternal education level, maternal anemia during pregnancy, chorioamnionitis, abnormal amniotic fluid, abnormal umbilical cord, placenta previa, placental abruption, Tujia Minority, preterm birth, and low birth weight may be related to the development of severe neonatal asphyxia.
Asphyxia Neonatorum ; epidemiology ; China ; Humans ; Incidence ; Infant, Newborn ; Retrospective Studies

OBJECTIVE: To evaluate the association between rotator cuff tear and the proximal migration of humeral head. METHODS: In this research, we retrospectively selected 30 patients with unilateral rotator cuff tear in Peking University People's Hospital from September 2015 to May 2016, who received magnetic resonance imaging (MRI) and X-ray of the painful shoulder before enrollment in this study, the duration between the two examinations was no longer than 1 week, and also there was no past history of surgery in the selected shoulders. There was no other exclusion criteria. Upward migration index (UMI) was the ratio between the distance of humeral head center to the lower surface of acromion, and the radius of humeral head circle, which could help to minimize the effect of anatomy difference and imaging magnification, compared with the traditional acromiohumeral distance (AHD). Then we introduced this index to stratify the selected 30 patients into 3 groups, and each group contained 10 patients, UMI of group 1 was >1 and ≤1.2, UMI of group 2 was >1.2 and ≤1.4, UMI of group 3 was >1.4. As the supraspinatus was most commonly affected by pathological change among the four rotator cuff tendons, we took it as the research object. Then we used the Spearman correlation analysis to evaluate the relationship between UMI and fatty degeneration, rotator cuff tear size and the thickness of ruptured supraspinatus tendon from X-ray and MRI. RESULTS: In the A-P view, the average UMI was 1.33 (1.02-1.51, SD: ±0.22). UMI and the tear size had a significant negative correlation (R=-0.584, P<0.01), and also there was a negative correlation between the fatty degeneration of the supraspinatus (R=-0.312, P=0.033). However, there was no correlation between UMI and the thickness of ruptured supraspinatus (R=0.127, P=0.071). CONCLUSION UMI is related with the fatty degeneration of supraspinatus and the tear size. The reduction of UMI is a predictable and reliable mark of rotator cuff tear and degeneration in clinic. Physicians can use physical examination and X-ray first when facing the patients with shoulder pain, which is convenient and helpful for evaluating rotator cuff tears.
Humans ; Humeral Head ; Magnetic Resonance Imaging ; Retrospective Studies ; Rotator Cuff ; Rotator Cuff Injuries ; Shoulder Joint

Tripterygium wilfordii 3-hydroxy-3-methylglutaryl coenzyme-A reductase (TwHMGR) is an important regulation site in terpenoids metabolic pathway in cytoplasm which is the first speed limit enzyme of MVA pathway. In order to investigate the effects of TwHMGR on the biosynthesis of triptolide and celastrol in Tripterygium wilfordii, the overexpression of TwHMGR (OE-HMGR) was studied in this paper. We cloned the full-length of TwHMGR to construct overexpression vector by Gateway technology then delivered the expression vector into Tripterygium wilfordii suspension cells by gene gun. qRT-PCR was used to detect the expression of TwHMGR:the expression of TwHMGR was increased to 1.75 folds over the control group (empty vector:pH7WG2D) in the overexpression group. The accumulation of triptolide and celastrol in the suspension cells of Tripterygium wilfordii was detected by UPLC, revealing that:the contents of triptolide and celastrol were increased to 163.93% and 190.04% of over the control group in the overexpression group. Based on these findings, the positive effect on the accumulation of active terpenoids, triptolide and celastrol in Tripterygium wilfordii was found and the results laid a foundation of the synthetic biology research on important active terpenoids in Tripterygium wilfordii.