Central nervous system（CNS） disorders are characterized by complex pathological mechanisms and the presence of the blood-brain barrier（BBB）， which significantly limits the effectiveness of drug therapy. Traditional drug delivery modes include oral administration， intravenous injection and transdermal delivery， which have certain advantages， but it is difficult for the drugs to effectively cross the BBB. Therefore， it is crucial to find drug delivery modes that can efficiently traverse the BBB. Nasal drug delivery， as a non-invasive method， can realize the targeted delivery of drugs to the CNS via three pathways， including olfactory neurons， trigeminal neurons and blood circulation， and shows a broad application prospect in the treatment of CNS diseases. Numerous studies have further confirmed that nasal drug delivery combined with novel drug delivery systems such as lipid nanocarriers， nanoparticles， nanoemulsions and composite in situ gels can effectively load the active components of traditional Chinese medicine（TCM）， and significantly increase drug concentration in the brain， which provides new strategies for the treatment of CNS diseases. In this paper， the current status of drug delivery for CNS diseases was systematically sorted out， the characteristics of nasal drug delivery were discussed in depth， and the research progress of passive targeting， active targeting， and "guiding the meridian" drug delivery strategies for the nasal-to-brain transport of TCM active components was summarized and analyzed， which was aimed to provide references and insights for the development of drugs for CNS diseases and the application of TCM in nasal-to-brain delivery.

Central nervous system（CNS） disorders are characterized by complex pathological mechanisms and the presence of the blood-brain barrier（BBB）， which significantly limits the effectiveness of drug therapy. Traditional drug delivery modes include oral administration， intravenous injection and transdermal delivery， which have certain advantages， but it is difficult for the drugs to effectively cross the BBB. Therefore， it is crucial to find drug delivery modes that can efficiently traverse the BBB. Nasal drug delivery， as a non-invasive method， can realize the targeted delivery of drugs to the CNS via three pathways， including olfactory neurons， trigeminal neurons and blood circulation， and shows a broad application prospect in the treatment of CNS diseases. Numerous studies have further confirmed that nasal drug delivery combined with novel drug delivery systems such as lipid nanocarriers， nanoparticles， nanoemulsions and composite in situ gels can effectively load the active components of traditional Chinese medicine（TCM）， and significantly increase drug concentration in the brain， which provides new strategies for the treatment of CNS diseases. In this paper， the current status of drug delivery for CNS diseases was systematically sorted out， the characteristics of nasal drug delivery were discussed in depth， and the research progress of passive targeting， active targeting， and "guiding the meridian" drug delivery strategies for the nasal-to-brain transport of TCM active components was summarized and analyzed， which was aimed to provide references and insights for the development of drugs for CNS diseases and the application of TCM in nasal-to-brain delivery.

OBJECTIVE：To investigate the activity of lycorine to the in vivo apoptosis of tumor cells in H 22-bearing mice and its mechanism. METHODS ：Kunming mice were inoculated subcutaneously with ascites of H 22 hepatoma mice in the armpit of forelimb to establish solid tumor model. After modeling ，mice were randomly divided into negative control group ，positive control group（hydroxycamptothecin 6 mg/kg），lycorine low-dose ，medium-dose and high-dose groups （10，20，40 mg/kg），with 10 mice in each group. Negative control group was given constant volume of normal saline intragastrically ，and administration groups were given relevant medicine intragastrically ，once a day ，for consecutive 7 days. After last medication ，the weight of tumor was detected and anti-tumor rate was calculated. Ascites tumor model of mice was established by intraperitoneal injection of H 22 hepatoma mice ascites ，and then were grouped with same method and given relevant medicine as above. After last medication ， survival time of mice was recorded and the life prolongation rate was calculated. The early apoptotic rate of tumor cells in mice was detected by flow cytometry. On the basis of normal control group （normal mice without tumor ），the mitochondrial membrane permeability of tumor cells in each group was investigated by Calcein AM staining. The changes of mitochondrial potential were investigated by Rhodamine 123 staining. Colorimetry and Western blot assay were adopted to detect the Caspase-3 activity and expression of apoptosis-related protein （Bcl-2，Bax，Cyt-C and Caspase- 9）. RESULTS ：Compared with negative control UN- group，the tumor weight of positive control group and lycorine PYSCT-2017208） groups were decreased significantly ，while the survival time was significantly prolonged ，and the early apoptotic rate of tumor cells was significantly increased （P＜0.05 or P＜0.01）；the anti-tumor rates were 39.41％ ， 23.36％ ， 36.50％ ， 56.93％，and life prolonga tion rates were 49.23％，29.09％， E-mail：ym913@yahoo.com.cn 50.19％，69.08％. Compared with normal control group ，the mitochondrial membrane permeability ，Caspase-3 protein activity and protein expression of Cyt-C and Caspase- 9 were significantly increased，while the mitochondrial membrane potential and Bcl- 2/Bax ratio were decreased significantly （P＜0.05 or P＜0.01）. Compared with negative control group ，mitochondrial membrane permeability and Bcl- 2/Bax ratio were decreased significantly in administration groups ，while mitochondrial permeability ，Caspase-3 protein activity and protein expression of Cyt-C and Caspase- 9 were significantly increased （P＜0.05 or P＜0.01）. CONCLUSIONS ：Lycorine can induce the apoptosis of tumor cells in H22-bearing mice ，the effects of which may be associated with opening mitochondrial membrane permeability transition pore to increase mitochondrial permeability ， decreasing mitochondrial membrane potential and up-regulating the expression of apoptosis-related proteins.

Objective:To investigate the curative efficacy of radical prostatectomy (RP) for T 4 stage prostate cancer invading bladder neck. Methods:The clinical data of 22 patients with T 4 stage prostate cancer invading bladder neck treated with RP from April 2013 to March 2021 were analyzed retrospectively. The mean age of the patients was (64.09±6.33) years, and the preoperative blood PSA was 57.70(39.40, 68.56) ng/ml. Preoperative MRI or PSMA-PET examination revealed bladder neck invasion, including 16 cases (72.73%) of urinary retention. Clinical stage of T 4N 0M 0 accounted for 40.91% (9/22), T 4N 1M 0 accounted for 45.45% (10/22), and T 4N 1M 1 accounted for 13.64% (3/22). Preoperative patients were not treated with neoadjuvant endocrine or chemotherapy. Laparoscopic or robotic assisted laparoscopic radical prostatectomy and pelvic lymph node dissection were performed. Results:The 22 operations were successfully completed without conversion. The operation time was(184.27±34.82) min, the amount of intraoperative bleeding was (210.91±83.03) ml, the retention time of drainage tube was (4.73 ± 1.03) days, the recovery of gastrointestinal function took 3 (2, 3) days, and the postoperative hospital stay was (6.68 ± 1.39) days. Postoperative pathology showed that the Gleason score of 7 points accounted for 4.54% (1/22), 8 points accounted for 13.64% (3/22), and 9 points accounted for 81.82% (18/22). The positive rate of margin was 81.82% (18/22). Pathological stage of T 4N 0M 0 accounted for 22.73% (5/22), T 4N 1M 0 accounted for 63.64% (14/22), and T 4N 1M 1 accounted for 13.64% (3/22), of which extracapsular or seminal vesicle invasion accounted for 90.91% (20/22). The incidence of postoperative complications above grade 3 was 9.09% (2/22), and the rate of urinary control recovery after 3 months of surgery was 90.91% (20/22). 16 patients with preoperative urinary retention were able to urinate normally after operation. All patients were treated with adjuvant androgen deprivation therapy (ADT) with or without antiandrogens, and 13 cases (59.09%) were treated with adjuvant radiotherapy. The postoperative PSA value before adjuvant treatment was 2.53 (0.51, 5.44) ng/ml. The median survival time was not reached. Two patients died of prostate cancer at 71 and 84 months and one patient died of heart disease at 28 months. Conclusions:RP surgery could effectively relieve the condition of urinary retention with low incidence of operative complications. Although the positive rate of surgical margin is high, RP could be used as one of the treatment options for T 4 stage prostate cancer invading bladder neck, while the long-term effect is still needed to be further analyzed.

Objective:To explore the clinical application of robot-assisted laparoscopic single-position nephroureterectomy and bladder sleeve resection for upper urinary tract urothelial carcinoma (UTUC).Methods:The clinicopathological data of 15 UTUC patients admitted to Union Hospital of Tongji Medical College of Huazhong University of Science and Technology from October 2018 to May 2020 were retrospectively analyzed. There were 8 males and 7 females, with a median age of 58.6 (ranging 52.6-69.6) years, including 8 cases of renal pelvic cancer, 2 cases of upper ureteral cancer, 5 cases of middle and lower ureteral cancer.The tumor located on the left side in 5 cases and right side in 10 cases. All 15 patients underwent robot-assisted one-step transperitoneal nephroureterectomy and bladder sleeve resection by the same surgeon. The patients were placed in a 70° healthy side lying position with a 10° head lower and foot high position. After routinely dissecting the kidneys and controlling the renal hilum, we continued to dissect the ureter down to the orifice of the bladder. The lymph node dissection was performed when dissecting the kidney and ureter. Then the ureter was resected like a sleeve and the bladder was sutured. Observation indicators, such as operation time, blood loss, postoperative drainage tube and urinary catheter placement days, were recorded.Results:All 15 patients were successfully completed the operation in the same position and the same robot berth without conversion. The median operation time was 103 (ranging 82-185) min, and the intraoperative median blood loss was 60 (ranging 30-120) ml. The postoperative median drainage catheter placement time was 3 (ranging 2-5) d, the postoperative median hospital stay was 5 (ranging 4-7) d, and the postoperative urinary catheters were placed for 14 days. Postoperative pathological examinations of 15 patients showed UTUC without positive margins. The median follow-up time was 15 (ranging 10-30) months. All 15 patients survived. One patient was found a recurrence in the bladder after cystoscopy. There was no tumor progression after bladder tumor resection and bladder perfusion chemotherapy, and no tumor recurrence or metastasis was seen in the remaining 14 cases.Conclusions:Robot-assisted single-position transperitoneal nephroureterectomy for UTUC does not need to change patient position and robot berth, which effectively shortens the operation time, and achieves good tumor control effect. The short-term follow-up results were satisfactory.

TORCH, which is considered as a series of pathogens, including the Toxoplasma gondii, Rubella virus, Cytomegalovirus or Herpes simplex virus, often infects the pregnant women to induce the the fetus or newborn infection by transplacental infection or exposure to contaminated genital tract secretions at delivery. Increasing evidence have been confirmed that the infection of TORCH may cause the miscarriage, premature birth, malformed fetus, stillbirth, intrauterine growth retardation, neonatal multiple organ dysfunction and other adverse pregnancy outcomes. For most TORCH-infections cases may lacking the effective treatments during pregnancy, and it is important to achieve the effacing monitoring of TORCH infections before and during pregnancy. The laboratory testing of TORCH has the great significance. However, the consensus opinions still need to improve the the standardization of TORCH testing process and the correct interpretation. Based on the characteristics of the TORCH detection method, this article gives a consensus opinion on the standardized detection and clinical application of TORCH from the laboratory perspective according to the characteristics and types of infection of different pathogens.

Objective To investigate the role of transient receptor potential melastatin 7 (TR PM7) in the protective role of sevoflurane preconditioning against hippocampal neuron injury caused by oxygen glucose deprivation (OGD).Methods Hippocampal neurons were harvested from postnatal day 1 SD rats,and randomly divided into 5 groups:control group (group C),sevoflurane group (group Sev),oxygen-glucose deprivation group (group OGD),sevoflurane+ OGD group (group SD) and sevoflurane+OGD+bradykinin group (group B).To build up the model of OGD,the neurons were cultured in a deoxygenated glucose-free medium and exposed to 95％ N2 and 5％％ CO2 in an anaerobic chamber equilibrated at 37℃ for 1.5 h,followed by replacement with glucose containing medium and return to a standard incubator for additional 24 h.The neurons in group C received no treatment.Group OGD was preconditioned with 2 ％ sevoflurane for 1 h.The neurons in group OGD were subjected to OGD.Group SD was preconditioned with 2％ sevoflurane for 1 h,followed by OGD at 24 h after the sevoflurane exposure.The neurons in group B was incubated in a medium supplemented with 200 μmol/L bradykinin (the selective agonist of TRPM7),followed sequen tially by the preconditioning of 2％ sevoflurane for 1 h and then OGD challenge.Twenty-four hours after re-oxygenation,The relative neuronal cell viability was determined by MTT assay,the neuronal apoptotic rate was analyzed by TUNEL assay,the protein expression of TRPM7 was detected by Western blot,the mRNA level of TRPM7 was estimated by real-time PCR,the neuronal release of IL-1β and TNF-α in the serum was measured by ELISA.Results Compared with group C,the mR NA and protein levels of TRPM7,the neuronal apoptotic rate,the mRNA and supernatant protein levels of IL-1β and TNFα were significantly up-regulated in group OGD (P＜0.05),whereas the cell viability was decreased (P＜0.05).Compared with group OGD,the mRNA and protein levels of TRPM7,the neuronal apoptotic rate,the mRNA and supernatant protein levels of IL1β and TNF-α were significantly down-regulated in group SD (P＜0.05),whereas the cell viability was increased (P＜0.05).Compared with group SD,the mRNA and protein levels of TRPM7,the neuronal apoptotic rate,the mRNA and supernatant protein levels of IL-1β and TNF-α were significantly up-regula ted in group B (P＜0.05),whereas the cell viability was decreased (P＜0.05).Conclusion Sevoflurane attenuates apoptosis and inflammatory responses induced by OGD via reduction of the overex pression of TRPM7 in the hippocampal neurons.

Objective To explore the value of prenatal MRI in the diagnosis of fetal simple expansion of lateral ventricle(ventriculomegaly), and follow up the nervous system development status after birth. Methods Simple expansion of the lateral ventricle fetus by prenatal MRI examination were collected in Huzhou Maternal and Child Care Hospital from May 2013 to June 2015, 126 cases of live births in expansion group, 50 normal cases were recruited in the same period as the control group. In expansion group, fetal subgroup analysis was done:(1) unilateral or bilateral lateral ventricle expasion:one group was 98 cases was lateral ventricle expansion (77.8%, 98/126), expansion of bilateral ventricle group was 28 cases (22.2%, 28/126). (2) Prenatal MRI in the diagnosis of the lateral ventricle of expansion: expansion of the lateral ventricle width was greater than 10.0 mm, if both sides were expanding, the expand width was the heavier one side, divided into 3 subgroups: ①Expansion in group A (lateral ventricle width 10.0-12.0 mm) were 88 cases (69.8%, 88/126).②Expansion in group B (lateral ventricle width 12.1-15.0 mm) were 29 cases (23.0%, 29/126). ③Expansion of group C (lateral ventricle width> 15.0 mm) were 9 cases (7.12%, 9/126). All 176 cases were followed up after birth at the 3rd, 6th, 12th, 18th month (corrected age was used for premature babies), and Gesell developmental schedules (GDS) were used to evaluate the neurobehavioral development. Results (1) The MRI results after birth:21 cases were followed up by MRI after birth. In group A, 11 cases had MRI and 9 were normal (the ventricular width<10.0 mm after birth) , the other 2 cases were stable (the ventricular width measured first time after birth was ≥10.0 mm, but the difference was within 2.0 mm from the MRI before birth). In group B, 4 cases had MRI, 1 was normal, 1 was stable, and 2 cases were getting better (the ventricular width measured first time after birth was ≥10.0 mm, but the width decreased more than 2.0 mm from the MRI before birth). In group C, 6 cases had MRI. 3 cases were getting better and 3 cases were stable. (2) Overall GDS results:expansion group after the birth of the 3rd, 6th, 12th, 18th month GDS evaluation results compared with control group, respectively, the differences were not statistically significant (all P>0.05). (3) The GDS results among the subgroups:in each evaluation after birth, there were no statistically significant differences between group A and the control group (all P>0.05). The GDS results of group B at the 3rd and 6th month were lower than those of the control group (P<0.05); while there were no statistically significant differences between the 2 goups at the 12th and 18th month (P>0.05). And for group C, statistically significant differences were found compared to the control group at each follow-up time (all P<0.05). (4) GDS results at different times after birth in the expansion group:there was no statistically significant difference between the results at the 3rd and 6th month (P>0.05). But when the result at the 3rd month was compared to the results of the 12th or 18th month, the differences were statistically significant (P<0.05). GDS result of 6th months after birth compared with 12th and 18th months, respectively, there were no statistically significant differences (P>0.05). There was no statistically significant difference between the results at the 12th and 18th month (P>0.05). (5) The GDS results in unilateral and bilateral ventricle expansion:at the 18th month, among the 98 unilateral cases, 86 (87.8%, 86/98) had normal GDS results(>85 scores);8 (8.2%, 8/98) had borderline results (75-85 scores);4 (4.1%, 4/98) had delayed results (<75 scores). Among the 28 bilateral cases, 23 (82.1%, 23/28) had normal GDS results;3 (10.7%, 3/28) had borderline results; 2 (7.1%, 2/28) had delayed results. There was no statistically significant difference (P>0.05). Conclusions Among the simple expansion of lateral ventricle, those whose ventricular width are≤12.0 mm may not need clinical treatment. If the width is between 12.1 to 15.0 mm, closely follow-up and targeted rehabilitation training after birth are recommended. When the width is more than 15.0 mm, the risk of the central nervous system function delay is significantly increased, and early intervention might improve the prognosis.

OBJECTIVE:To study the effects of Ⅰ,Ⅱ crystal and amorphous forms of lercanidipine hydrochloride on the preparation,and provide theoretical basis for its development and consistency evaluation. METHODS:X-ray powder diffraction (XRD),infrared spectrophotometry(IR)and differential scanning calorimetry(DSC)were adopted to identify the 3 crystal forms of lercanidipine hydrochloride. XRD was used to compare the effects of crushing,grinding,pressing technology,wetting granula-tion,adhesive solvents(water,ethanol)and drying temperature(50,60,70℃)on stability of 3 crystal forms of lercanidipine hy-drochloride;the dissolution in vitro in water,hydrochloride,pH 4.5 acetate buffer,pH 6.8 phosphate buffer were compared among 3 crystal forms of Lercanidipine hydrochloride tablet. RESULTS:XRD showed both Ⅰ,Ⅱ crystal forms had characteristic diffrac-tion peak with inconsistent 2 θ values,amorphous had no characteristic diffraction peak;IR showed 3 crystal forms had different absorption intensity and absorption peak number;DSC showed Ⅰ,Ⅱ crystal forms had obvious endothermic peak in 194.6 ℃, 207.3 ℃,respectively,amorphous had obvious endothermic peak in 86.1 ℃ and exothermic peak in 299.8 ℃. Crushing,grinding, pressing and drying temperature had no effects on the stability of 3 crystal forms;water had no effect on the stability of crystal in wetting granulation,ethanol may cause the change of Ⅰcrystal form. Except for the comparison between Ⅰ,Ⅱ crystal forms in hydrochloride (f2=68),the dissolution f2 of 3 crystal forms in 4 kinds of medium were lower than 50. CONCLUSIONS:XRD, IR,DSC methods can identify the 3 crystal forms of Lercanidipine hydrochloride tablet. When preparing lercanidipine hydrochlo-ride by Ⅰcrystal form,wetting granulation should avoid using ethanol as a adhesive solvent,instead of water. Different crystal forms can affect the dissolution in vitro of prepared Lercanidipine hydrochloride tablet.

Objective To analyze the effect of endophytic renal tumor growth characteristic on the short-term outcomes of robot-assisted laparoscopic partial nephrectomy (RALPN).Methods From March 2015 to October 2016,23 RALPN cases of endophytic renal masses and 68 RALPN cases of intermediate and exophytic renal tumors were retrospectively analyzed.There were no significant differences in age,gender,tumor side,history of abdominal surgery,benign and malignant cases of the two groups of patients (P ＞ 0.05).Patients with a completely endophytic mass had smaller tumors [(2.4 ± 0.5) cm vs.(3.9 ± 1.1) cm],and higher overall R.E.N.A.L.score (P ＜ 0.05).The differences of perioperative period and postoperative follow-up results were analyzed.Results All 91 RALPN cases were successfully done without conversion to open or radical nephrectomy.There were no significant differences in intraoperative blood loss,postoperative Hb decrease,intraoperative and postoperative blood transfusion rate,hospital days,positive tumor margins,and the incidence of Clavien-Dindo grade Ⅲ or above in the two groups (P ＞ 0.05).The endophytic group showed longer operative time [(95.6 ± 19.4) min vs.(75.3 ± 16.9) min],and longer renal warm ischemia [(25.2 ±5.4)min vs.(17.6 ±7.0)min].In the postoperative follow-up of 3 months to 22 months,all patients got disease-free survival.Conclusions RALPN for completely intraparenchymal renal tumors can be safely and effectively performed in experienced institutes.However,the long-term period of follow-up is still missing.