Toripalimab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma: RENOTORCH, a randomized, open-label, phase III study.

BACKGROUND: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. PATIENTS AND METHODS: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group. CONCLUSION: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975.

[The related factors of postoperative recurrence in trigeminalneuralgia patients undergoing fully neuroendoscopic microvascular decompression].

Objective: To evaluate the related factors of postoperative recurrence intrigeminal neuralgia (TN) patients treated with fully neuroendoscopic microvascular decompression (MVD). Methods: The clinical baseline data and preoperative MRI imaging data of 112 patients with TN treated by neuroendoscopic MVD from December 2008 to December 2020 in the Department of Neurosurgery, Beijing Shijitan Hospital Affiliated to Capital Medical University were retrospectively analyzed, including: area ratio of cerebellopontine area (CPA)(healthy side/affected side), trigeminal nerve(TGN)length ratio(healthy side/affected side), TGN angle ratio(healthy side/affected side), and criminal vessel type. Multivariate Cox proportional hazards model was used to analyze the factors affecting postoperative recurrence. Results: Among the 112 patients in this group, there were 49 males and 63 females. The age ranged from 20 to 82 (59±9) years, and the course of disease was 0.05 to 30.00 (5.60±5.15) years. Pain was located on the left side in 43 cases (38.39%) and on the right side in 69 cases (61.61%), respectively. All patients were followed up for more than 1 year, with an average follow-up time of 21.5 months, and 11 cases recurred. Multivariate Cox regression analysis revealed that disease duration≥3 years(HR=9.34, 95%CI:1.12-39.07), CPA area ratio(healthy side/affected side)>1 (HR=27.47, 95%CI:1.69-44.20), criminal vessel type with vein(HR=35.39, 95%CI:1.26-18.60) and criminal vessel type with arteriovenous (HR=46.07, 95%CI: 2.74-27.75) were the main factors influencing recurrence of MVD surgery (all P<0.05). Conclusion: The disease duration≥3 years, CPA area ratio(healthy side/affected side)>1, and criminal vessel type with vein/arteriovenous are the relevant factors that affect the recurrence rate after the fully neuroendoscopic MVD treatment for trigeminal neuralgia.

[Efficacy analysis of fully endoscopic microvascular decompression in primary trigeminal neuralgia via keyhole approach].

Objective: To explore the efficacy and technical features of fully endoscopic microvascular decompression(MVD) in primary trigeminal neuralgia(PTN) via keyhole approach. Methods: The clinical data of 97 patients with PTN underwent fully endoscopic MVD via keyhole approach in the Department of Neurosurgery, Beijing Shijitan Hospital, Capital Medical University from December 2014 to February 2019 was collected. During fully endoscopic MVD in PTN via keyhole approach, performer use natural clearance without grinding except developed rock bone crest or excessive retraction of the brain tissue, visually and panoramically observe and evaluate the CPA area, accurately identify the responsible vessels, to avoid the omission of responsible vessels or insufficient decompression. And the use of preplaced technology, bridging technology and submersible technology, ensure the efficacy of surgery and reduce the surgical side injuries.Barrow Neurological Institute (BNI) pain score was used to evaluate the efficacy and identify the recurrence. The surgical efficacy was analyzed. Results: The offending vessels were identified under endoscope in 96 cases. Among them, arterial compression was found in 77 cases, venous compression in 6 cases, and both arterial and venous compression in 13 cases. About the pain outcomes, 87 cases had immediate and complete relief of pain, 5 cases had almost relief of pain, 4 cases had partial relief of pain, and still needed medication control, but the dose was lower than that before operation, and 1 case had no obvious relief of pain. About complications, there were 4 cases of temporary facial numbness, 1 case of temporary hearing loss, both of them recovered after symptomatic treatment. There was no cerebral infarction or hemorrhage, intracranial or incision infection. All cases were followed up for 3.0-38.0 months with a median period of(22.4±2.2) months. During the follow-up periods, postoperative recurrence occurred in 3 cases. Conclusion: Fully endoscopic MVD for PTN through keyhole approach, provides panoramic view to avoid omission of offending vessels and reduce complications, seemed to be a safe and effective surgical method.

[Research on anxiety-like neurobehavior of zebrafish caused by lead exposure and its mechanism].

Objective: This study aims to explore whether lead exposure could cause anxiety of zebrafish larvae, and to explore its mechanism. Methods: In May 2020, zebrafish embryos 4 hours after fertilization (4 hpf) were collected, E3 culture medium was used as the control group, and different lead exposure concentrations (6, 12, 24, 48 µmol/L) as the poisoned group during the time was 140 h. The mortalities, hatching rates and deformity rates were calculated, the behavioral changes of 144 hpf larvae were observed (moving speed, moving distance, activity, absolute turn angle, the light-evoked startle response, darkness-evoked escape response and thigmotaxis) . The levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were detected in zebrafish larvae in the heads. ELISA kits were used to detect the expression of 5-hydroxytryptamine (5-HT) , dopamine (DA) , noradrenaline (NA) and corticotropin-releasing hormone (CRH) related to anxiety. Results: The mortalities rates of zebrafish embryos in the lead exposure concentration of 12, 24 and 48 µmol/L were higher than the control group, and the embryo hatching rates were lower than control group. The deformity rates of zebrafish larvae in the lead exposure concentration of 24 and 48 µmol/L were higher than control group (P<0.01) . The movement speed, activity and thigmotaxis of zebrafish larvae in the lead exposure concentration of 24 and 48 µmol/L were significantly lower than control group, the absolute turn angle were higher than control group (P<0.01) . The moving distance and darkness-evoked escape response of zebrafish larvae in the lead exposure concentration of 48 µmol/L group were lower than control group (P<0.05) . The light-evoked startle response of zebrafish larvae in the lead exposure concentration of 12, 24 and 48 µmol/L groups were lower than control group (P<0.05) . The ROS levels and MDA concentrations in the heads of larvae in the lead exposure concentration of 24 and 48 µmol/L were higher than control group (P<0.05) . The levels of NA and DA in the heads of the larvae in the lead exposure groups of 12, 24 and 48 µmol/L were lower than control group, and the levels of 5-HT and CRH in the heads of the larvae in the lead exposure groups of 24 and 48 µmol/L were higher than control group (P<0.05) . Conclusion: Lead exposure is toxic to zebrafish embryonic development and may cause anxiety-like neurobehavior changes and oxidative stress in zebrafish.

[Enhancer of zeste homolog 2 affects dental pulp inflammation by regulating macrophage chemotaxis].

OBJECTIVE: To investigate the expression changes of the epigenetic regulator enhancer of zeste homolog 2 (EZH2) during pulp inflammation and the effect of EZH2 on macrophages migration. METHODS: Rat dental pulp was stimulated with 10 g/L lipopolysaccharide (LPS) to establish a model of rat pulpitis at different stages of inflammation. Immunohistochemical staining was used to detect the expression changes of EZH2 during the progression of pulp inflammation. Immunofluorescence double staining was used to detect the expression of EZH2, CD68 and their colocalization. To screen the appropriate concentration of EZH2 recombinant protein to stimulate hDPCs and human leukaemia-derived monocytic cell line (THP-1) cells, the effects of different concentrations (1, 10, 20, 40, and 100 µg/L) of EZH2 recombinant protein on proliferation of human dental pulp cells (hDPCs) and human monocyte cell line THP-1 were detected by cell counting kit-8 (CCK-8). Transwell migration assay was used to detect the effect of supernatants of hDPCs treated with EZH2 recombinant protein on the migration of THP-1 cells. RESULTS: HE staining results showed that in the model of rat pulp inflammation induced by LPS, with the prolongation of LPS stimulation, the inflammation response of pulp gradually increased. Immunohistochemical results showed that EZH2 expression decreased within 8 h of LPS-induced dental pulp inflammation; but after 1, 3, and 7 d of stimulation, EZH2 expression gradually increased with the extension of the stimulation time. As for the normal rat dental pulp tissue, the positive expression of EZH2 was scattered in the odontoblast cell layer and the pulp proper. Compared with the control group, LPS stimulated the expression of EZH2 and CD68 in the infected dental pulp, and the colocalization of EZH2 and CD68 could be detected in macrophages. The results of CCK-8 suggested that the appropriate concentration of EZH2 recombinant protein to stimulate hDPCs and THP-1 cells was 20 µg/L. Transwell cell migration assay confirmed that compared with the supernatant of EZH2 untreated HDPCs group, the supernatant of EZH2treated hDPCs significantly promoted macrophage chemotaxis. CONCLUSION: EZH2 is involved in the development of pulpitis and promotes the chemotaxis of macrophages, which suggests that EZH2 may play an important regulatory role in the development of pulp inflammation.

[Analysis of 123 Cases of Forensic Psychiatry Testimony of Individuals Suspected of Road Traffic Offences].

ABSTRACT: Objective To explore the characteristics of individuals with mental disorders suspected of road traffic offences and to find their differences from normal offenders, in order to regulate mental disorder patients' driving activities and prevent road traffic offences. Methods One hundred and twenty-three cases of forensic psychiatry testimony of individuals suspected of road traffic offences between 2014 and 2019 from the West China Forensic Center of Sichuan Province were collected. Fisher exact probability test was used to compare the differences between offenders with mental disorders and without mental disorders in terms of demographic characteristics, criminological characteristics, psychiatric characteristics and criminal responsibilities. Results There was no statistical significance in the differences of demographic characteristics, vehicles and kinds of alcohol between the two groups （P>0.05）. The main type of road traffic related crimes committed by offenders with mental disorders was risky driving and were mainly evaluated as partial criminal responsibility, whereas most offenders without mental disorders committed crime of causing traffic casualties and all were evaluated as full criminal responsibility. There was statistical significance in the differences of the types of crime and the criminal responsibility rating between the two groups （P<0.05）. Meanwhile, patients with mental disorders were characterized by long course of disease and irregular treatment, and individuals diagnosed as having mental disorders caused by psychoactive substances accounted for a large proportion. Conclusion There are differences in the characteristics of road traffic-related crimes between mental disorder patients and normal people. It is of great practical significance for reducing road traffic offences to evaluate whether the individuals with mental disorders are fit for driving.

[Application of complete endoscopic technique in microvascular decompression related tovertebrobasilar artery compression].

Objective: To study the operative method, special technique and curative effect of complete neuroendoscopic microvascular decompression(MVD) related to vertebrobasilar artery compression. Methods: Thirteen patients with functional cranial nerve disease caused by vertebrobasilar artery as direct or indirect responsible vessel accepted complete endoscopic MVD, including 11 patients with hemifacial spasm and 2 patients with trigeminal neuralgia. The procedure and curative effect of endoscopic surgery were analyzed retrospectively. Results: All procedures of complete neuroendoscopic MVD were successfully completed.Intraoperative observation by endoscope showed that 6 cases were oppressed directly by vertebral artery, 2 cases were oppressed directly by basilar artery, 5 cases were combined oppressed by displaced basilar artery and other vessels (1 case was superior cerebellar artery and 4 cases were anterior inferior cerebellar artery). During the operation, Teflon sheets was placed directly into the compression point in 2 cases, the "Pre-placed" technique was used to place Teflon sheets in 7 cases, and the "Set up bridge" technique was used to place Teflon sheets in 4 cases. Follow-up for 8-38 months,the symptoms disappeared completely in 12 cases and improved in 1 case. No deaths and severe complications occurred, such as postoperative bleeding, cerebellar infarction and intracranial infection. Conclusion: MVD related to vertebrobasilar artery compression can be performed by complete neuroendoscopic technique, which can achieve sufficient decompression effect and curative effect.Flexible use of the special technology of placing Teflon sheets by single-hand under endoscope, such as the "Pre-placed" and "Set up bridge" technique, is an important technical guarantee for the successful completion of endoscopic MVD.

[Efficacy analysis of soft neuroendoscopic techniques in the treatment of chronic subdural hematoma].

Objective: To investigate the efficacy of soft neuroendoscopic techniques in the treatment of chronic subdural hematoma (CSDH). Methods: A retrospective analysis of 201 cases of CSDH diagnosed and treated at Beijing Shijitan Hospital (CMU) from January 2006 to December 2017 was conducted. From January 2006 to December 2010, 126 cases of CSDH were treated with skull drilling and drainage (non-endoscopic group). From January 2011 to December 2017, 75 cases of CSDH were treated with soft neuroendoscopy (endoscopic group). The operation time of the non-endoscopic and endoscopic groups, the hematoma clearance rate on the first day after surgery, the time of the drainage tube, the length of hospital stay, the incidence of complications, mortality and recurrence rate were compared. Results: There were no deaths in both groups. The average operation time of the non-endoscopic group was 43 min, compared with the average operation time of the endoscopy group of 50 min, there was no significant difference (P>0.05). The average hematoma clearance rate on the first day after surgery in the endoscopy group (98.2%) was significantly higher than that in non-endoscopic group (87.3%) (P<0.01). The average time of drainage tube in the endoscopy group (23 h) was significantly shorter than that in the non-endoscopic group (50 h) (P<0.01). On the first postoperative day, the proportion of patients with mRS≤3 in the endoscopic group was significantly higher than that in the non-endoscopic group (P<0.01). At the time of discharge, the proportion of patients with mRS≤3 in the endoscopy group was also significantly higher than that in the non-endoscopic group, P<0.05. There was no significant difference in the average hospital stay between endoscopy group (7 d) and non-endoscopic group (8 d) (P>0.05). The postoperative complication rate in the endoscopy group was significantly lower than that in the non-endoscopic group (P<0.01). During 0.5-8 years of follow-up, the recurrence rate of CSDH in the endoscopic group (5.33%) was significantly lower than that in the non-endoscopic group (15.07%) (P<0.01). Conclusion: The application of visualization features of soft neuroendoscopy in the treatment of CSDH can significantly improve hematoma clearance, shorten the time of drainage tube, reduce postoperative complications and recurrence rate, and improve surgical outcomes.

Polygraph Accuracy of Control Question Test in Criminal Cases.

ABSTRACT: Objective To explore polygraph accuracy of Control Question Test （CQT）and whether it could be influenced by examinee's education level and type of violation of law. Methods Real cases of CQT （n=104） and the data from MAO （n=296） were collected. The polygraph accuracy of CQT was calculated. Variance analysis on three groups of different education levels was used to compare their age, and then the chi-square test was employed to compare polygraph accuracy among the groups. Independent sample t test was used to compare the age of subjects in the two groups of different types of violation of law, and then chi-square test was used to compare the true positive rate and true negative rate of lie detection after integration. Results In CQT lie detection of criminal cases, the true positive rate was 87.00%, the false negative rate was 13.00%, the true negative rate was 82.20%, and the false positive rate was 17.80%. There was no statistical significance in the differences between the true positive rate and the true negative rate （P>0.05）. In CQT lie detection of the groups of different education levels, there was no statistical significance in the differences between the true positive rates （P>0.05） while the differences between the true negative rates had statistical significance （P<0.05）. There was no statistical significance in the differences of both the true positive rates and the true negative rates between the violent violation of law and non-violent violation of law （P>0.05）. Conclusion There is no significant difference between the efficiency of CQT lie detection of identifying criminals and excluding innocents. However, a comparatively high false positive rate and false negative rate still exist. The efficiency of CQT lie detection identifying criminals may not influenced by the examinee's education level and type of violation of law, but its efficiency of excluding innocents may be influenced by the examinee's education level.

Simple method for liquid analysis by laser-induced breakdown spectroscopy (LIBS).

As a fast-developing technique for in situ multi-element analysis method, laser induced breakdown spectroscopy - LIBS is, however, developing slowly on liquid analysis due to some technical difficulties. We propose a new method, namely capillary mode, to quantify the concentrations of the elements in solution using LIBS. A Nd:YAG laser with repetition of 10 Hz were used to analyze the solution of Na2CrO4 and no any sample preparation in measurements. The experimental results show that the splashing of liquid induced by laser pulses is decreased significantly and the pollution of mirrors is avoided effectively using liquid capillary mode. The results of quantitative analysis for liquid are also improved than other method. The calibration curves of Cr and Na are well characterized by straight lines and the regression coefficient values of the linear fit are better than 0.998. The limits of detection (LODs) of Cr and Na are determined to be 28.9 mg/L and 1.0 mg/L in this work, respectively. The experimental results show that the liquid capillary mode provides a more practical and very simple approach to improve accuracy of quantitative element analysis in liquids by LIBS technique.

[Endoscopic neurosurgery combined with intraventricular lavage for pyogenic ventriculitis].

Objective: To investigate the efficacy of endoscopic neurosurgery combined with intraventricular lavage for pyogenic ventriculitis. Methods: A retrospective analysis of 45 patients with pyogenic ventriculitis in six hospitals which included Beijing Shijitan Hospital and Peking Union Medical College Hospital from 2001 to 2017. Twenty-four patients (non-endoscopic group) were treated with external ventricular drainage combined with intraventricular antibiotics administration from 2001 to 2009. Twenty-one patients (endoscopic group) was treated by endoscopic neurosurgery combined with intraventricular antibiotics lavage from 2010 to 2017. The drainage time, mortality, and modified Rankin score (mRS) after 6 months of follow-up were compared between the two groups. Results: Drainage time: (20±6) days in the endoscopic group, and (42±10) days in the non-endoscopic group. There was a significant difference between the two groups (P<0.001). Days in hospital: (29±7) days in the endoscopic group, and (51±11) days in the non-endoscopic group. There were significant differences between the two groups (P<0.001). Mortality: 8 patients (33.3%) died in the non-endoscopy group, and 1 patient (4.76%) died in the endoscopy group. There was a significant difference between the two groups (P=0.017). After 6 months of follow-up, patients of mRS≤3 were 14 cases (66.67%) in the endoscopy group, and 7 cases (29.17%) in the non-endoscopic group. There was a significant difference between the two groups (P=0.001). Conclusion: Endoscopic neurosurgery combined with intraventricular antibiotics saline lavage for pyogenic ventriculitis is an effective assessment and treatment method, and it is worth further promotion and application.

Icariin promotes mouse hair follicle growth by increasing insulin-like growth factor 1 expression in dermal papillary cells.

BACKGROUND: Icariin is a major flavonoid isolated from Epimedium spp. leaves (Epimedium Herba), and has multiple pharmacological functions, including anti-angiogenesis, anti-oxidant, anti-inflammatory and immunoprotective effects. AIM: To investigate whether icariin can stimulate growth of hair follicles in mice and the underlying mechanism. METHODS: In vitro, the effect of icariin on hair growth was assessed by using a vibrissae hair follicle (VHF) organ-culture model. The proliferation of hair matrix keratinocytes and the expression of insulin-like growth factor (IGF)-1 in follicles were examined by double immunostaining for 5-bromo-2'-deoxyuridine and IGF-1, in the presence or absence of icariin. Dermal papilla cells (DPCs) were cultured and IGF-1 level was measured by reverse transcription-PCR and ELISA after icariin treatment. In vivo, the effect of icariin on hair growth was examined by gavage feeding of icariin to mice whose backs had been depilated, and the conversion of telogen to anagen hair was observed. RESULTS: Treatment with icariin promoted hair shaft elongation, prolonged the hair cycle growth phase (anagen) in cultured VHFs, and accelerated transition of hair cycle from telogen to anagen phase in the dorsal skin of mice. There was significant proliferation of matrix keratinocytes and an increased level of IGF-1 in cultured VHFs. Moreover, icariin treatment upregulated IGF-1 mRNA expression in DPCs and increased IGF-1 protein content in the conditioned medium of DPCs. CONCLUSIONS: These results suggest that icariin can promote mouse hair follicle growth via stimulation of IGF-1 expression in DPCs.

[High expression of hnRNPAB/Kap1 together promote poor prognosis in HCC].

Objective: To further understand the interaction protein spectrum of heterogeneous ribonucleoprotein AB (hnRNP AB), and to investigate their clinical significance in hepatocellular carcinoma (HCC). Methods: We carried out mass spectrometry to reveal the specific peptides of KRAB-associated protein 1 (Kap1) and hnRNPAB, and verified their interaction by immunocoprecipitation and western blotting. Expression of hnRNPAB/Kap1 proteins were detected by immunohistochemical staining in the tissue microarrays. Categorical data were analyzed by the chi square test or Fisher exact test; enumeration data between groups were compared using Student t-test or Wilcocon signed rank test; the cumulative recurrence and survival rates were evaluated using the Kaplan-Meier method and the differences were assessed using the log-rank test. Results: We identified Kap1 as a molecular partner for hnRNPAB in HCCLM3 cells and HepG2 cells as well. We found that the 5-year survival rate of the Kap1high patients was significantly lower than the survival rate of those of the Kap1low group (36% vs 59% , HR = 1.67, P < 0.001). Similarly, Kap1high HCC patients had the poorest prognosis at 5-years, with higher cumulative recurrence rate than Kap1low patients (72% vs 54%, HR = 1.66, P = 0.001). Univariate and Multivariate analyses revealed that hnRNPAB /Kap1 alone (HR = 1.35 /1.28, P = 0.001) or in combination with Kap1 (HR =1.24 /1.27, P < 0.05) were independent prognostic indicators for overall survival and time to recurrence. Conclusion: In HCC cells, hnRNPAB and Kap1 form protein complexes. The expression levels of hnRNPAB alone or in combination with Kap1 in HCC patients are important because they provide not only a predictor for HCC prognosis but also a therapeutic target for future studies.

Effects of extracellular matrix on the growth characteristics of human dermal papillae cells in vitro.

BACKGROUND: In humans, dermal papillae cells (DPCs) are surrounded by basal membranes. However, conventional in vitro culture conditions for DPCs do not include extracellular matrix (ECM). AIM: To investigate the effects of different ECM types on the characteristics of cultured human DPCs. METHODS: Freshly isolated human DPCs were inoculated onto plates precoated with type IV collagen, fibronectin, Matrigel or hyaluronate. Cell migration, growth and viability were measured. Real-time quantitative (q)PCR and western blotting were used to detect the influence of different ECM types on the expression of DPC-specific biomarkers. RESULTS: In planar culture, type IV collagen and fibronectin had a beneficial effect on the migration, aggregation and viability of DPCs, in contrast to Matrigel and hyaluronate. Real-time qPCR revealed that significantly increased expression of mRNA was seen only for neural cell adhesion molecule (NCAM) and α-smooth muscle actin (α-SMA) in the Matrigel group, whereas versican, NCAM and α-SMA all decreased significantly in the hyaluronate group. In the type IV collagen and fibronectin groups, mRNA expression of the above genes did not change significantly. Western blotting indicated that there were no significant differences in expression of the above proteins between the four groups and the control group. CONCLUSION: In planar culture, exogenous ECM types (Matrigel, type IV collagen, hyaluronate and fibronectin) changed the growth characteristics of DPCs, but they did not affect the characteristics associated with the biological functions of DPCs.

A simple and rapid model for hair-follicle regeneration in the nude mouse.

BACKGROUND: Methods for hair-follicle regeneration are important tools for investigating signalling and cytokines during hair-follicle morphogenesis and cycling. Several animal models for hair reconstitution have been established; however, these models have several shortcomings. AIM: To develop a simple and rapid model for hair induction in nude mouse. METHODS: We designed an improved flap model (IFM) for hair regeneration based on the existing flap assay. Histological sections and scanning electron microscopy were used to evaluate the regenerated hair. The fates of grafted cells were traced by fluorescence. The time required for hair induction was analysed and compared. RESULTS: IFM produced a large number of normal hairs, and the time required for hair induction using IFM was 20.67 ± 0.67 days, compared with 29.33 ± 0.67 days for the traditional flap assay. CONCLUSIONS: The time required for hair regeneration is considerably shortened with IFM. We speculate that this is due to increased blood supply at the transplantation sites.

Dynamical evaluation of vaginal micro-ecosystem in a Chinese woman with recurrent vulvovaginal candidiasis.

We reported a rare case of recurrent vulvovaginal candidiasis (RVVC) in this study. Through dynamic evaluation of the vaginal micro-ecosystem, we found that only depuratory degree, spores, blastospores, and hyphae were specific indicators and the "barometer" of RVVC development. Therefore, an understanding of vaginal micro-ecological changes can help clinicians to improve the treatment of patients with RVVC.

Side-by-side comparison of photodynamic therapy and pulsed-dye laser treatment of port-wine stain birthmarks.

BACKGROUND: Pulsed-dye laser (PDL)-mediated photothermolysis is the current standard treatment for port-wine stain (PWS) birthmarks. Vascular-targeted photodynamic therapy (PDT) might be an alternative for the treatment of PWS. OBJECTIVES: To compare clinical outcomes of PDT and PDL treatment of PWS. METHODS: Two adjacent flat areas of PWS lesions were selected from each of 15 patients (two male and 13 female; age 11-36 years) and randomly assigned to either single-session PDL or PDT. PDL was delivered using a 585-nm pulsed laser. PDT was carried out with a combination of haematoporphyrin monomethyl ether (HMME) and a low-power copper vapour laser (510.6 and 578.2 nm). Clinical outcomes were evaluated colorimetrically and visually during follow-up. RESULTS: A total of nine red PWS lesions and six purple PWS lesions were treated. For red PWS, colorimetric assessment showed that the blanching rates of PDL and PDT at 2 months ranged from -11% to 24% and 22% to 55%, respectively. For purple PWS, blanching rates of PDL and PDT ranged from 8% to 33% and 30% to 45%, respectively. Overall, there was a significant difference between the blanching effect of single-session PDL treatment and a single-session PDT treatment. CONCLUSIONS: This side-by-side comparison demonstrates that PDT is at least as effective as PDL and, in some cases, superior. The true value of PDT for the treatment of PWS deserves further investigation.

[Developmental and epileptic encephalopathy 85 caused by SMC1A gene truncating variation: 4 cases report and literature review].

Objective: To summarize the clinical phenotype of patients with developmental and epileptic encephalopathy 85 caused by SMC1A gene truncating variation. Methods: The clinical data of 4 patients with epileptic encephalopathy caused by SMC1A gene truncating variation from August 2016 to June 2020 were analyzed retrospectively. Related literatures up to October 2021 with the key words "SMC1A" "Developmental and epileptic encephalopathy 85" "SMC1A, epilepsy" and "SMC1A, truncating" in PubMed, CNKI, and Wanfang databases were searched. Relevant literature was summarized and reviewed. Results: These 4 patients were all female. The onset age of seizure were all in the infantile period. They were admitted to the hospital at 3, 2, 11 and 18 months respectively. Focal seizures occurred in all 4 patients, while 1 of them experienced infantile spasm. The characteristic of cluster was observed in all of them with an interval of 14 days to 5.0 months. The seizures were all refractory to different kinds of anti-seizure medications. All 4 patients had severe developmental retardation with microcephaly (head circumference<-2 s). The interictal electroencephalogram (EEG) was characterized by diffuse slow wave. The 4 SMC1A gene variants were p.Gly655fs, p.Glu811fs, p.Arg412fs and p.Ile143fs, all of which were de novo frameshift variation after parental validation. There were another 17 cases with SMC1A gene truncating variation reported in 6 English articles and 1 Chinese article. Among these 21 patients, who were all female, the onset of seizures occurred between 0.5 and 18.0 months of age. Seventeen cases (81%) had the characteristics of cluster attacks, and the intervals of attack cycles were different. Seizure types included generalized tonic-clonic seizure (12 cases (57%)), focal seizure (11 cases(52%)), myoclonic(4 cases(19%)), spasm (4 cases(19%)), atypical absence (3 cases(14%)), tonic seizure (2 cases (10%)), and atonia (1 case(5%)). In addition, 4 cases (19%) had status epilepsy. All patients had moderate to severe mental retardation. Microcephaly was found in all patients. Among 18 cases,EEG in 8 cases had diffuse slow wave background. Brain magnetic resonance imaging (MRI) was normal in 13 cases (62%). Other MRI changes included cerebellar atrophy (3 cases), thin corpus callosum (3 cases), and lateral ventricular enlargement (2 cases). Twenty patients did not respond well to antiepileptic drugs. Conclusions: The clinical phenotypes of patients with epilepsy encephalopathy 85 caused by SMC1A gene truncating variation are characterized by female, early-onset, clustering of seizures, development delay and microcephaly. Diffuse slow waves are shown in interictal EEG in partial. Response to treatment and prognosis are poor.

[Interleukin-1 receptor associated kinase 4 deficiency: a case report and literature review].

Objective: To summarize the clinical characteristics of children with interleukin-1 receptor associated kinase 4 (IRAK4) deficiency. Methods: The clinical data of a child with IRAK4 deficiency who was admitted to the Department of Neurology of Shenzhen Children's Hospital for several times from June 2019 to August 2020 were retrospectively analyzed. Related literature up to January 2021 with the key words "IRAK4 gene variation", and "interleukin-1 receptor-associated kinase 4 deficiency" in PubMed, CNKI, Wanfang, and CQVIP databases were searched. The clinical characteristics of this disease were summarized and analyzed. Results: The boy was 6 years of age and had recurrent respiratory tract infections. He was improved after antibiotic treatment. His clinical manifestation included Streptococcus pneumoniae meningoencephalitis, multiple sclerosis, invasive discitis and inflammatory bone destruction. Family-based whole exome sequencing showed that the boy had a homozygous frameshift variation in the IRAK4 gene, NM_016123.3:C.540del (p.Phe180leufs*26), and both parents were heterozygous. A total of 23 cases were reported in ten English articles. Together with this case, there were 24 cases, including 13 males and 11 females. The age of onset was 8 days to 7 years. The main manifestations were recurrent invasive bacterial infection, including 11 cases with Streptococcus pneumoniae meningitis, 9 cases with Streptococcus pneumoniae and (or) Staphylococcus aureus septicemia, 1 case with Pseudomonas aeruginosa meningitis, 1 case of salmonella infection, and 1 case with Staphylococcus aureus skin abscess. Only 1 case had recurrent virus infection. There were 2 patients with autoimmune diseases, 1 with autoimmune encephalitis and the other one with juvenile idiopathic arthritis. Among the 24 cases, 10 died (9 in infancy). Most of the surviving children were diagnosed early and received antibiotics preventively and intravenous immunoglobulin (IVIG). Their susceptibility to infection decreased year by year, and could be close to normal children at the age of 14 years. Among the 24 cases, 21 cases had homozygous variation of IRAK4 gene and 3 cases had complex heterozygous variation. There were 15 kinds of variation, including 9 kinds of frameshift variation, 4 kinds of nonsense variation and 2 kinds of missense variation. One candidate variation hotspot was c.877 c>T (3 cases). Conclusions: IRAK4 deficiency mainly manifest as recurrent and invasive bacterial infection, with Streptococcus pneumoniae meningitis or septicemia being the most common. A few patients are complicated with autoimmune diseases. The mortality rate is high in infancy, early diagnosis and treatment can avoid severe illness or death.

LncRNA HOTAIR aggravates myocardial ischemia-reperfusion injury by sponging microRNA-126 to upregulate SRSF1.

OBJECTIVE: Acute myocardial infarction (AMI) is a severe fatal disease throughout the world. Myocardial IR limits the recovery of impaired cardiac function in AMI patients. This study aims to elucidate the role of long non-coding RNA (lncRNA) HOTAIR in myocardial ischemia-reperfusion (IR) and the underlying mechanism, thus providing a novel therapy for AMI. MATERIALS AND METHODS: Myocardial IR model in mice was firstly constructed by LAD. Plasma levels of LDH, CK-MB, HOTAIR, and microRNA-126 in mice were detected. Subsequently, in vitro HR model was constructed in H9c2 cells. Regulatory effects of HOTAIR on proliferative ability, LDH release, and Caspase-3 activity in H2O2-induced H9c2 cells were determined. Relative levels of inflammatory factors in in vitro HR model were measured by enzyme-linked immunosorbent assay (ELISA). The regulatory loop HOTAIR/microRNA-126/SRSF1 was finally verified by Dual-Luciferase reporter assay. RESULTS: LDH and CK-MB were significantly released in mice with myocardial IR. HOTAIR was upregulated, while microRNA-126 was downregulated in IR mice and H2O2-induced H9c2 cells. Overexpression of HOTAIR stimulated proliferative ability, LDH release, and Caspase-3 activity in H2O2-induced H9c2 cells. Besides, overexpression of microRNA-126 inhibited the release of inflammatory factors in H9c2 cells undergoing HR induction. The regulatory loop HOTAIR/microRNA-126/SRSF1 was identified to influence IR development. CONCLUSIONS: HOTAIR aggravates myocardial IR by competitively binding SRSF1 with microRNA-126.