Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

Objective:To explore the effect of small-incision liposuction combined with subcutaneous adipose glandular tissue excision at the areolar margin for the treatment of fatty gynecomastia.Methods:From January 2018 to October 2022, 179 patients with gynecomastia were admitted to the Breast, Thyroid, and Plastic Surgery Department of the First Affiliated Hospital of Henan University and the Breast Surgery Department of Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, who underwent small incision liposuction combined with subcutaneous fat and gland tissue resection at the areolar edge, with ages ranging from 18 to 56 (35.0±8.1) years. The patients were followed up at 3 weeks, 3 months and 6 months after surgery to evaluate the treatment effect, patient satisfaction and complications.Results:The surgical time of 179 patients ranged from 26 minutes to 130 minutes, and intraoperative bleeding ranged from 10 ml to 50 ml. All patients underwent successful surgery and were discharged within 2-5 days. Postoperative subcutaneous haematoma was found in 3 patients (1.68%), nipple areola numbness in 32 patients (17.88%), subcutaneous effusion in 5 patients (2.79%) and epidermal blisters in 7 patients (3.91%). After 6 months of follow-up, 149 patients (91.41%) were satisfied.Conclusions:The treatment of gynecomastia by liposuction combined with subcutaneous adipose and glandular tissue excision through a small incision at the edge of the areola is aesthetically pleasing and less traumatic, with fewer complications; it is safe and worthy of clinical application.

Objective:To construct a fall risk prediction model for patients with hematologic malignancies and to provide a reference for the risk assessment and accurate management of falls.Methods:The prospective study design was adopted to facilitate the selection of 510 patients with hematologic malignant in Qilu Hospital of Shandong University for investigation, and relevant data such as patient demographic characteristics, disease treatment and drugs were collected. The LASSO-Logistic regression was used to screen the risk factors of falls in patients with hematologic malignancies, to construct a nomogram risk prediction model. The receiver operating characteristic curve (ROC) and calibration curve were used to evaluate the predictive performance of the model. Bootstrap resampling were used to validate internal validation of the model.Results:Among 510 patients with hematological malignancies, there were 273 males and 237 females, aged 53.0 (41.0, 63.0) years old. A total of 6 risk factors were included in the fall risk prediction model for patients with hematological malignancies, which were disease type ( OR = 0.185, 95% CI 0.061 - 0.562), body temperature ≥38 ℃ ( OR = 2.239, 95% CI 1.128 - 4.445), pain ( OR = 15.581, 95% CI 6.592 - 36.829), anemia ( OR = 4.097, 95% CI 1.536 - 10.927), days of bone marrow suppression ( OR = 3.341, 95% CI 1.619 - 6.893), and assessment of daily self-care ability ( OR = 3.160, 95% CI 1.051 - 9.506)(all P<0.05). The ROC curve of the fall risk prediction model was 0.884 (95% CI 0.841-0.927). The optimal threshold, sensitivity, and specificity of the risk prediction model were 0.248, 87.4% and 75.6%. The internal validation C statistic was 0.873. The Calibration curve was almost coincides with the ideal curve, and the model Brier score was 0.080. Conclusions:The constructed fall risk prediction model has good predictive performance, which can efficiently and objectively quantify the risk of falls, and provide a reference for the early assessment and effective prevention of falls in patients with hematological malignancies.

Endometriosis（EMs） is a common chronic inflammatory gynecological disease，affecting about 5%-10% of women of childbearing age worldwide，and has always been a major challenge in clinical treatment. Huposan， derived from the Experiential Prescriptions for Universal Relief （《普济本事方》）， has the effects of moving qi， activating blood，expelling blood stasis， and relieving pain. It is often used to treat EMs clinically and has achieved good curative effect. The relevant studies on the treatment of EMs by Huposan were retrieved from databases， such as CNKI，PubMed，Wanfang Data， and VIP for summarizing the mechanisms of action and clinical application of Huposan in the treatment of EMs， aiming to provide ideas and references for the basic research and clinical application of Huposan. As revealed by basic experiments，Huposan could exert therapeutic effects on EMs through resisting cell adhesion by reducing intercellular adhesion molecule 1（ICAM-1）content，decreasing concentrations of matrix metalloproteinase（MMP）-2 and MMP-9 against ectopic endometrial invasion，inhibiting vascular endothelial growth factor（VEGF）expression for antiangiogenesis，inhibiting the expression of tumor necrosis factor-α（TNF-α）， interleukin （IL）-6， and IL-1，reversing helper T cell（Th）1/Th2 balance shifts to regulate the body's immune mechanism，and reducing the serum levels of nitric oxide（NO）and nitric oxide synthase（NOS）. In clinic practice，Huposan has the effects of reducing ectopic lesions，relieving pain symptoms，reducing serum carbohydrate antigen 125（CA125）content，improving hormone levels，regulating endocrine and immune factors，and reducing postoperative recurrence rate. Huposan plays a therapeutic role in EMs through multiple targets and mechanisms，which is worthy of further exploration and clinical promotion.

Autophagy is a lysosome-mediated catabolic process that captures and degrades dysfunctional organelles and useless proteins during cellular stress process， which plays a dual role in cervical cancer. In the early stage of cervical cancer， autophagy inhibits the occurrence and development of cervical cancer by prohibiting the accumulation of oncogenic p62 protein. In the advanced stage of cervical cancer， inhibition of autophagy of cancer cells enhances the sensitivity of cancer cells to chemotherapeutic drugs， thus inhibiting their proliferation. In recent years， the research on Chinese medicine monomers regulating autophagy in the treatment of cervical cancer has attracted extensive attention from scholars at home and abroad. Chinese medicine monomers regulate the autophagy of cervical cancer cells through multiple pathways and multiple targets， so as to increase the apoptosis rate and reduce the resistance of cancer cells to chemotherapeutic drugs. Therefore， this paper reviewed the mechanism of Chinese medicine monomers in inhibiting cervical cancer through autophagy， expecting to find new breakthroughs in the discovery and development of preventive and therapeutic drugs for cervical cancer. By reviewing the literature， it was found that in the early stage of cervical cancer， Chinese medicine monomers activated autophagy to promote apoptosis of cancer cells， and the main mechanism was to increase lysosomal membrane permeability and chemotherapeutic sensitivity and activate intact autophagy flow. In the advanced stage of cervical cancer， inhibition of autophagy reduced the sensitivity of cancer cells to chemotherapy drugs by inhibiting the formation of autophagosomes and autolysosomes. The treatment of cervical cancer by Chinese medicine monomers regulating autophagy has achieved certain effect， but there are few clinical experimental studies and lack of reliable clinical theoretical basis. Therefore， it is essential to carry out more clinical experimental studies on Chinese medicine monomers regulating autophagy to treat cervical cancer， thus finding more reliable theoretical basis for the treatment of tumors.

Objective:To explore the value of Neoseq in screening and diagnosis of neonatal fatty acid oxidation disorders (FAOD).Methods:A retrospective case-control study was conducted on 163 500 live births in Changzhou city from April 2015 to April 2021. The following two models were adopted for FAOD screening and diagnosis. (1) Traditional mode: Heel blood samples were obtained from all subjects for initial screening using tandem mass spectrum (TMS), followed by next-generation sequencing (NGS) and other differential diagnostic testings for those with positive results. (2) Neoseq: Neoseq was performed on the true positive, negative and false positive cases according to the traditional mode screening results. The detection rate, additional discovery, reporting period, and other parameters of the two models for FAOD were described and compared.Results:(1) Detection and diagnosis of FAOD: A total of 18 confirmed cases of FAOD were detected through the traditional model, with an incidence of 1/9 083 in Changzhou city. The positive rate was 0.55% (907/163 500) for initial TMS and 0.04% (73/163 500) for the second. The positive predictive value was 2.0%(18/907), with a false positive rate of 98%(889/907) in the initial screening. (2) The results of Neoseq: ①Pathogenic mutations were detected in 16 of the 18 confirmed cases, and the coincidence rate of mutation sites between the two methods was 16/18. The other two confirmed cases were missed diagnosed by Neoseq, including one β-ketothiolase deficiency with only one detected pathogenic mutation and one medium-chain acyl-CoA dehydrogenase deficiency without any detected pathogenic mutation. ②No pathogenic mutations were detected in the 57 false-positive cases by Neoseq. ③Among the 100 negative cases in initial screening, DUOX2 heterozygous mutation, and MTTL1 hemizygous mutation were detected in one case each. ④The median period of results reporting was 43.5 d (28-104 d) for the traditional mode and 12 d (10-15 d) for the Neoseq mode. Conclusions:Neoseq has a high detection rate for FAOD. Combined with TMS screening, Neoseq reduces the false-positive rate of biochemical screening, rapidly identifies genetic causes by shortening the results waiting time and covers diseases that couldn't be detected by traditional biochemical methods.

Objective:To explore the method of establishing a modified demyelination and myelination regeneration model induced by dicyclohexanone oxalyl dihydrazone (CPZ) in mice with multiple sclerosis (MS), and to analyze the image markers of demyelination and myelination regeneration in mouse MS model.Methods:After the intragastrically administered with sodium carboxymethyl cellulose (CMCNa) for one week, a total of 30 C57BL/6 male mice were randomly divided into the control group ( n=10), the demyelination group ( n=10), and the remyelination group ( n=10). The mice of the control group were immediately performed MR scanning and pathological specimen obtaining; the mice in the demyelination group were administered with intragastrical CPZ-CMCNa once a day for 6 weeks for inducing demyelination, then received MR scanning and specimen obtaining with the same protocols used in control group; the mice in the remyelination group were administered with intragastrical CPZ-CMCNa once a day for six weeks for demyelination, then CPZ was withdrawn and normal diet was given for another four weeks. Then MR scanning and specimen obtaining were performed with the same protocols used in the other two groups. Regions of interest (ROIs) were set at the rostrum of corpus callosum (rCC), the bilateral normal appearing white matters (NAWM) of the rostrum of corpus callosum, and the bilateral cerebral cortex (Cx). The normalized T 2WI (T 2-normalized), fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) values were compared among the three groups by one-way ANOVA. Results:The demyelination and remyelination mice model of MS were successfully established. The T 2-normalized values of rCC in control group, demyelination group and remyelination group were 0.47±0.03, 0.72±0.04, 0.54±0.04, respectively, with statistically significant difference found ( F=90.511, P<0.05). Post-hoc multiple comparisons showed significant differences among those groups ( P<0.05). There was no significant difference of T 2-normalized value in NAWM and Cx among the three groups ( P>0.05). Moreover, there were significant differences in the FA values (0.36±0.04, 0.29±0.03, and 0.32±0.05), the MD values [(0.572±0.015), (0.598±0.034), and (0.626±0.043)×10 -3 mm 2/s], the AD values [(0.79±0.04), (0.77±0.06), and (0.83±0.04)×10 -3 mm 2/s], and the RD values [(0.46±0.02), (0.51±0.03), and (0.53±0.05)×10 -3 mm 2/s] of rCC of the control group, the demyelination group, and the remyelination group (all P<0.05). Significant difference was found in FA values between the demyelination group and the control group ( P<0.05), and in MD values between the remyelination group and the control group ( P<0.05), as well as in AD values between the remyelination group and the demyelination group ( P<0.05). There were also significant differences in RD values between the remyelination group and the control group, and the demyelination group and the control group (all P<0.05). However, no significant difference was found in all diffusion tensor imaging (DTI) metrics of NAWM and Cx among the three groups (all P>0.05). The LFB-eosin staining showed that the myelin sheath of rCC was lost in the demyelination group, and the rCC was partially regenerated and repaired in the remyelination group. Conclusion:The modified CPZ-CMCNa model can selectively induce demyelination and remyelination of rCC, and the changes of demyelination and remyelination of rCC in the modified CPZ-CMCNa model can be quantitatively detected by T 2WI combined with DTI, which might provide related theoretical basis for the study on dynamic changes of MS lesions.

Background Aluminum can induce irreversible structural and synaptic functional damage, and the associated mechanism may be related to the neurite damage regulated by glycogen synthase kinase-3β (GSK-3β)/collapsin response mediator protein 2 (CRMP2). Objective This experiment is conducted to investigate the effect of aluminum-maltolate [Al(mal)₃] on primary hippocampal neuron neurites in mice, and reveal the role of GSK-3β-CRMP2 in this process. Methods The hippocampus of newborn ICR mice (≤ 24 h old) was used for primary neuronal cultures. On the 5th day in vitro (DIV5), neuron purity detection were performed by confocal laser scanning microscopy. On DIV7, the neurons were transfected with lentiviral vector-mediated mNeonGreen. On DIV10, the neurons with mNeonGreen fluorescence in good growth state were treated with Al(mal)₃. The stage I experimental groups were blank control group, maltol group, 10 µmol·L⁻¹ Al group, 20 µmol·L⁻¹ Al group, and 40 µmol·L⁻¹ Al group. Then 20 µmol·L⁻¹ Al was used to establish a model of neurite injury and for the intervention. The stage II experimental groups were blank control group, dimethyl sulfoxide (DMSO) group, Al (20 µmol·L⁻¹) group, SB (GSK-3β inhibitor, 1 µmol·L⁻¹), and SB (1 µmol·L⁻¹)+Al (20 µmol·L⁻¹) group. CCK-8 method was used to detect the viability of neurons. The primary hippocampal neurons of mice were scanned with high content analysis system at 0 h and 48 h after Al or SB treatment, and the density and length of neurites were analyzed. Western blotting was used to detect the expression and phosphorylation levels of CRMP2 and GSK-3β in primary hippocampal neurons of mice. Results The immunofluorescence results showed that the purity of primary neurons was more than 90%. Compared with the blank control group in stage I, the cell viability rates of the 10, 20, and 40 µmol·L⁻¹ Al groups were decreased after 48h of Al(mal)₃ treatment (P<0.05), while the cell viability rate of the maltol group had no significant change. There was no significant difference in cell viability rate among the DMSO group, the SB group, and the control group after 48h of SB treatment, and the viability rate of neurons in the SB+Al group was higher than that in the Al group (P<0.05) in stage II. The 48 h/0 h ratios of average number and length of neurites in the control group were 90.13%±11.70% and 113.24%±8.34%, respectively. The 48 h/0 h ratios in the Al group were 56.47%±16.36% and 62.06%±6.75%, respectively, which were lower than those in the control group (P<0.05). The 48 h/0 h ratios of average number of neurites in the SB group (99.03%±21.83%) was not significantly different from that in the control group, but the 48 h/0 h ratio of average length of neurites in the SB group (128.72%±15.39%) was higher than that in the control group (P<0.05). The 48 h/0 h ratios of average number (72.59%±10.89%) and length of neurites (93.84%±14.65%) in the SB+Al group were significantly increased compared with those in the Al group (P<0.05). Western blotting results showed that: There was no significant difference in GSK-3β protein level among all groups; compared with the control group (1.00±0.18), the protein level of p-GSK-3β in the Al group (0.45±0.05) was significantly decreased, and that in the SB group (1.32±0.23) was significantly increased; the protein level of p-GSK-3β in the SB+Al group (0.80±0.05) was significantly higher than that in the Al group (P<0.05). Compared with the control group (1.00±0.07), the CRMP2 protein level in the Al group (0.66±0.11) was significantly decreased (P<0.05), while that in the SB group (1.01±0.02) was not significantly changed. Compared with the control group (1.00±0.13), the p-CRMP2 protein level in the Al group (1.50±2.18) was significantly increased, and that in the SB group (0.62±0.09) was significantly decreased (P<0.05); the protein level of p-CRMP2 in the SB+Al group (1.28±0.24) was lower than that in the Al group (P<0.05). Conclusion Aluminum may activate GSK-3β, increase CRMP2 phosphorylation level, and damage neurite growth.

Objective:To provide epidemiological data and clinical evidence for cosmetic adverse reactions.Methods:A retrospective clinical analysis was carried out on a total 820 outpatients (23 males and 797 females) suspected to be with cosmetic adverse reactions from January 2014 - October 2017, and average age of these patients was 7~75 (32.66±8.09) years. Suspicious cosmetics patch tests were performed in some patients. Suspicious cosmetics patch tests were performed in 687 patients.Results:Among 820 patients with cosmetic adverse reactions, women accounted for 97.20% and men accounted for 2.80%. Age distribution was most common among young people aged 21-40 years, accounting for 71.34%. The highest level of education was higher education, accounting for 59.69%. Occupational distribution was most commonly concentrated in employees and unemployed persons, accounting for 28.54% and 18.66%, respectively. A history of cosmetics allergies accounted for 17.28%. Cosmetic contact dermatitis was the most common clinical type of cosmetic adverse reactions, accounting for 92.70%. A total of 1682 suspected pathogenic cosmetics were involved. The positive rate of the cosmetic original patch test was 42.39%. Among the cosmetics with a positive patch test, moisturizing, anti-wrinkle and whitening freckle cosmetics accounted for the highest proportion, 31.59%, 15.09%, and 12.68%, respectively.Conclusions:Cosmetic contact dermatitis is the most common type of cosmetic adverse reaction. Patch testing is helpful in identifying the contact allergens in cosmetic adverse reaction.