Objective:To analyze the clinical and molecular genetic characteristics of patients with cerebrotendinous xanthomatosis (CTX) to increase the awareness of the disease among clinicians.Methods:The clinical data, including the age of onset and diagnosis, clinical manifestations, neuroimaging and neuroelectrophysiology and the genetic data of patients diagnosed with CTX in the Department of Neurology, Qilu Hospital of Shandong University from March 2017 to December 2023 were retrospectively collected and analyzed.Results:A total of 18 patients were enrolled in this study, including 12 males and 6 females.The onset age was 10 (6, 29) years, with a minimum onset age of 3 years and a maximum onset age of 32 years; the period from onset to diagnosis was 19.00 (8.75, 24.25) years, with the shortest being 6 months and the longest being 35 years. Among the 18 patients, 16 patients had symptoms and signs of spastic paralysis, 9 patients had cognitive impairment and peripheral neuropathy, 8 patients had cerebellar ataxia, 3 patients had mental disorders, 3 patients had autonomic nervous dysfunction, and only 2 patients had seizures. Among the non-neurological symptoms, 9 patients had Achilles tendon xanthoma, of whom 1 patient was accompanied by patellar tendon xanthoma; 8 patients had adolescent cataracts, 6 patients had chronic diarrhea since childhood. All patients underwent brain MRI examination, among whom 15 patients had cerebellar dentate nucleus involvement, 10 patients had corticospinal tract involvement and 2 patients had normal brain MRI. Fourteen patients underwent nerve conduction and electromyography examinations, among whom 9 patients presented with multiple peripheral neuropathy characterized by motor or motor sensory demyelination. A total of 17 CYP27A1 gene variants were detected in 18 patients. The c.1420C>T and c.1263+1G>A were the hot-spot mutations in this cohort. Conclusions:Spastic paralysis, cerebellar ataxia, tendon xanthoma and adolescent cataracts are typical manifestations of CTX. The cerebellar dentate nucleus and corticospinal tract are mainly involved on the neuroimaging. It should be noted that some patients lack the typical characteristics mentioned above. The c.1420C>T and c.1263+1G>A are the hot-spot mutations in this cohort.

Purpose: This study aimed to investigate reproductive concerns among breast cancer patients of reproductive age, analyze the influencing factors, explore the relationship between coping styles, fear of progression (FOP), and reproductive concerns, and identify the multiple effects of coping styles on the relationship between FOP and reproductive concerns among Chinese breast cancer patients. Methods: A cross-sectional, descriptive study was conducted among breast cancer patients in four tertiary grade A hospitals in Fujian, China, from January 2022 to September 2022. A total of 210 patients were recruited to complete paper-based questionnaires, which included the general data questionnaires, the Reproductive Concerns After Cancer Scale (RCACS), the Fear of Progression Questionnaire-Short Form (FOP-Q-SF), and the Medical Coping Modes Questionnaire (MCMQ). Structural equation models were utilized to evaluate the multiple effects of coping styles on FOP and reproductive concerns. Results: Reproductive concerns in breast cancer patients had a mean score of 53.02 (SD, 10.69), out of a total score of 90, and coping styles for cancer (confrontation, avoidance) were closely associated with FOP and reproductive concerns. FOP showed a significant positive correlation with reproductive concerns (r = .52, p < .01). At the same time, confrontation was significantly negatively correlated with both FOP (r = −.28, p < .01) and reproductive concerns (r = −.39, p < .01). Avoidance was positively correlated to both FOP (r = .25, p < .01) and reproductive concerns (r = .34, p < .01). The impact of FOP on reproductive concerns is partially mediated by confrontation and avoidance, with effect sizes of .07 and .04, respectively. These mediating factors account for 22.0% of the total effect. Conclusions The FOP directly impacted reproductive concerns, while coping styles could partially mediate the association between FOP and reproductive concerns. This study illustrates the role of confrontation and avoidance in alleviating reproductive concerns, suggesting that it is necessary to focus on the changes in reproductive concerns among reproductive-age breast cancer patients. Healthcare professionals can improve disease awareness and reduce patients' FOP, thereby promoting positive psychological and coping behaviors and ultimately alleviating reproductive concerns.

COVID-19 has swept globally and Pakistan is no exception.To investigate the initial introductions and transmissions of the SARS-CoV-2 in Pakistan,we performed the largest genomic epidemiology study of COVID-19 in Pakistan and generated 150 complete SARS-CoV-2 genome sequences from samples collected from March 16 to June 1,2020.We identified a total of 347 mutated positions,31 of which were over-represented in Pakistan.Meanwhile,we found over 1000 intra-host single-nucleotide variants(iSNVs).Several of them occurred concurrently,indicating possible interactions among them or coevolution.Some of the high-frequency iSNVs in Pakistan were not observed in the global population,suggesting strong purifying selections.The genomic epidemiology revealed five distinctive spreading clusters.The largest cluster consisted of 74 viruses which were derived from different geographic locations of Pakistan and formed a deep hierarchical structure,indicating an extensive and persistent nation-wide transmission of the virus that was probably attributed to a signature mutation(G8371T in ORF 1ab)of this cluster.Further-more,28 putative international introductions were identified,several of which are consistent with the epidemiological investigations.In all,this study has inferred the possible pathways of introduc-tions and transmissions of SARS-CoV-2 in Pakistan,which could aid ongoing and future viral surveillance and COVID-19 control.

Objective:To explore the effective method for treatment of small and short penis after hypospadias surgery.Method:s From November 2017 to November 2018, 57 children aged 4 to 14[mean age(7.91±2.89)years] with hypospadias who met the diagnostic criteria of small penis were reexamined at the First Affiliated Hospital of Xin-xiang Medical University.They were randomly divided into the physical treatment group and the drug treatment group according to the order of visits, and the untreated patients were included in the control group.Among them, 21 patients in the physical treatment group were treated with penile rehabilitation therapy apparatus, supplemented by Salvia mil-tiorrhiza bath (30 minutes/time, once/day, 10 days), and 20 patients in the drug treatment group were treated with Testosterone cream topically (3 times/day, 10 days). Penile relaxation length, stretch length, transverse and longitudinal diameters of glans in 2 groups before and after the treatment were measured.The relevant indexes of 16 patients in the control group measured before and after 10 days and compared with those in the treatment group.Result:s (1)The penile relaxation length in the physical treatment group increased from (25.48±6.13) mm to (30.72±6.49) mm, the length of stretch increased from (34.90±7.71) mm to (41.08±8.43) mm, the transverse diameter of glans increased from (14.81±3.40) mm to (16.57±3.42) mm, and the longitudinal diameter increased from (13.94±3.15) mm to (15.82±3.52) mm, and the differences were statistically significant (all P<0.05). (2)The penile relaxation length in the drug treatment group increased from (21.07±4.26) mm to (31.32±4.72) mm, the length of stretch increased from (31.94±7.96) mm to (45.39±7.24) mm, the transverse diameter of glans increased from (13.38±1.77) mm to (16.64±2.10) mm, and the longitudinal diameter increased from (13.09±1.77) mm to (16.62±1.86) mm, and the differences were statistically significant (all P<0.05). (3)There was no significant difference in penile relaxation length, the length of stretch, transverse diameter and longitudinal diameters of glans before and after 10 days in the control group (all P>0.05). (4) Compared with the control group, the penile relaxation length, the length of stretch, transverse diameter and longitudinal diameters of glans in the physical treatment group increased significantly, and the differences of growth values between the two groups were statistically significant (all P<0.05). (5) Compared with the control group, the penile relaxation length, the length of stretch, transverse diameter and longitudinal diameters of glans in the drug treatment group also increased significantly, and the difference of growth values between the two groups were statistically significant (all P<0.05). (6) The growth of penile relaxation length, the length of stretch and transverse and longitudinal diameters in the drug treatment group were higher than those in the physical treatment group, and the difference of growth values were statistically significant (all P<0.05). Conclusions:Both the negative pressure suction method and topical application of Testosterone cream are effective in the treatment of small and short penis after hypospadias surgery.However, Testosterone cream is difficult to obtain, and the treatment of negative pressure suction is simple, noninvasive, painless and free of adverse reactions.

Objective:To explore the effects of different doses of Ethephon on testes of male pups.Methods:Thirty-two 45-day-old healthy female Sprague-Dawley (SD) rats were randomly divided into the control group and the low dose, middle dose and high dose Ethephon groups by the random figure table.The female rats in the low dose, middle dose and high dose Ethephon groups were given 200, 400, and 800 mg/kg Ethephon solution, respectively.The control group was treated with 9 g/L saline.After the birth of the offspring, the mother rats were not administrated with any medications, and the male offspring rats were given Ethephon solution instead.Twelve offspring male rats were randomly selected from each group and killed at the age of 0, 14 and 28 days after birth.Fresh testicular tissues were stained with hematoxylin eosin (HE), and the morphological changes of testicular tissues were observed under light microscope.The apoptotic cells were labeled by terminal dexynucleotidyl transferase (TdT) mediated dUTP nick end labeling (TUNEL) method and the apoptosis index (AI) of spermatogenic cells was detected by fluorescence microscope.Results:(1) Compared with the newborn rats in the middle dose group, low dose group and control group, se-miniferous tubules in the newborn rats of the high dose group were slightly thicker, and seminiferous cells were arranged slightly in disorder.The AI of the newborn rats in high dose group was significantly higher than that in the control group (1.00±0.06 vs.0.41±0.03, P<0.01). The AI of the newborn rats in the middle dose group was not significantly different from that in the control group and the low dose group ( P>0.05). (2) The seminiferous tubules of the 14-day-old rats in the low dose, middle dose and high dose Ethephon groups were significantly thicker and arranged more loosely than those in the control group.Compared with the control group, there were very few seminiferous cells, which were arranged disorderly in the low dose, middle dose and high dose Ethephon groups.The AI of the 14-day-old rats in the low dose, middle dose and high dose Ethephon groups was (2.13±0.10), (2.18±0.10) and (3.90±0.23), respectively, which were significantly higher than that in the control group (1.00±0.02) ( F=2 508.36, P<0.01). There was no significant difference in the AI between the middle dose and low dose groups ( P>0.05). (3) Compared with the control group, the seminiferous tubules of the 28-day-old rats in the low dose, middle dose and high dose groups were significantly thicker and arranged much more loosely, and spermatogenic cells were even less and arranged in a severely disordered way.The AI of 28-day-old rats in the low dose group (5.52±0.13), the middle dose group (9.44±0.07) and the high dose group (14.56±0.27) was significantly higher than that in the control group (3.11±0.13) ( F=10 784.69, P<0.01). Conclusions:Ethephon can thicken the seminiferous tubules of newborn and young rats, cause the germ cells to arrange disorderly, promote the apoptosis of spermatogenic cells and reduce the ability of spermatogenesis.Moreover, a longer exposure of the rats to a higher concentration of Ethephon will result in more serious damage to testicular tissues.

On January 22, 2020, China National Center for Bioinformation (CNCB) released the 2019 Novel Coronavirus Resource (2019nCoVR), an open-access information resource for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 2019nCoVR features a comprehensive integra-tion of sequence and clinical information for all publicly available SARS-CoV-2 isolates, which are manually curated with value-added annotations and quality evaluated by an automated in-house pipeline. Of particular note, 2019nCoVR offers systematic analyses to generate a dynamic landscape of SARS-CoV-2 genomic variations at a global scale. It provides all identified variants and their detailed statistics for each virus isolate, and congregates the quality score, functional annotation,and population frequency for each variant. Spatiotemporal change for each variant can be visualized and historical viral haplotype network maps for the course of the outbreak are also generated based on all complete and high-quality genomes available. Moreover, 2019nCoVR provides a full collection of SARS-CoV-2 relevant literature on the coronavirus disease 2019 (COVID-19), including published papers from PubMed as well as preprints from services such as bioRxiv and medRxiv through Europe PMC. Furthermore, by linking with relevant databases in CNCB, 2019nCoVR offers data submission services for raw sequence reads and assembled genomes, and data sharing with NCBI. Collectively, SARS-CoV-2 is updated daily to collect the latest information on genome sequences, variants, hap-lotypes, and literature for a timely reflection, making 2019nCoVR a valuable resource for the global research community. 2019nCoVR is accessible at https://bigd.big.ac.cn/ncov/.

Objective:To evaluate the reliability and validity of Chinese version of Ureteral Stent-Related Symptom Questionnaire (USSQ) so as to provide a scientific tool for the symptom assessment of patients with indwelling ureteral stents.Methods:Following the translation principle of Brislin, the cultural adjustment of the questionnaire was completed according to the process of literal translation of the scale, back translation, expert committee discussion and pre-experiment, and the Chinese version of USSQ was formed. Inpatients with ureteral stents in the Urology Departments of 3 ClassⅢ Grade A hospitals in Urumqi from April 2018 to February 2019 were selected as research objects, and 485 questionnaires were collected by analyzing and testing the items and reliability and validity of the questionnaire.Results:Finally, 462 valid questionnaires were collected. The analysis results of the project suggested that the two items of S1 and S2 in the Chinese version of USSQ in the field of sexual life could be deleted ( P>0.05) , however, considering the rationality of the structure of the questionnaire, S1 should be retained. Cronbach's α coefficient of the questionnaire was 0.923, Cronbach's α coefficient of the six dimensions of urinary symptoms, physical pain, total health status, work performance, sexual life and additional problems was 0.703 to 0.918, retest reliability was 0.885, retest correlation coefficient of the six dimensions was 0.338 to 0.849 ( P<0.05) , and half reliability was 0.628. The content validity of the questionnaire was 0.887. Through exploratory factor analysis, the cumulative variance contribution rate of the nine principal factors was 68.995%. In the correlation analysis, except for the correlation coefficients in the field of sexual life and other fields were from 0.014 to 0.101 ( P>0.05) , the correlation coefficients in other dimensions were from 0.406 to 0.629 ( P<0.01) . The test results of criterion validity showed that the correlation coefficients of each dimension of the questionnaire with International Prostate Symptom Score (IPSS) , Incontinence Quality of Life Scale (I-QOL) and The 12-Item Short Form Health Survey (SF-12) were from 0.35 to 0.49 ( P<0.01) . Conclusions:In addition to the field of sexual life, the Chinese version of USSQ has good reliability and validity in the evaluation of symptoms in other fields, which can provide a basis for the investigation and improvement of related symptoms in patients with indwelling ureteral stents in China.

Objective: To investigate the effect of Ethephon on the testis pathological structure and apoptosis of spermatogenic cell in offspring male rats. Methods: Twenty-four healthy female SD rats of 45 days old were randomly divided into control group, low-dose Ethephon group, medium-dose Ethephon group and high-dose Ethephon group according to body weight.The male rats of the same age were selected to mate with female rats.The rats were fed with Ethephon solution of different concentrations or 9 g/L saline every day, and they were continued to be fed with Ethephon during pregnancy and lactation.At the age of 7 days and 14 days, 10 offspring male rats were randomly selec-ted from each group and were put to death.The testicular tissue was stained with HE, and the morphological changes in the testis were observed with light microscope; the apoptotic cells were labeled with terminal deoxynucleotidyl transfe-rase dUTP nick-end labeling (TUNEL method) and the apoptosis index(AI) of testis spermatogenic cells was detected with fluorescence microscope. Results: At the age of 7 days, the testis internal structure of the control group developed well, and the spermatic tubules were neatly and compactly arranged.In the low-dose Ethephon group, the seminiferous tubules of the testis were slightly smaller and the spermatogenic cells were loosely arranged compared with the control group.In the medium-dose Ethephon group, the testis seminiferous tubules were slightly disordered and the cell gap increased.In the high-dose Ethephon group, the testis development was poor, the diameter of seminiferous tubules decreased significantly, and the spermatogenic cells arrangement was in disorder.There was no statistically significant difference in spermatogenic cell AI between the low-dose group [(0.54±0.10)%] and the control group[(0.53±0.09)%] (P>0.05), while the spermatogenic cell AI in the medium-dose Ethephon group [(0.63±0.11)%] and the high-dose Ethephon group [(0.81±0.06)%] were higher than that in the control group, thus there exists a statistically significant difference (all P<0.01). The spermatogenic cell AI in the low-dose Ethephon group [(0.54±0.10)%] was lower than that in the medium-dose Ethephon group [(0.63±0.11)%], and the difference was statistically significant (P<0.05). The spermatogenic cell AI in the medium-dose Ethephon group was higher than that in the high-dose Ethephon group, and the difference was statistically significant (P<0.01). At the age of 14 days, the spermatogenic cells AI in control group, low-dose Ethephon group, medium-dose Ethephon group and high-dose Ethephon group were (0.54±0.08)%, (0.65±0.11)%, (0.77±0.11)%, and (0.88±0.10)% respectively, and the spermatogenic cells AI in all groups increased gradually, in which the differences were statistically significant (all P<0.01). Conclusions Excessive dose of Ethephon can induce pathological changes in testicular tissue and increase the apoptosis of spermatogenic cells, resulting in low fertility of offspring rats.

PURPOSE: This study was aimed to investigate the effect of pseudolaric acid B (PAB) on proliferation, invasion and epithelial-to-mesenchymal transition (EMT) in pancreatic cancer cells and to explore the possible mechanism. MATERIALS AND METHODS: The pancreatic cancer cell line SW1990 was cultured and treated with PAB dose- and time-dependent manners. Cell proliferation and invasion ability were measured by MTT assay and Matrigel/Transwell test, respectively. Semi-quantitative real-time polymerase chain reaction and Western blotting were conducted to detect the expression of EMT markers and the key molecules. Finally, nude mice subcutaneous transplantation tumor model was used to confirm the therapy efficacy of PAB. RESULTS: PAB could inhibit SW1990 cell proliferation and invasion in time- and dose-dependent manners. Vimentin, fibronectin, N-cadherin, Snail, Slug, YAP, TEAD1, and Survivin were down-regulated (p < 0.01), while E-cadherin, caspase-9, MST1, and pYAP were up-regulated (p < 0.05). Combined PAB and gemcitabine treatment markedly restricted the tumor growth compared with gencitabin or PAB alone groups. CONCLUSION: PAB could inhibit the proliferation and invasion ability of pancreatic cancer cells through activating Hippo-YAP pathway and inhibiting the process of EMT.
Animals ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/metabolism ; Cadherins ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation/drug effects ; Cytokines ; Deoxycytidine/analogs & derivatives ; Deoxycytidine/pharmacology ; Deoxycytidine/therapeutic use ; Diterpenes/pharmacology ; Diterpenes/therapeutic use ; Epithelial-Mesenchymal Transition/drug effects ; Female ; Humans ; Mice, Nude ; Neoplasm Invasiveness ; Pancreatic Neoplasms/diet therapy ; Pancreatic Neoplasms/pathology ; Real-Time Polymerase Chain Reaction ; Signal Transduction/drug effects ; Vimentin/metabolism

Objective To explore the clinical effect of negative pressure suction combined with washing by Chinese herbal bath to treat small penis in obese children at school age.Methods The data of 60 obese cases with small penis at the First Affiliated Hospital of Xinxiang Medical University from June 2016 to September 2017 were retrospectively analyzed,the age ranged from 7 to 15 years old,and the average age was (11.1 ± 2.0) years old,the body mass index(BMI) was 19.2-30.5,and the average BMI was 24.5 ± 2.6.Treatment group received the penis treatment with negative pressure instrument suction supplemented by traditional Chinese medicine bath treatment,once a day,20 minutes each times,10 days asa course,a totally of 2 treatment courses.Other 46 cases of male children who came to our hospital in the same period for physical exam were selected as healthy control group,aged 8-14 years old [(11.2 ± 2.1) years],BMI:14.6-21.0,mean 18.1 ± 1.6,and the relaxation length and elongation of 20 days before and after the normal growth state of the penis in the control group were measured.The length and elongation of the penis in the treatment group were compared with those of the healthy control group before and after treatment.Results The length of penile relaxation in the treatment group increased to (3.76 ±0.61) cm in comparison with that before treatment (2.94 ± 0.52) cm,and the difference was statistically significant (t =-7.82,P ＜ 0.05);the penis elongation increased compared with that before treatment (4.29 ± 0.67) cm to (5.37 ± 0.82) cm,and the difference was statistically significant (t =-7.91,P ＜ 0.05).The initial relaxation length of the control group was (3.96 ± 0.65) cm,(4.07 ± 0.65) cm 20 days after natural growth,the difference was not statistically significant (t =-0.82,P ＞ 0.05),the initial stretch length was (5.96 ± 0.92) cm,(6.03 ± 0.90) cm natural growth after 20 days,and the difference was not statistically significant (t =-0.37,P ＞ 0.05).Before and after treatment,the length of penis relaxation and elongation were significantly increased,but they didn't reach the normal level at the same age.Conclusions Negative pressure suction supplemented with Chinese herbal medicine bath has a significant effect on treating obese children with small penis.