Objective:To investigate the effects of chronic persistent hypoxia on hepatic function, histological morphology, and ultrastructure in aged mice, and to evaluate the protective role of pyrroloquinoline quinone(PQQ).Methods:Thirty-two 2-month-old (young group)and thirty-two 18-month-old(aged group)male C57BL6/J mice were each randomly divided into four groups (n=8 per group): normoxia+ normal saline (NS)group, normoxia+ PQQ group, hypoxia+ NS group, and hypoxia+ PQQ group.The normoxia+ NS and normoxia+ PQQ groups were housed under normoxic conditions[fraction of inspired oxygen(FiO 2)=21%], while the hypoxia+ NS and hypoxia+ PQQ groups were continuously exposed to a hypoxic environment[FiO 2=(10±0.5)%]simulated by a custom-made hypoxic chamber, maintaining a constant oxygen concentration for 24 hours per day.The normoxia+ NS and hypoxia+ NS groups received daily intragastric administration of NS, whereas the normoxia+ PQQ and hypoxia+ PQQ groups received daily intragastric administration of PQQ disodium salt(8 mg·kg -1·d -1).After 8 weeks of continuous intervention, blood samples were collected to measure red blood cell count, hemoglobin levels, and liver function-related biochemical indicators.Lung tissues were processed for HE staining, and liver tissues were processed for both HE staining and electron microscopy.The histological and ultrastructural features of each group were observed under light and electron microscopy, respectively, and the differences between the groups were compared and analyzed. Results:Compared with the normoxia+ NS groups, both young and aged hypoxia+ NS groups exhibited significant pulmonary arteriole narrowing( P<0.001), with markedly elevated red blood cell count and hemoglobin levels (all P<0.001), which were not alleviated by PQQ.Compared with the young normoxia+ NS group, the young hypoxia+ NS group showed significantly higher alanine aminotransferase (ALT)and lactate dehydrogenase (LDH)levels( Z=2.72, 2.53, P=0.007, 0.011), whereas the young hypoxia+ PQQ group exhibited LDH levels similar to those of the young normoxia+ NS group.The aged hypoxia+ NS group exhibited significant ALT elevation( t=2.66, P=0.013)compared with the aged normoxia+ NS group.Light microscopy revealed hepatocyte ballooning degeneration, mild fatty accumulation, and focal necrosis around central veins in the young hypoxia+ NS group, while the young hypoxia+ PQQ group exhibited no significant pathological damage but displayed numerous deeply stained binucleated hepatocytes.The aged normoxia+ NS group demonstrated hepatocyte ballooning degeneration and inflammatory cell infiltration around central veins, whereas the aged normoxia+ PQQ group exhibited no obvious pathological damage with scattered deeply stained binucleated hepatocytes.The aged hypoxia+ NS group exhibited significant necrosis following physiological oxygen concentration gradient distribution, while the aged hypoxia+ PQQ group displayed no obvious pathological damage with scattered deeply stained binucleated hepatocytes.Electron microscopy revealed that the aged normoxia+ NS group had reduced mitochondrial electron density ( P<0.001)and less developed rough endoplasmic reticulum compared with the young normoxia+ NS group.The young hypoxia+ NS group exhibited a smaller mitochondrial area( P<0.001), decreased mitochondrial matrix electron density( P<0.001), blurred or absent mitochondrial cristae, inactive rough endoplasmic reticulum, and increased accumulation of glycogen and lipid droplets compared with the young normoxia+ NS group, while the young hypoxia+ PQQ group maintained mitochondrial matrix electron density comparable to the young normoxia+ NS group.The aged hypoxia+ NS group exhibited larger mitochondrial area( P=0.001), decreased mitochondrial matrix electron density( P<0.001), blurred or absent mitochondrial cristae, mitochondrial edema, increased lysosomes, and elevated cytoplasmic electron density compared with the aged normoxia+ NS group.The aged hypoxia+ PQQ group exhibited reduced mitochondrial area( P<0.001)and restored mitochondrial matrix electron density to levels comparable with the aged normoxia+ NS group.The aged normoxia+ PQQ group demonstrated increased mitochondrial matrix electron density compared with the aged normoxia+ NS group( P<0.001). Conclusions:Chronic persistent hypoxia induces hepatic functional, histological and ultrastructural damage in mice, with more pronounced effects in aged animals.PQQ provides a certain degree of protection against these injuries.

Objective:To investigate the effects of chronic persistent hypoxia on hepatic function, histological morphology, and ultrastructure in aged mice, and to evaluate the protective role of pyrroloquinoline quinone(PQQ).Methods:Thirty-two 2-month-old (young group)and thirty-two 18-month-old(aged group)male C57BL6/J mice were each randomly divided into four groups (n=8 per group): normoxia+ normal saline (NS)group, normoxia+ PQQ group, hypoxia+ NS group, and hypoxia+ PQQ group.The normoxia+ NS and normoxia+ PQQ groups were housed under normoxic conditions[fraction of inspired oxygen(FiO 2)=21%], while the hypoxia+ NS and hypoxia+ PQQ groups were continuously exposed to a hypoxic environment[FiO 2=(10±0.5)%]simulated by a custom-made hypoxic chamber, maintaining a constant oxygen concentration for 24 hours per day.The normoxia+ NS and hypoxia+ NS groups received daily intragastric administration of NS, whereas the normoxia+ PQQ and hypoxia+ PQQ groups received daily intragastric administration of PQQ disodium salt(8 mg·kg -1·d -1).After 8 weeks of continuous intervention, blood samples were collected to measure red blood cell count, hemoglobin levels, and liver function-related biochemical indicators.Lung tissues were processed for HE staining, and liver tissues were processed for both HE staining and electron microscopy.The histological and ultrastructural features of each group were observed under light and electron microscopy, respectively, and the differences between the groups were compared and analyzed. Results:Compared with the normoxia+ NS groups, both young and aged hypoxia+ NS groups exhibited significant pulmonary arteriole narrowing( P<0.001), with markedly elevated red blood cell count and hemoglobin levels (all P<0.001), which were not alleviated by PQQ.Compared with the young normoxia+ NS group, the young hypoxia+ NS group showed significantly higher alanine aminotransferase (ALT)and lactate dehydrogenase (LDH)levels( Z=2.72, 2.53, P=0.007, 0.011), whereas the young hypoxia+ PQQ group exhibited LDH levels similar to those of the young normoxia+ NS group.The aged hypoxia+ NS group exhibited significant ALT elevation( t=2.66, P=0.013)compared with the aged normoxia+ NS group.Light microscopy revealed hepatocyte ballooning degeneration, mild fatty accumulation, and focal necrosis around central veins in the young hypoxia+ NS group, while the young hypoxia+ PQQ group exhibited no significant pathological damage but displayed numerous deeply stained binucleated hepatocytes.The aged normoxia+ NS group demonstrated hepatocyte ballooning degeneration and inflammatory cell infiltration around central veins, whereas the aged normoxia+ PQQ group exhibited no obvious pathological damage with scattered deeply stained binucleated hepatocytes.The aged hypoxia+ NS group exhibited significant necrosis following physiological oxygen concentration gradient distribution, while the aged hypoxia+ PQQ group displayed no obvious pathological damage with scattered deeply stained binucleated hepatocytes.Electron microscopy revealed that the aged normoxia+ NS group had reduced mitochondrial electron density ( P<0.001)and less developed rough endoplasmic reticulum compared with the young normoxia+ NS group.The young hypoxia+ NS group exhibited a smaller mitochondrial area( P<0.001), decreased mitochondrial matrix electron density( P<0.001), blurred or absent mitochondrial cristae, inactive rough endoplasmic reticulum, and increased accumulation of glycogen and lipid droplets compared with the young normoxia+ NS group, while the young hypoxia+ PQQ group maintained mitochondrial matrix electron density comparable to the young normoxia+ NS group.The aged hypoxia+ NS group exhibited larger mitochondrial area( P=0.001), decreased mitochondrial matrix electron density( P<0.001), blurred or absent mitochondrial cristae, mitochondrial edema, increased lysosomes, and elevated cytoplasmic electron density compared with the aged normoxia+ NS group.The aged hypoxia+ PQQ group exhibited reduced mitochondrial area( P<0.001)and restored mitochondrial matrix electron density to levels comparable with the aged normoxia+ NS group.The aged normoxia+ PQQ group demonstrated increased mitochondrial matrix electron density compared with the aged normoxia+ NS group( P<0.001). Conclusions:Chronic persistent hypoxia induces hepatic functional, histological and ultrastructural damage in mice, with more pronounced effects in aged animals.PQQ provides a certain degree of protection against these injuries.

Objective:To explore the safety and efficacy of radiofrequency in the treatment of overactive bladder(OAB).Methods:A prospective, multicenter, non-randomized controlled trial was conducted. Eligible patients were divided into test group and control group in Zhejiang Provincial People’Hospital, The First Affiliated Hospital of Wenzhou Medical University, and Sir Run Run Shaw Hospital affiliated to Zhejiang University School of Medicine from March 2019 to June 2020. Inclusion criteria: patients diagnosed with OAB, and bladder capacity>100ml. Exclusion criteria: pregnant and lactating women; patients with secondary OAB symptoms such as urinary tract obstruction; patients with uncontrolled urinary tract infection within 1 week; patients in stable stage by using other treatment methods; patients implanted with any nerve stimulator, cardiac pacemaker or implantable defibrillator; patients with malignant tumors, serious cardiovascular, cerebrovascular diseases, renal insufficiency or received BTX treatment in recent 12 months. The patients were allocated to test group and the control group in a ratio of 2∶1 according to the time sequence of the visit. The patients in the test group were treated with radiofrequency treatment. After entering the group, they were treated for 4 times at the 1st, 2nd, 7th and 8th week respectively. In the control group, the energy was turned off during the radiofrequency treatment. The patients were followed-up every week until the end of the 12th week. The treatment success rate [the average frequency of urination in 24 h was reduced more than 50% from the baseline or returned to the normal (≤8 times/day) or the average frequency of urgent urination in 24 h was reduced more than 50% from the baseline], the frequency of urination, urgent urination and nocturnal urination before and after treatment, the residual urine volume of the bladder, the quality of life (QOL) score and the occurrence of catheter related adverse events in two groups were compared.Results:114 patients were enrolled in the study, including 76 patients in the test group and 38 patients in the control group. There were no significant differences in the age [(44.2±12.8) vs. (41.7 ± 12.1) years old], male female ratio (13/63 vs. 4/34), average course of disease [2.0(1.2, 5.0) vs. 2.0 (1.0, 4.0) years], the frequency of urination[12.8 (10.6, 16.8) vs. 12.8 (10.3, 17.0) times], urgency urination [11.8(9.3, 15.8) vs. 11.8 (9.0, 17.0) times], nocturia [2.7 (1.3, 3.7) vs. 2.3(0.7, 3.3) times], residual urine volume of bladder [12.0 (3.0, 28.0) vs. 14.0 (3.7, 20.0) ml ] and the QOL score [5.0(4.0, 5.0) vs. 4.0(4.0, 5.0)]before the treatment between the two groups ( P>0.05). The treatment success rate in the test group was 76.3% (58/76), while 26.3% (10/38) in the control group, with a statistically significant difference ( P<0.01). There were significant differences between the test group and control group in the frequency of urination [9.7 (7.7, 12.0) vs. 12.9 (9.6, 15.7) times], urgent urination [7.3 (5.0, 10.0) vs. 11.7 (7.3, 15.3) times], nocturia [1.3 (0.7, 2.0) vs. 1.7 (1.0, 3.0) times] and the QOL score of the patients[3.0(1.0, 3.0) vs. 4.0(3.0, 4.5)]after the treatment(all P<0.05). The frequency of urination, urgency urination, nocturia, the residual urine volume and the QOL score in the test group were significantly improved ( P<0.05) after the treatment.The frequency of urination, nocturia, residual urine volume and the QOL score in the control group were improved ( P<0.05) after the treatment. 13 (11.4%) patients had catheter related adverse events. In the test group and the control group, there were 7 cases of macroscopic hemorrhage caused by the placement of instruments (5/76 vs. 2/38), 5 cases of acute urinary tract infection within 3 days (3/76 vs. 2/38), and 1 case of instrument breakage (catheter breakage) (0/76 vs. 1/38). There were no significant differences in the adverse events between the two groups ( P> 0.05). Conclusions:Radiofrequency treatment of OAB can effectively improve the symptoms of patients, improve the QOL of patients, and has low incidence of adverse events, with good efficacy and safety.

Abstract: Objective To investigate the clinical types of children's tinea capitis and the distribution of fungal pathogens in Wuhan from 2011 to 2020, and to provide scientific basis for the prevention, diagnosis and treatment of children's tinea capitis. Methods Laboratory data of children with tinea capitis in outpatient and inpatient department of dermatology in Wuhan No.1 Hospital from January 2011 to December 2020 were collected. A total of 542 cases of pediatric tinea capitis were included, with 239 male cases and 303 female cases. Microscopic examination of fungi and culture identification were performed on the affected skin lesions of the children. Chi-square test was used to analyze the differences in pathogen spectrum of children with different age groups and clinical type. Results Among the pediatric tinea capitis patients, the age group with the highest prevalence was preschool children（3 to <7 years old), accounting for 48.52%（263/542). The top three pathogenic fungi were Trichophytes violaceum（49.26%, 267/542), Microsporum canis（31.55%, 171/542) and Trichophyton mentagrophytes （9.96%, 54/542). Trichophyton violaceum was the main pathogen in all ages, followed by Microsporum canis. The infection rate of Microsporum canis in children over 7 years old was lower than that in children under 7 years old, and the infection rate of Trichophyton rubrum in infants was higher than that in other ages. The distribution of Trichophytes violaceum, Trichophyton mentagrophytes, Nannizzia gypseum and Microsporum ferrugineum was uniform in all age groups. Trichophytes violaceum and Trichophyton tousurans mainly caused black-dot ringworm, Microsporum canis mainly caused tinea alba, Trichophyton mentagrophytes,Nannizzia gypseum and Trichophytonrubrum mainly caused kerion. Except for Microsporum ferrugineum, the composition ratios of other fungi species showed statistically significant differences among different clinical types of tinea capitis（P<0.05). Conclusions Preschool children are the most commonly affected age group by pediatric tinea capitis, and black-dot ringworm caused by Trichophytes violaceum is the main clinical type. Analysis of the high-riskage group, pathogenic fungi and clinical types of tinea capitis in children can enhance the understanding of its epidemiological characteristics, which is helpful for early diagnosis and targeted standardized treatment of pediatric tinea capitis.

Aromatic compounds are a class of organic compounds with benzene ring(s). Aromatic compounds are hardly decomposed due to its stable structure and can be accumulated in the food cycle, posing a great threat to the ecological environment and human health. Bacteria have a strong catabolic ability to degrade various refractory organic contaminants (e.g., polycyclic aromatic hydrocarbons, PAHs). The adsorption and transportation are prerequisites for the catabolism of aromatic compounds by bacteria. While remarkable progress has been made in understanding the metabolism of aromatic compounds in bacterial degraders, the systems responsible for the uptake and transport of aromatic compounds are poorly understood. Here we summarize the effect of cell-surface hydrophobicity, biofilm formation, and bacterial chemotaxis on the bacterial adsorption of aromatic compounds. Besides, the effects of outer membrane transport systems (such as FadL family, TonB-dependent receptors, and OmpW family), and inner membrane transport systems (such as major facilitator superfamily (MFS) transporter and ATP-binding cassette (ABC) transporter) involved in the membrane transport of these compounds are summarized. Moreover, the mechanism of transmembrane transport is also discussed. This review may serve as a reference for the prevention and remediation of aromatic pollutants.
Humans ; Adsorption ; Bacteria/metabolism* ; Organic Chemicals ; Biological Transport ; ATP-Binding Cassette Transporters ; Polycyclic Aromatic Hydrocarbons/metabolism*

Objective:To optimize indirect immunofluorescence on salt-split skin (IIF-SSS), and to evaluate its performance in detection of bullous pemphigoid (BP) antibodies.Methods:Normal human foreskin and non-foreskin skin tissues were used to prepare salt-split substrates under 3 different experimental conditions: traditional group rotated at 4 ℃ for 48 - 72 hours, low-temperature immersion group soaked at 4 ℃ for 48 - 72 hours, room-temperature immersion group soaked at 25 ℃ (range: 23 - 27 ℃) for 24 hours. Serum samples were obtained from 20 patients with bullous pemphigoid (BP) in Hospital of Dermatology, Chinese Academy of Medical Sciences between August 2019 and August 2020, and subjected to IIF on the intact skin or salt-split substrates by using a multiple dilution method. Paired-sample t test was used for comparisons of means between two paired samples. Results:No dermal-epidermal separation was observed in the substrates prepared in the low-temperature immersion group at 48 - 72 hours, while dermal-epidermal separation occurred in the lower lamina lucida of the foreskin and non-foreskin substrates in the room-temperature immersion group and the traditional group. For the 20 patients with BP, the reciprocal end-point titers ( M[ Q1, Q3]) detected with the salt-split non-foreskin skin and salt-split foreskin in the room-temperature immersion group, and with the salt-split non-foreskin skin in the traditional group were 5 120 (2 560, 17 920), 1 280 (640, 2 560), 1 280 (640, 2 560), respectively. Moreover, 19 (95%) patients with BP showed that the reciprocal end-point titers detected with the substrates in the room-temperature immersion group were 1 - 5 times those in the traditional group ( t = 8.04, P<0.001), suggesting that the performance of salt-split skin in the room-temperature immersion group was superior to that in the traditional group in the detection of BP antibodies; however, there was no significant difference in the reciprocal end-point titers of BP antibodies between the salt-split foreskin in the room-temperature immersion group and salt-split non-foreskin skin in the traditional group ( t<0.001, P>0.05). The reciprocal end-point titers in 20 BP sera detected by conventional IIF on the intact non-foreskin skin and foreskin were 320 (160, 640) and 480 (160, 1 120), respectively; the reciprocal end-point titers detected by IIF on the salt-split foreskin and non-foreskin skin in the room-temperature immersion group, as well as on the salt-split non-foreskin skin in the traditional group, were all consistent with or 1 - 7 times higher than those detected by conventional IIF ( t = 6.47, 14.83, 5.26, respectively, all P<0.001) . Conclusion:The soaking method at room temperature 25 ℃ (23 - 27 ℃) for preparing salt-split substrates has advantages of short duration and simple procedure, and the sensitivity of IIF-SSS using the substrates prepared by this method is equal or superior to the traditional salt-split method for detecting BP antibodies.

Objective:To explore the clinical features of transplanted renal artery stenosis after pediatric donor kidneys in children.Methods:We retrospectively summarized the clinical data in five cases of transplanted renal artery stenosis undergoing deceased pediatric donor kidney transplantation from May 1, 2014 to June 30, 2021.Donor/receptor characteristics, diagnosis, treatment and prognosis were recorded.The median follow-up period was 29 months.The median age of five donors and recipients was 9 and 132 months respectively.En bloc renal allograft( n=2)and single kidney transplantation( n=3)were performed.End-to-side anastomosis was performed for renal arteries.The median diagnostic time of renal artery stenosis was 10(3-60)months post-transplantation.Except for one 3-year-old recipient with an earlier onset of stenosis, four stenotic cases during a rapid growth period had a maximal height increase of 30 cm post-transplantation.Three of them had a history of surgery at graft site, including previous kidney transplantation( n=1)and transplant urinary tract reconstruction( n=2). All five cases had hypertension and two showed an elevated serum level of creatinine.Ultrasound indicated a significantly elevated flow rate of >300 cm/s( n=4)and CTA/MRA indicated that the degrees of stenosis varied from 50% to 95%( n=5). Results:After balloon dilatation, stenosis either improved( n=2)or relapsed( n=2). Further stenting succeed( n=1)or failed( n=1). One case of stenosis was relieved partially after 6-month observation without any invasive treatment. Conclusions:As a serious complication, transplant renal artery stenosis is common after pediatric donor kidney transplantation.Too small size in donor kidney and rapid recipient growth may be specific risk factors.After diagnosis, balloon dilation is a preferred treatment.Stent placement should be cautiously employed.

Objective:To establish and verify a dynamic web-based nomogram for predicting futile recanalization after thrombectomy in acute ischemic stroke.Methods:Three hundred and four acute ischemic stroke patients admitted to the Second Affiliated Hospital of Soochow University from May 2017 to April 2021 were retrospectively enrolled. All these patients underwent mechanical thrombectomy and obtained successful recanalization. The eligible patients were randomly divided into training group ( n=216) and test group ( n=88) by 7∶3. The nomogram was established and internally validated with the data of the training group, and externally validated with the data of the test group. For the training group, multivariate Logistic regression analysis was performed by including all variables with P<0.05 in univariate analysis, and the independent predictors of futile recanalization were screened out to construct a nomogram. In the training group and the test group, the performance of the nomogram was verified by C-index, calibration chart and decision curve analysis respectively. Results:No significant difference was detected between the training group and the test group in futile recanalization [134/216 (62.0%) vs 56/88 (63.6%), χ 2=0.07, P=0.794]. Multivariate Logistic regression analysis showed that age ( OR=1.04,95% CI 1.00-1.08, P=0.033), National Institutes of Health Stroke Scale (NIHSS) score on admission ( OR=1.11,95% CI 1.04-1.19, P=0.001), neutrophil to lymphocyte ratio ( OR=1.19,95% CI 1.07-1.32, P=0.001), glycated hemoglobins ( OR=2.02,95% CI 1.34-3.05, P<0.001), poor collateral status ( OR=10.87,95% CI 4.08-29.01, P<0.001), postoperative high density ( OR=11.38,95% CI 4.56-28.40, P<0.001) were independent risk factors for futile recanalization. The C-index of this nomogram in the training group and the test group was 0.92 (95% CI 0.877-0.954, P<0.001) and 0.93 (95% CI 0.87-0.98, P<0.001), respectively. Conclusion:This web-based nomogram, including age, NIHSS score on admission, neutrophil to lymphocyte ratio, glycated hemoglobin, poor collateral status and postoperative high density, predicted individual probability of futile recanalization after mechanical thrombectomy with good discrimination and clinical utility.

Objective:To summarize the clinical characteristics and treatment of cytomegalovirus(CMV)infection in pediatric kidney transplant patients.Methods:From May 2014 to July 2021, a total of 9 cases(8.65%)of 104 pediatric kidney transplant recipients were diagnosed with CMV infection in our centre.Retrospective data was collected for these 9 paediatric recipients.The clinical characteristics of the disease, treatment data and outcomes were summarized.Results:The median age of the 9 children was 10 years(0.25-15 years), 6 of whom were treated with polyclonal antibody for immunity induction.CMV IgG was negative in 4 children before renal transplantation.Only one patient received anti-CMV prophylaxis.The median time from transplant to the diagnosis of CMV infection was 22(7-15)days.Among the 9 children, 7 had fever, pneumonia and diarrhea, 2 had no typical symptoms, three patients were complicated with viral, bacterial or fungal infections.Acute rejection occurred in 3 patients at the same time as CMV infection or after CMV DNA turned negative.Nine patients were cured and discharged after ganciclovir or valganciclovir treatment.Median time of CMV DNA negative transformation was 32(17-90)days.Conclusions:Pediatric transplant recipients are at particularly elevated risk of CMV disease.Antiviral prophylaxis should be initiated early after transplantation.

Objective:To investigate the clinical effect of saphenous artery perforating branch flap in repairing anterior knee soft tissue defects with patella exposure.Methods:From July 2010 to September 2017, 12 patients whose patella exposed due to anterior soft tissue defects of knee were treated. The 12 cases included 8 males and 4 females, aged from 24 to 60 years (42.6 years on average). The causes of injury included car accident in 5 cases, rolling injury in 3 cases, burn and scald in 2 cases, and postoperative patella fracture in 2 cases. The areas of the wounds ranged from 6 cm × 5 cm to 8 cm × 7 cm. The wounds were repaired by saphenous artery perforating flaps with the area ranged from 7 cm × 6 cm to 9 cm × 8 cm, and the donor sites were repaired with free skin grafting.Results:All the 12 cases ended up with the wounds healed primarily and no postoperative complications. The 12 cases were followed up for 6 months to 24 months, with an average of 12 months. The color, texture and appearance of the flaps were good, the thickness of the flap were moderate, and the function of knee joint was recovered well. Skin flap sensation was graded according to the criteria of the British Medical Research Society: 2 cases for Grade S 3+, 6 cases for Grade S 3 and 4 cases for Grade S 2. Conclusions:Saphenous artery perforating flap is an effective method to repair anterior knee soft tissue defect and patella exposure.