Objective To analyze the status of persistent human papillomavirus (HPV) infection and the distribution of viral subtypes in the Zhengzhou region. Methods Clinical data of 55239 patients who underwent HPV-DNA genotyping tests from 2018 to 2024 were collected. On the basis of HPV follow-up results, patients were divided into three groups: 849 cases of infection with the same HPV type, 255 cases of persistent infection with different HPV types, and 857 cases of transient HPV infection. Results Among the 9232 initially-screened patients who were positive with HPV, the high-risk HPV (HR-HPV) positive rate was 84.6% (7813/9232), and predominant subtypes were HPV-16 (20.8%), HPV-52 (17.2%), and HPV-53 (9.6%). The low-risk HPV (LR-HPV) positive rate was 15.4% (1419/9232), mainly HPV-81 (28.1%) and HPV-42 (27.0%). Among the 1961 follow-up cases, the rates of persistent and non-persistent infections with the same HPV type were 35.7% (701/1961) and 7.5% (148/1961), respectively. The rates of persistent and non-persistent infections with different HPV types were 10.9% (214/1961) and 2.1% (41/1961), respectively. Meanwhile, 43.7% (857/1961) tested negative upon follow-up. Among the 701 cases of persistent infection with the same HPV type, HR-HPV accounted for 85.7% (601/701), and LR-HPV accounted for 14.3% (100/701). Among the 214 cases of persistent infection with different HPV types, 89.7% (192/214) were high-risk transitions, and 10.3% (22/214) were low-risk transitions. Regardless of HPV types, HR-HPV was more likely to cause persistent infection than LR-HPV. In addition, over 60% of HR-HPV persistent infections resolved within 18 months, 30% developed into persistent infections, and only 15% of patients had persistent infections that last more than 24 months. Conclusion Persistent HPV infections are predominantly high-risk types. Most patients clear the infection within 18 months, approximately 30% develop persistent infections, and about 15% of patients have persistent infections that last more than 24 months. However, the HR-HPV persistent infection rates across different age groups slightly differ.

Atopic dermatitis (AD) is a prevalent inflammatory skin disorder in which patients experience recurrent eczematous lesions and intense itching. The colonization of Staphylococcus aureus (S. aureus) is correlated with the severity of the disease, but its role in AD development remains elusive. Using single-cell RNA sequencing, we uncovered that keratinocytes activate a distinct immune response characterized by induction of Il24 when exposed to methicillin-resistant S. aureus (MRSA). Further experiments using animal models showed that the administration of recombinant IL-24 protein worsened AD-like pathology. Genetic ablation of Il24 or the receptor Il20rb in keratinocytes alleviated allergic inflammation and atopic march. Mechanistically, IL-24 acted through its heterodimeric receptors on keratinocytes and augmented the production of IL-33, which in turn aggravated type 2 immunity and AD-like skin conditions. Overall, these findings establish IL-24 as a critical factor for onset and progression of AD and a compelling therapeutic target.
Dermatitis, Atopic/genetics* ; Interleukins/metabolism* ; Animals ; Methicillin-Resistant Staphylococcus aureus/immunology* ; Mice ; Keratinocytes/microbiology* ; Humans ; Interleukin-33/immunology* ; Inflammation/microbiology* ; Staphylococcal Infections/microbiology* ; Disease Models, Animal ; Hypersensitivity/microbiology* ; Mice, Inbred C57BL

Osteoporotic thoracolumbar fracture in the elderly will seriously reduce their quality of life and life expectancy. For osteoporotic thoracolumbar fracture in the elderly, spinal reconstruction is necessary, which should comprehensively consider factors such as the physical condition, fracture type, clinical characteristics and osteoporosis degree. While there lacks relevant clinical norms or guidelines on selection of spinal reconstruction strategies. In order to standardize the concept of spinal reconstruction for osteoporotic thoracolumbar fracture in the elderly, based on the principles of scientificity, practicality and progressiveness, the authors formulated the Clinical guideline for spinal reconstruction of osteoporotic thoracolumbar fracture in elderly patients ( version 2022), in which suggestions based on evidence of evidence-based medicine were put forward upon 10 important issues related to the fracture classification, non-operative treatment strategies and surgical treatment strategies in spinal reconstruction after osteoporosis thoracolumbar fracture in the elderly, hoping to provide a reference for clinical treatment.

Background::The study aimed to describe the aortic valve morphology in Chinese patients underwent transcatheter aortic valve replacement (TAVR) for symptomatic severe aortic stenosis (AS), and the impact of sizing strategies and related procedural outcomes.Methods::Patients with severe AS who underwent TAVR were consecutively enrolled from 2012 to 2019. The anatomy and morphology of the aortic root were assessed. "Downsize" strategy was preformed when patients had complex morphology. The clinical outcomes of patients who performed downsize strategy were compared with those received annular sizing strategy. The primary outcome was device success rate, and secondary outcomes included Valve Academic Research Consortium-3 clinical outcomes variables based on 1-year follow-up.Results::A total of 293 patients were enrolled. Among them, 95 patients (32.4%) had bicuspid aortic valve. The calcium volume (Hounsfield Unit-850) of aortic root was 449.90 (243.15-782.15) mm 3. Calcium is distributed mostly on the leaflet level. Downsize strategy was performed in 204 patients (69.6%). Compared with the patients who performed annular sizing strategy, those received downsize strategy achieved a similar device success rate (82.0% [73] vs. 83.3% [170], P= 0.79). Aortic valve gradients (downsize strategy group vs. annular sizing group, 11.28 mmHg vs. 11.88 mmHg, P = 0.64) and percentages of patients with moderate or severe paravalvular regurgitation 2.0% (4/204) vs. 4.5% (4/89), P = 0.21) were similar in the two groups at 30 days after TAVR. These echocardiographic results were sustainable for one year. Conclusions::Chinese TAVR patients have more prevalent bicuspid morphology and large calcium volume of aortic root. Calcium is distributed mostly on the leaflet level. Compare with annular sizing strategy, downsize strategy provided a non-inferior device success rate and transcatheter heart valve hemodynamic performance in self-expanding TAVR procedure.

Background: Peroral endoscopic myotomy (POEM) is safe and effective in the treatment of achalasia (AC). However, there are few reports on application of POEM in the elderly, and is limited by small sample size and short follow-up. Aims: To evaluate the efficacy and safety of POEM and its influential factors on AC in geriatric patients. Methods: A total of 215 AC patients received POEM from November 2012 to December 2018 at the First Affiliated Hospital of Nanjing Medical University were enrolled, and were divided into elderly group (≥60 years old) and non-elderly group (<60 years old). The clinical information, POEM procedure, efficacy and safety were compared, follow-up was performed, and influential factors were analyzed. Results: The disease course in elderly group was significantly longer than that in non-elderly group (P=0.002); the integrated relaxation pressure (IRP) of lower esophageal sphincter in elderly group was significantly decreased than that in non-elderly group (P=0.013). No significant differences in basic information, Chicago classification, POEM procedure, postoperative Eckardt score between the two groups were found (P>0.05). The median follow-up was 42 (29, 60) months. The rate of treatment failure or recurrence in elderly group was significantly increased than that in non-elderly group (17.5% vs. 7.4%, P=0.047). However, there was no statistical difference in incidence of clinical reflux between the two groups (P>0.05). The postoperative efficacy was correlated with preoperative IRP in elderly patients (P=0.033). The propensity score matching results showed that no significant difference in prognosis was found between the two groups. Conclusions: POEM is safe and effective for elderly patients with AC. However, the efficacy is lower in elderly patients than that in non-elderly patients due to the long course of disease and lower preoperative IRP.

Objective To study the effects of Poly(I:C) on lung adenocarcinoma A549 cells viability and illuminate the mechanism of Poly (I:C)-induced apoptosis in A549 cells.Methods A549 cells were transfected with the complex of Poly(I:C) and lipofectamine 3000.The viability of A549 cells was tested by methyl thiazolyl tetrazolium (MTF) method.The apoptotic cells were tested by flow cytometry.The caspase proteins were tested by Western blotting and the expressions of interferon-β (IFN-β) and CXCL-10 were assayed by real-time PCR.After employing the pan-caspase inhibitor Z-VAD-FMK and caspase-8 inhibitor Z-IETD-FMK,the variation of Poly (I:C) proapoptosis in A549 cells was observed.RNA interfering experiments were employed to knock down melanoma differentiation related antigen 5 (MDA5) or retinoic acidinduced gene Ⅰ (RIG-Ⅰ),and the above indexes were tested.Results The viability of A549 cells was significantly reduced to 74.92％ ±--6.24％ after 200 ng/ml Poly (I:C) transfection compared with that before transfection (95.32％ ± 3.05％,t =2.883,P =0.041).The apoptotic rates induced by 100,200,400 ng/ml Poly(I:C) were 9.97％-± 0.88％,23.63％-± 1.41％,32.57％-± 2.39％,respectively.All of them were higher than that in the control group (0.74％-± 0.15％),with significant differences (t =4.489,P =0.002;t =11.616,P =0.000;t =16.932,P =0.000).Besides,the death receptor pathway proteins such as TNF-related apoptosis inducing ligand (TRAIL),cleaved-caspase-8 and cleaved-caspase-3 increased obviously.MDA5/RIG-Ⅰ pathway was also activated dramatically and the expressions of IFN-β,CXCL-10 were significantly up-regulated.The apoptotic rates reduced to 3.17％ ± 0.66％,5.35％ ± 0.64％ with pancaspase inhibitor Z-VAD-FMK and caspase-8 inhibitor Z-IETD-FMK pretreatment,compared with the control group (15.87％ ±0.93％),and the differences were statistically significant (t =8.643,P =0.001;t =6.824,P =0.002).Moreover,the expressions of TRAIL,IFN-β and CXCL-10 induced by Poly (I:C) were inhibited with MDA5 or RIG-Ⅰ depletion.Conclusion Poly(I:C) can reduce the survival rate of A549 cells and promote the apoptosis mainly by activating the death-receptor pathway mediated by MDA5/RIG-Ⅰ probably,which may involve in IFN-β,CXCL-10.

Objective To assess the effects of PI3K/mTOR dual inhibitor NVP-BEZ235 on the distribution and degranulation of perivascularmast cells in the lung of hypobaric hypoxia rats.Methods SD male rats in the hypoxia group were raised in the specific hypoxic incubator (50.5 kPa).The intervene group received NVP-BEZ235 training (35 mg/kg) intervention once every two days.The control group was fed in the conditions comparable to the other groups at local pressure and normoxia environment.After 21 days, all rats were sacrificed with injection of 5％ pentobarbital sodium.Lung tissues were fixed and embedded in paraffin for further hematoxylin-eosin staining and toluidine blue staining.Results Compared with the control group, the number of pulmonary perivascular mast cells in the hypoxia group increased significantly.Hypoxia group had more mast cell accumulation and larger degranulation ratio around different diameters of pulmonary vessels (less than 50 μm, 50-100 μm, larger than 100 μm) than the control group (P< 0.05).The mast cell numbers decreased in NVP-BEZ235 intervention group compared with hypoxia group (P<0.05).The degranulation ratio of pulmonary vascular mast cells around 50-100 μm in the intervention group was smaller than the hypoxia group (P=0.000 3).Conclusion NVP-BEZ235 inhibits the aggregation of pulmonary perivascular mast cells and degranulation ratio of median diameter pulmonary perivascular mast cells in hypobaric hypoxia rats.

Objective To investigate error-related negativity characteristics of patients with internalizing mental disorders and its diagnostic value.Methods Fifty-five patients met with DSM-Ⅳ anxiety or depression criteria were sampled from outpatients and inpatients,and 20 normal adults were selected as control group.With Eriksen and Simon tasks as evoked stimuli,error-related negativities of each participant were acquired using Canada Stellate-64 channel EEG/ERP Instrument and BESA5.2 software,and the data of general information,clinical symptoms,reaction time,and error rate were collected.Results (1) Correct reaction time ((377.5±98.8) ms)and errors reaction time ((337.3±96.6)ms) of patient group were significantly longer than those of control group ((288.5±105.9)ms and (281.9±94.3)ms) on the Eriksen task and Simon task,and there were no significantly group differences on other indicators (P＞0.05).(2) ERN amplitudes at 6 sities (Fz =(4.97±5.74) μV,F3 =(5.50±4.59) μV,F4 =(6.26±6.79) μV,Cz =(4.74±5.51) μV,C3 =(5.44±4.8) μV,C4 =(5.50± 5.28) μV) of patients group were significantly greater than those of control group ((1.17± 1.47)μV,(2.22±3.95) μV,(3.40±2.55)μV,(2.28± 1.41) μV,(3.05±2.47) μV,(3.16±2.51) μV) on the Eriksen task.ERN amplitudes at Fz((5.43±6.61) μV) and F4((6.00±5.50)μV) of patient group were significantly were greater than those of control group ((2.05 ±2.34) μV,(3.09±2.86)μV) on the Simon task,and there were no significantly group differences on the ERN amplitudes at other sites (P＞0.05).(3) ERN latencies ((87.6±34.4) ms and (84.9±34.8) ms) of patient group at Fz and F4 were significantly longer than control group ((54.0±46.5) ms and (36.3±42.4)ms) on the Simon task,and there were no significantly group differences on the ERN latencies at other sites (P＞0.05).Conclusion The increased error related potentials suggest that patients with internalizing mental disorders has an internal error monitoring defects,and ERN might be a useful endophenotype for internalizing mental disorders.

Objective To study the beneficial effect and mechanism of Alcea rosea roots in nephrolithiasis model in-duced by 1%ethylene glycol in rats. Methods We randomly divided 60 male Wistar rats into six groups,including control group, model group, Alcea rosea roots lower-dose preventive group, Alcea rosea roots high-dose preventive group, Alcea ro-sea roots lower-dose curative group, Alcea rosea roots high-dose curative group. Control group was free to access food and water;model group was given 1%ethylene glycol drinking water and was fed with normal diet, preventive group was given 1%ethylene glycol drink and Alcea rosea roots in low (250 mg/kg) or high dose (500 mg/kg) each day, curative group re-ceived 1%ethylene glycol drink each day and Alcea rosea roots in low or high dose from day 15 to day 28. At the end of the experiment, various renal functional and injury markers such as urine volume, calcium, phosphate, magnesium, urea, creati-nine, and oxalate were evaluated using urine, serum, and kidney homogenates. The kidneys were removed and prepared for histological evaluation of calcium oxalate deposits. Results In model groups, urine output, urea, creatinine, 24 h urine Ca2+, and oxalate and MDA were increased compared to those in control group(P＜0.05). GSH and SOD were increased in preventative and curative groups compared to those in the model group(P ＜ 0.05). The urea, creatinine, 24 h urine Ca2+, urine oxalate, MDA were reduced in preventive and curative groups compared to those in the model group(P＜0.05). The number and size of calcium oxalate crystal deposits were also less and smaller, and the kidney damage was less severe in pre-ventive and curative groups compared to in the model group. Conclusion The extract of Alcea rosea roots can prevent and treat calcium oxalate urinary stone formation in rats and protect renal function.

Objective To compare the phaimacodynamics and circulatory function of domestic and imported rocuronium. Methods This is a five center study of rocuronium. Two hundred and ten ASA Ⅰ or Ⅱ patients aged 18-65 yr undergoing elective surgery under general anesthesia were randomly divided into 2 groups (n = 105 each): domestic rocuronium group (group Ⅰ ) and imported rocuronium group (group Ⅱ ) . Anesthesia was induced and maintained with TCI of propofol (target plasma concentration = 3 mg/L) and remifentanil (target effect-site concentration = 2-4 μg/L) . Tracheal intubation was facilitated with intravenous rocuronium 0.6 mg/kg. The N-M function was assessed by accelerography (TOF-Watch(R) SX, Organon, Netherlands) using TOF stimulation of ulnar nerve. Onset time, clinical duration, 75% recovery time,recovery indexes, the extent of maximal NM blockade and intubation conditions (ease of laryngoscopy, position of vocal cords and airway reaction) were monitored and recorded. BP and HR were also recorded. Results There were no significant differences in the onset time, clinical duration, recovery indexes, the extent of maximal N-M blockade, the intubation conditions, BP, HR and adverse reactions between groups Ⅰ and Ⅱ ( P ＞ 0.05) . The 75% recovery time was significantly longer in group Ⅱ than in group Ⅰ (P ＜ 0.05＝. Conclusion The pharmacodynamics of domestic and imported rocuronium is comparable. The two drugs have no adverse effect on the circulatory function.