OBJECTIVE: To compare clinical effects of external fixation and minimally invasive percutaneous plate osteosynthesis (MIPPO) after external fixation in treating open fractures of tibial shaft. METHODS: From January 2020 to June 2022, 151 patients with open fracture of tibial shaft treated with external fixation stenting were divided into external fixation group and combined group according to different surgical methods. There were 81 patients in external fixation group, including 48 males and 33 females, aged from 21 to 68 years old with an average of (42.58±7.44) years old;according to Gustilo classification, 49 patients with typeⅡ, 32 patients with type ⅢA;the time from injury to treatment ranged from 2.5 to 10 h with an average of (4.25±0.74) h;external fixed stenting was performed. There were 70 patients in combined group, including 42 males and 28 females, aged from 20 to 69 years old with an average of (41.39±7.02) years old;35 patients with type Ⅱ and 35 patients with type ⅢA according to Gustilo classification;the time from injury to treatment ranged from 3 to 9 h with an average of (4.31±0.85) h;MIPPO treatment was performed after external fixed stenting. The time of callus formation, fracture healing and complications were compared between two groups. Rasmussen score and Hospital for Special Surgery (HSS) score were used to evaluate functional recovery of knee joint at 6 months after operation. RESULTS: Both groups were followed up for 6 to 13 months with an average of (10.17±2.33) months. The time of callus formation and fracture healing were (13.98±4.02) d and (70.26±12.15) d in combined group, and (18.56±4.37) d and (79.87±15.41) d in external fixation group, respectively. Combined group was better than external fixation group in the time of callus formation and fracture healing (P<0.05). At six months after operation, Rasmussen and HSS scores in combined group were (26.79±3.11) and (83.36±9.44), which were higher than those in external fixation group (24.51±4.63) and (79.63±8.46) (P<0.05). In external fixation group, there were 2 patients with incision infection, 2 patients with nail tract infection, 1 patient with stent loosening, fracture displacement, delayed union and malunion, and 1 patient with biocompatibility reaction in combined group, with statistical significance between two groups (P<0.05). CONCLUSION MIPPO could accelerate callus formation and fracture healing, improve knee function, improve clinical effects and reduce complications in patients with open tibial shaft fractures after external and external fixation.
Humans ; Male ; Female ; Middle Aged ; Adult ; Aged ; Tibial Fractures/physiopathology* ; Fracture Fixation, Internal/methods* ; Retrospective Studies ; Bone Plates ; External Fixators ; Fractures, Open/physiopathology* ; Stents ; Young Adult

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Objective:To analyze the clinical characteristics,treatment effect and prognosis of patients with non-Hodgkin lymphoma(NHL)complicated by hypercalcemia.Methods:The clinical features,treatment and prognosis of 47 patients with NHL complicated by hypercalcemia in Ningde Municipal Hospital of Ningde Normal University and Affiliated Hospital of Nantong University from January 2018 to January 2023 were retrospectively analyzed.Results:Among the 47 lymphoma patients,33 cases were T-cell NHL,14 cases were B-cell NHL.The median serum calcium level of the 47 patients was 3.10(2.77-4.86)mmol/L,with 27 cases(57.4％)experiencing mild hypercalcemia(2.75-3.00 mmol/L),8 cases(17.0％)experiencing moderate hypercalcemia(3.00-3.50 mmol/L),and 12 cases(25.5％)experiencing severe hypercalcemia(＞3.50 mmol/L).All 47 patients were treated with hydration,alkalization,diuresis,etc.32 cases(68.1％)received combination chemotherapy,21 cases(44.7％)received salmon calcitonin treatment,and 3 cases were treated with denosumab in 5 patients with renal insufficiency.After treatment,38 patients'serum calcium gradually returned to normal,with a median recovery time of 6(1-18)days,while 9 patients still failed to recover their serum calcium after treatment and all died within 1 month.32 patients undergoing combination chemotherapy were evaluated for efficacy after 2-4 courses of chemotherapy.Among them,8 cases(25.0％)achieved complete response(CR),11 cases(34.4％)achieved partial response(PR),7 cases(21.9％)showed stable disease(SD),and 6 cases(18.8％)showed progressive disease(PD).The median follow-up time was 10 months.There were 13 cases of disease progression after combination chemotherapy and a total of 28 deaths.The survival time ranged from 0.8 to 23.7 months,and the median progression time was 4.9 months.Multivariate Cox regression analysis showed that the T-cell NHL,blood calcium＞3.5 mmol/L,and no decrease in blood calcium after treatment were independent risk factors for the OS,and the T-cell NHL was independent risk factors for the PFS.Conclusion:NHL complicated by hypercalcemia has a poor prognosis,and hypercalcemia can be used as one of the indicators reflecting the tumor burden.Patients with NHL complicated by hypercalcemia should be given more clinical attention and treated actively.

Objective To explore the related influencing factors of orthostatic hypotension in patients with multiple system atrophy(MSA).Methods A retrospective study was conducted on 40 elderly MSA patients with orthostatic hypotension(MSA group)admitted to our department from January 2024 to March 2025,and another 46 elderly healthy individuals without orthostatic hypotension who taking physical examination were subjected and served as control group.General clinical data and related clinical indicators were compared between the two groups,and the related serum biomarkers of orthostatic hypotension in MSA patients were analyzed.Results The levels of vitamin D,low-density lipoprotein cholesterol(LDL-C),and uric acid were significantly lower in the MSA group than the control group(P＜0.05,P＜0.01).Multivariate logistic regression analysis showed that vitamin D,LDL-C,and uric acid levels were risk factors for the occurrence of orthostatic hypotension in MSA patients(OR=0.677,95％CI:0.530-0.864,P＜0.01;OR=0.057,95％CI:0.007-0.434,P＜0.01;OR=0.972,95％CI:0.954-0.992,P＜0.01).ROC curve analysis indicated that the optimal cut-off value of vitamin D,LDL-C,and uric acid levels in predicting the occurrence of orthostatic hypotension in MSA patients was 21.850 μg/L,2.895 mmol/L,and 274.500 μmol/L,the sensitivity was 0.848,0.630 and 0.783,and the specificity was 0.792,0.750 and 0.667,and the AUC value was 0.862,0.683 and 0.748,respectively.Conclusion Monitoring serum biomarkers,such as vitamin D,LDL-C,and uric acid may be helpful for the risk assessment and management of orthostatic hypotension in MSA patients.

This article summarized Professor Liu Qiquan's clinical experience in the treatment of acne from the perspective of"internal retention and stagnation of heat pathogen".Professor Liu believes that the core pathogenesis of acne lies in the internal retention and stagnation of heat pathogen,which manifests as external skin inflammation,with the primary focus being on the heat pathogen.With the pathogen inside the body,the progress of disease and syndrome is related to"toxin,depression,blood stasis and deficiency".At the same time,the disease is also closely related to the dysfunction of the five-zang organs.Professor Liu points out that"to resist the outside,one must first settle the inside",and treats acne from the five internal organs.Based on the idea of"internal retention and stagnation of heat pathogen",according to the symptoms of the patients,the comprehensive use of methods to guide the treatment,such as penetrating turbidity,removing pathogenic factors and detoxifying heat,promoting qi and dispersing stagnant heat,cooling collaterals to control blood and breaking stasis heat,and restraining qi,softening yin and supporting deficiency heat,has been proved to have a good clinical effect.One medical case was attached as evidence.

Objective To use AI-assisted motor dysfunction assessment for quantitative evaluation of motor function in Parkinson's disease(PD)and multiple system atrophy-Parkinsonian type(MSA-P)in order to achieve accurate differential diagnosis.Methods A total of 105 participants aged ≥60 years were consecutively enrolled from the First and Third Medical Centers of Chinese PLA General Hospital between January and September 2024.Based on diagnostic criteria,they were divided into a PD group(48 cases),a MSA-P group(31 cases),and a control group(26 cases).The general information was collected,and the motor function was evaluated with Move-ment Dysfunction Assessment Software in order to assess the diagnostic value of the AI-assisted assessment in differentiating between PD and MSA-P.Results Significantly differences were observed among the three groups in terms of facial expression indicators,bilateral finger tapping frequency,bilateral hand movement frequency,right hand movement amplitude change rate,bilat-eral palm flipping frequency,bilateral toe tapping frequency,freezing load of bilateral toe tapping,bilateral leg flexibility frequency,right leg flexibility amplitude change rate,freezing load of bilat-eral leg flexibility,upright extension angular velocity,turnaround time,forward step frequency,backward step frequency,forward average stride length,backward average stride length,forward average walking speed,backward average walking speed,forward average step width,backward average step width,bilateral postural tremor frequency,bilateral postural tremor maximum am-plitude,bilateral action tremor frequency,bilateral action tremor maximum amplitude,and com-parison of bilateral resting tremor frequency(P＜0.05,P＜0.01).The MSA-P group exhibited significantly lower blink frequency,maximum amplitude and frequency of facial tremors,upright extension angular velocity,and step frequency,while higher ratio of mouth opening duration and longer turnaround time when compared with the PD group(P＜0.05,P＜0.01).The AUC value of the combined nine motor function indicators and the five facial expression indicators in differ-entiating PD from MSA-P was 0.943(95％CI:0.895-0.991,P=0.000)and 0.925(95％CI:0.870-0.981,P=0.000),respectively,both better than that of individual indicators.Conclusion Combi-nation assessment of facial expression,posture,gait with AI assistance can contribute to the dif-ferential diagnosis of PD and MSA-P.

Objective To compare functional differences of CD8+T cells in lung tissues between young and aged C57BL/6J mice during the contraction phase and memory immune response phase after infection with influenza A(H1N1)virus.Methods Lung tissues from young(3-month-old)and aged(24-month-old)C57BL/6J female mice without influenza virus infection were collected to prepare single-cell suspensions,which were stimulated with phorbol 12-myristate 13-acetate(PMA)/ionomycin or cluster of differentiation(CD)3/CD28 antibodies(T-cell antigen receptor/co-stimulatory signals)respectively(non-specific antigens stimulation).Flow cytometry intracellular cytokine staining(ICS)was performed on lung CD8+T cells to detect their secretion capacity of tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ).Young and aged C57BL/6J mice were infected intranasally with 490 PFU PR8 influenza virus,and reinfected with homologous influenza virus 28 days later.Lung tissues were isolated on day 28(the contraction phase)and day 32(the memory immune response phase)after primary infection.Influenza virus-specific MHC-Ⅰ tetramer staining was used to detect the proportion of virus-specific CD8+T cells in lung tissue CD8+T cells,and ICS was used to analyze TNF-α,IFN-γ,and granzyme B expression in CD8+CD44high T cell subset.Results After non-specific antigen stimulation,TNF-α and IFN-γ secretion capacity in lung tissue CD8+T cells of aged group mice was significantly higher than that of young group(P＜0.05).After virus-specific antigen stimulation,there were no statistically significant differences in the proportion of virus-specific CD8+T cells and the expression levels of TNF-α,IFN-γ,and granzyme B between the two groups of mice during the contraction phase(P＞0.05),while during the memory immune response phase,the proportion of virus-specific CD8+T cells and the expression levels of TNF-α,IFN-γ,and granzyme B in the aged group mice were significantly lower than those in the young group(P＜0.05).Conclusion CD8+T cells in aged mice maintain normal immune-related factor expression function under non-specific antigen stimulation,but show impaired immune-related factor expression function during antigen-specific memory immune response phase,suggesting that aging leads to defects in the formation or maintenance of CD8+T cell immune memory.

Lung cancer poses a serious threat to global public health security.Chemotherapy,as the main strategy for cancer treatment,faces challenges such as high toxicity and drug resistance.Anticancer peptides have the potential of being developed into new anticancer drugs due to their advantages of broad-spectrum anticancer activity,rapid action,and difficulty in generating drug resistance,but they also face shortcomings such as weak activity and strong toxic side effects.The weakly acidic microenvironment of tumors(pH 6.5-6.8)provides a good idea for the design of anticancer peptides of high-efficiency and low-toxicity.Previously,we designed the acid-sensitive antibacterial peptide pHly-1 using the wolf spider(Lycosa singoriensis)toxin Lycosin-Ⅰ as a template.In this study,we found that pHly-1 also had acid-sensitive anticancer activity.Further alanine scanning analysis of pHly-1 was carried out,and we ob-tained a mutant pHTP-2 with better acid sensitivity,whose IC50(half maximal inhibitory concentration)against A549 cells was 15.68 μmol/L at pH 6.6 and was greater than 100 μmol/L at pH 7.4.At pH 6.6,pHTP-2 could act on various lung cancer cell lines and induce the death of A549 cells by rapid ly-sis;at pH 7.4,500 μmol/L pHTP-2 had weak toxicity to red blood cells(the hemolysis rate was ap-proximately 38％)and primary myocardial cells(the inhibition rate was 49.7％,with P＜0.05).Analy-sis of its charge,particle size,morphology,and secondary structure showed that at pH 6.6,the histidine in the sequence of pHTP-2 was protonated,increasing the positive charge(P＜0.01),decreasing the hy-drated particle size(P＜0.05)and forming an α-helical structure to induce membrane lysis of A549 cells.At pH 7.4,it was deprotonated,the positive charge decreases,a β-sheet structure was formed and self-aggregation occurred,limiting its effect on the A549 cell membrane and showing weak activity.In summary,pHTP-2 could respond to the weakly acidic microenvironment of tumors to exert selective cyto-toxic activity,effectively overcoming the shortcomings of anticancer peptides such as low efficiency and high toxicity.Our findings suggest that it is a high-quality lead molecule for anticancer drugs.

Based on the traditional Chinese medicine theory that "all pain， itching， and sores are related to the heart"， this paper proposes treating recurrent aphthous ulcers from the perspective of the heart. It suggests that excessive heart fire and tissue erosion due to flaming fire in the heart meridian constitute the core pathogenesis of this condition. Hyperactive heart fire is identified as the key pathogenic factor， while heart yin deficiency， obstruction of the heart collaterals， and malnourishment of the heart spirit are considered significant contributing factors. Clinically， the treatment follows the principle of clearing heart fire as the main strategy， supplemented by nourishing yin， activating collaterals， and calming the spirit. The self-formulated Qingxin Yuchuang Formulation （清心愈疮方） serves as the base prescription， with flexible modifications incorporating the Yuyin Formulation （育阴方）， Huoxue Formulation （活血方）， and Yu'an Formulation （郁安方） to address specific syndromes involving heart yin deficiency， collateral blockage， and emotional disturbance.