Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Objective To explore the application effect of prone position ventilation combined with veno-venous extracorporeal membrane oxygenation (VV-ECMO) in the treatment of severe primary graft dysfunction (PGD) after lung transplantation. Methods The clinical data of 75 lung transplant recipients who developed severe PGD after lung transplantation and were treated with VV-ECMO from January 2021 to June 2024 at Wuxi People's Hospital Affiliated to Nanjing Medical University were collected. The patients with severe graft dysfunction after lung transplantation were divided into VV-ECMO group (control group, 45 cases) and prone position ventilation combined with VV-ECMO group (treatment group, 30 cases). The general data of the two groups of patients were compared, including the donors' clinical data (age, gender and oxygenation index, etc) and the recipients' clinical data [gender, age and body mass index (BMI), etc]. Cox regression analysis was used to analyze the influencing factors of the recipients' 30-day, 90-day and 180-day survival after surgery. The survival curves of the two groups of recipients were drawn using Kaplan-Meier method and compared using the log-rank test. Results The intensive care unit (ICU) stay time, ECMO application time and ventilator use time of control group were longer than those of treatment group. The proportion of male recipients and the BMI of control group were lower than those of treatment group. The 30-day, 90-day and 180-day survival of control group was worse than that of treatment group, and the differences were statistically significant (all P<0.05). The univariate Cox regression analysis of the recipients' 30-day survival after surgery showed that the recipients' BMI, history of diabetes, enlargement of the right atrium and right ventricle, intraoperative blood transfusion volume and intraoperative red blood cell transfusion volume were statistically significant (all P<0.05). The multivariate Cox regression analysis showed that the history of diabetes and enlargement of the right atrium and right ventricle were risk factors affecting the 30-day survival of lung transplant recipients (all P<0.05). The univariate Cox regression analysis of the recipients' 90-day survival after surgery showed that the recipients' BMI, history of diabetes, enlargement of the right atrium and right ventricle, intraoperative blood transfusion volume, intraoperative red blood cell transfusion volume and group variable were statistically significant (all P<0.05). The multivariate Cox regression analysis showed that the history of diabetes, enlargement of the right atrium and right ventricle and group variable were risk factors affecting the 90-day survival of lung transplant recipients (all P<0.05). The univariate Cox regression analysis of the recipients' 180-day survival after surgery showed that the recipients' BMI, history of diabetes, right atrium and right ventricle enlargement, intraoperative blood transfusion volume, intraoperative red blood cell transfusion volume and group variable were statistically significant (all P<0.05). The multivariate Cox regression analysis showed that the history of diabetes, enlargement of the right atrium and right ventricle and group variable were risk factors affecting the 180-day survival of lung transplant recipients (all P<0.05). The 30-day, 90-day and 180-day survival rates of control group were lower, and the differences between the two groups were statistically significant (all P<0.05), with a median survival time of 100 days in control group. Conclusions In the clinical treatment of severe PGD after lung transplantation, prone position ventilation combined with VV-ECMO may shorten ECMO application time, invasive ventilation time and ICU stay time, and improve the short-term prognosis of lung transplantation.

The regulatory processes in developmental biology research are significantly influenced by long non-coding RNAs (lncRNAs). However, the dynamics of lncRNA expression during human tooth development remain poorly understood. In this research, we examined the lncRNAs present in the dental epithelium (DE) and dental mesenchyme (DM) at the late bud, cap, and early bell stages of human fetal tooth development through bulk RNA sequencing. Developmental regulators co-expressed with neighboring lncRNAs were significantly enriched in odontogenesis. Specific lncRNAs expressed in the DE and DM, such as PANCR, MIR205HG, DLX6-AS1, and DNM3OS, were identified through a combination of bulk RNA sequencing and single-cell analysis. Further subcluster analysis revealed lncRNAs specifically expressed in important regions of the tooth germ, such as the inner enamel epithelium and coronal dental papilla (CDP). Functionally, we demonstrated that CDP-specific DLX6-AS1 enhanced odontoblastic differentiation in human tooth germ mesenchymal cells and dental pulp stem cells. These findings suggest that lncRNAs could serve as valuable cell markers for tooth development and potential therapeutic targets for tooth regeneration.
Humans ; RNA, Long Noncoding/metabolism* ; Odontogenesis/genetics* ; Tooth Germ/embryology* ; Cell Differentiation ; Gene Expression Regulation, Developmental ; Mesoderm/metabolism* ; Tooth/embryology* ; Gene Expression Profiling ; Sequence Analysis, RNA ; Dental Pulp/cytology*

AIM: To design and construct recombinant epitope nucleotides vaccine of glycoprotein B(gB)and glycoprotein D(gD)of herpes simplex virus type 1(HSV-1), and to investigate its immunoprotective effects and tissue expression in animal models.METHODS: The HSV-1 gB and gD epitope genes were selected and tandem assembled to construct the recombinant protein-coding gene X, which was transducted into the prokaryotic expression vector pET28(a). The recombinant protein was synthesized and utilized to generate monoclonal antibodies, which were subsequently used to immunize New Zealand white rabbits. The immunogenicity of the purified protein and the presence of polyclonal antibodies in the serum were tested through separating serum from cardiac blood, and the serum antibody titers were determined. The pcDNA3.1-X was successfully constructed as a eukaryotic expression vector and immunized the female BALB/c mice aged 4 to 6 wk via intramuscular injection. Serum antibodies and immune-related cytokines were quantified using enzyme-linked immunosorbent assay(ELISA). The expression of the X protein in the ocular, trigeminal ganglion, and brain tissues of the mice was assessed.RESULTS: The target polyclonal antibody was identified with a serum antibody titer of 1:3200 in the rabbit serum after immunized by recombinant protein X. Upon immunizing mice with the eukaryotic recombinant plasmid pcDNA3.1-X, the concentration of HSV-1 serum IgM antibodies of the experimental group was 12.13±0.85 ng/L, which was significantly higher than that of the vector control group(0.49±0.44 ng/L; t=21.07, P<0.001). The concentrations of cytokines interleukin IL-2, IL-4, IL-10, and IFN-γ in the experimental group were 11.63±0.60, 22.65±1.47, 85.75±14.12, and 114.90±6.39 ng/L, respectively, all of which were significantly higher than those in the vector control group and the blank control group(all P<0.05). Immunohistochemical staining revealed the presence of target protein X in the eyeball, trigeminal ganglion, and brain tissue.CONCLUSION: The HSV-1 gB and gD tandem epitope nucleotides vaccine pcDNA3.1-X was successfully constructed, which activates a remarkable immune response and is stably expressed in the eyeball, trigeminal ganglion, and brain tissue. This study provides a foundation for further research of an HSV-1 recombinant antigen epitope tandem vaccine.

Cataract surgery is one of the most common ophthalmologic procedures. Advances in technology and medical policies have made it more precise. Residual refractive errors and deviation of target diopters are a main cause of dissatisfaction among patients. Refractive enhancement after cataract surgery can correct or eliminate these errors, improving patients' visual quality of life. There are multiple options for correcting residual refractive errors. The best approach depends on factors like the cause of the error, degrees of residual refractive errors, type of intraocular lens, ocular comorbidities, and patient preference. This paper summarizes the incidence and types of residual refractive errors, advancements in refractive enhancement surgeries, and provides practical solutions for clinical practice.

Objective:To evaluate the short-term clinical outcomes of minimally invasive surgery for severe hallux valgus deformity using absorbable screw fixation.Methods:This retrospective study included 35 patients with severe hallux valgus deformities treated with third-generation minimally invasive Chevron and Akin osteotomies (MICA) using absorbable screws at the Foot and Ankle Surgery Department of Guangzhou Orthopedic Hospital from January 2022 to January 2023. The cohort consisted of 2 males and 33 females, with an average age of 56.75±13.27 years (ranging from 20 to 72 years).There were 18 cases of left foot and 17 of right. Preoperative and 12-month postoperative radiographic and clinical data were collected and analyzed. Radiographic evaluations included measurements of the hallux valgus angle (HVA) and intermetatarsal angle (IMA) on weight-bearing foot X-ray films. Clinical outcomes were assessed using the American Orthopaedic Foot and Ankle Society (AOFAS) hallux metatarsophalangeal-interphalangeal scale and the visual analogue scale (VAS) for pain. All complications during follow-up were recorded to comprehensively assess surgical outcomes and safety.Results:All the 35 cases successfully underwent the surgery, with a surgery time of 61.5±3.2 minutes and intraoperative blood loss of 5.4±1.2 ml. No patients lost follow-up, with a mean follow-up of 15.65±2.48 months (ranging from12 to 19 months). At the final follow-up, the AOFAS score significantly improved from 39.8±4.7 preoperatively to 92.3±4.1 postoperatively ( P<0.05), and the VAS significantly decreased from 8.7±1.2 to 1.8±0.8 ( P<0.05). The HVA decreased from 42.5°±4.1° to 12.5°±3.7° ( P<0.05), and the IMA decreased from 18.5°±2.8° to 7.3°±2.1° ( P<0.05). Radiographic follow-up demonstrated complete osseous union at the osteotomy sites in all cases, with no complications of nonunion or displacement. 7 patients with concurrent gastrocnemius tightness underwent gastrocnemius release, and 11 patients with associated transfer metatarsalgia were treated with Weil osteotomy ( n=8) or metatarsal head recontouring ( n=3), achieving satisfactory outcomes for all cases. Complications were minimal, with 2 cases of localized numbness around the surgical incision observed on postoperative day 3; the symptoms were gone spontaneously 3 months postoperatively. No other major complications, such as infection, hematoma, or neurovascular injury, were observed. Conclusion:Minimally invasive surgery using absorbable screw fixation effectively improves clinical function and symptoms in patients with severe hallux valgus deformities without any major complications, suggesting that it is a safe and effective treatment option.

Objective:To investigate the therapeutic efficacy of proximal ulnar osteotomy combined with autologous iliac bone grafting for the repair of chronic elbow varus with posteromedial rotational instability caused by coronoid process bone defects.Methods:A retrospective analysis was conducted on the data of 9 male patients with chronic elbow varus and posteromedial rotational instability caused by coronoid process bone defects who were treated with proximal ulnar osteotomy combined with autologous iliac bone grafting at Sichuan Provincial Orthopaedic Hospital from January 2017 to May 2024. The patients' ages ranged from 20 to 46 years, with an average of 29.78±8.77 years old. There were 3 cases on the right side and 6 on the left side. The height of the bone defect on the anteromedial surface of the coronoid process ranged from 5.24 to 12.23 mm, with an average of 9.01±2.61 mm. The time from injury to surgery ranged from 5 to 9 months, with an average of 6.78±1.39 months. During the operation, proximal ulnar osteotomy combined with autologous iliac bone grafting was used to repair the coronoid process bone defect. Simultaneously, the lateral ulnar collateral ligament was reconstructed using the suture anchors (3 patients) or repaired with autologous palmaris longus tendon (6 patients). Finally, a hinged external fixator was applied in all cases. The range of motion (ROM) of the elbow joint was recorded before and after the surgery. The visual analogue score (VAS) was used to evaluate the degree of pain, and the Mayo elbow performance score (MEPS) was employed to assess the elbow joint function.Results:All surgical incisions healed primarily, and no case of infection occurred. All 9 patients were followed up, with a follow-up period ranging from 11 to 25 months, and an average of 17.78 ± 5.16 months. The bone grafts all healed, with a healing time ranging from 3 to 5 months, and an average of 3.56±0.73 months. The elbow extension angles before surgery, at 6 months postoperatively, and at the last follow-up were 24.44°±14.24°, 11.11°±9.28°, and 2.22°±4.41°, respectively. The flexion angles were 118.89°±5.46°, 123.33°±5.00°, and 128.89°±3.33°, respectively. The flexion-extension ROMs were 94.44°±18.28°, 112.22°±13.02°, and 126.67°±7.07°, respectively. The pronation angles were 61.67°±6.12°, 61.67°±3.54°, and 67.22°±5.07°, respectively. The differences in these angles were all statistically significant ( P<0.05). The supination angles before surgery, at 6 months postoperatively, and at the last follow-up were 77.22°±7.55°, 78.89°±6.01°, and 79.44°±6.35°, respectively. The rotational ROMs were 138.89°±11.93°, 140.56°±7.26°, and 146.67°±10.31°, respectively. No statistically significant differences were observed ( P>0.05). The VAS scores before surgery, at 6 months postoperatively, and at the last follow-up were 6.89±0.78 points, 2.33±1.00 points, and 0(0, 0.5) points, respectively, and the difference was statistically significant ( H=23.216, P<0.001). The MEPS scores were 42.22±5.65 points, 76.67±7.05 points, and 95.00±7.50 points, respectively, and the difference was also statistically significant ( F=134.212, P<0.001). The cantilever test confirmed that none of the patients had elbow joint instability symptoms, and the patients were satisfied with the treatment effect. Conclusions:Proximal ulnar osteotomy combined with autologous iliac bone grafting, simultaneous repair or reconstruction of the lateral ligament complex, and fixation with a hinged external fixator is an effective treatment approach for chronic elbow varus with posteromedial rotational instability. This method can alleviate elbow pain, improve the ROM, and enhance elbow function in patients, yielding satisfactory short-term outcomes.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To observe the safety and short-term efficacy of using an autologous fascia lata sling (AFLS) for tension-free mid-urethral sling (MUS) in the treatment of stress urinary incontinence (SUI).Methods:Between February 2022 and December 2023, 11 patients with SUI underwent AFLS-MUS. Preoperative data were recorded, including basic patient information and completion of urinary distress inventory 6 (UDI-6). During surgery, AFLS was harvested through a small incision using a tendon extractor, and used as a sling for transobturator or retropubic MUS. Perioperative indicators were recorded, including surgical approach, operation time, intraoperative blood loss, postoperative hospital stay, duration of catheterization, perioperative complications (Clavien-Dindo classification), and surgical costs. Follow-ups included outpatient physical examination at 2 months postoperatively, and telephone follow-up at 6 months, 1 year, and annually thereafter. Follow-up content included the presence or absence of urinary leakage symptoms, UDI-6, satisfaction, patient global impression of improvement (PGI-I), and complications.Results:The age of the 11 patients was (54.8±10.9) years (range: 41-72 years), with body mass index of (23.9±1.8) kg/m2 (range: 21.4-27.3 kg/m2). All patients experienced urinary leakage after coughing, sneezing and physical activity, with positive SUI provocation tests. The preoperative UDI-6 was 50.0±21.6 (range: 16.7-79.2), the result of 1-hour pad test was (18.9±12.0) g (range: 2.5-71.2 g). Four cases underwent MUS only, with operation time of (98.0±13.3) minutes (range: 86-117 minutes), and intraoperative blood loss of (17.5±5.0) ml (range: 10-20 ml); 7 cases also underwent pelvic floor repair simultaneously. The postoperative hospital stay was (3.5±2.0) days (range: 2-9 days). The duration of catheterization was (4.5±3.8) days (range: 2-11 days), with postoperative urinary retention in three cases, one of which underwent sling release surgery due to severe postoperative voiding difficulty 1 week after MUS, with no other complications of Clavien-Dindo grade 2 or above. The cost of AFLS harvest plus MUS was (2 762±293) yuan. At the 2-month outpatient follow-up, all patients were free of urinary leakage symptoms, with UDI-6 of 2.3±1.9 (range: 0-8.3); satisfaction was "very satisfied" in 10 cases and "fairly satisfied" in 1 case, with PGI-I all being "much better", and pelvic examinations were normal. Telephone follow-up showed one case lost to follow-up, and the remaining 10 cases had follow-up time of (18.6±4.9) months (range: 7-26 months), all without urinary leakage, with UDI-6 of 2.7±2.6, satisfaction rated as "very satisfied", and PGI-I all "much better".Conclusion:This modified AFLS-MUS for the treatment of SUI shows good short-term efficacy and high safety in harvest site, with the need for more data accumulation and long-term follow-up.

OBJECTIVE To explore the diagnostic value of combined detection of microRNA(miRNA)and alpha-fetoprotein(AFP),protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ)in ascites and serum ex-tracellular vesicles(EVs)for hepatitis B virus(HBV)-related primary hepatocellular carcinoma(HCC).METHODS From Nov.2023 to Nov.2024,41 patients with liver cancer and 26 patients with liver cirrhosis who underwent ascites placement or ascites concentration and reinfusion procedures at the Fifth Medical Center of Chi-nese PLA General Hospital were selected as study subjects.Ascites and serum samples were collected.Real-time quantitative reverse transcription polymerase chain reaction(qRT-PCR)was used to detect the expression levels of miR-21,miR-125a,miR-150 and miR-200a in EVs.Chemiluminescence was used to measure the levels of AFP and PIVKA-Ⅱ in ascites,serum and EVs from ascites and serum.An artificial neural network was utilized to con-struct a combined diagnostic model of serum and ascites markers.RESULTS The area under the curve(AUC)for distinguishing HCC from liver cirrhosis using a combination of serum and other indicators was 0.933.The AUC for distinguishing HCC from liver cirrhosis using a combination of ascites and other indicators was 0.912.By screening all detected indicators using an artificial neural network and incorporating indicators with a relative im-portance＞0.5 into the diagnostic model,the model included four indicators:ascites AFP,ascites EVs miR-21,ascites EVs miR-200a and serum EVs miR-200a.This model had a sensitivity of 80.77％,a specificity of 87.80％and an AUC of 0.960 for distinguishing HCC from liver cirrhosis patients.CONCLUSION The combined diagnos-tic markers of miRNA,AFP and PIVKA-Ⅱ in ascites and serum-derived EVs have good application value in the diagnosis of HCC.