AIM: To investigate the preoperative ocular symptoms and the characteristics of asymptomatic ocular surface abnormalities in hospitalized patients with primary pterygium.METHODS: Cross-sectional study. Hospitalized patients diagnosed with primary pterygium and scheduled to receive pterygium excision surgery at the Xiamen Eye Center of Xiamen University from August 2022 to October 2022 were enrolled. Ocular surface disease index questionnaire(OSDI), six examinations including non-invasive tear film break-up time, Schirmer I test, tear meniscus height, lid margin abnormality, meibomian gland dropout and tear film lipid layer thickness, and anterior segment optical coherence tomography(AS-OCT)were performed and statistically analyzed.RESULTS: A total of 178 cases(178 eyes), with a mean age of 54.39±10.75 years old, were recruited, including 75 males(42.1%)and 103 females(57.9%). The average values of ocular surface parameters in these patients included OSDI: 11.47±9.69, tear film break-up time: 7.10±3.86 s; tear meniscus height: 0.16±0.07 mm, Schirmer I test values: 14.39±7.29 mm/5 min, and pterygium thickness: 504.74±175.87 μm. Totally 161 eyes(90.4%)presented with abnormal lid margin, 44 eyes(24.7%)presented with meibomian gland dropout score ≥4, 52 eyes(29.2%)presented with low lipid layer thickness. In the 6 objective examinations, abnormalities in at least 4 of these tests were found in 85.4% of eyes. Pterygium morphology was classified into four grades: 10 eyes(5.6%)of grade Ⅰ, 93 eyes(52.2%)of grade Ⅱ, 60 eyes(33.7%)of grade Ⅲ, and 15 eyes(8.4%)of grade Ⅳ. In patients with a higher grade of pterygium, the tear film break-up time was lower, and the proportion of abnormal lid margin was also significantly higher(P<0.05). The patients were further divided into two subgroups, including 121 eyes(68.0%)with normal OSDI <13 in the normal group and 57 eyes(32.0%)with OSDI ≥13 in the abnormal group. No significant difference was found in the proportion of meibomian gland dysfunction between the two groups of patients(71.9% vs. 71.9%, P=0.872). In addition, there were differences in the number of abnormal objective examinations(4.11±0.85 vs. 4.91±0.99, P<0.001).CONCLUSIONS: Asymptomatic ocular surface abnormalities were present preoperatively in patients hospitalized for primary pterygium. A comparable high incidence of structural or functional meibomian gland dysfunction existed in pterygium patients with or without apparent ocular discomfort. More attention should be paid to the ocular surface abnormalities in those asymptomatic patients before primary pterygium surgery.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To investigate whether Angelica Sinensis and Astragalus capsules(AAC)regulates myocardial autophagy in heart failure rats via the phosphatidylinositol 3 kinase(PI3K)/protein kinase(Akt)/mammalian target of sirolimus(mTOR)signaling pathway.Methods A rat model of heart failure was constructed by intraperitoneal 2.5 mg·kg-1 doxorubicin,and another 8 rats served as the control group.The modeling rats were randomly divided into model group,control group and experimental-L,-M,-H groups.Control group was given 30 mg·kg-1 3-methyladenine by intraperitoneal injection;experimental-L,-M,-H groups were given 150,300 and 450 mg·kg-1 AAC by gavage,respectively;blank and model groups were given the same quantity of sterile distilled water.Six groups were administered once daily for 6 weeks.The cardiac function was measured by ultrasound,and the expression levels of PI3K,Akt,mTOR,sequestosome 1(P62)and microtubule-associated light chain protein 3-Ⅱ/Ⅰ(LC3 Ⅱ/Ⅰ)in myocardial tissue were measured by Western blot.Results In the blank,model,control and experimental-H groups,the left ventricular ejection fraction values were(85.00±3.63)％,(56.75±4.83)％,(75.63±3.70)％and(72.75±4.23)％;the relative expression levels of PI3K were 1.00±0,0.28±0.05,0.64±0.08 and 0.74±0.16;phosphorylated Akt/Akt were 1.00±0,0.49±0.06,0.90±0.16 and 0.95±0.10;phosphorylated mTOR/mTOR values were 1.00±0,0.42±0.09,0.73±0.13 and 0.83±0.08;the relative expression levels of P62 proteins were 1.00±0,0.24±0.12,0.57±0.09 and 0.96±0.10;the relative expression levels of LC3 Ⅱ/Ⅰ proteins were 1.00±0,4.31±0.75,2.20±0.76 and 1.59±0.24,respectively.Compared to the model group,statistical significant were identified in the experimental-H and control groups(all P＜0.05).Conclusion AAC can regulate PI3K/Akt/mTOR pathway,inhibit myocardial autophagy and improve cardiac function in rats with heart failure.

OBJECTIVE To systematically evaluate the effectiveness of different treatment regimens as first-line treatment for metastatic urothelial carcinoma （UC） using a network meta-analysis （NMA） approach. METHODS Electronic databases including PubMed， the Cochrane Library， Embase， Wanfang Data， CNKI， and VIP were searched for randomized controlled clinical trials （RCTs） on first-line treatment for metastatic UC from January 1， 2010 to January 31， 2024. After literature screening and data extraction， a risk of bias assessment of included studies was conducted. R software （version 4.3.2） was used to perform the NMA. RESULTS A total of 11 RCTs involving 14 treatment interventions were included. No significant differences were noted in objective response rate among groups， with the combination of pembrolizumab， gemcitabine and cisplatin having the highest probability of ranking first. Regarding progression-free survival （PFS） and overall survival （OS）， no significant differences were observed among groups， while enfortumab vedotin combined with pembrolizumab showed a trend towards better PFS extension compared to gemcitabine combined with cisplatin [HR＝0.45， 95%CI（0.20，1.06）， P＝0.049]， and it had the highest probability of ranking first in both PFS and OS. CONCLUSIONS The combination of enfortumab vedotin and pembrolizumab may have an advantage in prolonging survival in the first-line treatments for metastatic UC.

Background: Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype–phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. Methods: In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. Results: Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. Conclusions We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.

OBJECTIVE To evaluate the effectiveness and safety of Panlongqi tablets in the treatment of fractures based on real-world research. METHODS From September 2021 to September 2023， fracture patients admitted to 33 medical institutions were collected retrospectively. Patients who received conventional treatment were divided into control group （n＝3 750）， and patients who received combination of Panlongqi tablets on the basis of conventional treatment were divided into observation group （n＝ 3 706）. Self-reported indicators of patients were collected through telephone follow-up at 0， 4， 7 and 14 days after treatment. The improvement values of pain score， swelling score and health utility value， as well as effective rate and adverse drug reactions were compared between 2 groups. The propensity matching score （PSM） method was adopted to perform baseline matching on patient’s age， gender， fracture site， fracture severity， surgical type， type of hospital， and other indicators. Statistical analysis was performed on each therapeutic effect indicator. RESULTS After PSM， a total of 6 425 patients were included， of which 3 055 were in the observation group and 3 370 were in the control group. After 14 days of treatment， the observation group showed significant improvement in pain score （4.768 vs. 4.353）， swelling fangshiyuan2008@126.com grading score （2.979 vs. 2.391）， and life quality utility value （0.430 vs. 0.363）， as well as effective rate （87.20% vs.75.99%） compared to the control group （P＜0.05）. The results of subgroup analyses conducted by gender， age， hospital type， and fracture site were consistent with the aforementioned results. In terms of safety， the observation group had no serious adverse reactions， with a total of 29 cases of mild adverse reactions such as dizziness， stomach pain， and allergies， with an incidence rate of 0.78%. CONCLUSIONS Panlongqi tablets combined with conventional treatment are significantly better than conventional treatment in improving pain， swelling， quality of life， and effective rate in patients with fractures， and have good safety.

Objective To investigate the efficacy of Dingxuan Decoction combined with vestibular function rehabilitation training in the treatment of Meniere's disease and to observe its effect on clinical symptoms and blood flow of vertebral artery.Methods A total of 100 patients with Meniere's disease of liver-kidney yin deficiency complicated with wind-water upward stirring type were randomly divided into an observation group and a control group,with 50 patients in each group.The control group was given conventional treatment and vestibular function rehabilitation training,and the observation group was treated with Dingxuan Decoction on the basis of treatment for the control group.The two groups were treated for 4 weeks and then were followed up for 6 months.The changes of traditional Chinese medicine(TCM)syndrome score,Dizziness Handicap Inventory(DHI)score,Tinnitus Handicap Inventory(THI)score,hearing visual analogue scale(VAS)score and vertebral artery blood flow in the two groups were observed before and after the treatment.After treatment,the TCM syndrome efficacy,hearing improvement and follow-up results were compared between the two groups.Results(1)After 4 weeks of treatment,the total effective rate for TCM syndrome efficacy of the observation group was 86.00%(43/50),and that of the control group was 62.00%(31/50),and the intergroup comparison showed that the TCM syndrome efficacy in the observation group was significantly superior to that in the control group(P＜0.01).(2)After 4 weeks of treatment,the hearing of patients in both groups was improved,and the total effective rate for the efficacy of hearing improvement in the observation group was 76.00%(38/50),while that in the control group was 46.00%(23/50).The intergroup comparison showed that the efficacy of hearing improvement in the observation group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the TCM syndrome scores,DHI score,THI score and hearing VAS scores in the two groups were all decreased compared with those before treatment(P＜0.05 or P＜0.01),and the decrease in the observation group was significantly superior to that in the control group(P＜0.01).(4)After treatment,the average blood flow velocity of the left vertebral artery(LVA)and the right vertebral artery(RVA)in the two groups were both increased compared with those before treatment(P＜0.05),and the increase in the observation group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(5)The results of 6-month follow-up after treatment showed that the incidence of Meniere's disease and the frequency of attack in the observation group were significantly reduced compared with those in the control group,and the episode duration in the observation group was significantly shorter than that in the control group,the differences being all statistically significant(P＜0.05 or P＜0.01).Conclusion Dingxuan Decoction combined with vestibular function rehabilitation training exert certain effect in treating patients with Meniere's disease of liver-kidney yin deficiency complicated with wind-water upward stirring type,and the therapy is effective on improving patients'clinical symptoms and vertebral artery blood flow,reducing the risk of recurrence and improving the quality of life of the patients.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

Objective To investigate the effect of MALAT1 expressions on cell proliferation and apoptosis in astrocytes by regulating mitogen-activated protein kinase(MAPK)/extracellular signal-regulated kinase(ERK1,2)pathway.Methods The MALAT1 gene was knocked down and over-expressed in C8-D1A cells by lentiviral and plasmid vectors,respectively.The expressions of MALAT1,cell proliferation-related markers(Ki67,MCM2,PCNA)and apoptosis-related proteins(Caspase-3,Bax,Bcl-2)were detected by quantitative real-time polymerase chain reaction(qPCR).CCK-8 assay and flow cytometry were used for cell proliferation and apoptosis in C8-D1A cells.Immunofluorescence was adopted to detect the protein expressions of Caspase-3 and Ki67.Western blotting was used to detect the protein expressions of Caspase-3,Bax,Bcl-2,ERK1/2,p-ERK1/2,p38MAPK and p-p38MAPK.Results Compared with the control group,over-expressed MALAT1 inhibited cell proliferation and induced cell apoptosis in C8-D1A cells while the knockdown of MALAT1 significantly enhanced cell proliferation and anti-apoptotic ability in C8-D1A cells.The proportion of C8-D1A cells in G0/G1-phase and G2/M-phase was higher than in the control group as evidenced by flow cytometry,but was lower in S-phase.Meanwhile,data showed that Caspase-3 was increased while p-ERK1/2 was decreased in terms of protein levels.The mRNA expressions of Ki67 and PCNA were decreased.After knockdown of MALAT1,the proportion of C8-D1A cells in S-phase was higher,but was lower in G2/M-phase.The protein expressions of Caspase-3 and Bax decreased while those of p-ERK1/2 and p-p38MAPK increased.The mRNA expressions of Ki67,MCM2 and PCNA were increased.The differences were all statistically significant(P＜0.05).Conclusion MALAT1 promotes astrocyte apoptosis and inhibits proliferation by regulating the MAPK/ERK1,2 signaling pathway.

Objective:To establish and validate reference intervals of serum vitamin K for healthy children in China.Methods:A cross-sectional study was conducted from January 2020 to May 2023, involving 807 healthy children aged 0 to 14 years, selected by stratified random sampling based on the population distribution of children in eastern, central, western, and northeastern China. Sample collection was carried out in 16 hospitals across 12 provinces, autonomous regions, and municipalities. Basic information of the children was collected using a standardized self-design questionnaire. Serum levels of vitamin K 1 and vitamin K 2 (menaquinone-4 (MK-4), menaquinone-7 (MK-7)) were measured using liquid chromatography-tandem mass spectrometry. The reference intervals was established by direct approach. The children were divided into different groups by age. Inter-group comparisons were conducted using the Kruskal-Wallis non-parametric test, and the reference intervals ( P2.5- P97.5) were determined using non-parametric methods. Screening 40 healthy children for small sample validation based on age groups within the reference range(25 from eastern, 10 from central, and 5 from western regions). Results:The age of the 807 children was 5.00 (2.00, 9.81) years, and 495 (61.3%) were males and 312 (38.7%) females. Reference intervals were established for 795 children, of whom 303 children were aged 1 month to 3 years and 492 were aged 4 to 14 years. The reference intervals for serum vitamin K 1 were 0.09-4.54 μg/L for children aged 1 month to 3 years, and 0.10-1.73 μg/L for 4-14 years. For MK-7, the intervals were 0.07-1.42 μg/L for 1 month to 3 years and 0.19-2.03 μg/L for 4-14 years. The reference intervals for MK-4 in children aged 1 month to 14 years were 0-0.42 μg/L. The measured values of serum vitamin K 1, MK-4, and MK-7 in the validation samples did not exceed the reference limit in more than 2 samples. Conclusion:Reference intervals for vitamin K 1, MK-4, and MK-7 in healthy children aged 1 month to 14 years have been established and validated, and can be used to assess vitamin K nutritional status in children.