Volume 105 · Issue 48 · 2025

Inner ear comorbidity (IEC) refers to a group of diseases caused by lesions in the cochlea, vestibule, and their neural pathways. These diseases are usually accompanied by hearing loss, tinnitus, vertigo and other symptoms simultaneously or dynamically alternating, forming a comorbidity phenomenon with inner ear dysfunction as the core. Inner ear comorbidities increase the complexity and cost of diagnosis and treatment, putting high difficulty and stress on clinicians and health systems. At present, the main symptoms are mostly treated in clinical practice, and the inherent connection between cochlea and vestibule and other systemic diseases is often ignored, making it difficult to accurately classify and target the disease. This article puts forward the definition and category of inner ear comorbid diseases, explains their inherent correlation and multiple drivers in the etiological mechanism, and proposes a precise typing paradigm for multimodal data integration. Moreover, in order to cope with the three challenges of cognitive fragmentation of multiple disease spectra, complexity of disease heterogeneity and fragmentation of medical system, it is urgent to build an interdisciplinary diagnosis and treatment platform, strengthen the research on systematic medicine perspective and full-chain mechanism, and promote the strategic transformation from symptom management to overall health maintenance, aiming to realize the goal of paying attention to inner ear comorbidity, implementing precise prevention and treatment, and effectively reducing disease burden.

von Hippel-Lindau (VHL) syndrome is an autosomal dominant hereditary disorder caused by germline heterozygous pathogenic variants of the VHL gene or promoter hypermethylation. It is characterized by multiple tumors and cystic lesions, primarily affecting the central nervous system, retina, kidneys, pancreas, adrenal glands, and other organs. In recent years, significant progress has been made in both basic and clinical research on VHL syndrome, particularly in genotype-phenotype correlations and targeted therapies, such as the clinical application of hypoxia-inducible factor-2α inhibitors. To further standardize the diagnosis and management of VHL syndrome in China, the Chinese Society of Rare Diseases of the Chinese Medical Association, the Beijing Society of Rare Diseases, and the Chinese Alliance for Genetic and Rare Diseases of the Urinary System of the Chinese Urological Association have updated the epidemiological, genetic, and clinical characteristics, diagnostic criteria, treatment strategies, and long-term management protocols based on the latest evidence-based medical findings and the "Chinese expert consensus for the diagnosis and treatment of von Hippel-Lindau syndrome" in the 2018 edition, and forms 12 recommended suggestions, aiming to provide scientific guidance for clinical practice.

To explore otologic symptoms and audiological features in patients with spontaneous intracranial hypotension (SIH), and provide reference for clinical diagnosis and treatment.

The clinical data of 348 patients with SIH who were hospitalized and treated at the Chinese PLA General Hospital from January 2001 to June 2025 were retrospectively reviewed. Demographic characteristics, otologic symptoms (hearing loss, tinnitus, ear fullness, dizziness/vertigo), audiological findings, and their associations were analyzed.

Among the 348 patients, there were 156 males (44.8%) and 192 females (55.2%). The mean age was (39.5±14.4) years, with the highest proportion in the 30-39-year group (28.7%, 100/348), followed by the 40-49-year group (20.7%, 72/348). All patients presented with headache. Ear symptoms were detected in 104 cases (29.9%). Among them, hearing loss was found in 43 cases (12.4%), with 25 bilateral cases (58.1%) and 18 unilateral cases (41.9%); 51 cases (14.7%) and six cases (1.7%) had tinnitus and ear fullness, respectively; 55 cases (15.8%) had dizziness/vertigo. Of the 34 patients who completed the audiological test, 32 cases (94.1%) had sensorineural hearing loss and two cases (5.9%) had conductive hearing loss. Of 68 ears assessed, mild, moderate, moderately severe, and severe loss occurred in 22, 13, four, and two ears respectively; mild-to-moderate loss accounted for 51.5% (35/68). Descending audiograms were most frequent (36.8%, 25/68), followed by notch (23.5%, 16/68), flat (22.1%, 15/68), and ascending types (17.6%, 12/68). Hearing loss occurred more frequently in the older age group (>18 years old) and in patients with tinnitus or dizziness/vertigo compared with other groups (all P<0.001).

Otologic symptoms are common in patients with SIH, with hearing loss, tinnitus, and dizziness/vertigo being predominant. Hearing loss is mainly mild-to-moderate sensorineural type, and the descending audiogram is the most frequent pattern.

To investigate the characteristics of theta rhythm functional connectivity and their clinical implications in patients with Meniere′s disease.

A cross-sectional study was conducted. Patients diagnosed with Meniere′s disease along with matched healthy controlsat the Department of Otolaryngology-Head and Neck Surgery, Shanghai Sixth People′s Hospital between August 2020 and January 2024 were enrolled. Phase-locking value (PLV) was used to calculate theta-band functional connectivity between brain regions in source space. Intergroup differences of the functional connectivity were compared, and its correlations with clinical characteristics were analyzed.

The study included 32 Meniere′s disease patients (9 males and 23 female) with a mean age of (54.8±11.9) years, along with 29 healthy controls (7 males and 22 females) with a mean age of (56.7±14.5) years. Compared with the healthy controls, Meniere′s disease patients exhibited enhanced theta functional connectivity within a network centered on the paracentral lobule and cingulate gyrus (all P<0.05). This enhanced connectivity between the medial/paracingulate gyri and the paracentral lobule positively correlated with the severity of subjective symptoms (r=0.355, P=0.046) and scores on the anxiety-autonomic symptom subscale (r=0.402, P=0.023). However, no statistically significant correlation was found with hearing levels or dynamic posturography scores (all P>0.05).

Patients with Meniere′s disease demonstrate enhanced theta rhythm functional connectivity involving the paracentral lobule and cingulate gyrus. This neural signature is dissociated from hearing loss and overall balance performance but is linked to subjective anxiety and autonomic symptoms.

To explore the association between blood lipid levels and prognosis in patients with sudden sensorineural hearing loss (SSNHL) and develop a predictive model.

The clinical data of unilateral SSNHL patients from the Chinese PLA General Hospital between January 2008 and December 2022 were retrospectively analyzed. Patients were divided into treatment-effective and ineffective groups based on their hearing recovery (prognosis) after treatment. Restricted cubic spline (RCS) analysis was used to examine the nonlinear relationship between blood lipid levels and prognosis. The data were randomly split into training and testing sets at a 7∶3 ratio using a computer-based algorithm, and sex-stratified predictive models for prognosis were developed using stepwise logistic regression. The performance of the models was evaluated through receiver operating characteristic (ROC) curves, Hosmer-Lemeshow goodness-of-fit tests, and decision curve analysis (DCA), respectively.

A total of 1 329 patients aged (41.4±10.9) years were included, with 682 males and 647 females. RCS analysis showed no nonlinear relationship between lipid metabolism indicators and prognosis in sudden sensorineural hearing loss (all P>0.05). The male predictive model included eight variables: age, low-density lipoprotein cholesterol (LDL-C), smoking, drinking, time of onset, tinnitus, vertigo, and audiogram type. The areas under the ROC curve (AUC) for the training set and validation set were 0.873 (95%CI: 0.839-0.908) and 0.823 (95%CI: 0.760-0.886), respectively. The female predictive model included sevenvariables: age, body mass index (BMI), triglycerides (TG), time of onset, vertigo, hearing level, and audiogram type. The AUC was 0.864 (95%CI: 0.828-0.901) for the training set and 0.833 (95%CI: 0.766-0.900) for the validation set. The model evaluation showed no significant bias in the Hosmer-Lemeshow test for both groups (both P>0.05). The DCA showed a positive net benefit for risk-threshold probabilities of 0-0.93 in both the training and validation sets for male patients. For female patients, the net benefit was positive for thresholds of 0-0.94 in the training set and across nearly the entire range in the validation set.

The prognosis of male patients is significantly influenced by smoking, drinking, and LDL-C metabolism disorders, while female patients are affected by BMI and TG levels. The predictive models based on blood lipid levels demonstrated good discrimination, calibration, and clinical applicability.

To investigate the effects of Zolpidem combined with Shugan Jieyu capsules on sleep quality and daytime cognitive function in patients with insomnia disorder with depressive symptoms.

Randomized controlled trial. Sixty patients with insomnia disorder with depressive symptoms prospectively recruited from Nanfang Hospital, Southern Medical University from March to October 2023, were randomly divided into an experimental group and a control group, with 30 patients in each group. The experimental group received oral administration of Zolpidem 10 mg/d and Shugan Jieyu capsules 0.72 g/d for 8 weeks, while the control group received oral administration of Zolpidem 10 mg/d and placebo 0.72 g/d for 8 weeks. Repeated-measures analysis of variance was used to assess changes in the insomnia severity index (ISI), Pittsburgh sleep quality index (PSQI), Epworth sleepiness scale (ESS), patient health questionnaire-9 (PHQ-9), working memory (low-load 1-back task, high-load 2-back task), and polysomnography at baseline, 4 weeks, and 8 weeks between the two groups.

A total of 59 patients completed the trial, with 30 in the experimental group [14 males, age (28.5±7.8) years] and 29 in the control group [9 males, age (26.5±5.3) years]. There were no statistically significant differences in age, gender, education level, body mass index, illness duration, apnea-hypopnea index (AHI) and periodic limb movement index (PLMI) between the two groups (all P>0.05). At week 4 and 8 of treatment, the ISI scores of the experimental group [(10.6±5.9) and (8.7±6.7), respectively] and the control group [(11.7±5.1) and (10.6±5.1), respectively] were lower than the baseline values (experimental group: 18.7±4.4) and (control group: 18.9±3.6). In addition, at weeks 4 and 8 of treatment, both groups showed lower PSQI scores, ESS scores, and PHQ-9 scores than baseline and higher N2 sleep stage, sleep efficiency, and accuracy of the high-load cognitive 2-back task than baseline values (all P<0.05). Among them, there was an interaction between the time and the group of high-load cognitive 2-back tasks (the improvement rates of the experimental group at week 4 and 8 were 9.4%±13.2% and 5.7%±13.8% respectively, and the improvement rates in the control group at week 4 and 8 were 20.1%±19.8% and 5.5%±8.7% respectively) (all P<0.05). There were no significant differences between the two groups in terms of ISI score, PSQI score, ESS score, PHQ-9 score, N2 sleep stage, sleep efficiency, and accuracy of 2-back tasks on high-load cognitive tasks at week 4 and 8 of treatment (all P>0.05).

Based on comparable improvements achieved in sleep quality and depressive symptoms, the combination of Zolpidem and Shugan Jieyu capsules showed further improvement in the recovery pattern of high-load working memory during the day.

To investigate the characteristics of event-related potential (ERP) in adult males with obstructive sleep apnea (OSA) comorbid with depressive state and their correlation with polysomnography (PSG) parameters.

Cross-sectional study. A total of 77 adult male OSA patients aged 18 to 60 from the Sleep Center of the Second Affiliated Hospital of Soochow University were prospectively enrolled between August 2023 and June 2024. General clinical data, Epworth sleepiness scale (ESS), Pittsburgh sleep quality index (PSQI), self-rating depression scale (SDS), self-rating anxiety scale (SAS), and PSG parameters were collected. Task-state EEG signals were acquired using a 64-channel system under an emotional facial stimulation paradigm. ERP components were analyzed, including the negative wave occurring at approximately 170 ms (N170) and the positive wave occurring at approximately 300 ms (P300) post-stimulus. Based on the apnea-hypopnea index (AHI) and SDS scores, patients were divided into two groups: the OSA without depressive state group (AHI≥5 events/h and SDS<50) and the OSA with depressive state group (AHI≥5 events/h and SDS≥50). Differences in relevant indicators between the two groups were compared. Spearman correlation analysis was employed to assess the relationships between ERP amplitude/latency and PSG parameters.

The 77 OSA patients had a mean age of (40.3±8.1) years. Among them, 51 were classified as the OSA without depressive state group, while 26 comprised the OSA with depressive state group, indicating a depression comorbidity rate of 33.8% in the OSA cohort. The OSA with depressive state group demonstrated significantly higher values compared to the OSA without depressive state group in the following parameters: hypertension comorbidity rate [46.2% (12/26) vs 21.6% (11/51)], ESS score [M (Q₁, Q₃): 10.0 (5.0, 15.0) vs 7.0 (4.0, 11.0) points], SDS [(55.2±4.4) vs (40.4±6.0) points], and SAS [(43.3±6.0) vs (37.9±7.4) points] (all P<0.05). The OSA with depressive state group exhibited a lower proportion of slow-wave sleep (SWS) compared to the OSA without depressive state group [7.1% (2.9%, 11.4%) vs 13.1% (6.8%, 19.3%), P=0.002], and a higher microarousal index [36.2 (24.9, 45.9) vs 27.9 (16.4, 39.4) events/h, P=0.034]. Furthermore, the N170 latencies at both the PO7 electrode [(261.5±22.4) vs (250.2±23.1) ms] and the PO8 electrode [(261.4±20.2) vs (246.8±23.2) ms] were longer in the OSA with depressive state group (all P<0.05). Correlation analyses revealed a negative correlation between N170 latency at the PO8 electrode and SWS percentage (r=-0.227, P=0.047). Additionally, N170 amplitudes at both the PO7 electrode (r=-0.351, P=0.002) and the PO8 electrode (r=-0.262, P=0.021) showed negative correlations with the microarousal index.

Adult male OSA patients with comorbid depression demonstrated prolonged N170 latency in response to emotional facial stimuli, and the alterations in its amplitude and latency were associated with sleep fragmentation.

To evaluate the effect of targeted therapy for primary aldosteronism (PA) on the clinical outcome of coexisting obstructive sleep apnea (OSA).

A prospective study was conducted on patients diagnosed with both PA and OSA in the Sun Yat-sen Memorial Hospital between June 2023 and January 2025. All patients received PA targeted treatment. Full-night portable sleep monitoring was performed before and 3-12 months after treatment. Participants were divided into the OSA improvement group or the non-improvement group based on the change in the apnea-hypopnea index (AHI). Differences in clinical characteristics before and after PA treatment, as well as between the two patient groups, were compared. Multivariate logistic regression model was employed to identify risk factors influencing the lack of OSA improvement.

A total of 46 patients were enrolled, including 35 males and 11 females, with a mean age of (51.0±12.0) years. Among them, 34 patients were classified into the OSA improvement group, while 12 patients into the non-improvement group the non-improvement group. Of these, 21 patients underwent unilateral adrenalectomy, and 25 received mineralocorticoid receptor antagonist therapy. Patients were followed up for a duration of [M (Q₁,Q₃)] 6.0 (3.0,8.0) months. After treatment, patients with PA complicated by OSA exhibited a reduction in antihypertensive medication use, the increases in serum potassium, renin activity, and serum creatinine levels, along with the decreases in plasma aldosterone and the aldosterone-to-renin ratio (all P<0.05). Specifically, the AHI declined from 23.8 (9.0,40.2) events/h to 13.1 (8.1,21.8) events/h (P=0.003). In the non-improvement group, baseline body mass index [(30.1±6.4) vs (25.8±5.0) kg/m²] and the clinical non-remission rate of PA [6/12 vs 5.9% (2/34)] were both higher than those in the improvement group (both P<0.05). Multivariate logistic regression model analysis revealed that a higher baseline body mass index (OR=1.18, 95%CI: 1.01-1.39) and clinical non-remission of PA (OR=11.69, 95%CI: 2.13-64.08) were risk factors for lack of improvement in OSA.

In patients with PA complicated by OSA, PA-targeted therapy effectively reduces OSA severity. Higher baseline body mass index and clinical non-remission of PA are identified as risk factors for unimproved OSA.

To compare the efficacy and safety of left hepatectomy with sequential embolization of the tumor-invaded right hepatic artery (RHA) followed by resection without reconstruction versus left hepatectomy with RHA resection and reconstruction for the treatment of hilar cholangiocarcinoma (HCCA).

A retrospective cohort of 10 HCCA patients undergoing the SERRHA protocol between January 2023 and January 2025 at the Sun Yat-sen Memorial Hospital, Department of Biliary and Pancreatic Surgery, was included (SERRHA group). A control group of 24 HCCA patients undergoing left hepatectomy with RHA resection and reconstruction between January 2014 and January 2025 was established (RRRHA group). Follow-up was conducted until April 30, 2025. The incidence of 90-day Clavien-Dindo≥Grade Ⅲ complications, R0 resection rates, and postoperative survival were compared.

The SERRHA group included 10 cases, aged (57.6 ± 16.3) years, with 3 males. The RRRHA group included 24 cases, aged (57.3 ± 11.1) years, with 15 males. In the SERRHA group, 2 patients (2/10) developed left liver abscesses post-embolization. There were no 90-day or in-hospital deaths. Median follow-up was 9.3 months (95%CI: 3.6-15.0). In the RRRHA group, there was 1 peri-operative death due to anastomotic haemorrhage. Median follow-up was 44.5 months (95%CI: 25.8-63.2). Median overall survival (OS) was 29.0 months (95%CI: 9.3-48.7), with 1-, 3-, and 5-year OS rates of 90.8%, 45.6%, and 20.3%, respectively. There were no statistically significant differences (P>0.05) between the SERRHA and RRRHA groups in 90-day Clavien-Dindo≥Grade Ⅲ complications [5/10 vs 20.8% (5/24)], R0 resection rate [4/10 vs 70.8% (17/24)], or 1-year OS (83.3% vs 90.8%).

For HCCA with RHA invasion where resection and reconstruction are difficult, left hepatectomy following RHA embolization demonstrates a certain degree of safety, and its short-term efficacy is similar to that of cases with RHA resection and reconstruction.

To investigate the clinical efficacy of short-term spinal cord stimulation (stSCS) in the treatment of segmental zoster paresis (SZP).

A retrospective analysis was performed to collect the clinical data of patients with SZP at the Department of Pain Medicine, Nanjing Hospital Affiliated to Nanjing Medical University from January 2023 to December 2024. The patients were divided into two groups based on whether they received stSCS therapy: the stSCS group (stSCS combined with medication) and the control group (medication only). Evaluations were performed before treatment (T₀) and at the following time points after treatment: day 14 (T₁), 1 month (T₂), 3 months (T₃), and 6 months (T₄). The following parameters were compared between the two groups at different time points: peak torque (PT) of elbow extensors and flexors at an angular velocity of 60°/s, motor nerve conduction velocity (MNCV) of the ulnar and median nerves, as well as scores on the Numerical Rating Scale (NRS) of pain, Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS).

The stSCS group consisted of 20 patients (8 males, 12 females) with a median [Q₁, Q₃] age of 73.5 (70.3, 77.3) years and disease duration of 0.9 (0.3, 1.6) months. The control group included 20 patients (6 males, 14 females) with a median age of 69.5 (64.5, 79.0) years and disease duration of 0.7 (0.4, 1.2) months. There were no statistically significant differences in age or gender between the two groups (all P>0.05). At the T₃ and T₄ follow-ups after treatment, the stSCS group demonstrated significantly higher elbow extensor PT [(24.7±1.8) Nm vs (21.9±2.3) Nm], flexor peak PT [(18.6±2.0) Nm vs (20.6±1.9) Nm], ulnar nerve MNCV [(49.0±1.8) m/s vs (52.4±2.3) m/s], and median nerve MNCV [47.3 (46.7, 48.1) m/s vs 51.1 (49.4, 52.1) m/s] compared to the control group, while NRS of pain, SAS, and SDS scores were significantly lower than those in the control group, with significant differences (all P<0.05). No serious stSCS-related adverse reactions occurred, and there were no patient deaths.

The stSCS facilitates the recovery of motor function, significantly alleviates pain, and effectively mitigates anxiety and depression symptoms in patients with SZP.

To investigate the molecular mechanism by which fibroblast growth factor 1 (FGF1) participates in neural tube defects (NTD) through regulating cell proliferation in a retinoic acid (RA)-induced mouse model, and to elucidate the role of FGF1 during neural tube closure in mice.

An NTD mouse model was established using RA induction, with mice divided into a treatment group and a control group (n=9 each). Pregnant mice in the treatment group received 28 mg/kg RA via gavage at embryonic day 7.5 (E7.5), while the control group received sesame oil. Embryonic brain vesicle tissues were collected at E8.5, E9.5, and E10.5 for RNA and protein extraction to assess gene expression. Embryonic brain sections from E9.5 and E10.5 were prepared for pathological examination and gene expression analysis. At the mouse embryonic brain tissue level, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate FGF1 mRNA expression, and immunohistochemistry (IHC) was performed to detect FGF1 protein expression. An FGF1 knockdown plasmid was constructed, and cell proliferation was assessed in vitro. Western blot was used to measure the expression of the proliferation marker proliferating cell nuclear antigen (PCNA), 5-Ethynyl-2′-deoxyuridine (EdU) staining was employed to evaluate cell proliferation, and flow cytometry was conducted to analyze apoptosis.

The RA treatment group of mice showed delayed embryonic development, abnormal brain structure, and unclosed neural tubes, inducing the formation of NTD mouse models. At the animal level, both the mRNA and protein expressions of FGF1 were abnormally highly expressed in the brain tissues of NTD mouse embryos at embryonic day 9.5 (E9.5) and E10.5 (P<0.001). At the cellular level, FGF1 was significantly highly expressed in HT-22 cells treated with RA (P<0.001), while its expression was significantly downregulated after FGF1 knockdown (P<0.001); the protein expression of PCNA (a cellular proliferation marker) in RA-treated cells was significantly increased (P<0.01), and this expression was significantly decreased after FGF1 gene knockdown in the RA-treated group (P<0.01). EdU staining experiments also showed that excessive cell proliferation occurred after RA treatment (P<0.001), whereas cell proliferation was reduced in RA-treated cells with FGF1 knockdown (P<0.001); flow cytometry analysis indicated that the proportion of apoptotic cells increased significantly after RA intervention (P<0.001), and this proportion continued to increase after FGF1 knockdown (P<0.05).

FGF1 was significantly upregulated in the RA-induced NTD model. Overexpression of FGF1 inhibited cell proliferation and induced apoptosis. Knockdown of FGF1 restored the reduced cell proliferation caused by RA intervention and further increased RA-induced apoptosis. It provides a new perspective on the mechanism of NTD and may serve as a potential biomarker for clinical diagnosis.

To explore the intracellular tolerance of Helicobacter pylori (Hp) to common clinical antibiotics.

One strain of Hp26695, HpATCC43504, and HpHXW02 each were used to infect human gastric mucosal epithelial cells. Divide human gastric mucosal epithelial cells into intracellular and extracellular groups. In the intracellular group, infect cells with the selected bacterial strain that causes the most severe vacuolization effect, and establish an intracellular infection model; Extracellular group: cultivate an equal amount of bacterial strains in conventional liquid culture without infecting cells. Using immunofluorescence staining to locate Hp and human gastric mucosal epithelial cells, analyzing fluorescence signals using confocal microscopy to verify the phenomenon of Hp entering cells. The minimum inhibitory concentrations (MIC) of four commonly used clinical antibiotics, clarithromycin, metronidazole, tetracycline, and amoxicillin, against the Hp26695 strain were determined using the microbroth dilution method. Then, four antibiotics with concentrations ranging from 0 to 4 MIC were used to treat the intracellular and extracellular groups for 12 h, respectively. The bacterial strains were cultured using the plate coating method, and the colony forming units (CFU), survival rate and relative survival rate of the two groups were compared.Three parallel experiments were set up for each group of antibiotics with different concentrations, and the experiment was repeated three times.

Among the three strains of Hp26695, HpATCC43504, and HpHXW02, the Hp26695 strain caused the most severe vacuolization lesions in human gastric mucosal epithelial cells. Therefore, the Hp26695 strain was used for subsequent experiments. Immunofluorescence and confocal microscopy observations confirmed that the strain can invade host cells. The MIC values of Hp26695 strain for clarithromycin, metronidazole, tetracycline, and amoxicillin are 0.031, 0.500, 0.125, and 0.250 mg/L. After antibiotic treatment, the CFU of Hp in the intracellular group were higher than those in the extracellular group: clarithromycin [at 1/2 MIC (162±9) vs (79±5), at MIC (115±6) vs (25±5), at 2 MIC (93±6) vs (15±5), at 4 MIC (81±6) vs (12±1)]; metronidazole [at 1/2 MIC (166±12) vs (110±12), at MIC (161±14) vs (55±7), at 2 MIC (93±8) vs (18±5), at 4 MIC (60±6) vs (7±3)]; tetracycline [at 1/2 MIC (153±13) vs (113±10), at MIC (131±12) vs (45±7), at 2 MIC (113±11) vs (28±6), at 4 MIC (95±8) vs (16±7)]; amoxicillin [at 1/2 MIC (168±14) vs (109±11), at MIC (136±10) vs (47±7), at 2 MIC (120±8) vs (32±7), at 4 MIC (109±12) vs (19±6)] (all P<0.001). After the concentration of antibiotics increased, the survival rates of Hp in both the intracellular and extracellular groups decreased to varying degrees, and the survival rate of Hp26695 strain in the intracellular group was higher than that in the extracellular group (all P<0.05). The relative survival rate of bacteria in the intracellular/extracellular groups was 0.99-7.24.

After internalization, Hp exhibit enhanced tolerance to clarithromycin, metronidazole, tetracycline, and amoxicillin.

This paper reports the diagnosis and treatment of a patient with lymphopithelioma-like tumor of intrahepatic bile duct with low malignant potential. A 59-year-old female was found to occupy the left lobe of the liver by B-ultrasound and MRI, followed by laparoscopic partial hepatectomy. The postoperative pathological diagnosis was a lymphoepithelioma-like tumor of intrahepatic bile duct with low malignant potential, and no other treatment was performed. Follow-up until 14 months postoperatively showed no tumor recurrence or metastasis. In this paper, the histological morphology, immunohistochemistry and molecular characteristics of this case were analyzed, and related literatures were reviewed, with the aim of improving the understanding of this type of tumor by pathologists.

Somatosensory tinnitus (ST) is a chronic subjective tinnitus associated with somatosensory systems such as the head and neck. It is typically characterized by adjustable tinnitus loudness or pitch through specific movements or local stimuli at sites such as the temporomandibular joint or head and neck. Studies suggest that abnormal trans-modal integration of the central nervous system may be the core pathogenesis of ST. At present, its diagnostic criteria are not uniform, which affects the comparability between different studies and the evidence-based evaluation of clinical treatment. Existing research evidence shows that treatment of identifiable somatic dysfunctions (such as temporomandibular joint disorders, cervical vertebral lesions, etc.) can significantly improve ST symptoms, which provides new ideas for the precise treatment of tinnitus. This paper systematically reviews the research progress of the neurobiological mechanism of ST, the evolution of diagnostic criteria and the treatment management methods, evaluates the diagnosis and treatment plan based on the existing evidence, and discusses the application prospect of treatment strategies such as integrated traditional Chinese and western medicine therapy and rehabilitation training, in order to provide a basis for promoting the individualized precise diagnosis and treatment of ST patients.

Deafness is one of the most common disabling diseases in humans, 60% of which are caused by genetic variation. With the release of human's first complete gap-free reference genome (T2T-CHM13) and the maturity of third-generation sequencing technology, more and more deafening genomic structural variants (SVs) have been detected. This paper introduces the occurrence process, pathogenic mechanism and detection methods of genomic SV, focusing on the research progress of different types of SV (such as inversion, translocation, insertion, deletion, duplication, complex SV, etc.) in hereditary deafness, which will help to improve the clinical diagnosis and evaluation process of this kind of complex hereditary deafness, so as to reduce the missed diagnosis rate and misdiagnosis rate.

Age-related hearing loss (ARHL) is a bilateral symmetrical sensorineural hearing loss caused by degenerative lesions of the auditory system. Its incidence is increasing year by year with the aging of the population, which seriously affects the cognitive function and social participation ability of the elderly. The main pathological changes of ARHL involve hair cells, stria vascularis, spiral ganglion neurons and central auditory pathway in inner ear. This paper systematically reviews the latest research progress of risk factors and pathogenesis related to ARHL, deeply discusses the influence of age, sex, race, genetics, environment, metabolic diseases and other factors on the disease process, and systematically summarizes the core roles of oxidative stress, mitochondrial dysfunction, aging-related inflammation and cochlear synaptic lesions in the development of ARHL from the molecular mechanism level.

Target simulation trials (TTE), which use real-world data to make causal inference through the design framework of simulated randomized controlled trials, have shown important value in the prevention and treatment of infectious diseases in recent years. This paper systematically summarizes the development process, design key points of TTE method and its application prospects and challenges in health hazard assessment, prevention effect and treatment effect assessment of infectious diseases. Although TTE has advantages in improving causal inference, taking into account timeliness and ethical feasibility, and applying extrapolation ability, it still faces challenges such as complex natural history of infectious diseases (such as asymptomatic infection and virus mutation), difficult data governance, and undetected confusion. In the future, we should strengthen the integration of multi-source data, methodological standards and multidisciplinary cooperation, further promote the application of TTE in the field of infectious disease prevention and control, and provide more reliable medical evidence for accurate prevention and control of infectious diseases and policy formulation.

The patient, a 50-year-old female, was admitted to the thoracic surgery department of Qingdao Municipal Hospital on December 2, 2022 due to "the discovery of a right lung nodule for 1 week". Prior physical health, no smoking history. Specialist examination showed no thoracic deformity, percussion of both lungs showed clear sounds, clear breathing sounds of both lungs, and no dry or wet rales were heard. All tests for lung cancer-related tumor markers were negative at admission. CT examination of head, whole abdomen and whole body bone imaging showed no obvious abnormalities. On December 3, 2022, the results of chest enhancement CT showed a mass of soft tissue density shadow in the middle lobe of the right lung, with a larger cross section of about 73 mm ×38 mm, corresponding bronchial truncation and uneven density. The enhancement scan showed mild to moderate enhancement, vascular enhancement shadow at the edge of the lesion, enlarged right hilar shadow, and lymph node shadow (Figure A is a pulmonary window image, with an arrow showing bronchial truncation; Figure B is a mediastinal window image, with an arrow showing vascular enhancement shadow). On February 6, 2023, general anesthesia and thoracoscopic right middle lobe resection + localized mediastinal lymph node dissection were performed. The pathological results showed poorly differentiated squamous cell carcinoma in the middle lobe of the right lung, with massive lymphocyte infiltration, and lymphoepithelioma-like carcinoma was considered, in which large necrosis, granuloma formation, cholesterol crystals, increased fibrous connective tissue, and cancerous tissue involving the pleura was seen (Figure C, hematoxylin-eosin staining ×100). Immunohistochemistry and in situ hybridization showed positive expression of CK, CK5/6, EBER-ISH, and negative expression of EMA (partially weakly positive), Ki67 (20% positive), CK7, CK20, CD56, TTF-1 and BerEP4 in tumor cells. Based on the clinical manifestations and pathological results, the diagnosis of lung lymphopithelioma-like carcinoma (PPLELC) was made. PPLELC is a rare subtype of non-small cell lung cancer. The typical CT manifestation is a single, well-defined and large round-like solid mass in the lung adjacent to the pleura or mediastinum. After enhancement, it is more specifically manifested as a vascular-like enhancement shadow at the tumor edge, forming a "vascular embedding sign". The pathological characteristics of PPLELC mainly show that a large number of lymphocyte infiltration is mixed in cancer cells. The cancer cells are usually polygonal, with large nuclei and syncytial arrangement. Surgical resection is the main treatment for patients with PPLELC, while multimodal treatment is usually used for patients with advanced or metastatic disease.