Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder primarily caused by pathogenic variants in the TSC1 or TSC2 genes. It is characterized by multisystem hamartomatous lesions and neuropsychiatric manifestations. Here we report a young male patient with TSC involving multiple organs, caused by a heterozygous frameshift mutation in TSC2 (c.2071delC, p.Arg691Alafs^*7). The patient initially presented with classic facial angiofibromas and hypomelanotic macules, and subsequently developed psychiatric and behavioral disturbances with auditory hallucinations. Neuroimaging revealed an intracranial mass lesion, which was confirmed as a subependymal giant cell astrocytoma on postoperative histopathology following surgery performed at an outside institution. After admission, the patient underwent a comprehensive diagnostic workup, and multidisciplinary treatment evaluation revealed extensive multisystem involve-ment, including the nervous system, skin, kidneys, lungs, heart, eyes, pancreas, liver and bones. Combined with relevant literature, this article discusses the molecular mechanisms, clinical phenotypes, and comprehensive management of TSC, in order to provide a reference for the standardized and individualized management of this disease.

Endoscopic transforaminal lumbar interbody fusion (TLIF) offers substantial advantages in the management of degenerative spinal diseases, including accelerated postoperative recovery. However, its technical complexity and steep learning curve pose risks for nerve root injury. Optimizing nerve root protection in full-endoscopic facet-sparing TLIF (FE fs-TLIF) and full-endoscopic facet-resecting TLIF (FE fr-TLIF) is essential for enhancing surgical safety. This study aimed to improve the nerve root protection in FE fs-TLIF and FE fr-TLIF by optimizing cage glider selection and insertion techniques based on the specific cage shape—banana-shaped or bullet-shaped. The goal was to ensure safe cage positioning and mitigate nerve root injury during discectomy, endplate preparation, and cage insertion. These strategies were validated through cadaveric simulations and clinical implementation. In FE fr-TLIF utilizing bullet-shaped (straight) cages, one-tip and two-tip cage gliders effectively protected the traversing nerve root by facilitating medial cage entry, thereby minimizing irritation of the exiting nerve root. Conversely, in FE fr-TLIF with banana-shaped cages, the lateral tilt of the cage holder during implantation required the use of a two-tip cage glider to protect the traversing and exiting nerve roots, thereby mitigating the potential risk of nerve irritation. In FE fs-TLIF, a one-tip cage glider is preferred for safeguarding the exiting nerve root, while the traversing root is inherently protected by the medial wall of the facet joint. The use of a two-tip cage glider in FE fs-TLIF can cause injury to the nerve root during glider insertion. In addition to the selection of cage gliders, improper cage insertion steps can also contribute to postoperative neurapraxia. The appropriate selection of cage gliders with corresponding insertion techniques is critical for nerve root protection in endoscopic TLIF. Tailoring these choices to the specific approach (FE fs-TLIF or FE fr-TLIF) and cage type (banana or bullet) enhances surgical safety and clinical outcomes.

This article reports a rare case of autoinflammatory disease presenting initially with skin induration and swelling after trauma as the initial manifestation, followed by progressive limb weakness. The patient was a middle-aged female who developed skin induration and swelling after trauma, which gradually progressed to limb weakness, dysarthria and bilateral facial paralysis, accompanied by livedo reticularis of the lower extremities, diffuse skin induration of the limbs, and beaded subcutaneous nodules in the right upper limb. The patient had a susceptibility to infection since childhood and a history of chronic livedo reticularis. Skin pathological examination revealed panniculitis. A comprehensive etiological screening for special infections and autoimmune diseases was completed with an unremarkable results, and whole-exome sequencing showed no abnormal findings. Following a multidisciplinary discussion combined with RNA sequencing results, the patient was diagnosed with an autoinflammatory disease, with a suspected type Ⅰ interferonopathy. Treatment with tofacitinib resulted in gradual improvement of clinical symptoms. This case highlights the importance of detailed medical history collection, systematic physical examination and multidisciplinary collaborative diagnosis and treatment, and underscores the pivotal role of molecular diagnosis in the confirmation of rare diseases. It can provide a reference for the clinical diagnosis and management of similar rare cases.

Introduction: Metabolic dysfunction–associated steatotic liver disease (MASLD) is common among patients with type 2 diabetes (T2D) and increases the risk of cirrhosis, yet fibrosis often remains clinically silent until hepatic decompensation occurs. Current diabetes guidelines recommend noninvasive fibrosis risk stratification, such as the fibrosis-4 index (FIB-4), during routine diabetes care, but real-world adoption remains unclear. This study aimed to evaluate the implementation of FIB-4 as a risk stratification tool in patients with T2D. Methodology: This was a retrospective study of consecutive patients with T2D who were seen in the Diabetes Clinic of University of Malaya Medical Centre in 2023. Patients were identified as having a higher risk of future cirrhosis based on elevated FIB-4 ≥1.3. Results: The data for 1,009 patients were analyzed, median age 62 (52–71) years, 40.7% male. Elevated FIB-4 was seen in 28.8% (291/1,009). Only 12.0% (35/291) with elevated FIB-4 were referred for further hepatology evaluation, whereas 3.3% (24/718) with low FIB-4 were referred. Among the patients with elevated FIB-4, those referred were more likely known to have hepatic steatosis, had higher alanine aminotransferase, aspartate aminotransferase, gammaglutamyl transferase, and lower low-density lipoprotein cholesterol and platelet count. Over a median follow-up of 1.71 (0.99–1.95) years, totaling 1,440 person-years, two liverrelated events (0.2%) occurred (one each in the elevated and low FIB-4 group, respectively). Sixteen patients (4.0%) experienced cardiovascular events, including one patient (0.6%) in the elevated FIB-4 group and 15 (2.9%) in the low FIB-4 group. Conclusion Despite automated FIB-4 reporting, this risk stratification tool was underutilized in T2D, resulting in missed opportunities for early identification and management of more severe liver disease. Integration of FIB-4 into diabetes care workflows, alongside structured referral pathways and clinician education, may improve early detection and reduce long-term hepatic complications in T2D.
Diabetes Mellitus, Type 2 ; Risk Assessment ; Liver Diseases ; Referral and Consultation

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

Objective To investigate the correlation between gut microbiota characteristics and immunotherapy efficacy in patients with advanced microsatellite stable (MSS) advanced gastrointestinal tumors. Methods Thirty patients with advanced MSS gastrointestinal tumors, including fourteen cases of gastric cancer and sixteen cases of colorectal cancer, who were admitted from November 1, 2022, to July 31, 2025 were enrolled. All patients underwent gut microbiota testing and received corresponding interventions on the basis of the results, followed by treatment with antiangiogenic agents combined with immunotherapy. Some patients additionally received probiotics or fecal microbiota transplantation. The primary endpoints were disease control rate (DCR) and objective response rate (ORR). The secondary endpoints were progression-free survival (PFS) and overall survival (OS). Univariate and multivariate Cox regression analyses were used to assess potential prognostic factors. Results Among the thirty patients, no complete response was observed. Two cases of partial response (PR), twelve cases of stable disease, and sixteen cases of progressive disease were recorded. The ORR was 6.7%, and the DCR was 46.7%. The median PFS was 6.4 months, and the median OS was 8.3 months. Both PR patients were classified as having a medium risk of gut microbiota dysbiosis and exhibited a Bacteroides-dominated enterotype. Multivariate analysis indicated that tumor type, liver metastasis, and bone metastasis were potential prognostic factors for PFS and OS. Conclusion Patients with a medium risk of gut dysbiosis may exhibit a relatively favorable response to immunotherapy, suggesting that gut microbiota status could serve as a potential biomarker for predicting treatment efficacy in advanced MSS gastrointestinal tumors.

AIM:To investigate the value of optical coherence tomography angiography(OCTA)indicators in the diagnosis of diabetic retinopathy(DR), and to provide patients with diabetic nephropathy(DN)with more sensitive OCTA screening indicators to detect concurrent DR at an early stage.METHODS: A total of 200 patients who treated in the ophthalmology department of the Seventh Affiliated Hospital, Sun Yat-sen University from 2022 to 2023 were included, including 95 first-diagnosed DR patients and 105 patients without DR, and all patients underwent OCTA examination and a collection of demographics and renal function parameters. After a quality check, automated measurements of the foveal avascular zone area, vessel density(VD), and perfusion density(PD)of both 3 mm×3 mm and 6 mm×6 mm windows were obtained.RESULTS: Using random forest and multivariate Logistic regression methods, we developed a diagnostic model for DR based on 12 variables(age, FBG, SBP, DBP, HbA1c, ALT, ALP, urea/Scr, DM duration, HUA, DN, and CMT). Adding specific OCTA parameters enhanced the efficacy of the existing diagnostic model for DR(outer vessel density in 6 mm×6 mm window, AUC=0.837 vs 0.819, P=0.03). In the study of DN patients, the parameters in the 6 mm×6 mm window improved the diagnostic efficacy of DR(inner VD; outer VD; full VD; outer PD; full PD).CONCLUSION:The outer VD in the 6 mm×6 mm window can enhance the efficacy of the traditional DR diagnostic model. Meanwhile, compared with the 3 mm×3 mm window, the microvascular parameters in the 6 mm× 6 mm window focusing on DN patients can be more sensitive to diagnosing the occurrence of DR.

BACKGROUND:Stem cell transplantation is a novel therapy for myocardial infarction,but the extremely hostile microenvironment in the infarct area results in low survival rate of stem cells and little long-term effect.Exercise preconditioning is a way to induce endogenous protective effects through exercise,which can be used as a new strategy for prevention and treatment of cardiac rehabilitation. OBJECTIVE:To evaluate whether exercise preconditioning potentiates the cardioprotective effects of adipose-derived stem cell transplantation following myocardial infarction in rats and to explore the mechanism of angiogenesis. METHODS:Six-week-old male SD rats were randomly divided into control group,modeling group,stem cell group,and stem cell plus exercise group.Acute myocardial infarction model was made by coronary artery occlusion,and sham operation was performed in control group.The stem cell plus exercise group underwent aerobic exercise for 8 weeks before modeling,and adipose-derived stem cell transplantation was performed 30 minutes after modeling.The stem cell group performed only adipose-derived stem cell transplantation.One and seven days after stem cell transplantation,the expression levels of myocardial total Akt(t-Akt),phosphorylated Akt(p-Akt),vascular endothelial growth factor(VEGF),total endothelial nitric oxide synthase(t-eNOS),and phosphorylated endothelial nitric oxide synthase(p-eNOS)protein were measured by western blotting,and the ratios of p-Akt/t-Akt and p-eNOS/t-eNOS were calculated.At 4 weeks after stem cell transplantation,the heart structure and function as well as myocardial blood flow were detected by color Doppler ultrasound diagnostic system.Myocardial infarction area was measured by TTC staining.Myocardial interstitial collagen deposition was examined by Masson staining.Myocardial capillary density was detected by immunofluorescence staining,and myocardial apoptosis was measured by TUNEL staining. RESULTS AND CONCLUSION:(1)Four weeks after stem cell transplantation:Compared with control group,left ventricular shortening fraction,left ventricular ejection fraction,myocardial capillary density,and myocardial blood flow decreased(P<0.05),myocardial infarction area,collagen volume fraction,and apoptosis increased(P<0.05)in the modeling group.Compared with the modeling group,the above indexes(except for left ventricular fractional shortening and left ventricular ejection fraction)in the stem cell group improved(P<0.05).Compared with the stem cell group,the above parameters were further improved in the stem cell plus exercise group(P<0.05).(2)One day after stem cell transplantation:Compared with the control group,the protein expression of t-Akt,p-Akt,VEGF,t-eNOS,p-eNOS and the ratio of p-Akt/t-Akt and p-eNOS/t-eNOS had no significant changes in the modeling group(P>0.05).Compared with the modeling group,there were no significant changes in the above indexes in the stem cell group(P>0.05),and p-Akt protein expression and the ratio of p-Akt/t-Akt were up-regulated in the stem cell plus exercise group(P<0.05).(3)Seven days after stem cell transplantation:Compared with the control group,the protein expression of p-Akt,VEGF,p-eNOS and the ratio of p-Akt/t-Akt and p-eNOS/t-eNOS were decreased in the modeling group(P<0.05).Compared with the modeling group,there were no significant changes in all parameters in the stem cell group(P>0.05),and the protein expression of p-Akt,VEGF p-eNOS and the ratio of p-Akt/t-Akt and p-eNOS/t-eNOS were increased in the stem cell plus exercise group(P<0.05).These findings confirm that exercise preconditioning can potentiate the therapeutic effect of adipose-derived stem cells on cardiac remodeling in rats with myocardial infarction,and its mechanism is associated with the promotion of myocardial angiogenesis and blood perfusion.

OBJECTIVE: To evaluate the short-term clinical efficacy of external fixation and internal fixation with steel plate in the treatment of unstable distal radius fractures (AO-23C type), based on the principles of Chinese osteosynthesis (CO). METHODS: Forty-eight patients with unstable distal radius fractures between January 2022 and February 2023 were retrospectively analyzed and divided into the CO external fixation group and internal fixation group. CO external fixation group consisted of 25 patients, including 7 males and 18 females, aged from 37 to 56 years old with an average of ( 52.6±11.3) years old. Among them, there were 7 patients of traffic accidents and 18 patients of falls, resulting in a total of 25 patients of closed fractures and no open fractures, the treatment was conducted using closed reduction and CO external fixation. The internal fixation group consisted of 23 patients, comprising 8 males and 15 females, age ranged from 41 to 59 years old, with an average age of(53.3±13.7) years old. Among them, 8 patients resulted from car accidents while the remaining 15 patients were caused by falls. All 23 patients were closed fractures without any open fractures observed. The technique of open reduction and internal fixation with steel plate was employed. The perioperative data, including injury-operation time, operation duration, blood loss, and length of hospital stay, were assessed in both groups. Additionally, the QuickDASH score and visual analogue scale (VAS) were evaluated. Range of motion and grip strength assessment, imaging findings such as palmar inclination angle, ulnar declination angle, radius length, articular surface step, intra-articular space measurements were also examined along with any complications. RESULTS: The follow-up duration ranged from 0 to 24 months, with an average duration of (16.0±3.8) months. The CO external fixation exhibited significantly shorter time from injury to operation (2.4±3.3) d vs (7.4±3.7) d, shorter operation duration (56.27±15.23) min vs (74.10±5.26) min, lower blood loss (14.52±6.54) ml vs (32.32±10.03) ml, and reduced hospitalization days (14.04±3.24 )d vs (16.45±3.05) d compared to the internal fixation group (P<0.05). The QuickDASH score at 12 months post-operation was (8.21±1.64) in the CO external fixation group, while no significant difference was observed in the internal fixation group (7.04±3.64), P>0.05. There were no statistically significant differences in VAS between two groups at 6 weeks, as well as 1 and 3 months post-surgery (P>0.05). Additionally, there were no significant disparities observed in terms of range of motion and grip strength between two groups at the 2-year follow-up after the operation (P>0.05). After 12 months of surgery, the CO external fixation group exhibited a significantly smaller palmar inclination angle (17.90±2.18) ° vs (19.87±3.21) °, reduced articular surface step (0.11±0.03) mm vs (0.17±0.02) mm, and shorter radius length (8.16±1.11) mm compared to the internal fixation group (9.59±1.02) mm, P<0.05. The ulnar deviation angle and intra-articular space did not show any significant difference between two groups (P>0.05). The reduced fell within the allowable range between the CO external fixation group (23 out of 25 cases) and the internal fixation group (21 out of 23 cases) was not statistically significant (P=0.29). There was no significant difference in complications between the two groups(P>0.05). CONCLUSION Both the CO external fixation and open reduction with plate internal fixation demonstrate clinical efficacy in managing unstable distal radius fractures. The CO external fixation offers advantages in shorter injury-to-operation times, reduced intraoperative blood loss, and decreased surgical durations, while radial shortening is more effectively controlled by internal fixation.
Humans ; Male ; Female ; Middle Aged ; Radius Fractures/physiopathology* ; Adult ; Bone Plates ; Fracture Fixation, Internal/methods* ; External Fixators ; Retrospective Studies ; Fracture Fixation/methods* ; Wrist Fractures