Serine protease inhibitor Kazal-type (SPINK) is a skin keratinizing protease inhibitor, which was initially found in animal serum and is widely present in plants, animals, bacteria, and viruses, and they act as key regulators of skin keratinizing proteases and are involved in the regulation of keratinocyte proliferation and inflammation, primarily through the inhibition of deregulated tissue kinin-releasing enzymes (KLKs) in skin response. This process plays a crucial role in alleviating various skin problems caused by hyperkeratinization and inflammation, and can greatly improve the overall condition of the skin. Specifically, the different members of the SPINK family, such as SPINK5, SPINK6, SPINK7, and SPINK9, each have unique biological functions and mechanisms of action. The existence of these members demonstrates the diversity and complexity of skin health and disease. First, SPINK5 mutations are closely associated with the development of various skin diseases, such as Netherton’s syndrome and atopic dermatitis, and SPINK5 is able to inhibit the activation of the STAT3 signaling pathway, thereby effectively preventing the metastasis of melanoma cells, which is important in preventing the invasion and migration of malignant tumors. Secondly, SPINK6 is mainly distributed in the epidermis and contains lysine and glutamate residues, which can act as a substrate for epidermal transglutaminase to maintain the normal structure and function of the skin. In addition, SPINK6 can activate the intracellular ERK1/2 and AKT signaling pathways through the activation of epidermal growth factor receptor and protease receptor-2 (EphA2), which can promote the migration of melanoma cells, and SPINK6 further deepens its role in stimulating the migration of malignant tumor cells by inhibiting the activation of STAT3 signaling pathway. This process further deepens its potential impact in stimulating tumor invasive migration. Furthermore, SPINK7 plays a role in the pathology of some inflammatory skin diseases, and is likely to be an important factor contributing to the exacerbation of skin diseases by promoting aberrant proliferation of keratinocytes and local inflammatory responses. Finally, SPINK9 can induce cell migration and promote skin wound healing by activating purinergic receptor 2 (P2R) to induce phosphorylation of epidermal growth factor and further activating the downstream ERK1/2 signaling pathway. In addition, SPINK9 also plays an antimicrobial role, preventing the interference of some pathogenic microorganisms. Taken as a whole, some members of the SPINK family may be potential targets for the treatment of dermatological disorders by regulating multiple biological processes such as keratinization metabolism and immuno-inflammatory processes in the skin. The development of drugs such as small molecule inhibitors and monoclonal antibodies has great potential for the treatment of dermatologic diseases, and future research on SPINK will help to gain a deeper understanding of the physiopathologic processes of the skin. Through its functions and regulatory mechanisms, the formation and maintenance of the skin barrier and the occurrence and development of inflammatory responses can be better understood, which will provide novel ideas and methods for the prevention and treatment of skin diseases.

ObjectiveFunctional near-infrared spectroscopy (fNIRS), a novel non-invasive technique for monitoring cerebral activity, can be integrated with upper limb rehabilitation robots to facilitate the real-time assessment of neurological rehabilitation outcomes. The rehabilitation robot is designed with 3 training modes: passive, active, and resistance. Among these, the resistance mode has been demonstrated to yield superior rehabilitative outcomes for patients with a certain level of muscle strength. The control modes in the resistance mode can be categorized into dynamic and static control. However, the effects of different control modes in the resistance mode on the motor function of patients with upper limb hemiplegia in stroke remain unclear. Furthermore, the effects of force, an important parameter of different control modes, on the activation of brain regions have rarely been reported. This study investigates the effects of dynamic and static resistance modes under varying resistance levels on cerebral functional alterations during motor rehabilitation in post-stroke patients. MethodsA cohort of 20 stroke patients with upper limb dysfunction was enrolled in the study, completing preparatory adaptive training followed by 3 intensity-level tasks across 2 motor paradigms. The bilateral prefrontal cortices (PFC), bilateral primary motor cortices (M1), bilateral primary somatosensory cortices (S1), and bilateral premotor and supplementary motor cortices (PM) were examined in both the resting and motor training states. The lateralization index (LI), phase locking value (PLV), network metrics were employed to examine cortical activation patterns and topological properties of brain connectivity. ResultsThe data indicated that both dynamic and static modes resulted in significantly greater activation of the contralateral M1 area and the ipsilateral PM area when compared to the resting state. The static patterns demonstrated a more pronounced activation in the contralateral M1 in comparison to the dynamic patterns. The results of brain network analysis revealed significant differences between the dynamic and resting states in the contralateral PFC area and contralateral M1 area (F=4.709, P=0.038), as well as in the contralateral PM area and ipsilateral M1 area (F=4.218, P=0.049). Moreover, the findings indicated a positive correlation between the activation of the M1 region and the increase in force in the dynamic mode, which was reversed in the static mode. ConclusionBoth dynamic and static resistance training modes have been demonstrated to activate the corresponding brain functional regions. Dynamic resistance modes elicit greater oxygen changes and connectivity to the region of interest (ROI) than static resistance modes. Furthermore, the effects of increasing force differ between the two modes. In patients who have suffered a stroke, dynamic modes may have a more pronounced effect on the activation of exercise-related functional brain regions.

PURPOSE: Emergency resuscitative thoracotomy (ERT) is a final salvage procedure for critically injured trauma patients. Given its low success rate and ambiguous indications, its use in blunt trauma scenarios remains highly debated. Consequently, our study seeks to ascertain the overall survival rate of ERT in blunt trauma patients and determine which patients would benefit most from this procedure. METHODS: A retrospective case-control study was conducted for this research. Blunt trauma patients who underwent ERT between January 2020 and December 2023 in our trauma center were selected for analysis, with the endpoint outcome being in-hospital survival, divided into survival and non-survival groups. Inter-group comparisons were conducted using Chi-square and Fisher's exact tests, the Kruskal-Wallis test, Student's t-test, or the Mann-Whitney U test. Univariate and multivariate logistic regression analyses were conducted to assess potential predictors of survival. Then, the efficacy of the predictors was assessed through sensitivity and specificity analysis. RESULTS: A total of 33 patients were included in the study, with 4 survivors (12.12%). Multivariate logistic regression analysis indicated a significant association between cardiac tamponade and survival, with an adjusted odds ratio of 33.4 (95% CI: 1.31 - 850.00, p = 0.034). Additionally, an analysis of sensitivity and specificity, targeting cardiac tamponade as an indicator for survivor identification, showed a sensitivity rate of 75.0% and a specificity rate of 96.6%. CONCLUSION The survival rate among blunt trauma patients undergoing ERT exceeds traditional expectations, suggesting that select individuals with blunt trauma can significantly benefit from the procedure. Notably, those presenting with cardiac tamponade are identified as the subgroup most likely to derive substantial benefits from ERT.
Adult ; Female ; Humans ; Male ; Middle Aged ; Case-Control Studies ; China ; Logistic Models ; Resuscitation/mortality* ; Retrospective Studies ; Survival Rate ; Thoracotomy/methods* ; Trauma Centers/statistics & numerical data* ; Wounds, Nonpenetrating/surgery*

Testicular histology based on testicular biopsy is an important factor for determining appropriate testicular sperm extraction surgery and predicting sperm retrieval outcomes in patients with azoospermia. Therefore, we developed a deep learning (DL) model to establish the associations between testicular grayscale ultrasound images and testicular histology. We retrospectively included two-dimensional testicular grayscale ultrasound from patients with azoospermia (353 men with 4357 images between July 2017 and December 2021 in The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China) to develop a DL model. We obtained testicular histology during conventional testicular sperm extraction. Our DL model was trained based on ultrasound images or fusion data (ultrasound images fused with the corresponding testicular volume) to distinguish spermatozoa presence in pathology (SPP) and spermatozoa absence in pathology (SAP) and to classify maturation arrest (MA) and Sertoli cell-only syndrome (SCOS) in patients with SAP. Areas under the receiver operating characteristic curve (AUCs), accuracy, sensitivity, and specificity were used to analyze model performance. DL based on images achieved an AUC of 0.922 (95% confidence interval [CI]: 0.908-0.935), a sensitivity of 80.9%, a specificity of 84.6%, and an accuracy of 83.5% in predicting SPP (including normal spermatogenesis and hypospermatogenesis) and SAP (including MA and SCOS). In the identification of SCOS and MA, DL on fusion data yielded better diagnostic performance with an AUC of 0.979 (95% CI: 0.969-0.989), a sensitivity of 89.7%, a specificity of 97.1%, and an accuracy of 92.1%. Our study provides a noninvasive method to predict testicular histology for patients with azoospermia, which would avoid unnecessary testicular biopsy.
Humans ; Male ; Azoospermia/diagnostic imaging* ; Deep Learning ; Testis/pathology* ; Retrospective Studies ; Adult ; Ultrasonography/methods* ; Sperm Retrieval ; Sertoli Cell-Only Syndrome/diagnostic imaging*

OBJECTIVE: Huachansu injection (HCSI), a promising anti-cancer Chinese medicine injection, has been reported to have the potential for reducing the toxicity of chemotherapy and improving the quality of life for colorectal cancer (CRC) patients. The objective of this study is to explore the synergistic and detoxifying effects of HCSI when used in combination with irinotecan (CPT-11). METHODS: To investigate the effect of HCSI on anti-CRC efficacy and intestinal toxicity of CPT-11, we measured changes in the biological behavior of LoVo cells in vitro, and anti-tumor effects in LoVo cell xenograft nude mice models in vivo. Meanwhile, the effect of HCSI on intestinal toxicity and the uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) expression was investigated in the CPT-11-induced colitis mouse model. Subsequently, we measured the effect of HCSI and its 13 constituent bufadienolides on the expression of UGT1A1 and organic anion transporting polypeptides 1B3 (OATP1B3) in HepG2 cells. RESULTS: The combination index (CI) results showed that the combination of HCSI and CPT-11 exhibited a synergistic effect (CI < 1), which significantly suppressing the LoVo cell migration, enhancing G2/M and S phase arrest, and inhibiting tumor growth in vivo. Additionally, the damage to intestinal tissues was attenuated by HCSI in CPT-11-induced colitis model, while the increased expression of UGT1A1 in HepG2 cells and in mouse was observed. CONCLUSION The co-therapy with HCSI alleviated the intestinal toxicity induced by CPT-11 and exerted an enhanced anti-CRC effect. The detoxifying mechanism may be related to the increased expression of UGT1A1 and OATP1B3 by HCSI and its bufadienolides components. The findings of this study may serve as a theoretical insights and strategies to improve CRC patient outcomes. Please cite this article as: Jiang B, Meng ZY, Hu YJ, Chen JJ, Zong L, Xu LY, Zhang XQ, Zhang JX, Han YL. Huachansu injection enhances anti-colorectal cancer efficacy of irinotecan and alleviates its induced intestinal toxicity through upregulating UGT1A1-OATP1B3 expression in vitro and in vivo. J Integr Med. 2025; 23(5):576-590.
Irinotecan/therapeutic use* ; Animals ; Glucuronosyltransferase/genetics* ; Humans ; Colorectal Neoplasms/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Nude ; Mice ; Up-Regulation/drug effects* ; Male ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Hep G2 Cells ; Cell Line, Tumor ; Intestines/drug effects* ; Amphibian Venoms

Aim To explore the mechanism of hydroxy-a-sanshool in the treatment of diabetic cardiomyopathy ( DCM) based on label-free quantitative proteomics detection technique. Methods DCM model was established by high fat diet and intraperitoneal injection of streptozotocin ( STZ) . They were divided into control group ( CON group ) , diabetic cardiomyopathy group (DCM group) and hydroxy-a-sanshool treatment group ( DCM + SAN group) . The cardiac function of mice was evaluated by echocardiography, the myocardial morphology was observed by pathology staining, the protective mechanism of hydroxy-a-sanshool on diabetic cardiomyopathy was speculated by proteomic technique , and the expression level of cAMP/PKA signaling pathway and key proteins were verified by Western blotting. Results Cardiac ultrasound and pathology staining showed that hydroxy-a-sanshool had protective effect on the heart of DCM mice. Label-free quantitative proteomic analysis was carried out between DCM + SAN group and DCM group, and 160 differential pro-teins were identified by proteomics, in which 127 proteins were up-regulated and 33 proteins were down regulated ; GO secondary functional annotations showed the biological process, molecular function and cellular component; KEGG enrichment analysis showed that cAMP signaling pathway was the most abundant; protein interaction network showed that PKA as the central node interacted with many proteins in the cAMP signaling pathway. Western blot showed that the relative expression of с AMP, PKA protein in DCM group was significantly lower than that in CON group ( P < 0. 05 ) , while the relative expression of cAMP, PKA protein in DCM + SAN group was significantly higher than that in DCM group ( P < 0. 05 ) . Conclusions Hydroxy-a-sanshool has protective effect on heart function of mice with diabetes, which plays a role through cAMP signaling pathway.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective:To evaluate the prevalence and distribution of ossification of ligamentum flavum (OLF) at the segments adjacent to the apex in patients with degenerative kyphosis.Methods:All of 74 patients with degenerative kyphosis from January 2018 to December 2021 were retrospective reviewed. All patients were taken anteroposterior and lateral radiographs, CT scan and magnetic resonance imaging (MRI) of the entire spine. Global kyphosis, the morphology of kyphosis and the occurrence of OLF at three segments adjacent to the kyphosis apex were recorded.Results:Of the 74 patients, 54 patients (73%) developed OLF in three segments adjacent to the kyphotic apex. The mean age of the 54 patients was 61.4±6.8 years, and the mean global kyphosis was 49.5°±21.2°. Among other 20 patients without OLF, the mean age was 56.1±7.5 years, and the mean kyphosis angle was 52.1°±19.1°. There was a statistically significant difference in ages ( t=2.92, P=0.005), but no statistically significant difference was observed regarding global kyphosis ( t=0.48, P=0.634). In these 74 patients, 9 patients had angular kyphosis, of which 8 (89%) developed OLF; of the 65 patients without angular kyphosis, 46 patients (71%) developed OLF. There was no significant difference between them (χ 2=1.32, P=0.251). Among the 54 patients diagnosed with OLF, 5 patients (9%) suffered ossification of the posterior longitudinal ligament (OPLL) and 20 patients (37%) suffered dural ossification; 43 patients (80%) developed OLF at proximal segments of apex, 6 patient (11%) developed OLF at distal segments of apex, and 5 patients (9%) developed OLF both at proximal and distal segments of apex. Thirty-two patients (59%) developed OLF at the first segment adjacent to the kyphotic apex, 27 patients (50%) developed OLF at the second segment, and 15 patients (28%) developed OLF at the third segment. Conclusion:Among patients with degenerative kyphosis, about 73% may development OLF within three segments adjacent to the kyphotic apex, and it mostly occurred within two segments adjacent to the apex proximally.

Objective:To evaluate the clinical outcomes and complications of second sacral alar-iliac (S 2AI) technique utilized in degenerative spinal deformity patients, and to analyze the potential risk factors for postoperative sagittal imbalance. Methods:From January 2014 to October 2020, a consecutive cohort of 39 degenerative spinal deformity patients who were treated with S 2AI were retrospectively reviewed, including 4 males and 35 females, aged 63.1±6.7 years (range, 43-73 years). All of the patients had a minimum of 2-year follow-up. According to the sagittal vertical axis (SVA) at the final follow-up, patients were divided into 2 groups. Sagittal balance group (SVA≤50 mm) and sagittal imbalance group (SVA>50 mm). Radiographic parameters including the Cobb's angle, coronal balance distance (CBD), thoracic kyphosis (TK), lumbar lordosis (LL), SVA, pelvic incidence (PI), pelvic tilt (PT) and sacral slope (SS) were measured in the standing radiographs before and after operation and at the latest follow up. Comparison was made between the two groups and the differences with statistical significance were analyzed with binary logistic regression analysis. Intraoperative and postoperative complications were recorded. The Scoliosis Research Society-22 (SRS-22) score were employed to evaluate the quality of life. Results:The average follow-up period was 30.3±9.1 months (range, 43-73 months). Eighteen patients (46%) were identified with sagittal imbalance at the last follow-up. Compared with the patients in the sagittal balance group, the preoperative SVA was significantly larger (83.1±56.2 mm vs. 48.1±51.1 mm, t=2.04, P=0.049) and the postoperative TK was significantly greater (27.8°±9.6° vs. 18.9°±13.4°, t=2.36, P=0.024) for patients in the sagittal imbalance group. Scores of pain domain (3.2±0.5 vs. 3.7±0.6) and self-image domain (3.4±0.8 vs. 3.8±0.6) in sagittal imbalance group were significantly lower than those of sagittal balance group ( P<0.05). Logistic regression analysis showed that larger preoperative SVA ( OR=1.02, P=0.028) and greater postoperative TK ( OR=1.09, P=0.022) were independent risk factors for the occurrence of sagittal imbalance during the follow-up periods. Conclusion:S 2AI screw fixation can achieve satisfying coronal deformity correction and great sagittal reconstruction after surgery in patients with degenerative spinal deformity. However, sagittal imbalance may still occur during the follow-up periods. Larger preoperative SVA and greater postoperative TK are independent risk factors for the occurrence of sagittal imbalance.

Objective:To investigate the clinical outcome and complications associated with utilizing sagittal plane stable vertebra-1 (SSV-1) as the distal instrumented vertebra (LIV) in posterior fusion of thoracic kyphosis with Scheuermann's Disease kyphosis (STK).Methods:A longitudinal study on patients with STK who underwent posterior correction and fusion surgery from January 2018 to June 2021 were conducted. All participants had a follow-up duration over two years. Patients were divided into two groups according to the segment of LIV: the SSV group, where LIV was located in SSV; and the SSV-1 group, where LIV was located in the vertebral body above SSV. The radiographic parameters, including global kyphosis (GK), lumbar lordosis (LL), and sagittal plane (SVA), LIV offset distance (LIV translation), pelvic incidence (PI), pelvic tilt (PT) and sacral slope (SS), were compared between the two groups. The SRS-22 scale was used to evaluate health-related quality of life at pre-operation and last follow-up, and the incidence of postoperative distal junctional kyphosis (DJK) was also recorded. Analytical techniques, such as Analysis of Variance and Mann-Whitney tests, were employed to compare inter-group differences.Results:A total of 57 patients were included in the study, 36 in the SSV group and 21 in the SSV-1 group. The average age for patients were 16.1±2.3 years (range 13-20 years), and the average follow-up time was 32.8±6.8 months (range 24-53 months). There were no statistically significant differences between the two groups in terms of gender, age, follow-up time, surgical time, intraoperative bleeding volume, and fusion level. Before surgery, the LIV deviation distance in the SSV group was significantly lower than that in the SSV-1 group (-7.9±11.0 mm vs. 31.5±11.5 mm, t=7.64, P<0.001). In the SSV group, the preoperative GK was 79.3°±10.5°, and the last follow-up GK was 44.4°±8.5°, which was significantly improved compared to preoperative value ( t=28.28, P<0.001); in the SSV-1 group, the preoperative GK was 81.1°±10.6°, and the value at 1-week post-operative was 44.9°±7.8°, which was significantly improved compared to pre-operative value ( t=22.23, P<0.001). At the last follow-up, it was 45.1°±8.7°, with a correction rate of 44.3%±8.5%. No significant difference was observed between the two groups in terms of GK, LL, SVA, PI, PT and SS at pre-operative, 1-week post-operative and last follow-up ( P>0.05). All patients had no intraoperative complications of nerve injury. During the follow-up period, one patient (1/21, 4.8%) developed DJK without complications such as proximal kyphosis, pseudarthrosis, or failed internal fixation. At the last follow-up, the functional score of SRS-22 in SSV-1 group improved from preoperative (3.5±0.54) to postoperative (4.1±0.62), with an average improvement rate of 19.2%±3.2%, and the difference was statistically significant ( t=3.74, P=0.001). These results indicating that the surgical treatment was effective in relieving the symptoms of the patients. Conclusion:Selecting SSV-1 as LIV in corrective surgeries for STK appears to produce commendable clinical results with minimal implant-associated complications over a two-year observation period.