ObjectiveTo compare the performance of different automatic evaluation methods for detecting pattern hallucinations generated by large language models （LLMs） in traditional Chinese medicine （TCM） syndrome differentiation and to identify a strategy with higher overall discriminative performance against expert manual judgment. MethodsA standardized TCM syndrome-differentiation dataset containing 598 cases was constructed from case reports published in Chinese core journals indexed by Peking University Core Journals or Chinese Science Citation Database. Each of the 598 cases was submitted to five Chinese LLMs， with each model generating one syndrome-pattern output per case， yielding 2990 outputs in total. The 598 outputs generated by Qwen3-Next-80B-A3B-Thinking were independently annotated for syndrome-pattern hallucinations by two licensed TCM physicians with intermediate or higher professional titles. Disagreements were adjudicated by a third licensed TCM physician with a senior associate professional title and more than 10 years of clinical experience. The resulting consensus annotations served as the reference labels for training and validating the automated evaluation method. Based on these reference labels， three categories of automated evaluation methods were developed and compared following a progressive strategy from text-level semantic similarity， to syndrome-element structural consistency， and finally multi-feature fusion. Method A employed sentence-embedding models based on semantic similarity between pattern texts. Method B adopted a rule-based threshold method using weighted Jaccard coefficients of disease-location and disease-nature syndrome elements. Method C utilized a machine-learning classifier integrating syndrome-element matching scores， missing and redundant syndrome-element counts， and multiple semantic-similarity features. Five-fold cross-validation was used to evaluate the discriminative performance of each method against manual judgment. The optimal method was then applied to uniformly assess the pattern hallucination rates of five LLMs. ResultsIn method A， text2vec-large-chinese showed best overall performance， with an area under the receiver operating characteristic curve （AUROC）， area under the precision-recall curve （PR-AUC）， F1-score， sensitivity， and specificity of 0.849， 0.884， 0.794， 0.801， and 0.691， respectively. In method B， the corresponding metrics of the rule-based syndrome-element Jaccard threshold method were 0.848， 0.851， 0.817， 0.845， and 0.684， respectively； those of the LLM-based syndrome-element Jaccard method were 0.872， 0.906， 0.795， 0.764， and 0.780， respectively. In method C， the multilayer perceptron （MLP） classifier showed the best overall performance， with AUROC， PR-AUC， F1-score， sensitivity， and specificity of 0.933， 0.951， 0.871， 0.857， and 0.846， respectively. Under the unified evaluation framework combining DeepSeek-R1 syndrome-element extraction and MLP classifier， the estimated pattern hallucination rates of the five LLMs ranged from 56.0% to 77.4%. ConclusionAmong the three automatic evaluation methods， Method C integrating syndrome-element discrepancy features and text semantic features using an MLP classifier showed the highest overall discriminative performance against manual judgment， and is more suitable for evaluating syndrome hallucinations in LLM-based TCM syndrome differentiation tasks.

One of the basic questions in the aging field is whether there is a fundamental difference between the aging of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-aging Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at an early age was observed, indicating its involvement in normal aging of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal aging. adeno-associated virus delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan. These findings demonstrate the complexity of aging in mammals and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.
Animals ; Mice ; RNA, Untranslated/metabolism* ; Aging/genetics* ; Mice, Transgenic ; Telomerase/metabolism* ; RNA/genetics* ; Hippocampus/metabolism* ; Humans ; Mice, Inbred C57BL

Objective:To explore the value of ultrasound features modified version 2022 of the Ovarian-Adnexal Imaging Reporting and Data System（O-RADS）Category 4 in the differential diagnosis of benign and malignant ovarian-adnexal tumors.Methods:Retrospective analysis was conducted in 501 cases with ovarian masses classified into 4 categories according to the 2022 version of O-RADS who were collected from 4 clinical centers［the Second Afliated Hospital of Harbin Medical University（188 cases），Zhejiang Provincial People's Hospital（146 cases），Sichuan Provincial Maternity and Child Health Care Hospital（90 cases），and Fuling Hospital of Chongqing University（77 cases）］from January 2018 to July 2024 with concomitant surgical resection.The 424 cases from 3 of the clinical centers（the Second Hospital of Harbin Medical University，Zhejiang Provincial People's Hospital，and Sichuan Maternal and Child Health Hospital）were randomly divided into a training group（339 cases）and an internal validation group（85 cases）according to an 8∶2 randomization，while the cases from the other clinical center（Fuling Hospital of Chongqing University）were selected as the external validation group（77 cases），and the pathological diagnosis was used as the “gold standard”.Univariate and multifactorial logistic regression analyses were performed on the ultrasound characteristics of the training group to screen the independent predictors associated with ovarian carcinogenesis，and to formulate the stratification rules for the 4 types of masses in O-RADS. The ROC curve of this stratification method was plotted and the area under the curve（AUC）was calculated，and it was validated in the internal validation group and the external validation group；and the diagnostic accuracy was compared with that of the 2022 version of O-RADS.Results:Univariate logistic analysis showed that cysts with solid components，≥ 4 papillary projections，smooth inner wall of the cyst，color flow score ≥ 3 points，and acoustic shadowing were independent predictors of ovarian cancer（all P < 0.05）；while multifactorial logistic analysis showed that cysts with a solid component and a color flow score ≥3 points were independent risk factors of ovarian cancer（all P < 0.05），and smooth cyst walls and acoustic shadows were independent protective factors（all P < 0.05）.The diagnostic accuracies of the modified training group，internal validation group，and external validation group were 73.7%，68.2%，70.1%，respectively，which were significantly higher than the diagnostic accuracies of the 2022 version of the O-RADS（38.9%，37.6%，33.8%）（all P < 0.05）.The diagnostic sensitivity，specificity and AUC of the training group were 0.871，0.652，0.762，respectively，while the internal validation group were 0.844，0.585，0.714，and 0.846，0.627，0.737 in the external validation group. Conclusions:Improvement of the 2022 version of O-RADS category 4 using ultrasound features may improve the identification of benign and malignant ovarian-adnexal tumors.

Objective To analysis the efficacy and safety of antiviral therapy in patients with chronic hepatitis B virus in indeterminate phase based on the new guidelines(2022 Edition of the Guidelines for the Prevention and Treatment of Chronic Hepatitis B).Methods A total of 170 patients with newly diagnosed HBV infection who visited the Third People's Hospital of Kunming from August 1,2020,to July 31,2024,were selected as study subjects.The clinical indicators of patients with normal ALT in the indeterminate phase were analyzed after 12 weeks,24 weeks,and 48 weeks of antiviral treatment,as well as those who did not receive antiviral treatment for 48 weeks.Results(1)Among the 170 patients with normal ALT during the indeterminate phase of HBV infection,the treatment group consisted of 125 patients(36 HBeAg positive and 89 HBeAg negative),while the untreated group had 45 patients.In the treatment group,the HBV-DNA load and HBsAg titer decreased significantly after 48 weeks compared to before treatment,with statistically significant differences(both P<0.05).In the untreated group,the HBV-DNA load showed an upward trend,and the HBsAg titer slightly decreased,with statistically significant differences(both P<0.05).(2)The CVR rate in the treatment group after 48 weeks was 66.67%(24/36)for HBeAg positive patients and 95.51%(85/89)for HBeAg negative patients,with a statistically significant difference(P<0.05).(3)The treatment group showed a significant decrease in GGT and AFP after 48 weeks compared to before treatment,while the untreated group saw an increase in ALT,GGT,and AFP,with statistically significant differences(all P<0.05).(4)The fibrosis indicators APRI,FIB-4,and LSM in the treatment group significantly decreased after 48 weeks compared to before treatment,with statistically significant differences(all P<0.05).(5)The safety indicators CREA,blood calcium,and blood phosphorus in the treatment group significantly decreased after 48 weeks compared to before treatment,with statistically significant differences(all P<0.05).Conclusion Expanding the antiviral treatment indications according to the new guidelines for patients with normal ALT in the indeterminate phase of HBV infection demonstrates good efficacy in controlling HBV-DNA,improving CVR rates,and enhancing fibrosis indicators,while also showing favorable renal safety.However,there may be a risk of osteoporosis due to calcium and phosphorus metabolism disorders,necessitating enhanced monitoring and prevention.

Objective:To observe the effect of applying intermittent theta burst stimulation (iTBS) in the rehabilitation of preschool children with autism spectrum disorder (ASD).Methods:Seventy preschool children with ASD were randomly divided into a control group and an experimental group, each of 35. Both groups were given routine rehabilitation training, while the experimental group was additionally provided with iTBS for 4 weeks. Before and after the treatment, the children′s language comprehension and expression ability were evaluated using the language retardation test and the Autism Treatment Assessment Scale (ATEC).Results:The language comprehension and expression of the children in both groups had improved after the treatment, but the children in the experimental group then had better language comprehension and expression abilities. And they scored better on average in the language, social interaction, cognition and behavior sub-sections of the ATEC. Their average total score was also lower.Conclusions:iTBS can safely and effectively improve the language comprehension ability and expression of preschool children with ASD.

AIM:This study aims to investigate whether triiodothyronine(T3)can enhance skin wound heal-ing by activating the the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of inter-feron genes(STING)signaling pathway to modulate the inflammatory phase.METHODS:Mice were randomly assigned to five groups:normal,control,T3,RU.521+T3,and RU.521(a cGAS inhibitor).With the exception of the normal group,a full-thickness skin defect model was established in the other groups.Wound healing was observed daily.Mice were euthanized on post-injury days 1,2,4,7,and 10,with five mice per group.Pathological changes and collagen fiber formation were assessed using hematoxylin-eosin(HE)and Masson staining,respectively.Immunohistochemical staining was performed to evaluate the expression of cGAS,STING,mouse EGF-like module-containing mucin-like hormone recep-tor-like 1(EMR1 or F4/80),C-X-C motif chemokine ligand 8(CXCL-8),and CXCL-10.Western blotting was conducted to measure protein levels of cGAS,STING,C-C motif chemokine ligand-2(CCL-2),and nuclear factor-κB(NF-κB).En-zyme linked immunosorbent assay(ELISA)was utilized to quantify the levels of interferon-β(IFN-β),interleukin-6(IL-6),and tumor necrosis factor α(TNF-α).RESULTS:From days 1 to 4 post-injury,the wound healing rate and collagen fiber formation in the T3 group were significantly greater than those in the control,RU.521+T3,and RU.521 groups(P＜0.05).Additionally,the T3 group displayed more favorable pathological changes compared to the other groups.No ex-pression of cGAS and STING was observed in the normal group,while low levels were found in the RU.521+T3 and RU.521 groups.The T3 and control groups exhibited higher expression levels,with the T3 group showing significantly ele-vated expression on days 1 to 4 post-injury(P＜0.05)but lower expression on day 7 compared to the control group(P＜0.05).The expression of the macrophage marker F4/80 was higher in the T3 group compared to the control,RU.521+T3,and RU.521 groups on days 1 to 7 post-injury(P＜0.05).Furthermore,chemokines CXCL-8,CXCL-10,and CCL-2 showed increased levels in the T3 group on days 1 to 2 or 1 to 4 post-injury(P＜0.05)but were lower at other time points(P＜0.05)compared with the control,RU.521+T3,and RU.521 groups.Additionally,the levels of pro-inflammatory fac-tors IFN-β,IL-6,TNF-α,and NF-κB in the T3 group were significantly higher on day 1 post-injury(P＜0.05),while lev-els on days 2 to 7 were lower compared to the control,RU.521+T3,and RU.521 groups(P＜0.05).CONCLUSION:T3 accelerates the healing of impaired skin wounds,potentially through the enhanced activation of the cGAS-STING signal-ing pathway.This process increases the expression of chemokines and pro-inflammatory factors and promotes macrophage recruitment during the early post-injury phase,ultimately regulating the inflammatory response.

AIM:This study aims to investigate whether triiodothyronine(T3)can enhance skin wound heal-ing by activating the the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of inter-feron genes(STING)signaling pathway to modulate the inflammatory phase.METHODS:Mice were randomly assigned to five groups:normal,control,T3,RU.521+T3,and RU.521(a cGAS inhibitor).With the exception of the normal group,a full-thickness skin defect model was established in the other groups.Wound healing was observed daily.Mice were euthanized on post-injury days 1,2,4,7,and 10,with five mice per group.Pathological changes and collagen fiber formation were assessed using hematoxylin-eosin(HE)and Masson staining,respectively.Immunohistochemical staining was performed to evaluate the expression of cGAS,STING,mouse EGF-like module-containing mucin-like hormone recep-tor-like 1(EMR1 or F4/80),C-X-C motif chemokine ligand 8(CXCL-8),and CXCL-10.Western blotting was conducted to measure protein levels of cGAS,STING,C-C motif chemokine ligand-2(CCL-2),and nuclear factor-κB(NF-κB).En-zyme linked immunosorbent assay(ELISA)was utilized to quantify the levels of interferon-β(IFN-β),interleukin-6(IL-6),and tumor necrosis factor α(TNF-α).RESULTS:From days 1 to 4 post-injury,the wound healing rate and collagen fiber formation in the T3 group were significantly greater than those in the control,RU.521+T3,and RU.521 groups(P＜0.05).Additionally,the T3 group displayed more favorable pathological changes compared to the other groups.No ex-pression of cGAS and STING was observed in the normal group,while low levels were found in the RU.521+T3 and RU.521 groups.The T3 and control groups exhibited higher expression levels,with the T3 group showing significantly ele-vated expression on days 1 to 4 post-injury(P＜0.05)but lower expression on day 7 compared to the control group(P＜0.05).The expression of the macrophage marker F4/80 was higher in the T3 group compared to the control,RU.521+T3,and RU.521 groups on days 1 to 7 post-injury(P＜0.05).Furthermore,chemokines CXCL-8,CXCL-10,and CCL-2 showed increased levels in the T3 group on days 1 to 2 or 1 to 4 post-injury(P＜0.05)but were lower at other time points(P＜0.05)compared with the control,RU.521+T3,and RU.521 groups.Additionally,the levels of pro-inflammatory fac-tors IFN-β,IL-6,TNF-α,and NF-κB in the T3 group were significantly higher on day 1 post-injury(P＜0.05),while lev-els on days 2 to 7 were lower compared to the control,RU.521+T3,and RU.521 groups(P＜0.05).CONCLUSION:T3 accelerates the healing of impaired skin wounds,potentially through the enhanced activation of the cGAS-STING signal-ing pathway.This process increases the expression of chemokines and pro-inflammatory factors and promotes macrophage recruitment during the early post-injury phase,ultimately regulating the inflammatory response.

Objective:To observe the effect of applying intermittent theta burst stimulation (iTBS) in the rehabilitation of preschool children with autism spectrum disorder (ASD).Methods:Seventy preschool children with ASD were randomly divided into a control group and an experimental group, each of 35. Both groups were given routine rehabilitation training, while the experimental group was additionally provided with iTBS for 4 weeks. Before and after the treatment, the children′s language comprehension and expression ability were evaluated using the language retardation test and the Autism Treatment Assessment Scale (ATEC).Results:The language comprehension and expression of the children in both groups had improved after the treatment, but the children in the experimental group then had better language comprehension and expression abilities. And they scored better on average in the language, social interaction, cognition and behavior sub-sections of the ATEC. Their average total score was also lower.Conclusions:iTBS can safely and effectively improve the language comprehension ability and expression of preschool children with ASD.

Objective:To explore the value of ultrasound features modified version 2022 of the Ovarian-Adnexal Imaging Reporting and Data System（O-RADS）Category 4 in the differential diagnosis of benign and malignant ovarian-adnexal tumors.Methods:Retrospective analysis was conducted in 501 cases with ovarian masses classified into 4 categories according to the 2022 version of O-RADS who were collected from 4 clinical centers［the Second Afliated Hospital of Harbin Medical University（188 cases），Zhejiang Provincial People's Hospital（146 cases），Sichuan Provincial Maternity and Child Health Care Hospital（90 cases），and Fuling Hospital of Chongqing University（77 cases）］from January 2018 to July 2024 with concomitant surgical resection.The 424 cases from 3 of the clinical centers（the Second Hospital of Harbin Medical University，Zhejiang Provincial People's Hospital，and Sichuan Maternal and Child Health Hospital）were randomly divided into a training group（339 cases）and an internal validation group（85 cases）according to an 8∶2 randomization，while the cases from the other clinical center（Fuling Hospital of Chongqing University）were selected as the external validation group（77 cases），and the pathological diagnosis was used as the “gold standard”.Univariate and multifactorial logistic regression analyses were performed on the ultrasound characteristics of the training group to screen the independent predictors associated with ovarian carcinogenesis，and to formulate the stratification rules for the 4 types of masses in O-RADS. The ROC curve of this stratification method was plotted and the area under the curve（AUC）was calculated，and it was validated in the internal validation group and the external validation group；and the diagnostic accuracy was compared with that of the 2022 version of O-RADS.Results:Univariate logistic analysis showed that cysts with solid components，≥ 4 papillary projections，smooth inner wall of the cyst，color flow score ≥ 3 points，and acoustic shadowing were independent predictors of ovarian cancer（all P < 0.05）；while multifactorial logistic analysis showed that cysts with a solid component and a color flow score ≥3 points were independent risk factors of ovarian cancer（all P < 0.05），and smooth cyst walls and acoustic shadows were independent protective factors（all P < 0.05）.The diagnostic accuracies of the modified training group，internal validation group，and external validation group were 73.7%，68.2%，70.1%，respectively，which were significantly higher than the diagnostic accuracies of the 2022 version of the O-RADS（38.9%，37.6%，33.8%）（all P < 0.05）.The diagnostic sensitivity，specificity and AUC of the training group were 0.871，0.652，0.762，respectively，while the internal validation group were 0.844，0.585，0.714，and 0.846，0.627，0.737 in the external validation group. Conclusions:Improvement of the 2022 version of O-RADS category 4 using ultrasound features may improve the identification of benign and malignant ovarian-adnexal tumors.

Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG^@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.