ObjectiveTo observe the prognosis effect of soluble programmed death ligand-1（sPD-L1） in treating patients with advanced lung adenocarcinoma treated with epidermal growth factor receptor-tyrosine kinase inhibitors（EGFR-TKIs） and the influence of Yiqi Yangyin Jiedu prescription. MethodA prospective cohort-controlled study was conducted to enroll patients treated with EGFR-TKIs in the first line of treatment，who were admitted to the Oncology Department of Longhua Hospital and Shanghai Chest Hospital from May 1^st， 2021 to June 30^th， 2023， and they were evaluated as non-progressive and identified with deficiency of Qi and Yin after one month of treatment. The patients were divided into an exposed group （EGFR-TKIs combined with Yiqi Yangyin Jiedu prescription） and a non-exposed group （EGFR-TKIs alone）according to whether or not they were treated with Yiqi Yangyin Jiedu prescription and were treated until disease progression， or death and intolerable adverse reactions occurred. The enzyme-linked immunosorbent assay （ELISA） was applied to detect the level of sPD-L1 in patients at the time of enrollment and disease progression，and Cox risk proportionality model was used to analyze the independent prognostic factors affecting disease progression of patients treated with EGFR-TKIs. ResultA total of 90 patients （39 in the exposed group and 51 in the non-exposed group） undergoing disease progression after EGFR-TKI treatment were enrolled. At the time of enrolment and after disease progression，the levels of serum sPD-L1 in the 90 patients were 12.06 （27.54） ng·L^-1 and 41.99 （62.93） ng·L^-1，respectively. Compared with that at the time of enrollment， the serum sPD-L1 level in the 90 patients was significantly increased after disease progression （P<0.01）. The serum sPD-L1 level in patients in the exposed group was 12.27 （24.78） ng·L^-1 and 29.57 （61.12）ng·L^-1 respectively at the time of enrolment and after disease progression. In the non-exposed group， patients had serum sPD-L1 levels of 11.81 （28.46） ng·L^-1 and 49.54 （74.12） ng·L^-1 respectively at the time of enrolment and after disease progression. Compared with that at the time of enrollment， the serum sPD-L1 level in the two groups of patients was significantly increased after disease progression （P<0.01）. In addition， compared with that in the non-exposed group， the sPD-L1 level in the exposed group was greatly reduced after disease progression（P<0.01）. Cox multifactorial analysis showed that sPD-L1 level and age at the time of enrolment were associated with patients' progression-free survival（PFS），and that low levels of sPD-L1 （<12.06 ng·L^-1） prolonged the PFS and reduced the risk of disease progression in patients treated with EGFR-TKIs compared with high levels of sPD-L1. ConclusionElevated sPD-L1 level is a poor prognostic factor for the long-term efficacy of EGFR-TKIs，and treatment with Yiqi Yangiin Jiedu prescription can down-regulate sPD-L1 level of patients treated with EGFR-TKIs.

ObjectiveTo establish an educational intervention framework of electronic picture books for children with autism spectrum disorder (ASD) based on Creative Problem Solving (CPS) model, and observe the effect on social function. MethodsElectronic picture books were designed using CPS model, including the program of reading, interactive animation design and associated artistic activities. From March to June, 2023, 24 children with mild to moderate ASD were recruited from Maanshan Institute of Special Education, and randomly assigned into experimental group 1 (CPS-based cognitive picture book interventions, n = 8), experimental group 2 (CPS-based social picture book interventions, n = 8) and control group (Bloom's Taxonomy-based picture book interventions, n = 8), and received the interventions for four weeks, with a total of twelve times. They were assessed with speech, social, perceptual and health behavior using Autism Treatment Evaluation Checklist (ATEC) before and after treatment, and the differences were calculated. ResultsThere was a significant difference among the groups in the social and perceptual scores differences (F > 4.344, P < 0.05) and a near-significant difference in the health behaviour score difference (F = 2.921, P = 0.076). Post Hoc test showed that the differences in social scores were higher in both experimental groups than in the control group (P < 0.05); the difference in perceptual scores was significantly higher in experimental group 1 than in experimental group 2 (P < 0.01), but there was no significant difference with the control group (P > 0.05); the difference in health behavior scores was higher in experimental group 2 than in the control (P < 0.05), and the difference in experimental group 1 was slightly higher than in the control group (P = 0.072). ConclusionElectronic picture book interventions based on the CPS model may be more effective in enhancing social, perceptual and health behavior in children with ASD, but there may be differences among models.

AIM: To explore the factors influencing heart rate(HR)changes during small incision lenticule extraction(SMILE)surgery by monitoring HR trends at different time points of the procedure.METHODS: Prospective cohort study. A total of 69 patients who underwent SMILE surgery at the Laser Vision Correction Center of Xi'an No.1 Hospital from April to May 2024 were enrolled. Before the surgery, patients completed the State Anxiety Inventory(S-AI, questions 1-20)to assess their preoperative anxiety scores related to the next day's surgery. Baseline HR was recorded using medical pulse oximeter, and real-time HR was recorded during patient positioning, lenticule scanning, lenticule separation and extraction, and the application of postoperative eye drops.RESULTS: The HR during patient positioning was 83.61±13.87 bpm, which was significantly different from the baseline HR(77.52±10.88 bpm), HR during lenticule separation and extraction(75.54±12.52 bpm), and HR during postoperative eye drop application(76.65±10.54 bpm; all P<0.001). When stratified by median age, older patients(>26 years)had the HR during lenticule separation and extraction 76.27±9.93 bpm, which differed from the HR at positioning(84.82±14.10 bpm)and at lens scanning(82.76±13.72 bpm; all P<0.005). Stratified by gender, the HR of male patients at positioning was the highest(85.31±16.61 bpm), which differed significantly from the baseline HR(78.26±12.63 bpm), HR during lenticule separation and extraction(77.14±14.59 bpm), and HR during postoperative eye drop application(77.11±12.49 bpm; all P<0.005). There was no correlation between HR during positioning and preoperative anxiety scores(r=0.124, P=0.418).CONCLUSION: HR changes during SMILE surgery vary with different procedural stages, peaking during patient positioning and reaching the lowest point during lenticule separation and extraction. Older patients showed higher HR during positioning, and male patients exhibited higher HR during positioning.

The pathogenesis of chronic wound healing is complex. It is often difficult to heal due to a long course of disease， difficulty in treatment， and it seriously affects the quality of life in patients. The active ingredients， couplet medicinals， and compound formulas of traditional Chinese medicine （TCM） possess unique advantages in the treatment of chronic wound healing. The phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway is extremely critical in the treatment of chronic wound healing by regulating a series of biological processes， including cell apoptosis， angiogenesis， and inflammatory responses. This article reviews the relevant research on the regulation of the PI3K/Akt signaling pathway by TCM to promote chronic wound healing. It has been found that the active ingredients of TCM （such as geniposide， astragaloside， and ginsenosides， etc.）， and compound formulas （such as Chonghe ointment， Huanglian ointment， Shirun shaoshang ointment， etc.） mainly reduce inflammatory responses， promote angiogenesis， regulate cell autophagy， and accelerate wound healing by activating the PI3K/Akt signaling pathway； at the same time， there are also a few couplet medicinals（ such as Huangqi-Honghua） and compound formulas （such as Xiangpi Shengji ointment） that exert anti-inflammatory effects by inhibiting this signaling pathway， to promote wound healing.

ObjectiveTo investigate the efficacy of ovarian tissue cryopreservation and autologous transplantation in preserving fertility and ovarian endocrine function in patients with cervical cancer. MethodsA 26-year-old patient with stage ⅡA1 cervical cancer underwent ovarian tissue harvesting and cryopreservation during cancer surgery. Following complete remission of the cancer， autologous ovarian tissue transplantation was performed. Follow-up monitoring included assessment of menopausal symptoms， hormone levels， and follicular development. ResultsSix months after transplantation， follicle-stimulating hormone levels decreased to 6.60 U/L， and estradiol levels increased from ＜10.00 ng/L to 89.00 ng/L. At 10 months after transplantation， ultrasound monitoring confirmed follicular development and physiological ovulation in the transplanted ovarian tissue. By 15 months after transplantation， follicle-stimulating hormone levels remained stable at 7.24 U/L， and estradiol levels further increased to 368.00 ng/L. Over 2 years after transplantation， the patient successfully gave birth to a healthy baby through assisted reproductive technology. ConclusionThe restoration of endocrine and ovulation functions in the transplanted cryopreserved ovarian tissue， followed by successful pregnancy， demonstrates the clinical success of ovarian tissue transplantation.

ObjectiveTo establish a quality evaluation method for Zhuye Shigao granules（Zhuye Shigaotang） based on fingerprint and determination of index components， and to investigate the therapeutic effect of Zhuye Shigao granules on mice with cold-dampness pestilence attacking lung syndrome. MethodsThe fingerprint of Zhuye Shigao granules was established by high performance liquid chromatography（HPLC）， and the methods for determination of total calcium， orientin， isoorientin， ginsenosides Rg₁， Re and Rb₁ and other 2 index components were established. Fifty ICR mice were randomly divided into the blank group， model group， Zhuye Shigao granules low， medium and high dose groups（9.3， 18.6， 37.2 g·kg^-1·d^-1）， with 10 mice in each group. In addition to the blank group， the model mice with cold-dampness pestilence attacking lung syndrome was prepared by nasal drip of lipopolysaccharide combined with cold-dampness environment. Each administration group was given the corresponding liquid by gavage according to the dose， while the blank group and model group were given the same volume of normal saline by gavage. Then， the body temperature and organ index of mice in each group were measured， hematoxylin-eosin（HE） staining was used to investigate the lung tissue injury of mice in each group， and enzyme-linked immunosorbent assay（ELISA） was used to detect the changes of tumor necrosis factor-α（TNF-α）， interleukin（IL）-lβ， IL-6， IL-10 levels in serum and lung tissue， as well as immunoglobulin（Ig）A and IgM levels in serum. ResultsThe fingerprint similarity of 10 batches of Zhuye Shigao granules was>0.950， and 20 common peaks were calibrated. Seven of them were identified， including peak 11（isoorientin）， peak 12（orientin）， peak 14（apioside liquiritin）， peak 15（liquiritin）， peak 17（apioside isoliquiritin）， peak 19（isoliquiritin） and peak 20（liquiritigenin）. The results of quantitative analysis showed that the content range of each index component in 10 batches of Zhuye Shigao granules was as follows：Total calcium of 9.978-11.294 mg·g^-1， isoorientin of 0.033-0.041 mg·g^-1， orientin of 0.046-0.055 mg·g^-1， ginsenoside Rg₁+ginsenoside Re of 0.748-0.762 mg·g^-1， ginsenoside Rb₁ of 0.151-0.197 mg·g^-1， liquiritin of 1.106-1.366 mg·g^-1， glycyrrhizic acid of 0.904-1.182 mg·g^-1_. Compared with the blank group， the body temperature of mice in the model group was significantly increased， the organ indexes of liver， lung and spleen were significantly decreased， the organ index of thymus was significantly increased， HE staining of lung tissue showed infiltration of inflammatory cells， a small amount of serous exudation was observed in the alveoli， and lung tissue was damaged. After the intervention of Zhuye Shigao granules， the pathological changes were improved compared with the model group. The expression levels of IL-1β， IL-6 and TNF-α were significantly increased， the expression level of IL-10 was significantly decreased in serum and lung tissue. The levels of IgA and IgM in serum were significantly decreased（P<0.01）. Compared with the model group， the body temperature， the organ indexes and immune factor levels in serum and lung tissue of mice in the Zhuye Shigao granules medium and high dose groups were significantly reduced（P<0.05， P<0.01）. ConclusionIn this study， the quality evaluation of Zhuye Shigao granules was carried out based on fingerprint combined with determination of index components， and the fingerprint of four herbs（Lophatheri Herba， Ophiopogonis Radix， Pinelliae Rhizoma and Glycyrrhizae Radix et Rhizoma） in this formula and the determination of 8 index components were established. The therapeutic effect of Zhuye Shigao granules on mice with cold-dampness pestilence attacking lung syndrome may be related to inhibiting inflammatory response and mediating immune regulation.

Dentatorubral-pallidoluysian atrophy（DRPLA） is a rare autosomal dominant neurodegenerative disease caused by CAG triplet expansion in the atrophin 1 （ATN1） gene. Up to now， the pathogenesis of DRPLA remains unclear. The main clinical features of DRPLA include myoclonus， epilepsy， ataxia， choreoathetosis， and cognitive impairment. DRPLA has great clinical heterogeneity， and the number of CAG repeats is negatively correlated with age of onset and disease severity. Some patients with late-onset DRPLA may have atypical manifestations without typical imaging changes， which brings challenges to the diagnosis of the disease. This article reviews the pathogenesis， pathological features， clinical and imaging manifestations， diagnosis， and potential treatment of DRPLA， in order to deepen the understanding of this disease.
Ataxia ; Myoclonus

ObjectiveTo explore the effect of timosaponin BⅡ （TBⅡ） combined with icariin （ICA） on osteoclast （OC）-osteoblast （OB） coupling and decipher the mechanism from the cellular level. MethodsThe cell counting kit-8 （CCK-8） was used to assess the effects of different concentrations of TBⅡ and different concentrations of TBⅡ+ICA on the growth of RAW264.7 cells. Soluble receptor activator of nuclear factor-κB ligand （sRANKL） was used to induce the differentiation of RAW264.7 pre-osteoclasts into osteoclasts. The cells were allocated into sRANKL， TBⅡ （1， 5， 10 μmol·L^-1）， and TBⅡ+ICA groups. Tartrate-resistant acid phosphatase staining was performed to assess the effects of TBⅡ and TBⅡ+ICA on osteoclast differentiation. Real-time quantitative polymerase chain reaction （Real-time PCR） was conducted to examine the effects of TBⅡ+ICA on the expression of key genes involved in osteoclast differentiation and osteoclast-derived coupling factors. The osteogenic differentiation conditioned medium mixed with osteoclast supernatant was used to induce osteogenic differentiation of MC3T3-E1 cells. Alkaline phosphatase staining and alizarin red S staining were employed to determine the effect of TBⅡ+ICA on osteogenic differentiation. Real-time PCR was employed to evaluate the effects of conditioned medium on key genes involved in osteogenic differentiation. ResultsTBⅡ at 1， 5， 10 μmol·L^-1 had no significant effect on the cell survival rate. Compared with the sRANKL group， TBⅡ inhibited osteoclast differentiation in a dose-dependent manner and achieved the best effect at 10 μmol·L^-1 （P<0.01）. Compared with the sRANKL group， different concentrations of TBⅡ down-regulated the mRNA levels of osteoclast differentiation-related genes c-Fos， RANK， and RANKL （P<0.05）. None of 10 μmol·L^-1 TBⅡ， 10 μmol·L^-1 TBⅡ+10^-4 μmol·L^-1 ICA， or 10 μmol·L^-1 TBⅡ+10^-3 μmol·L^-1 ICA affected the viability of RAW264.7 cells. TBⅡ and/or ICA inhibited osteoclast differentiation （P<0.01）， and TBⅡ + ICA had the best effect （P<0.01）. Compared with the sRANKL group， TBⅡ and/or ICA down-regulated the mRNA levels of c-Fos， RANK， and RANKL （P<0.05）. The single application of TBⅡ and ICA had no significant effect on the mRNA levels of Wnt10b， Cthrc1， and C3a， while TBⅡ+ICA exerted up-regulating effects （P<0.05）. Compared with those in the blank group， the bone differentiation and mineralization abilities of the normal osteogenic induction group and each osteogenic induction + osteoclast supernatant group were improved （P<0.01）. Compared with the blank group， the normal osteogenic induction group and the osteogenic induction + osteoclast supernatant group showed up-regulated mRNA levels of Runx2 and OCN （P<0.01）. ConclusionTBⅡ+ICA can inhibit osteoclast differentiation， maintain the normal osteoclast-osteoblast coupling， and promote osteogenic differentiation.

Ulcerative colitis （UC）， a chronic， non-specific inflammatory bowel disease with typical symptoms such as abdominal pain， diarrhea， and bloody stools， demonstrates a high relapse rate and difficulty in curing. Sishenwan， first recorded in Internal Medicine Abstract （Nei Ke Zhai Yao）， are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney， and astringing the intestine and stopping diarrhea. In recent years， Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors， including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term， its side effects， high relapse rate， and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan， used alone or in combination with Western medicine or other Chinese medicine compound prescriptions， significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus， pus， and blood in stools， and persistent abdominal pain， reduce Mayo scores and the relapse rate， and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen， isopsoralen， and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level， Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future， a full-chain system covering syndrome differentiation， targeting， and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics， providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.

Ulcerative colitis （UC）， a chronic， non-specific inflammatory bowel disease with typical symptoms such as abdominal pain， diarrhea， and bloody stools， demonstrates a high relapse rate and difficulty in curing. Sishenwan， first recorded in Internal Medicine Abstract （Nei Ke Zhai Yao）， are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney， and astringing the intestine and stopping diarrhea. In recent years， Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors， including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term， its side effects， high relapse rate， and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan， used alone or in combination with Western medicine or other Chinese medicine compound prescriptions， significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus， pus， and blood in stools， and persistent abdominal pain， reduce Mayo scores and the relapse rate， and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen， isopsoralen， and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level， Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future， a full-chain system covering syndrome differentiation， targeting， and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics， providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.