Purpose: Dual anti–human epidermal growth factor receptor 2 (HER2) drugs have become the standard regimen for neoadjuvant systemic treatment (NST) to HER2-positive breast cancer patients. However, the efficacy varies greatly among patients with different HER2 protein expression levels. Materials and Methods: A total of 575 HER2-positive breast cancer patients from multiple centers throughout China from 2013 to 2022 were retrospectively analyzed. We compared clinicopathological features in different HER2 immunohistochemistry classes (HER2 2+/in situ hybridization [ISH] + or HER2 3+), and their difference in response to NST and survival with single or dual anti-HER2 drugs. Drug sensitivity assays were used to evaluate different efficacy of anti-HER2 drugs in vitro. Results: Compared to HER2 3+ subgroup, the HER2 2+/ISH+ group had a higher proportion of hormone receptor–positive status (48.7% vs. 76.1%, p < 0.001), more HER2 protein loss after NST, lower pathological complete response (pCR) rate (46.07% vs. 16.24%, p < 0.001), and tended to have worse disease-free survival (DFS). In HER2 2+/ISH+ patients, treated with pertuzumab and trastuzumab in combination had no significant improvement in pCR (19.12% vs. 12.24%, p=0.287) and DFS (p=0.908) than using alone. Drug sensitivity assay showed poor efficacy with dual anti-HER2 drugs in HER2 2+/ISH+ cell lines; however, fam-trastuzumab deruxtecan drugs had a satisfactory effect. Conclusion Owing to the differences in clinicopathological features and treatment efficacy, we considered the HER2 2+/ISH+ group to be a distinct subtype and defined it as the HER2-moderate–positive subgroup. In this subgroup, dual anti-HER2 drugs did not exert significant improvement in pCR and DFS. Therefore, treatment optimization is warranted, with antibody-drug conjugate drugs as potential options.

Objective:To investigate exercise fear condition and its influencing factors in patients with coronary heart dis-ease(CHD)involving in phase Ⅱ cardiac rehabilitation after percutaneous coronary intervention(PCI).Methods:Conven-ience sampling was performed among cardiac rehabilitation patients from a Shanxi grade-A tertiary hospital between Janu-ary 2023 and June 2023.General data questionnaire,Tampa Scale for Kinesiophobia-Short Version for Heart patients(TSK-SV H),the Multidimensional Scale of Perceived Social Support(MSPSS)and the Post Percutaneous Coronary In-tervention Health Literacy Scale(PPCIHLS)were used for assessment.Pearson and Spearman rank correlation analyses were applied to investigate the relationships between social support factors and health literacy factors with patients'fear of exercise;multivariate linear regression models and quantile regression models were used to analyze the influencing factors of fear of exercise.Results:Among the 118 patients,average TSK-SV H score was(33.78±3.79)points;10.2％patients showed significant fear.The correlation analysis showed that PPCIHLS score was negatively correlated with TSK-SV H score(r=-0.423,P＜0.001).Results from multivariate regression analysis indicated that health literacy,cardiac func-tion class and drinking status affected the average score of exercise fear(P＜0.05 all).The quantile regression model pro-vided additional insights,showing that the impact of factors such as living situation,drinking status,cardiac function class and health literacy on exercise fear varied across different quantiles.Notably,cardiac function class had a consistently posi-tive effect on TSK-SV H score at various quantiles.Conclusion:Improving health literacy and tailored rehabilitation plans are vital to reduce exercise fear and improve cardiac rehabilitation effect.

Objective To explore the brain damage of SD rats under different time points of hypobaric hypoxia exposure.Methods A rat high-altitube cerebral edema(HACE)model was constructed by simulating an altitude of 6 000 m in a hypobaric hypoxia animal experimental chamber.Thirty-six SD male rats were randomly divided into the control group and the hypobaric hypoxia exposure 3,7 and 14 d groups,with 9 rats in each group.Except for the control group,the rats in each group were continuously exposed to hypobaric hypoxia for 3,7,and 14 d.At the end of the modeling period,serum was collected by blood sampling via the abdominal aorta,and brain tissue samples were taken.The wet-to-dry ratio(W/D)of brain tissue was calculated,and the levels of relevant oxidative enzymes in serum and brain tissue were measured.The expression levels of hypoxia-inducible factor-1α(HIF-1α)and aquaporin 4(AQP4)mRNAs in brain tissue were detected by real-time fluorescence quantitative polymerase chain reaction.Results The W/D of brain tissues in the control group and the group exposed to hypobaric hypoxia for 3,7 and 14 d were 4.46±0.12,4.98±0.16,5.07±0.18 and 4.95±0.07;the superoxide dismutase contents were(111.86±2.45),(90.73±1.48),(79.64±2.56)and(55.33±1.45)U·g-1;the glutathione contents were(126.91±5.18),(125.26±1.53),(56.20±2.17)and(122.73±1.78)μg·mL-1;the malondialdehyde contents were(230.94±2.00),(362.65±3.28),(407.34±3.47)and(237.50±1.59)nmol·g-1;the relative expression levels of HIF-1 α mRNA were 1.00±0,2.99±0.49,4.72±0.49 and 1.91±0.28;the relative expression levels of AQP4 mRNA were 1.00±0,2.62±0.34,8.38±0.84 and 5.27±0.42,respectively.Statistically significant differences were found between the above indexes in the 3,7 and 14 d of hypobaric hypoxia exposure group compared with the control group(P＜0.05,P＜0.01).Conclusion Different time of hypobaric hypoxia exposure can up-regulate the expression of AQPs proteins in HACE rats and cause the disruption of the blood-brain barrier,and the HACE model constructed in the hypobaric hypoxia chamber with 6 000 m intervention for 7 d was more stable.

AIM:To analyze differential proteins associated with the pathogenesis of dry eye(DE)using bioinformatics methods, in order to reveal their potential molecular mechanisms.METHODS: Articles published in PubMed and EMBASE databases from the inception of the database to August 31, 2023, that used proteomic methods to detect protein expression in clinical samples of dry eye were searched. Differential proteins were selected and further analyzed using the STRING database and Cytoscape software for hub gene screening and module analysis. Protein-protein interaction(PPI)analysis, gene ontology(GO)functional annotation, and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed.RESULTS: A total of 21 articles were included, identifying 74 differentially expressed proteins. The most frequently occurring differential proteins were calgranulin A(SA1008), lipocalin-1(LCN1), lysozyme C(LYZ), mammaglobin-B(SCGB2A1), proline-rich protein 4(PRR4), transferrin(TF), and calgranulinB(S100A9). The top 10 hub genes were serum albumin(ALB), tumor necrosis factor(TNF), interleukin 6(IL6), IL1B, IL8, matrix metalloproteinase 9(MMP9), alpha-1-antitrypsin(SERPINA1), IL10, complement component 3(C3), and lactotransferrin(LTF). Module analysis suggested MMP9 and PRR4 as seed genes. KEGG analysis showed that differential proteins were mainly enriched in the IL17 signaling pathway(61.9%).CONCLUSION: The results reveal potential molecular targets and pathways for DE and confirm the association between the pathogenesis of DE and inflammation. Further in-depth research is needed to confirm the significance of these biomarkers in clinical practice.

Objective:To observe the effect of point injection at Zusanli(ST36)plus abdominal point application on gastrointestinal dysfunction after laparoscopic surgery.Methods:A total of 204 patients with gastrointestinal dysfunction after laparoscopic surgery were recruited and divided into four groups using the random number table method,with 51 cases in each group.The control group received conventional postoperative intervention.In addition to the treatment in the control group,the point injection group was given point injection at Zusanli(ST36),the application group was offered abdominal point application,and the integrated group received point injection at Zusanli(ST36)and abdominal point application.The treatment lasted 3 consecutive days in all four groups.The recovery time of gastrointestinal function indicators and the incidence rate of postoperative nausea and vomiting(PONV)were observed and recorded.Before and after treatment,the visual analog scale(VAS)was used to assess abdominal pain intensity,the venous blood type 1 helper T cells/type 2 helper T cells(Th1/Th2)was determined,the serum levels of interleukin(IL)-6 and interferon(IFN)-γ were detected using the enzyme-linked immunosorbent assay,and the plasma levels of motilin and gastrin were measured using radioimmunoassay.Results:Compared to the control group,the first exhaust time,the first defecation time,and the time of restoring fluid diet came earlier in the other three groups(P<0.05)and were earlier in the integrated group than in the point injection and application groups(P<0.05).The point injection,application,and integrated groups had a lower PONV incidence rate than the control group,and the integrated group was lower than the point injection and application groups(P<0.05).The intra-group comparisons showed that the VAS score and the levels of IL-6 and INF-γ decreased after treatment in all four groups(P<0.05);the point injection,application,and integrated groups were lower than the control group(P<0.05),and the integrated group was lower than the point injection and application groups(P<0.05).The intra-group comparisons also demonstrated that the levels of Th1/Th2,motilin,and gastrin increased after the intervention in the four groups(P<0.05);the point injection,application,and integrated groups were higher than the control group(P<0.05),and the integrated group was higher than the point injection and application groups(P<0.05).Conclusion:Point injection at Zusanli(ST36)plus abdominal point application can encourage postoperative exhaust,defecation,and the recovery of diet fluid,alleviate postoperative abdominal pain,reduce PONV,balance Th1/Th2,and regulate the secretion of motilin and gastrin in patients with gastrointestinal dysfunction after laparoscopic surgery.

Objective:To observe the preventive and treatment effects of warming needle therapy on peripheral neuropathy after albumin-bound paclitaxel plus cisplatin chemotherapy.Methods:Eighty patients who received albumin-bound paclitaxel plus cisplatin chemotherapy after being diagnosed with cancer were divided into an observation group and a control group using the simple random allocation table method,with 40 cases in each group.The control group received methylcobalamin dispersible tablets via oral administration,and the observation group received warming needle therapy.They were observed for the incidence of chemotherapy-induced peripheral neuropathy(CIPN),Levi's specific sensory neurotoxicity grading,brief pain inventory(BPI)score,nerve conduction velocities of the limbs,and traditional Chinese medicine(TCM)symptom scores before treatment,at the 21st day of the first cycle of chemotherapy(D1),and the 21st day of the second chemotherapy cycle(D2).The clinical efficacy was assessed at D2.Results:The incidence of CIPN was 92.5%in the control group,higher than 75.0%in the observation group(P<0.05).At D2,the number of people graded 0 on Levi's specific sensory neurotoxicity grading was larger in the observation group than in the control group,and the number of those graded 2 was smaller in the observation group(P<0.05);the observation group had a higher markedly effective rate than the control group(P<0.05).At D2,the BPI general score,BPI pain intensity score,and BPI pain interference score significantly dropped in the observation group compared to those before treatment(P<0.05).At D1,the motor nerve conduction velocity(MNCV)and sensory nerve conduction velocity(SNCV)of the limbs decreased in both groups compared to those before treatment;at D2,the MNCV and SNCV increased in the two groups compared to D1 and were higher in the observation group than in the control group(P<0.05).At D1,the TCM symptom scores increased in both groups compared to those before treatment,and the observation group was lower than the control group in comparing the scores of numbness in the extremities and poor appetite(P<0.05).At D2,the observation group showed decreases in all TCM symptom scores compared to D1 except for the scores of nausea and vomiting and poor appetite(P<0.05),while the control group had no significant changes in the TCM symptom scores compared to D1(P>0.05);the observation group was lower than the control group in comparing each symptom score(P<0.05).There were no significant adverse reactions in either group over the study period.Conclusion:Compared to oral administration of methylcobalamin dispersible tablets,warming needle therapy shows certain strengths in managing CIPN after albumin-bound paclitaxel plus cisplatin chemotherapy,and it can better improve chemotherapy-induced gastrointestinal reactions.

Objective:To discuss the efficacy of treating allergic rhinoconjunctivitis(ARC)with intranasal acupuncture at Neiyingxiang(EX-HN9)and Biqiu(Extra)points and the effects on inflammatory cells.Methods:A total of 207 ARC patients were recruited and divided into an observation group(104 cases)and a control group(103 cases)using the random number table method.The control group was prescribed desloratadine dispersible tablets and azelastine hydrochloride eye drops for 1 week,and the observation group was given additional acupuncture at bilateral Neiyingxiang(EX-HN9)and Biqiu(Extra)points,once daily consecutively over 1 week.The clinical efficacy was compared between the two groups when the treatment finished.Before and after treatment,both groups were scored using the rhinoconjunctivitis quality of life questionnaire(RQLQ),and the levels of blood eosinophils(EOS)and interleukin(IL)-17 were detected.The cured cases were observed for recurrence rate at the 6-month follow-up.Results:The observation group had more significant clinical efficacy than the control group(P<0.05).After treatment,The RQLQ score declined in both groups(P<0.05)and was lower in the observation group than in the control group(P<0.05).After the intervention,the levels of blood EOS and IL-17 dropped in the two groups and were lower in the observation group than in the control group(P<0.05).At the 6-month follow-up among the cured cases,a lower recurrence rate was found in the observation group compared to the control group(P<0.05).Conclusion:Based on conventional medications,acupuncture at Neiyingxiang(EX-HN9)and Biqiu(Extra)points can notably enhance the clinical efficacy in treating ARC patients,reducing the inflammatory cells and lowering the recurrence rate.

The Shanghai-style pediatric Tuina(Chinese therapeutic massage)school,a renowned academic school of pediatric Tuina in China,was founded by Professor JIN Yicheng,a mentor of the National Senior Traditional Chinese Medicine(TCM)Experts'Clinical Experience Inheritance Class and a distinguished TCM practitioner in Shanghai.This academic school has now been perpetuated through four generations.Prof.JIN Yicheng,a pioneering leader in modern China's pediatric Tuina,has dedicated sixty years to medical practice with unwavering benevolence and adherence to"principled innovation".While delving into traditional and ancient teachings,he has also embraced contemporary advancements.Building upon the essence of traditional pediatric Tuina,he integrated distinctive techniques from various Tuina schools,including the Yi Zhi Chan Tuina school,rolling manipulation Tuina school,and Neigong Tuina school.He also assimilated the quintessence of historical pediatric Tuina literature,the experience of modern Shanghai-based pediatric Tuina masters,and folk techniques while incorporating his years of clinical insights.This synthesis finally led to the formulation of the academic thought of"reinforcing healthy Qi and unblocking regulation"in Shanghai-style pediatric Tuina that guides clinical practice.Specifically,he comprehensively applies techniques such as"unblocking regulation of Zang-Fu organs","unblocking regulation of the four seas","unblocking regulation of the water and fire",and"unblocking regulation of the back"to the prevention and treatment of pediatric diseases across internal medicine,external medicine,orthopedics,and otolaryngology,which has significantly enhanced clinical efficacy and expanded the applicable age range and scope of Tuina for pediatric health issues,more aligning with the characteristics of children and adolescents'health challenges and current clinical demands,and paving a new way in preserving and developing traditional pediatric Tuina.

Objective:To observe the improving effects of Tuina(Chinese therapeutic massage)plus exercise therapy on joint alignment and walking function in children with genu varum(GV).Methods:Sixty-six children with GV were divided into an exercise therapy group and a Tuina plus exercise therapy group using the random number table method,with 33 cases in each group.Both groups received identical exercise therapy,while the Tuina plus exercise therapy group was additionally offered Tuina manipulation treatment.The intervention course lasted 12 weeks in both groups.Before and after the intervention,the three-dimensional gait analysis was adopted to assess the spatiotemporal parameters,kinematics,and kinetic characteristics of lower-limb joints in children with GV.Results:The GV angle was reduced after intervention in the Tuina plus exercise therapy group(P<0.05),but there was no significant change in the exercise therapy group(P>0.05).After treatment,the Tuina plus exercise therapy group demonstrated a notable decrease in the step length,walking speed,peak forefoot adduction angle,and peak ankle inversion moment(P<0.05),suggesting the correction of the ankle joint's compensatory pathological changes.In the exercise therapy group,the foot progression angle(FPA)and gait deviation index(GDI)increased markedly after the intervention(P<0.05),indicating improved overall kinematic function.Conclusion:The combined use of Tuina manipulations and exercise therapy can produce significant effects in correcting the knee joint's torsion,both coronally(GV angle)and horizontally(ankle inversion moment,FPA,and forefoot adduction angle),while exercise therapy alone can markedly improve the overall kinematic parameters(FPA and GDI).

Objective:To observe the clinical efficacy of against-lateral correction Tuina(Chinese therapeutic massage)in treating atlanto-axial joint disorder(AAJD)and imaging changes.Methods:A total of 142 patients with AAJD were recruited.They were randomly allocated to a trial group and a control group using the random number table method,with 71 participants in each group.The trial group was treated with against-lateral correction Tuina 3 times weekly.The control group was offered conventional physical traction therapy once daily.The interventions lasted 2 weeks in both groups.The two groups of participants were observed before and after treatment for their changes in the global pain scale(GPS)score,visual analog scale(VAS)score for dizziness assessment,cervical range of motion(ROM)in rotation,and the extent of atlanto-dental displacement.Results:The GPS and VAS scores dropped after treatment in both groups(P<0.05)and were lower in the trial group than in the control group after treatment and at the follow-up(P<0.05).Participants in the trial group achieved a significant increase in the cervical ROM in rotation after treatment and at the follow-up compared to the pre-treatment value(P<0.05)and surpassed the control group(P<0.05);the control group only showed an increase in the left-side rotation(P<0.05).After the intervention,neither the intra-group nor the between-group comparison revealed significant differences in the extent of atlanto-dental displacement(P>0.05),though the trial group presented an improving tendency.Conclusion:Compared to physical traction,the against-lateral correction Tuina method works more significantly in improving pain,dizziness,and ROM in AAJD patients.