1.HER2 in Metastatic Colorectal Cancer: Diagnostic and Therapeutic Opportunities and Challenges
Zhao-Tao PAN ; Feng-Yu GAI ; Chen CHEN ; Tong LI ; Yan-Ping QING
Progress in Biochemistry and Biophysics 2026;53(4):936-950
Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the second leading cause of cancer-related mortality worldwide. Despite therapeutic advancements over recent decades, the prognosis for patients with metastatic CRC (mCRC) remains poor. Approximately 2%-4% of mCRC cases exhibit human epidermal growth factor receptor 2 (HER2) amplification or overexpression, defining a distinct molecular subtype. This HER2-positive status is strongly associated with primary resistance to anti-epidermal growth factor receptor (EGFR) therapies, which are the standard of care for patients with RAS wild-type tumors. Beyond its well-established role in breast and gastric cancers, HER2 has emerged as a pivotal biomarker and actionable therapeutic target in mCRC. However, selecting appropriate treatment strategies remains challenging due to patient heterogeneity and diverse molecular subtypes. This review systematically summarizes the molecular biology, diagnostic strategies, and advances in targeted therapies for HER2-positive mCRC. On the diagnostic front, we discuss the applications of immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), next-generation sequencing (NGS), and circulating tumor DNA (ctDNA) detection technologies. We highlight discrepancies in diagnostic criteria across key clinical trials—such as HERACLES, DESTINY, and MOUNTAINEER—underscoring the urgent need for standardized, CRC-specific definitions to ensure consistent patient selection and comparability of efficacy data across studies. Although NGS enables comprehensive genomic profiling, its cost-effectiveness relative to traditional methods must be carefully considered. Therapeutically, we summarize clinical trial data for HER2-directed agents, including tyrosine kinase inhibitors (TKIs) such as tucatinib and lapatinib, monoclonal antibodies like trastuzumab, bispecific antibodies, and antibody-drug conjugates (ADCs) such as trastuzumab deruxtecan. We review dual-targeting strategies and note recent FDA approvals that represent significant milestones in second-line treatment. Additionally, we explore the potential of combining immune checkpoint inhibitors with HER2-targeted therapies to enhance antitumor immunity through mechanisms including antibody-dependent cellular cytotoxicity (ADCC) and modulation of the tumor microenvironment. ADCs enable precise delivery of cytotoxic payloads, reducing off-target toxicity while effectively inhibiting oncogenic pathways. A substantial portion of this review is dedicated to dissecting the molecular mechanisms underlying primary and acquired resistance to HER2-targeted therapies—persistent challenges that limit clinical benefit. These mechanisms include reactivation of downstream signaling pathways such as PI3K/AKT/mTOR and MAPK, concurrent mutations in genes like KRAS or BRAF, and alterations in HER2 expression that compromise treatment efficacy. For instance, specific HER2 mutations (e.g., L755S) can reduce drug binding affinity, while ctDNA monitoring facilitates early detection of emerging resistance clones during disease progression, thereby enabling timely therapeutic adjustments. Tumor heterogeneity and dynamic interactions with the microenvironment further complicate resistance patterns observed in clinical practice. HER2-targeted therapy represents a new frontier in precision oncology for mCRC, offering renewed hope for improving patient outcomes. Realizing this potential will require continued optimization of diagnostic algorithms and treatment workflows. Future efforts must focus on overcoming resistance, validating liquid biopsy approaches for dynamic monitoring, and establishing unified clinical guidelines. HER2 has become an essential biomarker for stratifying mCRC patients beyond traditional RAS and BRAF status, underscoring the shift from empiric treatment to biomarker-driven precision medicine. International, multidisciplinary collaboration will be critical to validate emerging biomarkers and refine treatment algorithms globally.
2.Meta-analysis of the clinical efficacy and safety of Jianwei xiaoshi oral liquid in the treatment of functional dyspepsia in children
Ping RONG ; Guiyun PAN ; Juan WEI ; Tengda LI ; Xilian ZHANG
China Pharmacy 2025;36(7):867-873
OBJECTIVE To evaluate the clinical efficacy and safety of Jianwei xiaoshi oral liquid in the treatment of functional dyspepsia (FD) in children, and provide evidence-based basis for clinical use of the drug. METHODS Retrieved from CNKI, VIP, Wanfang, CBM, Cochrane Library and PubMed, randomized controlled trials (RCTs) about Jianwei xiaoshi oral liquid in the treatment of FD in children were collected from the inception to Apr. 2024. The control group was treated with conventional western drugs (including gastrointestinal motion-promoting, antacids or acid-suppressing drugs), and the trial group was treated with Jianwei xiaoshi oral liquid alone or combined with conventional Western drugs (drug dosage and course of treatment were the same as the control group). Meta-analysis was performed using RevMan 5.3 software after quality evaluation with the Cochrane risk bias assessment tool 6.1. RESULTS Totally 16 literature were employed which included 1 962 patients. The results of meta-analysis showed that the total clinical effective rate of Jianwei xiaoxi oral liquid in the treatment of FD in children of trial group was significantly higher than that of the control group [RR=1.18, 95%CI (1.13, 1.22), P<0.000 01]. In this study, subgroup analysis was conducted on the usage and dosage, course of treatment, and combination or not in trial group, as well as the type of conventional Western drugs. The results showed that the total clinical effective rate of trial group was significantly higher than that of control group; the relief time of abdominal distension and abdominal pain in trial group [MD=-2.54, 95%CI (-3.10, -1.98)], loss of appetite relief time [MD=-2.12, 95%CI (-2.63, -1.61)], nausea and vomiting relief time [MD=-1.70, 95%CI (-2.27, -1.14)], and belching relief time [MD=-1.61, 95%CI (-2.44, -0.78)] were shorter than that of the control group significantly (P<0.05). In addition, compared with control group, the levels of gastrin [SMD=1.63, 95%CI (0.98, 2.29)] and motilin [SMD=2.06, 95%CI (1.58, 2.54)] as well as gastric antral emptying rate [MD=5.99, 95%CI (2.78, 9.21)] in trial group were increased significantly, while the level of somatostatin was decreased significantly [SMD=-1.30, 95%CI (-1.57, -1.02)] (P≤0.000 3). CONCLUSIONS Jianwei xiaoshi oral liquid, whether used alone or in combination with other medications, and regardless of the treatment course or dosage and usage, is effective in treating FD in children, with good safety.
3.Association Between Vitamin D Status and Insulin Resistance in Adolescents: A Cross-sectional Observational Study
Xiaoyuan GUO ; Yutong WANG ; Zhibo ZHOU ; Shi CHEN ; Mei ZHANG ; Bo BAN ; Ping LI ; Xinran ZHANG ; Qiuping ZHANG ; Kai YANG ; Hongbo YANG ; Hanze DU ; Hui PAN
Medical Journal of Peking Union Medical College Hospital 2025;16(3):577-583
To investigate the correlation between vitamin D nutritional status and insulin resistance in pubertal adolescents. This cross-sectional observational study employed convenience sampling to recruit 2021-grade(8th grade) students from Jining No.7 Middle School in Shandong Province on June 5, 2023. Data collection included questionnaires, physical examinations, and imaging assessments to obtain general information, secondary sexual characteristics development, and bone age. Venous blood samples were collected to measure fasting blood glucose(FBG), fasting insulin(FINS), homeostasis model assessment of insulin resistance(HOMA-IR), and 25-hydroxyvitamin D[25(OH)D] levels. Spearman correlation analysis and multivariate linear regression models were used to examine the associations between serum vitamin D levels and FBG, FINS, and HOMA-IR. The study included 168 pubertal adolescents[69 females(41.1%), 99 males(58.9%); mean age(13.27±0.46) years]. All participants had entered puberty based on sexual development assessment. Vitamin D deficiency was observed in 41 participants(24.4%), insufficiency in 109(64.9%), and sufficiency in 18(10.7%). The median HOMA-IR was 3.49(2.57, 5.14).Significant differences were found across vitamin D status groups for HOMA-IR [4.45(2.54, 6.62) Vitamin D deficiency/insufficiency is prevalent among pubertal adolescents, and serum vitamin D levels show a significant inverse association with insulin resistance. These findings suggest the potential importance of vitamin D status in metabolic health during puberty.
4.Body Composition Profiles and Associated Factors in Adolescents UndergoingLong-term Regular Exercise
Yutong WANG ; Xiaoyuan GUO ; Hanze DU ; Hui PAN ; Wei WANG ; Mei ZHANG ; Bo BAN ; Ping LI ; Xinran ZHANG ; Qiuping ZHANG ; Hongshuang SUN ; Rong LI ; Shi CHEN
Medical Journal of Peking Union Medical College Hospital 2025;16(3):591-597
To investigate body composition and associated factors in adolescents undergoing long-term regular sports training. This prospective longitudinal cohort study employed convenience sampling to recruit adolescents receiving structured athletic training at Jining Sports Training Center in June 2023. Baseline measurements included height, weight, body mass index (BMI), blood pressure, heart rate, waist circumference, and hip circumference. Questionnaires assessed sleep duration, screen time, and household income. Follow-up measurements in June 2024 repeated these assessments while adding bioelectrical impedance analysis for body composition (lean mass, skeletal muscle mass, fat mass, and body fat percentage). Linear regression models examined associations between training type (direct-contact vs. non-contact sports) and follow-up body fat percentage, BMI, and waist circumference as dependent variables, adjusting for covariates. The study included 110 adolescents (39 female, 71 male) with median age 13.21 years (IQR: 12.46-14.33). Participants comprised 65 direct-contact and 45 non-contact athletes. Baseline prevalence rates were 27.27% for overweight/obesity, 24.55% for elevated waist circumference, and 16.36% for elevated blood pressure. At follow-up, corresponding rates were 24.55%, 26.36%, and 13.64% respectively. The elevated blood pressure subgroup showed significantly higher waist circumference ( Despite regular athletic training, substantial proportions of adolescents exhibited overweight/obesity, abdominal obesity, and elevated blood pressure, warranting clinical attention. Training modality appears to influence body composition changes, with direct-contact sports associated with more favorable adiposity-related outcomes.
5.Comparison of the efficacy of remimazolam and propofol in the induction and maintenance of general anesthesia in elderly patients undergoing thoracoscopic lobectomy
Chun LIU ; Juan HU ; Yu HUANG ; Jinqiu YANG ; Junjie LI ; Ping YANG ; Pengfei PAN
China Pharmacy 2025;36(16):2040-2045
OBJECTIVE To compare the clinical efficacy and safety of remimazolam and propofol in general anesthesia induction and maintenance for elderly patients undergoing thoracoscopic lobectomy. METHODS A total of 86 elderly lung cancer patients who underwent thoracoscopic lobectomy at Chongqing University Three Gorges Hospital from February to July 2024 were selected and divided into the propofol group and the remimazolam group according to the randomized numerical table method, with 43 cases in each group. During anesthesia induction, patients in the propofol group and the remimazolam group were intravenously administered 2 mg/kg of Propofol medium- and long-chain fat emulsion injection or 0.25 mg/kg of Remimazolam tosilate for injection, respectively; during anesthesia maintenance, the two groups received intravenous infusion of 6-10 mg/(kg·h) of Propofol medium- and long- chain fat emulsion injection or 1-3 mg/(kg·h) of Remimazolam tosilate for injection, respectively. The anesthesia effects, anesthesia-related indicators, intraoperative opioid and muscle relaxant dosages, Ramsay sedation score, numerical rating scale (NRS) score, and hemodynamic parameters were compared between the two groups, and the occurrence of adverse drug reactions was recorded. RESULTS A total of 41 patients in the propofol group and 43 patients in the remimazolam group completed the trial. The proportion of patients with grade Ⅰ anesthesia effect in the remimazolam group was significantly higher than that in the propofol group, while the proportion of patients with grade Ⅱ anesthesia effect was significantly lower than that in the propofol group (P<0.05). In this group, the disappearance time of eyelash reflex, the time taken for the bispectral index to drop to 60, and the Ramsay sedation scores (2 and 6 hours after operation) were all significantly prolonged or increased, while the recovery time, NRS scores (2 and 6 hours after operation), and the incidence of intraoperative hypotension were all significantly shortened or reduced; moreover, the improvements of the above sedation/NRS scores exhibited a time-dependent pattern within 2 to 24 hours after operation (P<0.05). Compared with before anesthesia induction (T0), the heart rate [except at 2 min after medication (T1), 60 min after anesthesia (T4), and at the end of surgery (T5) in the remimazolam group] and mean arterial pressure [except at T1 in the remimazolam group] of patients in both groups significantly decreased at T1, 5 min after medication (T2), at the start of surgery (T3), T4, and T5 (P<0.05). Meanwhile, regional cerebral oxygen saturation significantly increased in both groups. Furthermore, the heart rate and mean arterial pressure of patients in the remimazolam group were significantly higher than those in the propofol group at T1, T2 and T4 (P<0.05). No statistically significant differences were observed between the two groups in terms of postanesthesia care unit stay time, dosage of opioids and muscle relaxants, regional cerebral oxygen saturation, or peripheral oxygen saturation at various time points (P>0.05). CONCLUSIONS Compared to propofol, remimazolam demonstrates superior anesthesia effects when used for the induction and maintenance of general anesthesia in elderly patients undergoing thoracoscopic lobectomy. It not only provides more stable intraoperative hemodynamics and shortens the postoperative recovery time but also effectively reduces the incidence of intraoperative hypotension.
6.Extracorporeal blood purification therapy for acute poisoning in Jiangsu Province, China: a cross-sectional, multicenter real-world study
Li QIAO ; Jinsong ZHANG ; Jianrong CHEN ; Lijun LIU ; Ping GENG ; Hong SUN ; Yeping DU ; Zhiguang TIAN ; Jianjun MA ; Rushan YANG ; Jiancheng DONG ; Zheng QIN ; Shanshan WU ; Yumin PAN ; Yigang WU
Chinese Journal of Emergency Medicine 2025;34(3):369-375
Objective:To investigate the current application of blood purification in the treatment of acute poisoning within Jiangsu Province and to evaluate the impact of extracorporeal blood purification on the clinical outcomes of critically poisoned patients.Methods:This multicenter, cross-sectional real-world observational study followed patients presenting with poisoning to the emergency departments of nine hospitals in Jiangsu Province between June 2015 and May 2019. Data were collected on demographic characteristics, vital signs within the first hour of emergency presentation, treatment modalities, length of hospital stay, and survival outcomes. Clinical data from patients who underwent extracorporeal blood purification were compared with those who did not, using the Wilcoxon rank-sum test and Chi-square test.Results:A total of 4 178 poisoning cases were included between June 2015 and May 2019. Among them, 21.7% (908/4 178) received blood purification therapy, while 78.3% (3 270/4 178) did not. Hemoperfusion (90.4%) was the most frequently employed method, followed by continuous renal replacement therapy (CRRT) (4.4%). In combined blood purification modalities, 4.8% underwent hemoperfusion combined with CRRT, 0.1% received hemoperfusion with plasma exchange, and another 0.1% underwent hemoperfusion combined with both CRRT and plasma exchange. Among patients who underwent blood purification, pesticide poisoning was the most prevalent (76.3%), with the most common toxic agents being paraquat (23.7%), dichlorvos (8.7%), methamidophos (5.2%), omethoate (4.0%), and glyphosate (3.7%). Compared to the non-blood purification group, patients in the blood purification group were more likely to present within the first hour with a low Glasgow Coma Scale (GCS) score (3-8) (22.6% vs. 9.7%, P <0.05), low mean arterial pressure (8.0% vs. 3.2%, P <0.05), longer hospital stays [5(3,9) days vs. 2(1,4) days, P <0.05] and a higher in-hospital mortality rate (21.1% vs. 5.3%, P <0.05). Follow-up via telephone 28 days after discharge revealed a survival rate of 78.9%, with a mortality rate of 21.1% in the blood purification group. Conclusions:Hemoperfusion is the most commonly utilized blood purification technique for treating poisoning in Jiangsu Province, with pesticides being the primary toxic agents treated. Although the mortality rate is higher in the blood purification group, the intervention may still contribute to improved patient outcomes.
7.Type II Leydig cell hypoplasia caused by LHCGR gene mutation: a case report.
Ke-Xin JIN ; Zhe SU ; Yan-Hua JIAO ; Li-Li PAN ; Xian-Ping JIANG ; Jian-Chun YIN ; Jia-Qiang LI
Chinese Journal of Contemporary Pediatrics 2025;27(2):225-228
The patient, assigned female at birth and aged 1 year and 7 months, presented with clinical manifestations of 46,XY disorders of sex development. The external genitalia exhibited a severely undermasculinized phenotype. Laboratory tests and gonadal biopsy indicated poor Leydig cell function and good Sertoli cell function. Genetic testing revealed compound heterozygous mutations of c.867-2A>C and c.547G>A (p.G183R) in the LHCGR gene. The patient was ultimately diagnosed with type II Leydig cell hypoplasia. Type II Leydig cell hypoplasia presents a broad spectrum of clinical phenotypes, characterized by a lack of parallel function between Leydig cells and Sertoli cells, and significant individual variability in spermatogenesis and gender assignment. This condition should be considered when there is poor Leydig cell function but good development of Wolffian duct derivatives.
Female
;
Humans
;
Infant
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Disorder of Sex Development, 46,XY/genetics*
;
Leydig Cells/pathology*
;
Mutation
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Receptors, LH/genetics*
;
Testis/abnormalities*
8.46,XY disorder of sex development caused by PPP1R12A gene variants: a case report.
Wei SU ; Zhe SU ; Jing-Yu YOU ; Hui-Ping SU ; Li-Li PAN ; Shu-Min FAN ; Jian-Chun YIN
Chinese Journal of Contemporary Pediatrics 2025;27(8):1017-1021
The patient was a boy aged 1 year and 9 months who presented with 46,XY disorder of sex development (DSD), with severe undermasculinization of the external genitalia. Laboratory tests and ultrasound examinations showed normal functions of Leydig cells and Sertoli cells in the testes. Genetic testing revealed a novel pathogenic heterozygous variant, c.1186dupA (p.T396Nfs*17), in the PPP1R12A gene. Thirteen cases of PPP1R12A gene variants have been reported previously. These variants may cause isolated involvement of the genitourinary or neurological systems, or affect other systems/organs including the digestive tract, eyes, heart, etc. Patients with DSD typically present with a 46,XY karyotype and variable degrees of undermasculinization involving the external genitalia, gonads, and reproductive tract. This article reports a child with 46,XY DSD accompanied by growth retardation caused by a heterozygous variant in the PPP1R12A gene, which expands the clinical disease spectrum associated with PPP1R12A gene variants.
Humans
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Male
;
Infant
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Disorder of Sex Development, 46,XY/etiology*
;
Protein Phosphatase 1/genetics*
9.Nasal nitric oxide in preschool children with chronic rhinosinusitis
Meiling WU ; Jiewei LIU ; Ping LIU ; Rifu WEI ; Shang GAO ; Huifeng LI ; Xiaochun PAN
Chinese Archives of Otolaryngology-Head and Neck Surgery 2025;32(7):451-454
OBJECTIVE Analyze the nasal nitric oxide(NNO)of CRS children,and explore the clinical value of NNO in the diagnosis and treatment of CRS in children.METHODS CRS children diagnosed in the outpatient clinic were selected,and were divided into CRS with and without AR according to their allergen results.VAS score and NNO test were performed for them.Healthy children during the same period were selected as the control group.Finally their results were compared and analyzed.RESULTS The NNO of CRS children with and without AR were(193±62)ppb and(138±49)ppb,both lower than the control group's[(243±51)ppb];There were negative correlations between NNO and VAS scores in CRS children without AR before and after treatment;The NNO of CRS children with and without AR were significantly increased after treatment(P<0.05);NNO has high predictive value for diagnosing CRS children without AR(P<0.01).CONCLUSION The levels of NNO in different types of CRS were lower than normal,and CRS children without AR was lower than those with AR.NNO could assist in the diagnosis of CRS,dynamically reflect the severity of nasal inflammation,and help to distinguish the allergic status of CRS.

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