Advances on Clinical Application of Adaptive Radiotherapy in Treatment of Nasopharyngeal Carcinoma / 肿瘤防治研究

Radiotherapy is the first treatment choice for nasopharyngeal carcinoma. With the rapid development of image-guided radiotherapy, adaptive radiotherapy (ART) has become widely available in clinical practice. ART may be implemented to monitor the anatomical or physiological variations of patients using dynamic imaging technology and feedback information during the treatment course, including geometric changes (size, shape, and position) of tumor and normal organs. ART also allows the modification of the treatment plan to accurately deliver the maximize dose to target and minimize normal tissue explosion. This review discusses the physics basis of ART and its state-of-art application and potential pitfalls.

Current status and future perspectives on the methods of prognosis evaluation for intrahepatic cholangiocarcinoma / 中华外科杂志

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary malignant tumor in the liver after hepatocellular carcinoma. Its incidence and mortality rates have increased worldwide in recent years. Surgical resection is the best treatment modality for ICC;however,the overall prognosis remains poor. Accurate evaluation of post operative prognosis allows personalized treatment and improved long-term outcomes of ICC. The American Joint Commission on Cancer TNM staging manual is the basis for the standardized diagnosis and treatment of ICC;however,the contents of stage T and stage N need to be improved. The nomogram model or scoring system established in the analysis of commonly used clinicopathological parameters can provide individualized prognostic evaluation and improve prediction accuracy;however,more studies are needed to validate the results before clinical use. Meanwhile,imaging features exhibit great potential to establish the post operative prognosis evaluation system for ICC. Molecular-based classification provides an accurate guarantee for prognostic assessment as well as selection of populations that are sensitive to targeted therapy or immunotherapy. Therefore,the establishment of a prognosis evaluation system,based on clinical and pathological characteristics and centered on the combination of multidisciplinary and multi-omics,will be conducive to improving the long-term outcomes of ICC after surgical resection in the context of big medical data.

Thalamocortical Circuit Controls Neuropathic Pain via Up-regulation of HCN2 in the Ventral Posterolateral Thalamus / 神经科学通报·英文版

The thalamocortical (TC) circuit is closely associated with pain processing. The hyperpolarization-activated cyclic nucleotide-gated (HCN) 2 channel is predominantly expressed in the ventral posterolateral thalamus (VPL) that has been shown to mediate neuropathic pain. However, the role of VPL HCN2 in modulating TC circuit activity is largely unknown. Here, by using optogenetics, neuronal tracing, electrophysiological recordings, and virus knockdown strategies, we showed that the activation of VPL TC neurons potentiates excitatory synaptic transmission to the hindlimb region of the primary somatosensory cortex (S1HL) as well as mechanical hypersensitivity following spared nerve injury (SNI)-induced neuropathic pain in mice. Either pharmacological blockade or virus knockdown of HCN2 (shRNA-Hcn2) in the VPL was sufficient to alleviate SNI-induced hyperalgesia. Moreover, shRNA-Hcn2 decreased the excitability of TC neurons and synaptic transmission of the VPL-S1HL circuit. Together, our studies provide a novel mechanism by which HCN2 enhances the excitability of the TC circuit to facilitate neuropathic pain.

Clinical and genetic analysis of a child with Alazami syndrome due to compound heterozygous variants of LARP7 gene / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical phenotype and genetic basis of a child with Alazami syndrome (AS).@*METHODS@#A child who presented at Tianjin Children's Hospital on June 13, 2021 was selected as the study subject. The child was subjected to whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing.@*RESULTS@#WES revealed that the child has harbored two frameshifting variants of the LARP7 gene, namely c.429_430delAG (p.Arg143Serfs*17) and c.1056_1057delCT (p.Leu353Glufs*7), which were verified by Sanger sequencing to be respectively inherited from his father and mother.@*CONCLUSION@#The compound heterozygous variants of the LARP7 gene probably underlay the pathogenesis in this child.

Analysis of KIF1A gene variant in a Chinese pedigree affected with Spastic paraplegia type 30 / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a Chinese pedigree affected with hereditary spastic paraplegia type 30 (HSP30).@*METHODS@#A proband presented at the Second Hospital of Shanxi Medical University in August 2021 was selected as the study subject. The proband was subjected to whole exome sequencing, and candidate variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The proband was found to have harbored a heterozygous c.110T>C variant in exon 3 of the KIF1A gene, which can cause substitution of isoleucine by threonine at position 37 (p.I37T) and alter the function of its protein product. The same variant was not found in his parents, elder brother and elder sister, suggesting that it has a de novo origin. Based on the guidelines of the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic (PM2_Supporting+PP3+PS2).@*CONCLUSION@#The c.110T>C variant of the KIF1A gene probably underlay the HSP30 in the proband. Above finding has enable genetic counseling for this family.

Design and development of a novel infrared mild moxibustion device / 中国针灸

To make up for the shortcomings of traditional mild moxibustion, according to the principle and technical operation characteristics of traditional mild moxibustion, combined with temperature control technology, a novel infrared mild moxibustion device is developed, which is capable of real-time accurate temperature control. This novel infrares mild moxibustion device is composed of a host computer and an infrared radiation head. The host computer includes four modules: power supply, human-computer interaction interface, micro control unit (MCU) and drive circuit. The infrared radiation head mainly includes an infrared heater and a temperature sensor. This novel infrared mild moxibustion device is easy to operate. The electrothermal heating tablet can generate infrared radiation of 3 000-13 000 nm. After the temperature of the infrared heater is stabilized, the range of temperature change is ±0.50 ℃, realizing the goal of precise temperature control. In addition, it can operate moxibustion treatment at multiple acupoints at the same time, which is conducive to the dose-effect evaluation of mild moxibustion.

Post-stroke dysphagia treated with four-step acupuncture therapy for opening orifices and benefiting throat combined with neuromuscular electrical stimulation: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical efficacy on post-stroke dysphagia treated with four-step acupuncture therapy for opening orifices and benefiting throat combined with neuromuscular electrical stimulation.@*METHODS@#Sixty patients with post-stroke dysphagia were randomly divided into an observation group and a control group, with 30 cases in each group. The neuromuscular electrical stimulation was adopted in the control group. Besides the treatment as the control group, in the observation group, the four-step acupuncture therapy for opening orifices and benefiting throat was supplemented. Step 1: the three areas of scalp acupuncture on the affected side were stimulated. Step 2: pricking method was operated on the posterior pharyngeal wall. Step 3: bleeding technique was operated at Jinjin (EX-HN 12) and Yuye (EX-HN 13). Step 4: deep insertion of needle was operated at three-pharynx points. The needles were retained for 30 min at the three areas of scalp acupuncture and the three-pharynx points. The intervention of each group was delivered once daily, 6 times a week, at the interval of 1 day. One course of treatment was 1 week and 4 successive courses were required. The rating of Kubota water swallow test, the score of standardized swallowing assessment (SSA) and the rating of Rosenbek penetration- aspiration scale (PAS) were observed before and after treatment in patients of the two groups. The incidence of clinical complications and clinical efficacy were compared between the two groups.@*RESULTS@#Compared with those before treatment, the rating of Kubota water swallow test, the scores of SSA and the rating of PAS of patients in the two groups were decreased after treatment (P<0.01), and the values of the observation group were lower than those of the control group after treatment (P<0.05). The incidence of clinical complications in the observation group was 13.3% (4/30), lower than 36.7% (11/30) in the control group (P<0.05). The total effective rate in the observation group was 93.3% (28/30), which was better than 70.0% (21/30) in the control group (P<0.05).@*CONCLUSION@#The four-step acupuncture therapy for opening orifices and benefiting throat combined with neuromuscular electrical stimulation can improve the swallowing function of patients with post-stroke dysphagia and reduce the incidence of clinical complications.

Relationship Between p53， EGFR and Radiotherapy Resistance of Head and Neck Squamous Cell Carcinoma / 中山大学学报(医学科学版)

Head and neck cancers are the seventh most common type of cancer in the world， among which more than 90% are squamous cell carcinomas（HNSCC）. Radiotherapy is one of the important treatments for HNSCC， and the sensitivity of tumor cells to the therapy is a key factor influencing the efficacy of treatment. p53 is one of the most common mutated genes in HNSCC， and epidermal growth factor receptor（EGFR） is overexpressed in many HNSCC. Both of these genes could enhance cellular DNA repair， which may be related to the radiotherapy resistance of HNSCC. This review focuses on the mechanisms by which tumor cells escape radiation-mediated apoptosis through p53 and EGFR-mediated DNA repair.

Preliminary experience of suprapubic three-arm robot-assisted laparoscopic radical prostatectomy / 中华泌尿外科杂志

To evaluate the feasibility and safety of suprapubic three-arm robot-assisted laparoscopic radical prostatectomy (STA-RLRP). Fifteen patients with prostatic cancer underwent STA-RLRP. All the 15 procedures were completed successfully, without the need for ancillary trocars or additional instruments. No patient required conversion to standard laparoscopy or open surgery. STA-RLRP is feasible and safe with good short-term tumor control, satisfactory recovery of urinary control function and good cosmetic outcome, which is worthy of clinical application.

Study on the construction of modular and multidisciplinary nutrition innovation platform in Shanghai / 上海预防医学

ObjectiveTo determine the situation and challenges of innovation platforms in China， and to explore the construction strategy of Shanghai Nutrition Innovation Platform， which is suitable for Shanghai and may achieve the research and transformation of nutrition innovation and population health， so as to coordinate， unite and gather the superior resources of all parties and promote nutrition innovation. MethodsConstruction scheme and operational mechanism of Shanghai Nutrition Innovation Platform were explored by literature review， expert consultation and questionnaire. ResultsThere were various forms of innovation platforms in China. However， challenges were identified， such as decentralizing force， resource rearrangement and insufficient sharing effect. Shanghai Nutrition Innovation Platform adopted a modular organizational structure， which was divided into central group， node group， and subject group. Shanghai Center for Disease Control and Prevention， as the central organization， is responsible for the platform operation management. The expert database as an academic committee selected key organizations from nutrition-related universities， research institutes， academic associations， centers for disease control and prevention， hospitals and the industry. Based on the opening of its own innovation resources， the platform made effective use of external innovation resources and formed a closely integrated nutrition innovation network of multiple disciplines. ConclusionThis study promotes the construction of innovation platform model of cooperation， co-construction and resource sharing， and provides reference for the construction of innovation platform in China.

Surgical management of total cavopulmonary connection procedure in functional single ventricle with separate hepatic venous drainage / 中国胸心血管外科临床杂志

@#Objective    To investigate the management of hepatic vein (HV) in patients with functional single ventricle (FSV) and separate hepatic venous drainage (SHVD) undergoing total cavopulmonary connection (TCPC) and evaluate this kind of surgery. Methods    The clinical data of 32 consecutive patients with SHVD who underwent modified TCPC operation from August 2005 to January 2017 in our center were retrospectively analyzed. There were 25 males and 7 females with an average age of 2-19 (8.0±5.0) years and body weight of 11-66 (25.4±15.8) kg. Results    There were 20 patients with heterotaxy syndrome and 12 patients with other types of FSV. SHVD was diagnosed preoperatively in 27 patients, among whom 20 patients were connected by intra-extracardiac Gore-Tex conduit, and the other 7 patients were connected by extracardiac Gore-Tex conduit. Because of the missed diagnosis of SHVD, the other 5 patients showed severe decrease of blood oxygen saturation in the early postoperative period and underwent re-operation soon. The postoperative blood oxygen saturation was 92.0% (90.0%, 96.0%), central venous pressure was 10-23 (15.5±3.5) mm Hg, mechanical ventilation assisted time was 16.0 (7.5, 24.0) h, and ICU stay time was 3.0 (2.0, 5.5) d. There were 3 early and 1 late deaths. Conclusion    Intra-extracardiac conduit is an effective and feasible modified TCPC operation for patients with FSV and SHVD, while the surgical details need to be formulated in combination with individual anatomical structure. Preoperative missed diagnosis of SHVD must be avoided. Otherwise, after TCPC, a large amount of stealing blood from HV with low circulation pressure into atrium would lead to unacceptable hypoxemia.

Comprehensive therapy for advanced unresectable hepatocellular carcinoma / 中华普通外科杂志

Objective:To investigate the efficacy and safety of comprehensive therapy in the treatment of advanced unresectable hepatocellular carcinoma.Methods:Clinical data of 34 patients with primary liver cancer admitted to Peking Union Medical College Hospital from Nov 2018 to Dec 2020 initially evaluated as unresectable were treated firstly by combined therapy and then underwent reevaluation for further management.Results:A total of 34 patients completed the integrative treatment, and no serious adverse events occurred. Among them, 6 patients were evaluated as partial remission, and underwent successful tumor resection, tumors in 7 patients were stable, and 21 patients suffered from disease progression.Conclusion:After comprehensive therapy, unresectable tumors in some patients could reduce and be rendered resection.

A case report of primary renal immature teratoma / 中华泌尿外科杂志

Teratoma is a rare tumor, mainly occurring in the ovary, sacrococcygeal region, testis, central nervous system and mediastinum, rarely occurring in the kidney, and adult immature teratoma originating in the kidney is extremely rare. A case of adult left renal immature teratoma was reported in this paper. After radical nephrectomy, pathological examination found that the tumor tissue contains malignant epithelial tissue and a small number of brain tissue. BEP regimen chemotherapy was performed after operation.The patient was followed up for 26 months, and died of organ failure caused by systemic metastasis.

Comparison of efficacy and safety of preoperative and postoperative concurrent chemoradiotherapies for stage Ⅲ-Ⅳ A gastric cancer / 中华放射医学与防护杂志

Objective:To compare the efficacy and safety of preoperative and postoperative concurrent chemoradiotherapies in the treatment of stage Ⅲ-Ⅳ A gastric cancer patients who underwent D2 lymphadenectomy with R0 resection. Methods:A retrospective analysis was conducted on the clinical data of patients with stage Ⅲ-Ⅳ A gastric cancer who underwent D2 lymphadenectomy with R0 resection in the Affiliated Cancer Hospital of Zhengzhou University from 2012 to 2019. Among these patients, 25 received preoperative chemoradiotherapy (group A) and 22 received postoperative chemoradiotherapy (group B). The disease-free survival (DFS), overall survival (OS), local recurrence rate, distant metastasis rate, and adverse reactions were compared between both groups. The total dose, single dose, fractions, and duration of radiotherapy for all the patients were 45-50.4 Gy, 1.8-2.0 Gy, 25-28 fractions, and 5-6 weeks, respectively. The target areas were delineated in accordance with the ASTRO and EORTC-ROG guidelines. Results:There was no statistical difference in clinical baseline characteristics between the two groups. The median follow-up was 48 months (3-72 months). The 1-year OS of group A was significantly higher than that of group B (92% vs. 54.5%, χ2= 5.68, P = 0.017). The 3-year OS and DFS of the two groups were 56% vs. 40.9% ( P> 0.05) and 51.4% vs. 31.8% ( P> 0.05), respectively. There was no significant difference in the local recurrence rate between both groups ( P> 0.05), but the distant metastasis rate of group A was significantly lower than that of group B ( χ2= 6.01, P = 0.014). There was no significant difference in digestive side effects and myelosuppression between both groups ( P> 0.05). Conclusions:For patients with stageⅢ-Ⅳ A gastric cancer after D2 lymphadenectomy with R0 resection, the preoperative and postoperative chemoradiotherapies yield similar efficacy and safety. However, compared to postoperative chemoradiotherapy, preoperative chemoradiotherapy improves the 1-year OS and reduces the distant metastasis rate.

Relationship Between Podocyte Autophagy and Diabetic Nephropathy and Regulation of Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Diabetic nephropathy （DN） is one of the serious microvascular complications of diabetes mellitus （DM），and is the main cause of end-stage renal disease（ESRD） worldwide. Although lowering blood glucose and，lowering blood pressure and blocking the renin-angiotensin-aldosterone system（RAAS） can reduce blood glucose，blood pressure and urinary protein to a certain extent，it is still difficult to prevent the progression of DN sometimes. The curative effect of traditional Chinese medicine on DN has been confirmed，but its mechanism is has not been fully clarified. Autophagy is a highly conserved lysosomal degradation pathway in mammals that removes protein aggregates and damaged organelles to maintain cell homeostasis. Podocyte，also known as glomerular epithelial cells，is an important component in maintaining the homeostasis of glomerular filtration barrier，and podocyte injury is considered to be a central link in the occurrence and development of DN. As a highly differentiated cell，podocyte maintains a high level of autophagy to maintain its homeostasis under physiological conditions. In DN state，mammalian target of rapamycin （mTOR），AMP-activated protein kinase （AMPK），silent information regulator 1（SIRT1） and other nutritional signaling pathways as well as intracellular stress response signaling pathways such as oxidative stress，endoplasmic reticulum stress ，and hypoxia stress，etc.，affect podocyte autophagy of podocytes， and ultimately leading to podocyte injury and the progression of DN. In recent years，regulation of podocyte autophagy has become one of the hot spots in DN research，and has also received extensive attention in the field of Chinese medicine. A review and summary of the domestic and international literature in this field reveals that Chinese medicine can affect podocyte autophagy in multiple pathways and targets. Nevertheless， those studiesbut mainly focuses on two nutrient-sensing signaling pathways，mTOR and AMPK，and there lacks more comprehensive and in-depth mechanism studies. In addition，the current research mainly concentrates focuses on the field of Chinese medicine monomers and Chinese medicine compounds，and rarely studies multi-component Chinese medicinelacking research on Chinese medicine component drugs and single drugs，and the research still lacks there is a lack of hierarchy. The regulatory mechanism of Chinese medicine on podocyte autophagy of podocytes in DN state in Chinese medicine still needs to be further studied in depth and systematically.

Study on the quantitative evaluation parameter system for basic acupuncture manipulations based on 3D motion tracking technology / 中国针灸

OBJECTIVE@#To establish a quantitative evaluation parameter system for basic acupuncture manipulations based on 3D motion tracking technology, and to further analyze the characteristics of acupuncture manipulation.@*METHODS@#The motion tracking system Simi Motion Ver.8.5 was used to collect parameters of acupuncture manipulations, so as to establish a quantitative evaluation system mainly in spatial control parameters, time control parameters and stability parameters. Based on the evaluation parameter system, data of acupuncture manipulations (even reinforcing-reducing manipulation using lifting-thrusting technique and twirling technique) were collected from 19 teachers majored in acupuncture-moxibustion, of which the characteristics were analyzed and were compared with the results tested by traditional ATP-Ⅱ acupuncture manipulation parameter determination apparatus (ATP-Ⅱ).@*RESULTS@#The evaluation parameter system could quantitatively analyze the basic acupuncture manipulations in 3 aspects, i.e. space, time and stability. Acupuncture manipulations were performed by shifting the needle body in a certain range along X, Y and Z axes. The amplitude and speed of thumb movement were greater than those of index finger. The time-history of lifting was similar to thrusting, while the time-history of twirling to left was similar to twirling to right in even reinforcing-reducing manipulation. The coordinate-time curve of finger movement of the evaluation system had consistent wave pattern compared with the voltage-time curve generated by ATP-Ⅱ.@*CONCLUSION@#The quantitative evaluation parameter system based on 3D motion tracking technology can objectively evaluate basic acupuncture manipulations, and show the characteristics of different manipulations and the movement details of finger joints.

Real-world research perspective: Evaluation of early follow-up outcomes in patients with partial and transitional atrioventricular septal defects / 中国胸心血管外科临床杂志

@#Objective    To study the clinical characteristics of patients with partial and transitional atrioventricular septal defects (P/TAVSDs) in our hospital, and to evaluate the early follow-up outcomes from a real-world research perspective. Methods    The clinical data of all patients diagnosed with P/TAVSDs from January 1, 2018 to July 12, 2020, in our hospital were collected, and all patients' examination results were used as the real-world follow-up data, univariable Cox risk proportional model was used to analyze the outcomes. A total of 93 patients were finally included in the analysis, 72 with partial and 21 with transitional AVSD. There were 38 males and 55 females at age of 182.0 months (20.0 d to 779.5 months). Results    Univariable Cox proportional risk model suggested that at least one cardiac malformation (HR=15.00, 95%CI 3.00 to 75.00, P=0.001), preoperative moderate or greater mitral regurgitation (HR=6.60, 95%CI 1.70 to 26.00, P=0.007), and preoperative moderate or greater tricuspid regurgitation (HR=13.00, 95%CI 3.10 to 51.00, P<0.000 1) were  risk factors for moderate or greater postoperative atrioventricular valve regurgitation. Conclusion    Children with coarctation of the aorta or partial pulmonary vein connection, moderate or greater preoperative mitral regurgitation, and moderate or greater preoperative tricuspid regurgitation need to be alerted to the risk of moderate or greater postoperative atrioventricular valve regurgitation. Real-world data, with relaxed statistical P values and combined expertise, can suggest clinical conclusions that are close to those of high-quality retrospective studies.

Analysis of HLA allele-specific antibodies and Eplets in patients with platelet transfusion refractoriness / 中国输血杂志

【Objective】 To analyze the specificity and Eplets of HLA allele-specific antibody in patients with platelet transfusion refractoriness (PTR). 【Methods】 HLA-A and B genotypes were detected by PCR-SBT, and HLA-Ⅰ antibodies in patients′ serum were detected by Luminex single antigen beads coating method. IPD-IMGT/HLA Database was used to find the differential amino acids of allele-specific antibodies, and HLA Eplet database was used to analyze the registry Eplets. 【Results】 HLA allele-specific antibodies were found in 12 out of 82 patients with PTR.After sequence alignment, a total of 18 differential amino acids were found, such as 19E>19K, 166D>116E, 167G>167W and so on. Among these differential amino acids, 16 registry Eplets were retrieved such as 19E>19K, 95I>95L, 113YD>113HD and so on.The amino acid substitution of 166DG>166EW, 70Q>70H, 67S>67Y, 94I>94T, 82LR>82RG, and 211G>211A may form new Eplets that have not been registered.The antigens of A11, A24, B15, B27 and B38 can be further subdivided into HLA narrow specific antigens. 【Conclusion】 It was found that there were HLA allele-specific antibodies in patients with PTR, suggesting that high-resolution typing of HLA-A, B should be carried out for these patients and platelet donors in HLA compatible transfusion of PTR.

Analysis of HLA-Ⅰ antibody specificity and estimation of antigen immunogenicity: 96 patients recieved genotype-matched platelet transfusions / 中国输血杂志

【Objective】 To analyze the specificity of HLA class-Ⅰ antibody in the patients received HLA-matched platelet transfusions and estimate the relative immunogenicity of HLA-Ⅰ antigens. 【Methods】 The samples from 96 patients who suffered from platelet transfusion refractorines(PTR) and applied for transfusion with genotype-matched platelet were collected. The specificity of HLA I antibody was detected by Luminex technique, and the antibody expression level was analyzed according to MFI. The mismatch rate of HLA antigen and relative immunogenicity of the population were estimated according to the allele frequency distribution of HLA-A and B loci as well as the yielding frequency of antibody. 【Results】 HLA-Ⅰ antibodies were detected in all 96 patients, with varied species of antibodies. The average positive yielding rates of antibodies corresponding to HLA-A, -B and -C magnetic bead coated antigens (97 in total) were 0.38, 0.47 and 0.28, respectively. Among the HLA-A and -B loci in the Zhejiang population, HLA-A2, A11, A24 and HLA-B60, B46, B58 were the antigens with higher frequency, and their relative immunogenicity was 0.403, 0.283, 0.342, and 0.100, 0.067, 0.178, respectively. 【Conclusion】 The specificity of HLA-Ⅰ antibodies in PTR patients is different, which confirms that the relative immunogenicity differs by HLA-A and -B antigens.

The substitution of SERCA2 redox cysteine 674 promotes pulmonary vascular remodeling by activating IRE1α/XBP1s pathway

Pulmonary hypertension (PH) is a life-threatening disease characterized by pulmonary vascular remodeling, in which hyperproliferation of pulmonary artery smooth muscle cells (PASMCs) plays an important role. The cysteine 674 (C674) in the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2 (SERCA2) is the critical redox regulatory cysteine to regulate SERCA2 activity. Heterozygous SERCA2 C674S knock-in mice (SKI), where one copy of C674 was substituted by serine to represent partial C674 oxidative inactivation, developed significant pulmonary vascular remodeling resembling human PH, and their right ventricular systolic pressure modestly increased with age. In PASMCs, substitution of C674 activated inositol requiring enzyme 1 alpha (IRE1α) and spliced X-box binding protein 1 (XBP1s) pathway, accelerated cell cycle and cell proliferation, which reversed by IRE1α/XBP1s pathway inhibitor 4μ8C. In addition, suppressing the IRE1α/XBP1s pathway prevented pulmonary vascular remodeling caused by substitution of C674. Similar to SERCA2a, SERCA2b is also important to restrict the proliferation of PASMCs. Our study articulates the causal effect of C674 oxidative inactivation on the development of pulmonary vascular remodeling and PH, emphasizing the importance of C674 in restricting PASMC proliferation to maintain pulmonary vascular homeostasis. Moreover, the IRE1α/XBP1s pathway and SERCA2 might be potential targets for PH therapy.