Volume 104 · Issue 22 · 2024

With rapid socio-economic development and the acceleration of population aging, the average life span of human beings has increased significantly. Individuals suffering from the co-existence of multiple diseases (multimorbidity) have become a new normal in public health and posed severe challenge to human health. Multimorbidity significantly reduces the quality of life, increases disability and mortality risks, complicates disease treatment and care and increases burden of the healthcare system with higher costs. This commentary discusses the definition of multimorbidity and common public misconceptions, then assesses its profound impact on overall public health, socio-economic development and healthcare system. We also proposes the potential strategies to meet the challenges posed by multimorbidity. The main aim is to raise awareness of multimorbidity, advocate proactive responses to improve public health and build a healthy society through the development of prevention and treatment systems and promote precision prevention and treatment for multimorbidity.

Obstructive sleep apnea (OSA) is a sleep breathing disorder characterized by snoring during sleep and cessation of breathing accompanied with nocturnal hypoxemia and daytime sleepiness. It has a high morbidity rate among bariatric surgery candidates and may lead to various perioperative risks. The purpose of this guideline is to standardize the diagnosis and treatment process of obstructive sleep apnea during the perioperative period of bariatric surgery and to improve patient outcomes and perioperative safety.

The bronchial provocation test (BPT) is an important clinical examination to detect airway hyperresponsiveness, primarily in diagnosing asthma with FEV₁≥70% of predicted value, including typical asthma and atypical asthma such as cough variant asthma and chest tightness variant asthma. BPT is a valuable tool in differentiating asthma from other chronic airway diseases and assessing the efficacy of asthma treatment. Despite its clinical significance, BPT remains largely underused in clinical practice, primarily due to limited knowledge of its importance and inadequate availability of medical professionals, equipment and medications in primary care settings. In response to this gap, the China Asthma Group of Chinese Thoracic Society has drafted this expert consensus to enhance knowledge and application of BPT among clinical practitioners. This expert consensus specifically focuses on the classic direct provocation agent methacholine, covering general principles and classification of BPT; indications, contraindications, and clinical applications; result interpretation; analyzing potential reasons and coping strategies for false positive and false negative test results; and finally, providing safety precautions and emergency measures. The aim of this expert consensus is to promote the standardized application of BPT.

To develop and evaluate the simplified Chinese versions of motion sickness susceptibility questionnaire (MSSQ)-long (MSSQ-L) and MSSQ-short (MSSQ-S).

A cross-sectional study was conducted in May 2023 among 3 426 university students at North China University of Science and Technology. The Chinese versions of MSSQ-L and MSSQ-S were distributed, and item selection for Simplified Chinese versions of MSSQ-L and MSSQ-S was performed based on item response rates, item-total correlations, Cronbach′s alpha coefficients, and standard deviations. Forty-five male and forty-five female participants were recruited from the initial survey population to complete Coriolis acceleration endurance testing and fill out the simplified Chinese versions of MSSQ-L and MSSQ-S, and Graybiel symptom severity score questionnaire. Internal consistency, external consistency, criterion validity, discriminant validity, and predictive accuracy for motion sickness severity were assessed.

A total of 3 111 valid responses were received for the Chinese versions of MSSQ, yielding an effective response rate of 90.8% (3 111/3 426). Among the 3 111 students surveyed, there were 965 males and 2 146 females, with a mean age of (19.5±1.4) years. The highest usage rates for item were observed for cars (98.9%, 3 077/3 111) and buses (98.8%, 3 073/3 111). The simplified Chinese versions of MSSQ-L and MSSQ-S consisted of four and eight items, respectively. The Cronbach′s alpha coefficients were 0.900 and 0.953 for the simplified Chinese versions of MSSQ-S and MSSQ-L, respectively, with test-retest reliabilities of 0.895 and 0.908. Criterion validity coefficients were 0.814 and 0.765 for the simplified Chinese versions of MSSQ-S and MSSQ-L, respectively. In terms of discriminant validity, significant differences were observed between mild and moderate susceptibility groups [0(0, 3) vs 6(2, 10), P=0.006] and between moderate and severe susceptibility groups [6(2, 10) vs 9(6, 13), P=0.030] for the simplified Chinese version of MSSQ-S. Significant differences were also observed between mild and moderate susceptibility groups [5(0, 3) vs 7(3, 10), P=0.001], but not between moderate and severe susceptibility groups [7(3, 10) vs 7(3, 10), P=0.081] for simplified Chinese version of MSSQ-L. The overall predictive accuracy for motion sickness severity improved from 55.6% (50/90) to 62.2% (56/90) for the simplified Chinese version of MSSQ-S and from 54.4% (49/90) to 58.9% (53/90) for the simplified Chinese version of MSSQ-L, but with no statistically significant differences (both P>0.05).

The simplified Chinese versions of MSSQ-L and MSSQ-S demonstrates good reliability and validity. The simplified Chinese version of MSSQ-S exhibits satisfactory discriminant validity, and can serve as a simple and efficient tool for assessing motion sickness susceptibility.

To investigate the prognostic value of coronary artery calcium score (CACS) and computed tomography-derived fractional flow reserve (CT-FFR) for major adverse cardiovascular events (MACE) in patients with stable coronary artery disease (CAD).

The data for this prospective study were derived from a prospective clinical trial at a single center. This trial enrolled stable CAD patients who underwent coronary CT angiography (CCTA) in General Hospital of Eastern Theater Command from April 2018 to March 2019 and had coronary artery stenosis of 25%-80%. Patients were assigned to either the control group or trial group according to CCTA time. Patients in control group were provided with only a standard CCTA report, while patients in trial group were provided with both a standard CCTA report and the corresponding CT-FFR results. The study included patients who underwent ECG-gated calcium scoring CT scans in this trial. CT-FFR value at 2 cm distal to the narrowest stenosis of each vessel was calculated. The minimum CT-FFR value was recorded as the patient level and CT-FFR≤0.80 was defined as a positive result. All patients were followed up for MACE, including all-cause death, nonfatal myocardial infarction, and acute coronary syndrome leading to unplanned revascularization. Multivariable Cox proportional hazards regression analysis was used to identify variables associated with MACE occurrence, and the Concordance index (C-index) was used to represent the performance of the models for predicting MACE occurrence based on clinical, anatomical, and CT-FFR parameters.

A total of 783 patients were finally statistically analyzed, with a age of (62.0±10.8) years, of whom 64.6% (506 cases) were male. There were 383 patients in the trial group and 400 patients in the control group, with a median follow-up time of 35.3 months. A total of 81 MACE cases occurred during the follow-up. The incidence of MACE in trial group (8.1%, 31/383) was significantly lower than that in control group (12.5%, 50/400)(χ²=4.095, P=0.043). CACS≥300, stenosis≥70% and CT-FFR≤0.80 [HR (95%CI) were 2.14 (1.01-4.52), 5.38 (3.44-8.42) and 16.91 (9.21-31.04), all P<0.05] showed predictive value for MACE. The predictive ability of the CT-FFR model is significantly better than that of the CACS model and the stenosis degree model [C-index (95%CI) were 0.850 (0.823-0.874), 0.653 (0.618-0.686) and 0.718 (0.685-0.749), all P≤0.001]. The comprehensive model with added CACS and stenosis degree did not significantly improve the predictive value of the CT-FFR model [C-index (95%CI) were 0.867 (0.841-0.890), 0.850 (0.823-0.874), P=0.584].

CT-FFR has a high predictive value for MACE in patients with stable CAD, the combination of CT-FFR and CACS did not increase the predictive power of CT-FFR.

To investigate the effect of Dapagliflozin, sodium-glucose cotransporter 2 inhibitor (SGLT2i), on contrast-induced acute kidney injury (CIAKI) in patients with type 2 diabetes mellitus (T2DM) after percutaneous coronary intervention(PCI).

A cohort study. The clinical data of 366 patients with coronary heart disease combined with T2DM who underwent PCI in the Department of Cardiology, Tianjin University Chest Hospital, from June 2021 to June 2022 were retrospectively analyzed, including 218 males and 148 females, aged (64.6±11.0) years old. According to whether the patients had used Dapagliflozin or not, the selected patients were divided into SGLT2i group(n=124) and control group(n=242). The changes in cardiac indicators, renal function, and inflammatory response indicators before and 72 hours after PCI treatment were analyzed and compared between the two groups. The incidence rate of CIAKI in the two groups was analyzed, and the influencing factors of CIAKI were analyzed by multivariate logistic regression. The major adverse cardiac events (MACE) were recorded during the follow-up period of the two groups, and Kaplan-Meier survival analysis and log-rank test were used to compare the differences in MACE occurrence between the two group.

The left ventricular ejection fraction (LVEF) of the SGLT2i group was lower than that of the control group, and the proportion of patients with LVEF<45% and CIAKI risk score were higher than those of the control group, with statistical significance (all P<0.05). 72 h after PCI treatment, β-2 Microglobulin(β-2MG), cystatin-C(Cys-C), and neutrophil gelatinase-associated lipocalin (NGAL) in both groups were all increased compared to those before PCI treatment, with statistical significance (all P<0.05).β-2MG, Cys-C, and NGAL in SGLT2i group were all lower than those in the control group, with statistical significance(all P<0.05).The levels of interleukin-6(IL-6), hypersensitive C-reactive protein (hs-CRP), and malondialdehyde in both groups of patients increased compared to preoperative levels, while the levels of superoxide dismutase (SOD) decreased compared to preoperative levels, with statistical significance (all P<0.05). The levels of IL-6, hs-CRP, and malondialdehyde in the SGLT2i group were lower than those in the control group, while SOD was higher than that in the control group, with statistical significance (all P<0.05). Among all patients included, 34 cases experienced CIAKI (9.8%), and the incidence of CIAKI in the SGLT2i group was lower than that in the control group [4.8% (6/124) vs 11.6% (28/242),P=0.037]. Multivariate logistic regression analysis showed that the use of dapagliflozin was a protective factor for CIAKI in T2DM patients receiving PCI treatment (OR=0.321, 95%CI: 0.127-0.816, P=0.017). After a follow-up of 14.0 (12.0, 16.2) months, the incidence of MACE in SGLT2i group was lower than that in the control group (7.3% vs 12.8%, P=0.048).

Dapagliflozin may reduce the risk of CIAKI and MACE in T2DM patients after PCI treatment. Its mechanism may be related to the anti-inflammatory and antioxidant effects of SGLT2i.

To prepare interleukin-1β-targeted nanoantibodies and observe their effects on apoptosis in hypoxic cardiomyocyte of mice.

Using DNA recombination technology, the pET-16b and pHEN1 expression vectors were used to construct the prokaryotic expression plasmids of interleukin-1β-targeted nanobodies (pET-16b-4G6M-VHH, pET-16b-5BVP-VHH, pET-16b-5MVZ-VHH, pHEN1-4G6M-VHH, pHEN1-5BVP-VHH and pHEN1-5MVZ-VHH, where VHH is a variable domain of heavy chain antibody, 4G6M-VHH, 5BVP-VHH, 5MVZ-VHH were three interleukin-1β-targeted nanoantibodies respectively). The constructed plasmids were transferred into Escherichia coli Rosetta2 (DE3) for induction of expression and nickel column purification, respectively. The sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting were employed to identify the expression product and purified product, and the enzyme-linked immune sorbent assay (ELISA) was performed to determine their affinity. The cardiomyocyte hypoxia model was used with the highest affinity IL-1β-targeted nanobody (pHEN1-5MVZ-VHH), and cell survival and apoptosis rates were detected (the experiment was divided into normal control group, hypoxia model group, blank plasmid group and 12.5, 25.0, 50.0 μg/ml pHEN1-5MVZ-VHH treatment groups).

SDS-PAGE and Western blotting results showed that the anti-interleukin-1β (IL-1β) nanobodies with a relative molecular mass of about 15 000 were successfully obtained. Likewise, ELISA results found that the nanobodies expressed in pHEN1 vector group had higher affinity for IL-1β antigen compared with pET-16b vector group (4G6M-VHH group: 3.20±0.03 vs 1.20±0.03, P<0.001; 5BVP-VHH group: 3.18±0.06 vs 1.21±0.02, P<0.001; 5MVZ-VHH group: 3.38±0.05 vs 1.62±0.04, P<0.001). Additionally, the results of cell survival assay and apoptosis assay detected that compared with the hypoxia model group, HL-1 cell activity was significantly increased in the 25.0 μg/ml and 50.0 μg/ml pHEN1-5MVZ-VHH treatment groups [(75.55±2.23)% vs (46.90±2.51)%, P<0.001; (74.36±1.96)% vs (46.90±2.51)%, P<0.001], and apoptosis rate was significantly reduced [(6.83±0.27)% vs (10.24±0.76)%, P<0.001; (6.68±0.38)% vs (10.24±0.76)%, P<0.001].

4G6M-VHH, 5BVP-VHH, and 5MVZ-VHH are expressed by both pET-16b and pHEN1 expression vectors and the nanobodies produced by the pHEN1 vector display enhanced antigen affinity. Furthermore, in hypoxic cardiomyocytes, pHEN1-5MVZ-VHH treatment reduces cell apoptosis.

This study reports a family of patients with 11β-hydroxylase deficiency (11β-OHD) caused by a novel mutation in the CYP11B1 gene, and analyzes its clinical and genetic characteristics. The clinical data of a patient with intractable hypertension at Air Force Medical Center on May 16, 2014 were retrospectively analyzed. The patient was clinically diagnosed with congenital adrenal cortical hyperplasia. The clinical data of the patient were further collected and the peripheral blood samples of the patient, his parents and his sister were collected for CYP11B1(NM_000497) gene sequencing, suggesting that the patient had compound heterozygous mutations in exon 1:c.199delG, p.Glu67Lysfs*9 and exon 5:c.905_907 delATGinsTT, p.Asp302Valfs*23, both of which were pathogenic variants. The patient′s father and sister carried heterozygous mutations in exon 1:c.199delG, p.Glu67Lysfs*9, and the mother carried heterozygous mutations in exon 5:c.905_907delATGinsTT, p.Asp302Valfs*23. This study is the first to report a new compound heterozygous mutation in exon 1:c.199delG and exon 5 c.905_907 delATGinsTT of CYP11B1 gene, enriching the database of 11β-OHD mutations and providing information to further understand the genetic mechanism of the disease.

A 32-year-old female with recurrent polychondritis was first diagnosed in ophthalmology. Physical examination showed thinning of sclera in both eyes, inflammatory cells in the anterior chamber and vitreous body, and cystoid macular edema of the fundus. The left auricle is red and swollen, the external auditory canal is narrow, and there is no tenderness. The ophthalmologic diagnosis was uveitis in both eyes, macular edema in both eyes, and thinning of the sclera in both eyes. The rheumatology and immunology department consulted and diagnosed recurrent polychondritis. After 8 months of systemic immunosuppression treatment, the left auricle redness and swelling improved significantly, the visual acuity of both eyes improved, the intraocular inflammation was controlled, and the macular edema resolved.

This paper reports the treatment of a patient with complex urinary tract infection caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) using bacteriophage. The patient had been paraplegic for more than 30 years due to trauma, and had a long-term indwelling urinary catheter complicated with neurogenic bladder. The urine culture was CRKP, and the ceftazidime avibactam treatment relapsed after discontinuation. The phage "cocktail" bladder instillation was used to achieve a fast and good therapeutic effect.

This case is a 54-year-old male patient with recurrence at the surgical site after rectal cancer surgery and invasion of bladder, prostate, bilateral seminal vesicles, S_3~5He was admitted to hospital with complications such as rectovesical fistula and deep perianal infection. After the multidisciplinary collaborative group discussed and evaluated, they underwent combined resection of recurrent pelvic organs after rectal cancer surgery (recurrent pelvic lesions with anus combined with part of small intestine, whole bladder, prostate, bilateral seminal vesicles, pelvic wall muscles, S_3~5Resection + basement membrane biological patch combined with pedicled omental flap to reconstruct the pelvic floor + ileal cystostomy + colostomy), the tumor was radically resected, and pelvic regional hyperthermia perfusion chemotherapy was performed 48 and 72 hours after operation, during which there was no obvious adverse reaction. The postoperative recovery was good, and no obvious recurrence or metastasis was observed after 3 months follow-up.

A series of research results have been achieved in 2023 for each type of breast cancer. In the field of hormone receptor positivity, early breast cancer cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor adjuvant intensive therapy has added new options, and advanced breast cancer new target drugs protein kinase B inhibitors and novel antibody drug conjugates (ADC) have achieved important research results. In the field of human epidermal growth factor receptor 2 (HER2) -positive breast cancer, trastuzumab combined with pyrrotinib provides a new option for neoadjuvant therapy and first-line treatment of recurrence and metastasis, and new anti-HER2 ADC drugs have achieved new breakthroughs. In the field of triple-negative breast cancer, immunotherapy has more adequate evidence in the first-line treatment of neoadjuvant and recurrence and metastasis. ADC drugs targeting trophoblast cell surface antigen 2 (Trop-2) bring new hope, and the combined application of ADC drugs and immunotherapy has the initial effect. The author summarizes the important research results of breast cancer in 2023 as follows, in order to better guide clinical practice.

Polycystic ovary syndrome is the most common endocrine and metabolic disease in women of childbearing age, and its pathogenesis and pathophysiological changes are not very clear. Folic acid, as a water-soluble vitamin, plays a key role in the synthesis, repair and metabolism of one-carbon units and homocysteine, and is closely related to endocrine disorders such as hyperhomocysteinemia, insulin resistance, oxidative stress and chronic inflammation in polycystic ovary syndrome. In this paper, the research on the correlation between folate metabolism and polycystic ovary syndrome reported in the literature in recent years was reviewed, and the research progress on the correlation between folate metabolism and polycystic ovary syndrome was expounded from the relationship between folate and homocysteine, insulin resistance, oxidative stress and chronic inflammation, so as to provide new ideas for clinical treatment and basic research of polycystic ovary syndrome.

The patient, a 28-year-old male, went to the Department of Respiratory and Critical Care Medicine of the First Affiliated Hospital of Zhengzhou University because of "interstitial changes in both lungs were found for 3 years, fever and dyspnea for 4 days". Physical examination 3 years ago revealed interstitial changes in both lungs, which were not treated. Fever appeared in 4 days, showing relaxed fever, accompanied by cough, expectoration, and progressive dyspnea. No previous history of chronic diseases such as hypertension or diabetes. Deny that the relative has a history of similar disease and familial genetic disease. After admission, chest CT examination showed diffuse lesions in both lungs, considering interstitial changes and infection in both lungs. After anti-infective treatment, body temperature returned to normal, cough and dyspnea gradually alleviated. One month later, reexamination of chest CT showed diffuse miliary nodules in both lungs, some of which were dense, with clear and sharp edges. Stripe and flake calcification shadows were seen in both lungs, mainly in both lower lungs, linear calcification shadows were seen in bilateral pleura, and narrow and long translucent bands were seen in the lateral chest wall and the outer edge of the lungs (Figures 1 and 2). Considering the possibility of pulmonary alveolar microlithiasis (PAM), whole exon sequencing of peripheral blood indicated heterozygous nonsense mutation and frameshift mutation of chromosome 4p15.2, mainly involving exons 8 and 13 of SLC34A2 gene, and confirmed the diagnosis of PAM. PAM is a rare autosomal recessive genetic disease, characterized by abnormal calcium deposition in some organs, especially in the lungs. Calcification can also be seen in some extrapulmonary organs such as kidney, gallbladder, ureter, seminal vesicles, pleura and heart in some patients with PAM. Lung transplantation is currently the only known effective treatment for PAM.