2021年 · 第134卷第09期

The survival of patients with breast cancer has been greatly improved by comprehensive treatment including surgery, radiotherapy, and systemic treatment, among which surgical treatment remains the mainstay. Breast surgeons must not only master surgical skills but also develop the ability to treat disease comprehensively. To improve the ability of breast surgeons in China to diagnose breast cancer early, perform reasonable surgical treatment, and provide comprehensive treatment orientation, the Chinese Society of Breast Surgery (CSBrS) has reported the key issues in the diagnosis and treatment of invasive breast cancer through opinion collection and expert discussion. The group evaluated the relevant evidence using the grading of recommendations assessment, development, and evaluation system and developed the clinical practice guideline for diagnosis and treatment in patients with invasive breast cancer: CSBrS practice guidelines 2021 with the aim of providing guidance for the clinical practice of breast surgeons in China.

Breast fibroadenoma is the most common benign tumor of the breast in women, and can occur at all ages. However, these tumors are more commonly seen in women aged 15 to 35 years.^[1]Most fibroadenomas often undergo self-limited growth and usually stabilize after several years. The clinical diagnosis is mainly based on clinical palpation and ultrasonographic examination, while the golden standard diagnosis is pathological examination. To standardize the clinical diagnosis and treatment of breast fibroadenoma, the Chinese Society of Breast Surgery (CSBrS) conducted a literature review of experts’ opinions, and determined the key clinical questions for the clinical practice guideline of breast fibroadenoma. The group evaluated the relevant evidences using the grading of recommendations assessment, development, and evaluation system, and developed the clinical practice guideline for breast fibroadenoma: CSBrS practice guideline 2021, with the aim of providing clinical practice guidance to breast surgeons in China.

Hypotension is a common complication caused by spinal anesthesia (SA), which may have adverse impacts on the condition of the parturient and fetus. Liquid infusion was found to be relatively effective for reducing the incidence of hypotension. However, the question of whether colloid preload can optimize hemodynamic variables in the cesarean section remains controversial. This study aims to determine the effects of colloid preload on the incidence of hypotension induced by SA in elective cesarean section.

Related keywords were searched on PubMed, EMBASE, and Cochrane Library from inception dates to May 2020. Studies included were evaluated for eligibility and quality. The primary outcome was the intra-operative incidence of hypotension and severe hypotension. The secondary outcomes included the lowest intra-operative systolic blood pressure, the maximal intra-operative heart rate, the intra-operative needs of ephedrine and phenylephrine, the incidence of maternal nausea and/or vomiting, and neonatal outcomes (umbilical artery pH and Apgar scores). Apart from the above, RevMan 5.3 was used for the data analysis.

Altogether nine randomized controlled trials were included in the meta-analysis. There were no significant differences in the incidence of intra-operative hypotension, severe hypotension, or neonatal outcomes between the colloid preload group and control group, except for the umbilical artery pH.

This meta-analysis suggests that colloid preload does not significantly reduce the incidence of hypotension associated with SA in elective cesarean section.

The superfamily of aldo-keto reductases (AKRs) is composed of over 190 members and can be classified into 16 different families (visit www.med.upenn.edu/akr).AKR1C3(C3 subtype of aldosterone reductase family 1) refers to the firstAKRin family 1, subfamily C, and is encoded by theAKR1C3gene.AKR1C3was first cloned and expressed from a human prostate cDNA library. This protein is a soluble monomeric NADP(H) (nicotinamideadenine dinucleotide phosphate or reduced form of nicotinamide adenine dinucleotide phosphate) dependent oxidoreductase. TheAKRproteins exhibit at least 40% sequence identity at the amino acid level and have an (α/β) 8-barrel structure within their structure. Especially,AKR1C3has 86% sequence identity withAKR1C1,AKR1C2, andAKR1C4[Supplementary Figure 1, http://links.lww.com/CM9/A460].AKR1C3is known to be involved in the metabolism and biosynthesis of estrogen, androgen, progesterone, and prostaglandin, etc.^[1]

Tumor microenvironment mainly includes fibroblasts, macrophages, endothelial cells, and immune cells. The heterogeneity of tumor immune microenvironment (TIME) affects the response of different patients to immunotherapy. Cancer immunotherapy using immune checkpoint inhibitiors (ICIs), which can be achieved by antibodies blocking the programmed cell death 1 (PD-1)/programmed death ligand-1 (PD-L1) or the cytotoxic T lymphocyte-associated protein 4 (CTLA-4) pathway alone or in combination, prompts a new paradigm shift in oncology. However, the response rates to the ICIs in cancer patients are relatively low and the results of the reported biomarkers for predicting the treatment efficacy are conflicting. Therefore, novel and reliable biomarkers are urgently needed to monitor tumor-specific immune responses, avoid immune-related adverse events, and improve clinical efficacy.

Ulcerative colitis (UC) and Crohn’s disease (CD) are two major types of inflammatory bowel disease (IBD). In recent decades, the use of biological agents, including antitumor necrosis factor (TNF), anti-integrins, anti-interleukin (IL)-12/IL-23, and Janus kinase (JAK) inhibitors, has promoted clinical remission and mucosal healing and reduced surgeries, hence significantly improving the quality of life of IBD patients. However, it was reported that approximately 20% to 30% UC patients did not respond to anti-TNF treatment in clinical trials (primary nonresponders), and the response in an additional 15% to 30% of patients was lost over time.^[1]Additionally, it was reported that primary nonresponse to anti-integrin therapy occurred in 43% of UC patients in clinical trials.^[2]In a real-world multicenter study, 32.1% of UC patients treated with vedolizumab did not reach clinical response at week 14.^[3]For long-term efficacy, only 33% of UC patients maintained clinical response at 400 treatment weeks.^[4]

Heart disease is a major cause of human death worldwide. The switching/sucrose non-fermenting (SWI/SNF) complex plays a crucial role during heart development and heart disease. Brahma-related gene 1 (Brg1), a critical adenosine triphosphatase (ATP) catalytic subunit of the SWI/SNF complex, participates in several physiological and pathological processes by utilizing the energy generated by ATP hydrolysis to regulate gene transcription, DNA repair, and DNA replication. AndBrg1is involved in systemic diseases, including nervous, cardiovascular, and immune system diseases. Recently, the role ofBrg1in heart disease has been studied in-depth. Increasing evidence has implicatedBrg1in oxidative stress mechanism, apoptosis, proliferation, and cardiac remodeling during heart disease.^[1,2]These findings have suggested thatBrg1is involved in disease development through diverse physiological functions [Figure 1].

Thyroid dysfunction is associated with cardiovascular diseases. However, the role of thyroid function in lipid metabolism remains partly unknown. The present study aimed to investigate the causal association between thyroid function and serum lipid metabolism via a genetic analysis termed Mendelian randomization (MR).

The MR approach uses a genetic variant as the instrumental variable in epidemiological studies to mimic a randomized controlled trial. A two-sample MR was performed to assess the causal association, using summary statistics from the Atrial Fibrillation Genetics Consortium (n = 537,409) and the Global Lipids Genetics Consortium (n = 188,577). The clinical measures of thyroid function include thyrotropin (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) levels, FT3:FT4 ratio and concentration of thyroid peroxidase antibodies (TPOAb). The serum lipid metabolism traits include total cholesterol (TC) and triglycerides, high-density lipoprotein, and low-density lipoprotein (LDL) levels. The MR estimate and MR inverse variance-weighted method were used to assess the association between thyroid function and serum lipid metabolism.

The results demonstrated that increased TSH levels were significantly associated with higher TC (β = 0.052, P = 0.002) and LDL (β = 0.041, P = 0.018) levels. In addition, the FT3:FT4 ratio was significantly associated with TC (β = 0.240, P = 0.033) and LDL (β = 0.025, P = 0.027) levels. However, no significant differences were observed between genetically predicted FT4 and TPOAb and serum lipids.

Taken together, the results of the present study suggest an association between thyroid function and serum lipid metabolism, highlighting the importance of the pituitary-thyroid-cardiac axis in dyslipidemia susceptibility.

Fetal weight is an important parameter to ensure maternal and child safety. The purpose of this study was to use three-dimensional (3D) limb volume ultrasound combined with fetal abdominal circumference (AC) measurement to establish a model to predict fetal weight and evaluate its efficiency.

A total of 211 participants with single pregnancy (28-42 weeks) were selected between September 2017 and December 2018 in the Beijing Obstetrics and Gynecology Hospital of Capital Medical University. The upper arm (AVol)/thigh volume (TVol) of fetuses was measured by the 3D limb volume technique. Fetal AC was measured by two-dimensional ultrasound. Nine cases were excluded due to incomplete information or the interval between examination and delivery >7 days. The enrolled 202 participants were divided into a model group (134 cases, 70%) and a verification group (68 cases, 30%) by mechanical sampling method. The linear relationship between limb volume and fetal weight was evaluated using Pearson Chi-squared test. The prediction model formula was established by multivariate regression with data from the model group. Accuracy of the model formula was evaluated with verification group data and compared with traditional formulas (Hadlock, Lee2009, and INTERGROWTH-21^st) by paired t-test and residual analysis. Receiver operating characteristic curves were generated to predict macrosomia.

AC, AVol, and TVol were linearly related to fetal weight. Pearson correlation coefficient was 0.866, 0.862, and 0.910, respectively. The prediction model based on AVol/TVol and AC was established as follows: Y=-481.965+ 12.194TVol + 15.358AVol + 67.998AC, R²_adj = 0.868. The scatter plot showed that when birth weight fluctuated by 5% (i.e., 95% to 105%), the difference between the predicted fetal weight by the model and the actual weight was small. A paired t-test showed that there was no significant difference between the predicted fetal weight and the actual birth weight (t= -1.015, P = 0.314). Moreover, the residual analysis showed that the model formula’s prediction efficiency was better than the traditional formulas with a mean residual of 35,360.170. The combined model of AVol/TVol and AC was superior to the Lee2009 and INTERGROWTH-21^st formulas in the diagnosis of macrosomia. Its predictive sensitivity and specificity were 87.5% and 91.7%, respectively.

Fetal weight prediction model established by semi-automatic 3D limb volume combined with AC is of high accuracy, sensitivity, and specificity. The prediction model formula shows higher predictive efficiency, especially for the diagnosis of macrosomia.

ClinicalTrials.gov, NCT03002246; https://clinicaltrials.gov/ct2/show/NCT03002246?recrs=e&cond=fetal& draw=8&rank=67.

The association of lipids and cancer has varied greatly among different cancer types, lipid components and study populations. This study is aimed to investigate the association of serum lipids and the risk of malignant lesions in esophageal squamous epithelium.

In the "Endoscopic Screening for Esophageal Cancer in China" (ESECC) trial, serum samples were collected and tested for total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol at the time of subject enrollment. Cases were defined as malignant esophageal lesions identified by baseline endoscopic examination or by follow-up to May 31, 2018. Controls were randomly selected using incidence density sampling in the same cohort. Conditional logistic models were applied to identify the association of serum lipids and the risk of malignant esophageal lesions. Effect modification was evaluated by testing interaction terms of the factor under assessment and these serum lipid indicators.

No consistent association between serum lipid levels and esophageal malignant lesions were found in a pooled analysis of 211 cases and 2101 controls. For individuals with a family history of esophageal cancer (EC), high TC, and LDL-C were associated with a significantly increased risk of having malignant lesions (odds ratio [OR]_{Highvs.Low TC} = 2.22, 95% confidence interval [CI]: 1.14-4.35; OR_{Highvs.Low LDL-C} = 1.93, 95% CI: 1.01-3.65). However, a negative association was observed in participants without an EC family history (OR_{Highvs.Low TC} = 0.69, 95% CI: 0.48-0.98, P_interaction = 0.002; OR_{Highvs.Low LDL-C} = 0.50, 95% CI: 0.34-0.76, P_interaction < 0.001).

In this study, we found that the association of serum lipids and malignant esophageal lesions might be modified by EC family history. The stratified analysis would be crucial for population-based studies investigating the association of serum lipids and cancer. The mechanism by which a family history of EC modifies this association warrants further investigation.

Normal tension glaucoma (NTG) is a less pressure-dependent type of glaucoma with characteristic optic neuropathy. Recently, the biomechanical mechanism has been thought to account for glaucomatous optic neuropathy to some degree. We intended to compare dynamic corneal response parameters (DCRs) among patients with primary open-angle glaucoma with normal tension or hypertension and controls. The correlations between DCRs and known risk factors for glaucoma were also analyzed.

In this cross-sectional study, 49 NTG subjects, 45 hypertension glaucoma (HTG) subjects, and 50 control subjects were enrolled. We compared the differences in DCRs using corneal visualization Scheimpflug technology among the NTG, HTG, and control groups. We also analyzed the correlations between DCRs and known risk factors for glaucoma (eg, central corneal thickness [CCT], intraocular pressure [IOP], etc).

The maximum inverse concave radius (NTG: 0.18 [0.17, 0.20] mm^-1; control: 0.17 [0.16, 0.18] mm^-1; P= 0.033), deformation amplitude ratio of 2 mm (DAR 2 mm, NTG: 4.87 [4.33, 5.39]; control: 4.37 [4.07, 4.88]; P < 0.001), and DAR 1 mm (NTG: 1.62 [1.58, 1.65]; control: 1.58 [1.54, 1.61]; P < 0.001) were significantly higher in NTG than in the controls. The integrated radius (IR, NTG: 8.40 ± 1.07 mm^-1; HTG: 7.64 ± 1.31 mm^-1; P = 0.026) and DAR 2 mm (NTG: 4.87 [4.33, 5.39]; HTG: 4.44 [4.12, 5.02]; P < 0.007) were significantly higher, whereas the stiffness parameter at the first applanation (SP-A1, NTG: 91.23 [77.45, 107.45]; HTG: 102.36 [85.77, 125.12]; P = 0.007) was lower in NTG than in HTG. There were no significant differences in the DCRs between HTG and control groups (P > 0.05). In the univariate and multivariate analyses, some of the DCRs, such as IR, were negatively correlated with CCT and IOP, whereas SP-A1 was positively correlated with CCT and IOP.

The cornea was more deformable in NTG than in HTG or controls. There were no significant differences in corneal deformability between HTG and controls. The cornea was more deformable with the thinner cornea and lower IOP.

Although osteopontin (OPN) is expressed in the liver and pigment gallstones of patients with hepatolithiasis, its role in pigment gallstone formation remains unclear. This study aimed to explore the function of OPN in pigment gallstone formation.

Rats were fed a chow diet (CD) or lithogenic diet (LD) for 10 consecutive weeks; blocking tests were then performed using an OPN antibody (OPN-Ab). Incidence of gallstones and levels of several bile components, OPN, tumor necrosis factor alpha (TNF-α), and cholesterol 7 alpha-hydroxylase (CYP7A1) were analyzed. To determine TNF-α expression in hepatic macrophages and both CYP7A1 and bile acid (BA) expression in liver cells, recombinant rat OPN and recombinant rat TNF-α were used to treat rat hepatic macrophages and rat liver cells, respectively. Chi-square or Fisher exact tests were used to analyze qualitative data, Student t-test or one-way analysis of variance were used to analyze qualitative data.

Incidence of gallstones was higher in LD-fed rats than in CD-fed rats (80% vs. 10%, P < 0.05). BA content significantly decreased in bile (t= -36.08, P < 0.01) and liver tissue (t= -16.16, P < 0.01) of LD-fed rats. Both hepatic OPN protein expression (t= 9.78, P < 0.01) and TNF-α level (t= 8.83, P < 0.01) distinctly increased in the LD group; what’s more, CYP7A1 mRNA and protein levels (t= -12.35, P < 0.01) were markedly down-regulated in the LD group. Following OPN-Ab pretreatment, gallstone formation decreased (85% vs. 25%, χ² = 14.55, P < 0.01), liver TNF-α expression (F = 20.36, P < 0.01) was down-regulated in the LD group, and CYP7A1 expression (F = 17.51, P < 0.01) was up-regulated. Through CD44 and integrin receptors, OPN promoted TNF-α production in macrophage (F= 1041, P < 0.01), which suppressed CYP7A1 expression (F = 48.08, P < 0.01) and reduced liver BA synthesis (F= 119.4, P < 0.01).

We provide novel evidence of OPN involvement in pigmented gallstone pathogenesis in rats.

In 1986, Burkhoff and Sagawa^[1]observed that left ventricular pressure decreased linearly as the QRS duration (QRSd) increased in a pacing experiment. Subsequently, it became recognized that either left bundle branch block (LBBB) or right ventricular pacing could result in prolonged QRSd, with potential deleterious effects on cardiac function and increased risk of atrial fibrillation (AF), heart failure, and mortality.^[2]Although previous clinical trials have demonstrated that patients with LBBB and heart failure could benefit from biventricular pacing (ie,biventricular cardiac resynchronization therapy [BiV-CRT]), 30% to 40% of such patients do not respond to BiV-CRT and approximately an additional 10% of patients remain untreated owing to an unsuitable coronary sinus vein. With the development of appropriate implant tools, His bundle pacing (HBP) has become increasingly important to enhance pacing as an adjunctive therapy in heart failure treatment. Various studies have demonstrated that CRT utilizing HBP (His-CRT) may be valuable in patients with no response or failure to place a BiV-CRT. However, HBP has higher pacing threshold and lower R-wave amplitude shortcomings and cannot correct LBBB in patients with distal conduction system disease.

Stroke is the second leading cause of death globally and accounts for an estimated 5.5 million deaths each year worldwide.^[1]Revascularization of the carotid artery is one of the key procedures to reduce the incidence of stroke. Chronic total occlusion (TO) and near-total occlusion (NO) of the carotid artery are rare. Treatment for TO and NO is controversial with potential complications, including periprocedural stroke, intracranial hemorrhage, and carotid-cavernous fistula (CCF).^[2]There have been attempts to implement carotid artery endarterectomy (CEA) and endovascular treatment, but the success rates were far from satisfactory. For patients with TO, the success rate of revascularization is around 40% and 60%, respectively, for CEA and endovascular technique.^[3]For patients with NO, the morbidity and mortality rates are 3% and 9%, respectively.

The incidence of congenital uterine anomalies (CUA) appears to be higher than previously thought owing to improved diagnostic imaging modalities.^[1]A recent systematic review has estimated the prevalence to be 5.5% in the unselected population, 8.0% in infertile women, and 13.3% in those with a history of miscarriage. The commonest anomaly across all populations appear to be the septate variety (ie, canalization defects) followed by the bicornuate variety (ie, fusion defects).^[2]Another meta-analysis has shown that several adverse reproductive outcomes associated with CUA, such as increased miscarriage rates, increased preterm delivery rates, and increased perinatal mortality rates.^[3]

Pathologically, retroperitoneal liposarcoma (RPLS) is a group of malignant tumors, which originates from adipose tissue in retroperitoneal space, accounting for almost 70% of all retroperitoneal tumors. RPLS has no optimal treatment. Surgical resection (R₀/R₁) is the most effective therapy; however, recurrence rate is very high. Grossly incomplete surgical resection (R₂) is an important risk factor for early recurrence of RPLS.^[1]

To the Editor: Rheumatoid arthritis (RA) is an autoimmune disease characterized by invasive arthritis, affecting approximately 1% of the global population. Young and middle-aged women are prone to RA and can experience one or more pregnancies during the course of the disease. The developmental origins of health and disease describes how health hazards occurring at a young age could affect one’s health in later life.^[1]RA exposure during pregnancy can consequently influence the health of the offspring. This paper discusses the pregnancy status of women with RA and the possible influence of RA on the health of the offspring.

To the Editor: Chronic endometritis (CE) is a subtle type of inflammation characterized by the persistent presence of plasma cells in the stroma of the endometrium and is usually asymptomatic, only slight symptoms, such as abnormal uterine bleeding, pelvic pain, dyspareunia, or leucorrhea.

To the Editor:Interstitial lung disease (ILD) is a common extra-articular manifestation in patients with connective tissue diseases (CTDs), including rheumatoid arthritis (RA), which contributes significantly to the disease burden and excess mortality.^[1]It has been well-recognized that RA-associated ILD (RA-ILD) patients have a threefold higher risk of death than RA patients without ILD.^[2]However, among approximately 30% of ILD patients, the specific diagnosis cannot be made from clinical findings and high-resolution computed tomography features, resulting in diagnostic and management uncertainty.^[3]Noninvasive blood biomarkers with diagnostic and prognostic utility may, therefore, provide alternative information for identifying vulnerable patients,^[4]especially in clinical settings with limited medical resources. Dickkof-1 (DKK1) protein level was found to increase in lung tissue specimens from donors and idiopathic pulmonary fibrosis (IPF) patients.^[5]In this context, the DKK1 was able to alter Wnt-induced epithelial cell proliferation in a dose-dependent manner,^[5]implying clinical relevance of DKK1 in both ILD and RA.

To the Editor: There is limited evidence as to the association between outpatient visits in dermatology and meteorological factors. A previous study has focused on the effects of meteorological factors on a certain disease, and seemed to lack systematic analysis for a class of diseases.^[1]Here, we investigated the short-term effects of meteorological factors on the number of daily outpatient visits for skin diseases.

To the Editor:Infective endocarditis (IE) is a rare complication of hypertrophic cardiomyopathy (HCM) that may lead to fatal outcomes if the infection is not effectively controlled. We report three cases of hypertrophic obstructive cardiomyopathy (HOCM) complicated with IE, two of which were successfully treated by mitral valve replacement (MVR) and septal myectomy (SM) due to lack of clinical response to antibiotics, worsening heart failure, and severe mitral regurgitation.

To the Editor:Fulminant type 1 diabetes mellitus (FT1DM) is characterized by a rapid loss of β-cell functions, negative antibody to islet cells, ketoacidosis, and elevated pancreatic enzymes.^[1]In a nationwide survey in Japan, elevated pancreatic enzymes and abdominal pain were found in 98% and 70% of patients with ketoacidosisonset FT1DM, respectively. However, abdominal computed tomography (CT) showed no abnormalities. The increased pancreatic enzymes were related to diabetic ketoacidosis. Several Japanese scholars have reported that FT1DM appeared after acute pancreatitis (AP). So far, no such cases have been reported in China. Here, we report two cases of FT1DM following AP, review previous cases, and speculate the relationship between AP and FT1DM. Informed consents were obtained from both patients.

To the Editor: Targeted muscle reinnervation (TMR) is a surgical technique of multiple nerve transfers, providing a potential of improved intuitive prosthetic control via surface electromyography (sEMG) in the high-level upper extremity amputees.^[1]However, there is a risk that some of the reinnervations might be unsuccessful, especially for the ulnar nerve.^[2]Both the quality control of nerve stumps and the receptor are important factors for the surgery. Assessing the nerve stumps during the surgery and finding more muscles as receptor might address the problem. Biceps, triceps, and brachialis muscles were mostly chosen as receptors for reinnervation in the trans-humeral amputees. Pectoralis major and pectoralis minor were mostly chosen as receptors for reinnervation in the shoulder disarticulation patients.^[3]The deltoid muscle, which is composed of anterior, middle, and posterior parts, and supplied respectively by different branches of the axillary nerve, might be an addition option to increase the amount of receptor muscles.^[4]During the surgery, assessment of the location of residual nerve stumps with good quality or the specific branches dissected for receptor reinnervation is challenging.^[5]We conducted a study of two trans-humeral level amputees, who underwent TMR using posterior part of the deltoid muscle as one of the receptors and performing nerve assessment with intra-operative electrophysiological examination.

To the Editor: Ulcerative colitis (UC) is traditionally known to be confined to the large bowel. The presence of upper gastrointestinal (GI) involvement has long been considered as a sign of Crohn disease (CD) rather than UC. However, involvement of the upper GI and small intestine has previously been reported in UC.^[1,2]Importantly, both the symptoms and endoscopic features easily lead to a misdiagnosis of acute erosive or infectious gastroduodenitis. The present case highlights the need to consider upper GI involvement of UC as a differential diagnosis. This case may prompt physician to recognize the possibility of an adult-onset UC subtype involving the upper GI; to consider whether upper GI involvement should be classified as a special and rare type of UC like CD, suggesting that it may be a high-risk factor for active disease or poor prognosis; and to determine whether more aggressive treatment are needed for patients with this kind of condition.